Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareHomocysteine, Renal Biomarkers, Glucose, Glycated Hemoglobin and Lipid Profile in Diabetic Nephropathy Patients from Gaza Strip
English0108Yassin MMEnglish Alghora SSEnglish Alnajjar MKEnglish Yasin MMEnglishIntroduction: Homocysteine is recently speculated as an indicator for the development of diabetic nephropathy. Objective: To assess homocysteine in various stages of diabetic nephropathy and its correlation with other biochemical parameters. Methods: A mini questionnaire, and analysis of blood and urine were employed in 120 patients with type 2 diabetes (40 normo-, 40 micro- and 40 macroalbuminuric) and 40 non-diabetic controls. Results: Urinary albumin was significantly elevated in patients with normoalbuminuria (22.3±5.2 mg/g), microalbuminuria (146.7±80.7 mg/g) and macroalbuminuria (348.0±37.6 mg/g) than controls (15.9±4.8 mg/g), in microalbuminuria and macroalbuminuria versus normoalbuminuria, and in macroalbuminuria versus microalbuminuria. There were also significant increases in serum urea and creatinine in diabetic groups. Serum homocysteine behaves like urinary albumin in being significantly higher in diabetic groups (17.1±4.8, 20.3±5.9 and 22.9±5.5 µmol/l, respectively) than controls (13.4±3.7 µmol/l), in microalbuminuria and macroalbuminuria versus normoalbuminuria, and in macroalbuminuria versus microalbuminuria. Serum glucose, HbA1c, cholesterol, triglycerides and LDL-C were significantly increased whereas HDL-C was significantly decreased in diabetic groups. There were significant positive correlations of serum homocysteine with urinary albumin (r=0.564, PEnglish Serum homocysteine, Renal parameters, Glycated hemoglobin, Lipids, Diabetic nephropathy, Gaza StripINTRODUCTION
Diabetes mellitus is a metabolic disorder of endocrine origin with persistent increase of blood sugar. Prolonged hyperglycemia leads to serious damage to the heart, blood vessels, eyes, kidneys and nerves. The World Health Organization (WHO) estimated that around 422 million people all over the world are diabetic, and the annual deaths approach 1.6 million as a result of diabetes and its complications.1 These figures are expected to rise steadily over the coming few decades. Two major types of diabetes were identified; type 1 and type 2. Patients with type 2 diabetes have more complications than in type 1 patients, causing higher rate of morbidity and mortality.2 The prevalence of type 2 diabetes mellitus in Gaza Strip is relatively high and estimated at 16.8% in adults aged 42 to 74 years.3
Diabetic nephropathy is the manifestation of diabetic microangiopathy in the kidney, and is characterized by persistent albuminuria and a progressive decline in renal function.4 Appearance of albumin in urine in the range of 30-300 mg/g or microalbuminuria is the first clinical sign of diabetic nephropathy. Increase of urinary albumin excretion to more than 300 mg/24 hours is the case of macroalbuminuria which indicates the disease progression, usually accompanied with other diabetes complications such as retinopathy, cardiovascular disease (CVD) and neuropathy.5 More than 50% of patients with diabetes will progress to diabetic nephropathy in 10 to 20 years, making it one of the main causes of end-stage renal disease.6 Therefore, early detection and proper treatment of diabetic nephropathy are particularly important for patients prognosis.
Homocysteine is a sulphur-containing intermediary amino acid which is derived by the demethylation of the essential amino acid methionine.7 The main metabolic organs of homocysteine are liver and kidney. The normal range of serum homocysteine level is between 4.4 and 10.8 µmol/l. A condition of increasing levels of serum homocysteine beyond 15µmol/L is named as hyperhomocysteinemia.8 Elevation of serum homocysteine may be due to genetic insufficiencies of the enzymes needed for its metabolism, to nutritional deficits in vitamins B12, B6 and folic acid, or to medical conditions such as CVD.9,10 Several studies have also been indicated that homocysteine is closely related to the development of diabetic nephropathy.11,12 Hyperhomocysteinemia is reported to be a risk factor for diabetic nephropathy; which can directly produce cytotoxicity, lead to oxidative stress and synergistic glycation end products, and thereafter damage vascular endothelium and induce microvascular injury.13
Although type 2 diabetes and its complications account for approximately 5.7% of all Palestine mortalities3, there is a lack of diagnosis and/or under-reporting of the disease and its progression towards the end-stage renal disease. This necessitates searching for other diagnostic markers for diabetic nephropathy, besides the traditional ones. The published articles on diabetic nephropathy among Palestinians are few and recent.5 There is no previous study investigates homocysteine status among diabetic nephropathy patients in Gaza Strip. To our best knowledge, this is the leading investigation of homocysteine level and its correlations with other biochemical parameters in diabetic nephropathy among type 2 diabetic patients in Gaza Strip. Understanding of homocysteine status and its variation, as well as its relation during trans changes to diabetic nephropathy, could offer diagnostic and management values on the progression of this life-threatening disease.
MATERIALS AND METHODS
Type of study design and target population
This is a case-control investigation. A total of 120 patients with type 2 diabetes were chosen from the main and representative Diabetic Care Unit in Gaza Strip (Al Rimal Medical Center); previously diagnosed according to the World Health Organization diagnostic criteria for diabetes.14 The diabetic patients were three groups: Group I comprised 40 patients (20 males and 20 females) with normoalbuminuria (Urinary albumin300 mg/g). The exclusion criteria were urinary tract infection, hypertensive patients (Blood pressure ≥140/90 mmHg), pregnant women, and women under hormonal therapy. Forty non-diabetic healthy individuals (20 males and 20 females) were chosen randomly from general population in Gaza Strip, and constituted the control group. Patients and controls were age matched (40 to 65 years old).
Ethical consideration
Helsinki committee provided us with written approval to perform this study under the ethical number PHRC/HC/28/13 in Gaza Strip, and an informed consent form was signed by all patients and controls prior to commence the study.
Questionnaire interview and patients’ records
Patients and controls filled in a mini questionnaire designed to suit the purpose of the study. The questions were simple, clear, direct, and depend on diabetes clinic questions adopted by the Palestinian Ministry of Health with some modifications.15 The majority of the questions were of the yes/no category, which provide a dichotomous choice.16 The questionnaire was piloted with 12 individuals (3 from each study group) not involved in the population sample. The questions were related to age, education, employment, family history of diabetes and diet. Clinical data including diagnosed diabetic complications and duration of diabetes were obtained from the patients’ records.
Urine and blood analysis
Blood and random urine samples were obtained from all participants. A fraction of blood was placed into EDTA vacutainer tube to determine HbA1c. The remainder quantity of blood was placed into a plastic tube, and left for a short period without anticoagulant to allow blood clotting. Blood samples in plastic tubes and urine samples were centrifuged at 4000 rpm/10 min using a Rotina 46 Hettich Centrifuge, Japan. Then, the obtained serum and urine samples were analyzed. Albumin concentration in urine was measured by Immunoturbidimetry-Latex assay using BioSystems kit, Spain.17 Serum homocysteine was quantitatively analyzed by enzymatic colorimetric method, using Globe diagnostics kit, Italy.18 The urease glutamate dehydrogenase/UV and the alkaline picrate procedures were employed for serum urea and creatinine measurement, using the BioSystems kit, Spain.19,20 The method employed for determination of serum glucose was glucose oxidase/glucose peroxidase (POD), using Labkit Kits, Spain.21 HbA1C was estimated through determination of glycated hemoglobin in blood as a whole with the use of Stanbio Kit, Texas-USA.22 The cholesterol oxidase/POD and the glycerol phosphate oxidase/POD assays were followed in the determination of serum cholesterol and triglycerides, using the BioSystems kit, Spain.23,24 The precipitating procedure was applied for measurement of high-density lipoprotein cholesterol, using Labkit kit, Spain25, and finally, low-density lipoprotein cholesterol was calculated using the empirical relationship of Friedewald.26
Statistical analysis
The obtained data were computer analyzed using IBM SPSS statistics version 22. A simple frequency of the study variables was presented. Chi-square (c2) was applied to show the difference between variables. Yates's continuity correction test, c2(corrected), was employed when not more than 20% of the cells had an expected frequency of < 5. The continuous variables were expressed as mean ± standard deviation and compared using the independent one-way analysis of variance (ANOVA) to test the relationship between various diabetic groups and controls. Bonferroni test served to test the difference within different studied groups. To examine the correlations between homocysteine and other studied parameters, the test of Pearson's correlation was used. The level of significance was considered when the probability values (P)Englishhttp://ijcrr.com/abstract.php?article_id=4289http://ijcrr.com/article_html.php?did=4289
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Martella BM, Veiga GRL, Alves BCA, Azzalis LA, Junqueira VBC, Gehrkei FS, et al. The importance of homocysteine levels in the prognosis of patients with chronic renal disease and in hemodialysis patients. J Bras Patol Med Lab 2018;54(3):170-6.
Rujaswini T, Praveen D, Chowdary PR, Aanandhi MV, Shanmugasundaram P. A review on association of serum homocysteine in diabetic neuropathy. Drug Invent Today 2018;10(2):154-6.
Chrysant SG, Chrysant GS. The current status of homocysteine as a risk factor for cardiovascular disease: a mini-review. Expert Rev Cardiovasc Ther 2018;16(8):559-65.
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Wang T, Wang Q, Wang Z, Xiao Z, Liu L. Diagnostic value of the combined measurement of serum hcy, serum cys C, and urinary microalbumin in type 2 diabetes mellitus with early complicating diabetic nephropathy. ISRN Endocrinol 2013;2013:407452.
Guo J, Ren W, Li X, Xi G, Liu J. Correlation between hyperhomocysteine and serum cystatin C in diabetic nephropathy. Biomed Res 2017;28(11):5153-57.
Xu W, Tang S, Xiang M, Peng J. Serum homocysteine, cystatin C as biomarkers for progression of diabetic nephropathy. Pteridines 2019;30:183-8.
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Palestinian Ministry of Health. Diabetic questionnaire, Diabetic clinic records. Palestine: Gaza Strip; 2006.
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Bergmeyer HU. Methods of enzymatic analysis. second ed. New York: Academic Press; 1974. Weinheim: Verlag Chemie.
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Trinder P. Determination of glucose in blood using glucose oxidase. Ann Clin Biochem 1969;6:24e33.
Trivelli LA, Ranney HM, Lai HT. Hemoglobin components in patients with diabetes mellitus. N Engl J Med 1971;284(7):353e7.
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareSpatial Patterns and Temporal Trends of Human Leishmaniasis Incidence in Khemisset Province, Morocco
English0915Hanna MEnglish Boussaa SEnglish Raghay KEnglish Mabchour IEnglish Fadli MEnglishLeishmaniases are parasitic diseases caused by Leishmania species and transmitted by the phlebotomine sandflies. In Morocco, Leishmaniases are a major public health problem with two clinical forms: cutaneous and visceral Leishmaniasis. Khemisset Province is one of the Moroccan regions where cases of both cutaneous and visceral Leishmaniasis were reported without official data about epidemiological status. Epidemiological and entomological investigations were conducted in Khemisset Province based on 20-year epidemiological data (1997-2016). The results showed the presence of both clinical forms of Leishmaniasis in the study area. All ages and both genders were affected by these different forms of the disease. Five sandfly species were identified morphologically in the study area with the dominance of Phlebotomus sergenti (61.11%). The Province of Khemisset should be regarded as a potential focus for Leishmaniasis in the region because of the presence of all the components of the disease transmission cycles. It is suggested that the competent authorities monitor the Khemisset area constantly to prevent the danger and spread of this epidemic.
EnglishLeishmaniasis, Phlebotomy, Sandfly, Epidemiology, Morocco, Epidemic
Introduction:
Leishmaniasis is a complex of diseases caused by Leishmania species and transmitted by a Phlebotomine sandfly (Diptera:Psychodidae). These parasitic diseases present a wide range of clinical symptoms and epidemiological entities. It is among the second most apparent resurging vector-borne disease, after Malaria; that currently threaten 350 million people in 88 countries.1 In Morocco, Leishmaniasis outbreaks are endemic and constitute a major public health threat.2 The cutaneous (CL) and visceral (VL) forms coexist with three species of parasites (Leishmania major, L. tropica and L. infantum) which share responsibility for cases of cutaneous leishmaniasis, while only L. infantum is responsible for the visceral.3
Three major sandfly vectors were found associated with dynamics of VL across Morocco; Phlebotomus ariasi, P. perniciosus and P. longicuspis, .P. papatasi and P. sergenti are the proven vectors of L. major and L. tropica, respectively.4,5 Several mammals’ reservoirs were associated with the disease transmission across the country; dogs for zoonotic VL, rodents for zoonotic CL and human for anthroponotic CL.6
The problem of Leishmaniasis has been identified as a priority for the national Ministry of Health. Since 1995. Leishmaniasis has become a notifiable disease and in 1997 our country invested in the fight against these diseases by implementing an action plan with general objectives as early management of cases of VL and disease control in outbreaks of cutaneous leishmaniasis.2
Khemisset is one of the Moroccan regions where epidemiological status of human Leishmaniasis is unknown. In spite of the presence of canine Leishmaniasis, and its position beside the active Leishmaniasis outbreaks in central Morocco: in the Fez-Meknes region, and in the Benimellal-Khenifra region, no data about entomological or epidemiological investigations, in Khemisset region, were recorded.7, 8
The objective of our investigation is to study, for the first time, the epidemiological status of leishmaniasis in Khemisset province where cases of both forms of human leishmaniasis have been recorded.
Materials and Methods
Study area:
Administratively, Khemisset Province is part of Rabat - Salé - Kenitra region (Figure 1), the total area of the province is 781,000 hectares, of which 47.7% is agricultural land, 40.6% forest and 11.7% rangeland and wasteland.9 The province is made up of 4 Circles, 32 rural municipalities and three urban municipalities. In 2014, the total population was 542025 inhabitants with the majority in rural municipalities.10
The dominant climate type in the region is semi-arid to arid with some years characterized by a sub-humid climate when annual rainfall exceeds 600mm/year.11 geographically; Khemisset province is composed of two entities: plateaus and depressions.12
Epidemiological data:
The present study is a retrospective analysis of the leishmaniosis status at Khemisset province. Epidemiological data were obtained from the register of the Laboratory of Epidemiology and Environmental Health, in the local Delegation of Ministry of Health. The authorization has been obtained from the Regional and local Health Department to examine these registers.
All microscopic preparations concerning leishmaniasis cases, carried out in the different health districts of KhemissetProvince, are sent and archived in this laboratory. Thereby, we collected 20-year epidemiological data (1997-2016) for analysis.
Entomological data:
Specimens were collected from ten stations in the study area using 30sticky traps by the station during the entomological season (May-July 2018). Thus, traps were placed in the evening, in different biotopes, and recovered the next morning. Traps were prepared with A4 sheets coated with castor oil. The collected specimens were stored in 70° alcohol for lightening and rapid assembly in the chloral balm for species identification.13
The identification was made morphologically by examining the male genitalia, female spermathecae and pharynges based on the key for the determination of Moroccan sandflyMahjour et al. (1997), and referring to Boussaa Samia, (2008), for the identification of species of the subgenus Larroussius.3,14
Results
Epidemiological status of leishmaniasis in Khemisset:
According to epidemiological data, both forms of leishmaniasis (CL and VL) were recorded in Khemisset Province (Table 1). According to epidemiological data (Table 1), both forms of leishmaniasis (CL and VL) were recorded in Khemisset Province. The rural area is more affected by leishmaniasis cases (76%) compared to (15%) in urban areas. The epidemiological profile of leishmaniasis in our study area assumes that the disease affects both sexes and different age groups (Figure 2). The epidemiological profile of leishmaniasis in our study area assumes that the disease affects both sexes and different age groups (Figure 2). Figure 3 shows the distribution of leishmaniasis forms according to age.
Spatiotemporal trends of leishmaniasis in Khemisset:
Figure 4 presents maps illustrating the spatial evolution of visceral leishmaniasis (a) and cutaneous leishmaniasis (b) in Khemisset Province based on epidemiological data. Analysis of secular trend of leishmaniasis (both VL and CL) cases (Figure 5) shows that the highest number of 6 cases was noted in 2010. The seasonal fluctuation of leishmaniasis cases recorded in the study area (Figure 6) shows the difference in the number of visceral leishmaniasis cases recorded by season.
Sandfly species composition in Khemisset:
Thus, our entomological investigations were conducted in urban and rural municipalities of Khemisset Province where leishmaniasis cases were detected in the study area as shown in Table 2. The study area covered an altitude range of 225-1221m.
Table 3 shows the percentages of different species collected in our study area where five species were morphologically identified. Five species were identified morphologically. Phlebotomussergenti was the most dominant species (61.11%), followed by P. longicuspis (20.37%), Sergentomiyaminuta (11.11%), P. ariasi (5.56%) and P. perniciosus (1.85%).
Discussion
As noted recently in Morocco, both forms of leishmaniasis coexist in several northern and central regions, such as Taza, Moulay yaacoub, SidiKacem, Chefchaoune, El Haouz and Lhoceima.2 In the study area, the recorded VL cases are due to Leishmania infantum while L. tropical and L. major are responsible for the cases of CL. The visceral leishmaniasis by L. infantum is the dominant form (52%) of leishmaniasis in the province. Results suggesting the local L. infimum transmission cycle since Natami et al. (2000), reported canine leishmaniasis by L. infantumin this area with a serape valence of 16.71%.15. Concerning the rural area is more infected with leishmaniasis than the urban area, this results is in line with the WHO reports confirming the rural nature of this disease.16 Thus far, leishmaniasis affects the rural sector more than the urban sector in Morocco, as confirmed by different investigations in leishmaniasis foci in northern and central Morocco.17
The results show that there is no relationship between sex and leishmaniasis. It is statistically confirmed, whether visceral (P=0.19) or cutaneous (P=0.23) form. But results confirmed a relationship between leishmaniasis and patient age. Our result is in agreement with those of other works. In Morocco as 81% of VL cases are less than 9 years old (Mahjour et al. 1997).3 In Tunisia, Aounet al.(2009), concluded that children under five years old are the most affected group by VL. Globally, VL is known as infantile disease but it can affect adults, particularly in HIV-L. infantum co-infection condition. 3, 18, 19 On the other hand, the age-specific risk depends on the parasitic species and the population's exposure history. Thus, in endemic area of L. infantum, the median age of clinical cases of VL tends to be lower (generally < 5 years), while it occurs in adults mainly in cases of severe immune deficiency.20, 21
Concerning CL distribution according to age groups (Figure 3), 52% of cases range between 15 and 49. These results are consistent with the results found in other regions in Morocco by Arroub et al. (2012) , in Tunisia by Abda et al. (2010 ) and in Iran by Fazaeli et al. (2009) showing that the young population is the most affected by CL.22-24
For the visceral form we can see that in 1997, five municipalities were affected by the disease while between 1998 and 2016, the number of affected municipalities increased from 5to 14 (Figure 4-a) For cutaneous form we can see that in 1997, one municipality was affected by the disease while between 1998 and 2016, the number of affected municipalities increased from 1 to 10 (Figure 4-a). As a secular trend of leishmaniasis cases (both LV and CL) the highest number of 6 cases was noted in 2010 as well. According to the same distribution (Figure 5), only VL was recorded between 1997 and 1999, while CL was introduced since 2000. In 1997-2016 period, VL cases peaked in 2003 whereas CL cases peaked ten years later in 2013 (Figure 5). We noted also the dominance of the visceral form until 2010, then, CL cases became more frequent.
Most cases of visceral leishmaniasis were detected in December and July. This seasonality could be related to the seasonal dynamics of vector species and the incubation period of the disease. For cutaneous leishmaniasis, the recording of cases is spread over a precise period, with an absence of cases in April, August and September. Studying the sandfly species composition and its bionomics is an interesting tool for a better understanding of the disease transmission dynamic and it contributes to the planning for the prevention and control against leishmaniasis particularly in the areas where the risk of leishmaniasis extension is thought to be significant.
The vector species for two clinical forms of leishmaniasis in Morocco coexist in our study area; namely Phlebotomus sergenti, the proven vector of CL caused by L. tropica and the three species (P. longicuspis, P. ariasi and P. perniciosus) of VL caused by L. infantum.4 Results explain the presence of cases of both clinical forms of leishmaniasis in the Khemisset Province and confirm the hypothesis of local transmission cycles. The Zonerisk of leishmaniasis can be characterized by vector abundance (The abundance of vector species is an important risk factor for characterization of a leishmaniasis endemic area). According to biotopes, entomological data (Table 1) shows the presence of sandfly in both urban and rural areas, with altitudes between 225 and 1221m. The five species were collected in rural area; while only P. sergenti collected in urban area. The sandfly species diversity in rural areas is favored by the presence of reservoir animals coupled with poor hygiene and sanitation facilities, and the abundance of organic matter.2
In Morocco, sandfly seasonality is widely studied. In semi-arid area of Marrakech (at 466m), P. sergenti was active especially during the period of April–May–June and absent in the rest of the year.13 In semi-arid area of Chichaoua Province (at 1148 m), P. sergenti population reached peak density during July and August and was lowest from September through November.25
For Larroussius species activity, in semi-arid area of Ourika (at 850 m), P. perniciosus, P. longicuspis and P. ariasi activities show a bimodal seasonal trend with two abundance peaks, in summer (May–June–July) and in autumn (September–October), while in Yabora (at 1155 m), their activities show a mono-modal annual pattern with a long activity period extending from March to November with the highest density recorded in June.25 P. sergenti and Larroussius species activities determine necessarily the seasonal fluctuation of leishmaniasis cases recorded in the study area (Figure 6).
Conclusion:
The number of cases recorded in our study area is not alarming but obviously informative on the local presence of all the components of the disease transmission cycle. Consequently, the Province of Khemisset should be regarded as a potential focus for leishmaniasis because of the following tangible reasons:
- Leishmania species, confirmed by recorded human cases;
- Animal reservoir, confirmed by canine leishmaniasis cases;
- Proven vectors of CL and VL in Morocco
- Active human leishmaniasis foci in the region with human population movements;
Taking into consideration the under-reporting of human cases, particularly in rural areas, the results of the present study are enough for continuous epidemiological surveillance to prevent the risk.
Acknowledgement:
We are very grateful to all medical staff in the Health Delegation of the Moroccan Ministry of Health in Khemisset province. Also, the authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Source of funding:Nil
Conflict of Interest:Nil
Authors’ Contribution:
Author's name
Contribution
Hanna Marwa
Writing the article
BoussaaSamia
Critical revision of the article
Raghay Kawtar
Data analysis and interpretation
Mabchour Insaf
Interpretation of data
Mohamed Fadli
Final approval of the article
Englishhttp://ijcrr.com/abstract.php?article_id=4290http://ijcrr.com/article_html.php?did=4290
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Moroccanministry of Heath. 2008.Bilan des activités des programmes de lutte contre les maladies parasitaires Ministère de la Santé. Direction d’épidémiologie, p230.
Hanna M., Boussaa S, and Fadli M. 2018. Contribution à l’étude de l’effet des changements climatiques sur la biodiversité des phlébotomes dans la région de zemmour, Maroc, Proceedings of the First National Colloquium :"Biotechnology of Natural Substances and the Environment" Khenifra April 19th,p 118-121
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Boussaa S. 2008. Epidémiologie des leishmanioses dans la région de Marrakech, Maroc: effet de l’urbanisation sur la répartition spatio-temporelle des Phlébotomes et caractérisation moléculaire de leurs populations. 2008. Thèse de Ph.D. Strasbourg 1.
El Aasri A., El Madhi Y., Najy M., El Rhaouat O, Belghyti D. 2016. Epidemiology of cutaneous leishmaniasis in SidiKacem province, northwestern Morocco (2006–2014). As. Pac. J. Tro. Dis,6(10), 783-786.
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Elkohli M., Laqraa E., Adlaoui E., Faraj C.2015. Abondance et distribution spatiotemporelle de Phlebotomus sergenti, vecteur de la leishmaniose cutanée à Leishmania tropica, au Maroc, Bulletin de l’institut national d’hygiéneedition semestrielle janvier-juinN°3 ministére de la santé royaume du Maroc, pages 2-3
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareExploring Coverage of Non-communicable Diseases in Newspapers
English1621Chitra M KotianEnglish Kumar SumitEnglish Shubha H.S.EnglishIntroduction: Non-communicable diseases (NCDs) are posing a major public health challenge in all countries globally. The print media, especially newspapers, can play a significant role in sensitizing people about the various risk factors, disease symptoms, available treatments, and recommendations for a healthy lifestyle. This study aimed to analyze the coverage of NCDs in English and Kannada daily newspapers and to understand the perspective of physicians and journalists towards it. Methods: Content analysis of two newspapers was carried out for assessing the coverage of articles based on NCDs. It was followed by carrying out in-depth interviews with 11 physicians and 11 journalists to understand their perspectives on coverage of NCDs in daily newspapers. Thematic analysis of the in-depth qualitative interviews was done manually to identify codes and categories. Results: The percentage of the total area occupied by NCD-related news in the daily newspaper was minimal (0.07%). According to the physicians, the coverage of health in newspapers was insufficient, and the presence of health products advertisements was misleading. The in-depth interviews with journalists revealed barriers in health reporting like difficulty in understanding medical terminologies, lack of insight into topics that need attention, and time constraints. Conclusions: This study directs attention towards better communication between health professionals and journalists for improved health coverage in newspapers
EnglishContent analysis, Health communication, Journalists, Newspapers, Non-communicable diseases, Physicians, qualitative studyIntroduction:
Non-communicable diseases (NCDs) are posing a significant public health challenge. In 2016, they accounted for 71% of the deaths globally and 61.8% of India's deaths.1,2 Majority of the NCDs are preventable, and the mass media can play a crucial role in creating public awareness. Newspapers are an essential source of daily information and can shape public perceptions regarding major health issues. In India, 407 million people read daily newspapers (2017 Indian Readership Survey report), an 8% increase compared to the 2014 IRS report.3 There is a rise in the circulation of regional newspapers owing to the increasing literacy rates in the rural population.
For public health professionals to channelize mass media to disseminate health awareness information, it is essential to understand print media's functioning and health coverage status in newspapers. Physicians, as well as journalists, play essential roles in disseminating health communication. However, both groups have different set of views and opinions. There have been limited studies exploring doctors' and journalists' perspectives on health reporting in newspapers, particularly in the Indian subcontinent. The study aimed to understand the newspaper reportage of NCDs by analyzing the coverage and exploring physicians' and journalists' perspectives towards it.
Methods:
Our qualitative study was conducted in Udupi, Karnataka, India, between January to June 2018. The study was carried out in two phases. The first phase included carrying out a content analysis of two newspapers for assessing the health content in particular to the coverage of articles on non-communicable diseases. This was followed by carrying out in-depth interviews with 11 physicians and 11 journalists to understand their perspectives on coverage of non-communicable diseases in daily newspapers.
Phase 1 (Content analysis):
Content analysis of two newspapers, English' Times of India' (TOI) and Kannada' Udayavani' was conducted for issues from 1st October and 31st December 2017 including supplements and health advertisements. A coding sheet was developed for carrying out the content analysis considering the following parameters: day of the week, page no., the section of the newspaper, graphics, no. of images, total area, type of article, and the theme/ topic of the article. The data was entered and analyzed in MS Excel 2016.
Phase 2 (In-depth interviews):
A total of 11 physicians and 11 journalists were interviewed for the study. Prior appointment was taken from both the physicians and journalists. The interviews with the physicians were carried out at their clinic, and the interviews with the journalists were carried out in their respective offices. The interviews were audio-recorded after obtaining written informed consent from the participants. On average, the interviews lasted for 30-45 minutes. The interviews were carried out in English and Kannada as per the convenience of the participants. After the interviews, the transcripts of the interviews were prepared, and accordingly, the translation was done. Thematic analysis of the in-depth qualitative interviews was done manually to identify codes and categories.
Ethical approval: The ethical clearance for the study was obtained from the Institutional Ethics
Committee (IEC 794/2017).
Results:
Content analysis results
The percentage of the total area occupied by NCD-related articles between October to December 2017 in TOI was 0.06% and 0.07% in Udayavani (Table 1). Out of 680 health-related content published in both newspapers, 163 were NCD-related. Among the 163 articles, 50.92% (n=83) were articles on NCDs, and 49.07% (n= 80) were NCD related advertisements. Among the 83 articles on NCD, 34 were published in TOI, and 49 were in Udayavani. Table 2 describes the frequency of the different categories of NCD-related news articles printed in these two newspapers. The NCD-related awareness articles were higher in Udayavani due to the weekly health supplement Arogyavani. The English newspaper had more of NCD-based news stories, editorials, feature articles, reports of the journal published research articles as compared to the Kannada newspaper. Advertorials were present in Udayavani.
Figure 1 compares the frequency of NCD-related news articles and advertisements in the TOI and Udayavani. The percentage of NCD-related advertisements in the Kannada newspaper was high as compared to that of the English newspaper. Udayavani provided more news coverage to NCD-related camps and awareness programs and articles on diabetes and chronic respiratory diseases. In contrast, the TOI focused more on articles related to cancer, mental health, and eye-related chronic diseases(Figure 2). Among the NCD-related advertisements (n=80), 54% were related to products like pain relief oil, and diabetes medication, and 46% were related to hospital services and healthcare providers. No NCD-related article appeared on the front page of either English or Kannada newspaper.
Qualitative analysis results
The qualitative analysis was done under two main categories for physicians and journalists: 1) Perceptions on reporting of non-communicable diseases, 2) Suggestions to improve health reporting. The qualitative analysis for the journalists included an additional category of factors affecting health reporting. Findings are reported along with quotes from the participants.
Physicians
Category 1: Perceptions on reporting of non-communicable diseases
Code: Health seeking behaviour
The majority of the physicians believed that newspapers could play a role in promoting the health-seeking behavior of the people. Especially in rural areas, health articles published in the regional newspapers can be a source of information, increasing awareness, thereby leading to an increase in screening. "Many times, it has happened that patients walk into our clinic with a newspaper cut out of a health article saying that I think I have the same symptoms which are described here. This is the sign of a very nicely written article where the patient could relate to his symptoms in an article, and he could come to a health professional seeking assistance." (Physician 3)
Code: Insufficient NCD coverage
The physicians expressed that there was insufficient coverage of lifestyle diseases in the daily newspapers. They felt the weekly health supplement carried out health-related information; however, on other days, there is insufficient health news coverage. "Media have dedicated one day I think to talk with a doctor. However, the highlight is on important occasions like World Heart Day and Doctor's Day, but other than that, there is no proper space given for covering the non-communicable disease." (Physician 4)
Code: Misleading advertisements
The physicians opined that the presence of a large number of advertisements on NCDs was misleading. Most of the time, the placement of these health-related advertisements was next to the health awareness articles, thereby attracting the readers' attention. Some physicians reported that many patients came to them with complications faced because of these advertised products. The physicians believed that the media should thoroughly regulate the advertisements in the newspapers."People are misguided by these advertisements because the people are fed up with their diseases. They will try to find an easy way to get a cure. Advertisements take advantage by misusing people's emotions and selling stuff that does not have any medical records or proper studies. Some people have got a habit of buying medicines over the counter just by seeing these advertisements." (Physician 5)
Category 2: Suggestions to improve health reporting
Code: Consulting a physician before publishing
Most of the physicians felt that the healthcare article should be checked by a medical professional for accuracy and relevance before printing in the newspaper. They felt that, at times, newspaper tends to sensationalize health news to attract the attention of the readers, often leading to fear and panic. "Form a panel with physicians who are genuinely interested and take their help to come out with concrete write up or way of presenting with regards to medical terms." (Physician 6)
Code: Writing easily understandable health articles
Many of the physicians felt that it is vital to write articles that a layperson can easily understand. Most of the awareness articles that are being written include a lot of technical terms that are difficult for the public to grasp.
Code: Continuity of the health articles
The physicians also believed that the awareness articles that are published in the newspapers should not be one-time but a series of articles on a particular topic. "Suppose today if they write one article about diabetes, the same article must be continued next week. Sometimes they will write one article and next week they will write another topic, people end up forgetting." (Physician 2)
Journalists
Category 1: Perceptions on reporting of non-communicable diseases
Code: The importance is given to immediacy
The majority of the journalists believed that newsworthy articles get reported in newspapers. Thus, health awareness articles were often not prioritized. "When it comes to news, health awareness articles cannot attract readers, like there are days like diabetes day that is fine but if an article on five people affected by malaria, there will be many readers for that" (Journalist 4)
Code: News articles catered as per rural/urban readers
The English newspaper carried more articles on cancer, mental health, and chronic disease. The journalists explained the difference in the audience of newspapers. The English newspaper usually targets readers in the city area, so it publishes articles according to the needs of the urban readers. Meanwhile, the Kannada newspapers target the rural population, hence news coverage on health camps was beneficial as it could make people aware of it. "English newspaper people read it for knowledge, leisure, and they don't go often for such camps, they usually directly go to the doctor. Kannada newspapers write about camps with regional readers in mind. People from rural areas who get health checked for the first time generally go for the free camps reading from Kannada newspapers." (Journalist 6)
Code: Advertisements are a source of revenue and catered to readers
The majority of the journalists opined that advertisements are one of the significant sources of revenue for the newspaper. The differences in the number of advertisements were because it is expensive to print advertisements in an English newspaper as compared to the regional newspaper.
Category 2: Factors affecting health reporting for journalists
Code: Difficulty in understanding medical terminologies
Many journalists said that the most significant barrier while reporting health news was the difficulty in understanding various medical terminologies and later simplifying and writing them in newspapers.
Code: Lack of insight into topics that need attention
The journalists opined that although they are interested in covering health issues, they lack insight into the health issues that need attention. The journalists felt that with guidance on topics that needs to be covered, they could report health issues better.
Code: Time and space constraints in newspapers
The journalists opined that daily newspapers are time-bounded, unlike a periodical, and found it challenging to devote time to health news. Space constraints in the newspaper were another restricting factor. The reporters usually must go by the space allotted to them to cover health issues. The journalists felt that the newspaper should allocate a health column or designated space for carrying out health stories.
Code: Interest/Motivation of journalists
Covering health issues depends on the interest levels of the journalist. Journalists with a science background had more interest in covering health news than a journalist without a science background who felt covering health news was similar to crime, politics, or sports.
Category 3: Suggestions to improve health reporting
Code: Need for better health reporting training
Most of the journalists believed that they lacked the skills needed to write health articles and there was a need for a training workshop. They felt it was essential that the workshop be skill-based. "Those who give training should have an idea of how newspapers and media work; otherwise, it is of no use. They only think from their perspective." (Journalist 2)
Code: Sharing health research findings through media
Few journalists opined that there was a need for printing more Indian-based research in the newspaper. "Health-based research articles always get published in research journals, but the findings are not conveyed to the mass. So, if it comes to the newspaper, then it is more interesting. People will come to know what is happening." (Journalist 5)
Code: Communication between the medical sector and media
The most critical need was to bridge the gap in communication between physicians and journalists. Few journalists did often interact and clarify their doubts with doctors. However, for others, there was still a lack of interaction with the medical fraternity. The journalists felt that there was difficulty in accessing information from them.
Figure 3 summarizes the key findings of physicians' and journalists' perceptions on coverage of non-communicable diseases in newspapers.
Discussion:
To the best of our knowledge, this is the first Indian study of its kind to analyze the coverage of health, especially NCDs and explore the perspectives of journalists and physicians on it. Content analysis of TOI and Udayavani revealed that the percentage of the total area occupied by NCD-related articles was minimal (0.07%). The percentage of NCD-related news articles in English newspapers was higher as compared to the percentage of NCD-related advertisements. However, it was the opposite in the case of the Kannada newspaper, whereby the percentage of NCD-related advertisements was higher as compared to news articles. Similar findings were seen in the study by Gupta A, Sinha AK.4 They reported that health-related news ranked first followed by advertisements in the English newspaper, whereas in the Hindi newspaper advertisements of health-related products and health care providers were more as compared to health articles. In our study, we observed that there was no NCD-related news article that appeared on the front page of the newspaper of either English or Kannada newspaper for three months. Maheshwar M and Rao D5 in their study of quantitative analysis about nutrition and health messages during February 2010 in English (The Hindu) and Telugu (Eenadu) newspapers also did not find any nutrition-related article on the front page of either of the newspaper.
According to the thematic analysis of in-depth interviews with the physicians, it found that the physicians believed that newspapers could play an essential role in increasing awareness regarding NCDs. They opined that health issues could be addressed through newspapers and brought to the attention of the readers; however, health is not given much prominence in the newspaper.
The factors affecting health reporting in the newspapers identified by the journalists in this study included difficulty understanding medical terminologies, lack of insight into topics that need attention, time and space constraints, interest/motivation of journalists, and getting news verified from physicians. Similar findings were noted in a Norwegian study by Larsson et al.6 and a study conducted by Ashoorkhani M et al.7 in Iran. A study by Melinda Voss8 among health reporters in five Midwestern states revealed that one-third of the participants found understanding and reporting key health topics to be difficult, and 73% reported that health training was needed. Similarly, a cross-sectional study conducted in Isfahan, Iran, revealed that 97% of the journalists interviewed were eager to participate in specialized health education for health news reporting.9 Our study supports this finding as the majority of the journalists felt the need for training or workshop for better health reporting.
In our study both the physicians and journalists believed that newspapers could help to improve health awareness among the people. Both groups felt that the coverage of health in the newspapers was less. The physicians felt that efforts are needed to improve the quality of health articles published in newspapers. The journalists felt the need for guidance and feedback from physicians for writing health-related articles better. Thus, there is clearly a need for coordination between physicians and journalists to improve health reporting in daily newspapers.
Conclusion
Findings from our study reveal that the overall space occupied by health news and articles on NCDs in daily newspapers was less. Kannada newspaper carried more NCD-related advertisements in the newspaper as compared to the English newspaper. There was also a difference in the specific NCD topics covered by both newspapers. Qualitative interviews with the physicians revealed that the overall space and coverage for NCDs were insufficient, and the presence of NCD-related advertisements was misleading. The interviews with journalists showed that the priority was given more towards news that attracted the readers' attention, and most of the time, the articles were catered as per the rural/urban readers. Journalists also felt the need for guidance of the physicians for writing better health articles. Thereby, we conclude that there is a communication gap between physicians and journalists that need to be bridged, a focus that has not been highlighted in prior studies in public health and media studies.
Limitation of the study: Our study's limitations were that the content analysis was done for only two newspapers and a shorter duration.
Acknowledgement: The authors wish to acknowledge the contributions of Dr. Prakash Narayan, Associate professor, Prasanna School of Public Health Source of Funding: None
Conflict of interest: Authors have no conflict of interest.
Authors’ Contribution:
All authors (CMK, KS, SHS) contributed to the study's conception and design. The literature review, data collection and analysis were performed by CMK. The first draft of the manuscript was written by CMK. All authors (CMK, KS, SHS) were involved in the editing and review of the final manuscript. All authors read and approved the final manuscript.
Englishhttp://ijcrr.com/abstract.php?article_id=4291http://ijcrr.com/article_html.php?did=42911. World Health Organization. WHO | NCD mortality and morbidity. 2018. Available from: https://www.who.int/gho/ncd/mortality_morbidity/en/
2. Dandona L, Dandona R, Kumar GA, Shukla DK, Paul VK, Balakrishnan K et al. Nations within a nation: variations in epidemiological transition across the states of India, 1990-2016 in the Global Burden of Disease Study. Lancet. 2017 Dec 2;390(10111):2437–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29150201
3. Indian readership survey. IRS 2017 KEY TRENDS. 2018. Available from: http://mruc.net/uploads/posts/a27e6e912eedeab9ef944cc3315fba15.pdf
4. Gupta A, Sinha AK. Health Coverage in Mass Media: A Content Analysis. J Commun. 2010;1(1):19–25. Available from: https://pdfs.semanticscholar.org/98bd/13e0acb9fa6b0470a78504e5a3fa18a7a6f2.pdf
5. Maheshwar M, Rao DR. Quantitative Analysis of Nutrition and Health Messages in Indian Print Media. Public Heal Res. 2012;2012(2):28–31. Available from: http://journal.sapub.org/phr
6. Larsson A, Oxman AD, Carling C, Herrin J. Medical messages in the media--barriers and solutions to improving medical journalism. Health Expect. 2003 Dec;6(4):323–31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15040794
7. Ashoorkhani M, Gholami J, Maleki K, Nedjat S, Mortazavi J, Majdzadeh R. Quality of health news disseminated in the print media in developing countries: a case study in Iran. BMC Public Health. 2012 Dec 9;12(1):627. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22873836
8. Voss M. Checking the pulse: Midwestern reporters’ opinions on their ability to report health care news. Am J Public Health. 2002 Jul;92(7):1158–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12084701
9. Keshvari M, Yamani N, Adibi P, Shahnazi H. Health journalism: Health reporting status and challenges. Iran J Nurs Midwifery Res. 2018;23(1):14. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29344040
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareLaboratory Findings in Treatment & Prognostication of COVID-19
English2228Anuradha SekaranEnglish Swapna SEnglish Shruthi DulalaEnglish Maddipati Veda Ganga RiteshEnglish Jagadeesh Kumar VEnglish Nitin JagtapEnglish Naveen Chandra ReddyEnglish Sandeep LakhtakiaEnglish Duvvur Nageshwar ReddyEnglishIntroduction: Majority of COVID-19 patients present with mild disease. 20% of patients progress to severe disease and have high mortality, because of hyperinflammation, cytokine storm development, viral mutation and lack of specific targeted medication. Critical analysis of laboratory parameters and potential biomarkers aids in assessing the evolution of disease, rapid identification of severe cases, identification of possible impending cytokine storm and guide appropriate medical management. Aim: The aim of the current study is to identify the significance of laboratory parameters that assist in disease categorization, so as to initiate early medical management. Materials and Methods: Between April 1 to April 15 2021, we retrospectively and prospectively included 200 patients admitted with COVID-19 infection (COVID-19 RTPCR positive and CORADS >3). Clinical assessment including history and associated comorbidities were noted at admission. Correlation of laboratory parameters was performed with disease category along with duration of hospitalization and clinical outcome. Results: Out of 200 COVID-19 patients, there were 145 males (72.5%). Severe disease patients had significantly higher neutrophil percentage, ESR, lower absolute lymphocyte count, elevated serum Ferritin and LDH. Non-survivors had low oxygen saturation, high absolute neutrophil count, Neutrophil to lymphocyte ratio (NLR), ferritin, D-dimer, IL-6 and low platelets at admission. Conclusion: Laboratory parameters are rapid, simple, cost-effective and aid in early diagnosis in assessing the severity of disease by indicating changes in immune and clotting system. Dynamic measurements help in timely institution of treatment strategies.
English Biomarkers, COVID-19, CORADS, Fibrinolysis, Hypoxia, PandemicINTRODUCTION
COVID-19 infection due to SARS-CoV-2 is a fifth documented pandemic, declared as global health emergency by WHO.1
Due to sudden drastic increase in numbers of COVID-19 patients worldwide, treatment in intensive care units has become a challenge, and seriously affected the health resources all over the globe. SARS-CoV-2 in minor population of elderly patients and with preexisting clinical comorbidities such as cardiovascular diseases, diabetes, respiratory disease and other conditions show critical disease progression to severe stage involving lung and other organs and few of these patients require ventilation, plasma and ECMO therapy. Early identification of severe forms is essential for triaging of patients and control progression of the disease. 2
Currently majority of COVID-19 patients have mild self-limiting disease due to vaccination and mild herd immunity. 20% of COVID-19 are complicated and develop bacterial superinfections, organ dysfunction and progress to severe acute respiratory distress syndrome. 3
Cytokines are released by immune system cells and have a role in intercellular signaling. COVID-19 has an aggressive dysregulated inflammatory response of pro- inflammatory cytokines leading to hyperinflammation known as cytokine storm which causes tissue damage resulting in multiorgan failure including heart failure, septic shock, DIC, thromboembolism and death. Common laboratory parameters and potential biomarkers aid in assessing the disease evolution, effective and rapid identification of severe cases and for therapeutic management and particularly for home isolation patients.4
MATERIALS & METHODS:
STUDY DESIGN:
A prospective and retrospective study was conducted over a period of 15 days (between April 1 to April 15). A total 200 COVID-19 patients have been included in our study who were admitted in AIG hospital. All the symptomatic patients with RTPCR positive, CORADS >3 were included. Clinical history with associated comorbidities, laboratory parameters at different points of time (day 0, 3, 5, 10), treatment and outcome were analyzed. Correlation of laboratory parameters was done with disease categorization along with duration of hospitalization and treatment provided. Patient details were kept confidential.
INCLUSION AND EXCLUSION CRITERIA:
All patients with confirmed COVID-19 positive by RTPCR from nasal and throat swab and HRCT Chest findings CORADS 3 or more along with clinical symptoms were included. Associated co-morbidities documented include - Hypertension, Diabetes mellitus, Respiratory illness, cardiovascular disease, immunosuppression, patients on chemotherapy.
COVID-19 positive without any clinical symptoms or having CORADS< 3, those under home quarantine were excluded. Any readmitted patients after discharge were also excluded.
Ethical clearance was obtained from the Hospital ethical committee.
DATA COLLECTION:
Throat and nasal swabs for molecular identification of SARS-CoV-2 using nucleic acid amplification tests. Reverse transcriptase quantitative polymerase chain reaction (RTPCR) were obtained from COVID-19 patients using standard techniques as per ICMR recommendations.
Investigations included - complete blood picture (CBP), Erythrocyte sedimentation rate (ESR). Coagulation profile which includes Prothrombin time (PT)/ Activated partial thromboplastin time (APTT) / D-dimer, Liver function tests (LFT), Renal function tests (RFT). Inflammatory markers included serum Ferritin, Interleukin-6 (IL-6), Lactate dehydrogenase (LDH), Troponin and C reactive protein (CRP). Fasting blood glucose was not included in the analysis. All investigations were done at hospital using standard procedures on fully-automated analyzers.
An analysis of presenting symptoms, CT Chest, laboratory parameters over the days of admission (repeated based on clinical condition), treatment and outcome were noted (from electronic medical records).
For patients with mild disease, investigations were done once in 5 days. For patients with moderate or severe disease and those with clinical deterioration, the laboratory parameters were done more frequently (usually once in 2 to 3 days).
DEFINITION OF CLINICAL SEVERITY OF COVID-19:
According to clinical management protocol of COVID-19 published by the Government of India, Ministry of Health and Family Welfare, the infection has been classified into 4 categories based on clinical manifestations - mild, moderate, severe category and severe with sepsis. In this study, patients were categorized into three - mild, moderate and severe disease. Mild disease patients have symptoms such as fever, cough, sore throat, nasal congestion, malaise, headache with no breathlessness or Hypoxia (normal oxygen saturation) and no imaging symptoms of pneumonia. Moderate diseases are patients with fever and or hypoxia, dyspnea, cough, including SpO2 < 94% (range 90 -94%) on room air, respiratory rate > 24 per minute (pneumonia with no signs of severe disease). Severe diseases are patients with clinical signs of pneumonia plus anyone of the following: respiratory rate >30 breaths/min, severe respiratory distress, or SpO2800ng/ml in normal individual and >1000-1200ng/ml in 60-70 years of age. 13
Potential risk factors during hospitalization are DIC, infection, dehydration, mechanical ventilation and use of central venous catheter.14 Terpos et al. reported hypercoagulability is common and patients with elevated PT, APTT, FDP and D-dimer are associated with life-threatening DIC which needs continuous vigilance and prompt intervention. 15 Our study shows no significant difference in D-dimer, PT, and APTT between mild, moderate and severe cases. This may be due to small number of patients in our study.
INFLAMMATORY BIOMARKERS:
Dysregulation of cytokines and chemokines leads to pathological activation of innate and adaptive immunity that causes ‘cytokine storm’ syndrome (CSS). IL-6 is a cytokine that controls the immune response, cell proliferation and differentiation and is associated with pleiotropic functions such as acute-phase response. Increased levels of IL-6 (cut off- 80pg/L) in COVID-19 patients are associated with inflammation and extensive lung damage. IL-6 acts as a therapeutic target and using IL-6 inhibitors (Tocilizumab) can arrest the cytokine storm and cytokine storm-associated organ damage.16 Our study shows that the level of IL-6 was low in mild cases when compared with the moderate and severe cases, and also high in non-survivors. WBC in collected blood samples on storage continue to release interleukins leading to erroneous high values. Repeat testing may be sent to same lab for comparison. 16
CRP is an acute-phase reactant and a sensitive marker of inflammation, infection, tissue damage and production is stimulated by cytokines. The significant elevation is seen in early stages of infection, especially the severe grade reflecting lung lesions. Elevation of CRP often may precede CT findings. CRP value correlates with level of inflammation and acts as early prognosticator for severe cases. 12 In our study, there was no statistically significant difference between severe and mild cases However, mean level of CRP was higher in the severe group.
Procalcitonin is a glycoprotein and its synthesis is increased due to cytokines. Higher procalcitonin (PCT) concentrations (usually ≥0.05 ng/ml) can distinguish between severe and non-severe disease due to Covid-19, suggesting its prognostic significance. However, a recent meta-analysis reported a marginal benefit (by 0.2 ng/ml). 17 Among critically ill COVID-19 patients, PCT and CRP elevation may be associated not only with the inflammatory response but also with the higher frequency of bacterial super-infections (up to 50% rate among non-survivors).18 In our study, procalcitonin was not included in the analysis.
Ferritin is an acute-phase reactant elevated in inflammatory conditions and is a direct indicator of cellular damage. Ferritin synthesis is controlled by cytokines. Extreme higher values leads to increased expression of pro and anti-inflammatory cytokines, a hallmark of hyperferritinemia syndrome (macrophage activation syndrome). Values over 800ng/ml is directly related to organ damage and is an indication for steroid initiation with clinical correlation values over 2000ng/ml portend poor prognosis in hospitalized COVID-19 patients.19Henry et al. reported ferritin as a surrogate marker of immune dysregulation and prognosis and shows a direct correlation between serum ferritin and poor survival.7 Zhou et al. reported that both ferritin and IL-6 concentrations showed higher values in non-survivors in comparison to discharged patients, and increased as the patient deteriorates. 20 Our study shows an increase of IL-6 in non-survivors when compared to survivors, and increase in moderate and severe cases when compared to mild cases.
ACE2 is a receptor that mediates virus entry into host cell and its expression is increased in patients with diabetes mellitus which enhances susceptibility to COVID-19. We have not analyzed variations of blood glucose in current study. Increased ALT, AST, Total bilirubin and decreased albumin in COVID-19 patients might be due to viral cytopathic effects, drug-induced or systemic inflammatory response. 21
Mortality rate among admitted patients with COVID-19 was 8.5% in our study, higher in severe disease 34.8% (8/23). The mortality rate is more due to selection bias as more sick patients got admitted. The categorization into mild, moderate & severe changed over time with more proper definition of disease. As observed in other parts of country in initial phase of pandemic, lack of patient awareness in approaching hospital for early treatment could also be the reason. There was no difference in mortality in male and female.
LIMITATIONS OF STUDY:
This was a single-centre study with small number of study subjects and thus might have a selection bias. This study finding need to be corroborated with a large population
CONCLUSION:
Laboratory parameters have diagnostic and prognostic value. Dynamic measurements of laboratory parameters correlate with disease severity and will be predictors for the clinical evaluation of COVID-19 patients for better monitoring and therapeutic interventions.
ACKNOWLEDGMENT: Authors would like to thank technical and hospital staff for providing material for publication.
DECLARATIONS:
Source of funding: Granules India Grant
Conflicts of interest: None declared
Ethical approval: Approval letter is attached.
AUTHOR’S CONTRIBUTION STATEMENT:
1. Anuradha Sekaran - Conception of study, Data analysis, interpretation and critical revision
2. Swapna S - Data analysis and Review of manuscript
3. Shruthi Dulala – Data collection, Analysis
4. Maddipati Veda Ganga Ritesh – Data collection, Analysis
5. Jagadeesh Kumar V – Review of manuscript
6. Nitin Jagtap - Statistical analysis and manuscript review
7. Naveen Chandra Reddy - Clinical data analysis
8. Sandeep Lakhtakia - Review of manuscript
9. Duvvur Nageshwar Reddy - Review of manuscript
Englishhttp://ijcrr.com/abstract.php?article_id=4292http://ijcrr.com/article_html.php?did=42921. Liu YC, Kuo RL, Shih SR. COVID-19: The first documented coronavirus pandemic in history. Biomed j.2020. Aug 1; 43(4):328-33.
2. Velavan TP, Meyer CG. Mild versus severe COVID-19: laboratory markers. J Infect Dis Med .2020 Jun 1;95:304-7.
3. Directorate General of Health Services (EMR Division), Ministry of Health & Family Welfare, Government of India. March 31, 2020.
4. Chen Q, Yu B, Yang Y, Huang J, Liang Y, Zhou J, et al. Immunological and inflammatory profiles during acute and convalescent phases of severe/critically ill COVID-19 patients. Int Immunopharmacol .2021 Aug 1;97:107685
5. Bernheim A, Mei X, Huang M, Yang Y, Fayad ZA, Zhang N et al. Chest CT findings in coronavirus disease-19 (COVID-19): relationship to duration of infection. Radiology .2020 Feb 20:200463.
6. Zhao K, Li R, Wu X, Zhao Y, Wang T, Zheng Z et al. Clinical features in 52 patients with COVID-19 who have increased leukocyte count: a retrospective analysis. Eur J Clin Microbiol Infect Dis .2020 Dec;39(12):2279-87.
7. Skevaki C, Fragkou PC, Cheng C, Xie M, Renz H. Laboratory characteristics of patients infected with the novel SARS-CoV-2 virus. J Infect .2020 Aug 1;81(2):205-12.
8. Tan L, Wang Q, Zhang D, Ding J, Huang Q, Tang YQ, et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct Target Ther .2020 Mar 27;5(1):1-3.
9. Yan X, Li F, Wang X, Yan J, Zhu F, Tang S et al. Neutrophil to lymphocyte ratio as prognostic and predictive factor in patients with coronavirus disease 2019: a retrospective cross-sectional study. J Med Virol .2020 Nov; 92(11):2573-81.
10. Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li C, et al. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. J Transl Med. 2020 May 20;18(1):206.
11. Soraya GV, Ulhaq ZS. Crucial laboratory parameters in COVID-19 diagnosis and prognosis: an updated meta-analysis. Medicina clinica .2020 Aug 28; 155(4):143-51.
12. Zeng F, Huang Y, Guo Y, Yin M, Chen X, Xiao L, et al. Association of inflammatory markers with the severity of COVID-19: a meta-analysis. Int J Infect Dis .2020 Jul 1;96:467-74.
13. He X, Yao F, Chen J, Wang Y, Fang X, Lin X, et al. The poor prognosis and influencing factors of high D-dimer levels for COVID-19 patients. Sci Rep. 2021 Jan 19; 11(1):1-7.
14. Li Q, Cao Y, Chen L, Wu D, Yu J, Wang H, et al. Hematological features of persons with COVID-19. Leukemia. 2020 Aug; 34(8):2163-72.
15. Ponti G, Maccaferri M, Ruini C, Tomasi A, Ozben T. Biomarkers associated with COVID-19 disease progression. Crit Rev Clin Lab Sci .2020 Aug 17; 57(6):389-99.
16. Vatansever HS, Becer E. Relationship between IL-6 and COVID-19: to be considered during treatment. Future Virol .2020 Dec; 15(12):817-22.
17. Zhang J, Wang X, Jia X, Li J, Hu K, Chen G, et al. Risk factors for disease severity, unimprovement, and mortality in COVID-19 patients in Wuhan, China. Clin Microbiol Infect .2020 Jun 1;26(6):767-72.
18. Henry BM, De Oliveira MH, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med 2020.Jul 1;58(7):1021-8.
19. Banchini F, Cattaneo GM, Capelli P. Serum ferritin levels in inflammation: a retrospective comparative analysis between COVID-19 and emergency surgical non-COVID-19 patients. World J Emerg Surg .2021 Dec;16(1):1-7.
20. Gómez-Pastora J, Weigand M, Kim J, Wu X, Strayer J, Palmer AF, et al. Hyperferritinemic in critically ill COVID-19 patients–is ferritin the product of inflammation or a pathogenic mediator Clin Chim Acta .2020 Oct;509: 249–251.
21. Chen J, Wu C, Wang X, Yu J, Sun Z. The impact of COVID-19 on blood glucose: a systematic review and meta-analysis. Front Endocrinol .2020;11: 574541.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareA Cross-sectional Study on Quality of Life of Menopausal Women in Rural Area, Chengalpattu District, Tamil Nadu
English2932Jennifer G.H.EnglishIntroduction: In India, though various studies have been carried out on menopausal symptoms, majority of them were hospital-based. During menopause they experience changes which may affect their quality of life, severity and impact of the symptoms vary extremely from person to person and population to population. Hence this study attempted. Objectives: To assess and determine the factors associate with the quality of life among menopausal women in rural area, Chengalpattu district. Methodology: A community-based cross-sectional study conducted in rural areas of Chengalpattu district for duration of two months among women. 100 women aged 45 to 60 years, were selected by convenient sampling method, who were willing to give a consent were included and those who had regular bleeding were excluded. Primary data were collected using Semi structure questionnaire with MENQOL scale by interview method; analyzed using SPSS 16V. Descriptive statistics Mean, SD and Percentages were calculated and chi square test used to determine the factors at 5% α. Results: 30% of women attained their menopause before 40 years; 10% were in peri-menopausal period; 18% had Hysterectomy. 35% had vasomotor symptoms; 47% Psychosocial symptoms, 67% physical symptoms and 14% sexual problems. Conclusion: Family support and choice of lifestyle modification along with supportive therapy should be encouraged. These may require intensive health education for pre and menopausal women and for the community at large.
English Menopause, Quality of Life, Peri-menopausal period, Community based study, Vasomotor, Psychosocial problemsIntroduction:
The women were in middle age and beyond experience, a period of transition from the reproductive to the non-reproductive stage of life, is the cessation of menstruation known as menopause.1,2,3 the literature says that during pre and peri-menopausal periods women were undergoing experiences such as hot flashes, night sweats, sleep and mood disorders, impaired memory, lack of concentration, nervousness, depression, insomnia, bone and joint complaints and reduction of muscle mass etc.2,3,4,5,6,7
Some women have severe symptoms that greatly affect their personal and social functioning and quality of life.3,4,5,6 They have to cope with these changes and accept their new role in society and family.7 The women in the menopausal period, their health demands are more in Indian scenario due to increase in life expectancy in recent years.7,8,9 There is large efforts are required to educate and make women aware of menopause symptoms.7,8,9 Creating awareness will help in early recognition of symptoms, reduction of discomfort and fear and enable to seek appropriate medical care if necessary.10 The literature review also explains that national health authorities need to examine the post-menopausal women and should anticipate the provider of relevant health services, and education promotion activities to cope with the health needs of women in their postmenopausal years.9,10,11 Hence this study attempted; the objective of this study is to assess and determine the factors associated with the quality of life among the menopausal women in rural areas, the Chengalpattu district.
Methodology:
The Community based cross-sectional study was carried out among menopausal women (45-60 years) who reside in Pullipakkam and colony, Thimmavaram for more than a year. Women aged 45 to 60 years and in the peri-menopausal period who were willing to participate were included women having regular menstrual bleed were excluded.
The sample size of 100 were calculated with a reference article by Poomalar et al with prevalence of 80% with 10% of relative precision at 95 % confidence interval. The study participants were obtained by a convenient sampling method. The semi-structured questionnaire was used to collect information such as demographic profile, morbidity, diet, physical exercises and gynecological history from the study participants. The MENQOL scale was used to assess the quality of life under four domains. The data was collected by interview method after obtaining the written informed consent. The study got approved from Institutional Ethics committee (Human studies) with reference number 24/2016.
The Scale contains four domains such as vasomotor, psychosocial, physical and sexual; the total score was categorized as mild, moderate and severe. The data was entered in MS Excel and analyzed using SPSS software 16V. Frequency and percentage was calculated for all categorical variables and Mean and SD was calculated for domains. Chi-squared test was used to find the association between the variables and QOL domains at 5% level of significance.
Results:
In this study, 41% women in age 45-50 years followed by 30% in 55 to 60 years. 61% women were illiterate and 26 % were under primary. The frequency of occupational status being housewife was 78% and being unskilled was 17%. The frequency of socioeconomic status of women being Grade 1 is 62%. The distribution of Family size is 1-5 members was 77 and being 6-10 members were 22%. The majority were married 61% and being widow were 32%. Majority were living in a nuclear family 53% and being joint family was 29%
47% were had 1 to 2 children and 39% 3 to 4. Regarding, Age at menarche 78 % were attained in the age of 10 to 15 years. In this study 10% were in the perimenopausal stage, 18% had hysterectomy due to various reasons such as over bleeding, fibroid uterus etc. Figure 1 describes the age at menarche among study participants.22% had early menopause in lesser than 40 years, 43% had in 41 to 50 years the rest were in >50 years.
The frequency of abortion 25% had one or two abortions. Table 1 describes the distribution of morbidity among the study participants. The majority of them had DM 22% followed HT, Joint pains etc. only 11% had habit of walking as physical exercise. As per WHO classification of body mass index 31% are overweight and 21% are obese.
Table 2 explains the percentages of symptoms under each domain after converting the score. Figure 2 explains the grade of severity of menopausal symptoms which affect the quality of life of study participants. In this study 35% had vasomotor symptoms, 47% had Psychosocial symptoms,67% had Physical symptoms and 14% had sexual symptoms.
Discussion:
Present study contains only 10% of women in a menopausal transition state which is less when compared to study on QOL in rural area conducted by Poomalar et al (2013).18 In the current study mean age of menopause was found to be 44.25 years which was almost similar to study conducted on QOL among post-menopausal women of west bengal 2017 by Karmakar et al.7,17
The severity levels to menopausal symptoms of physical, psychosocial, vasomotor and sexual domains were backache, poor memory, and lack of energy. Regarding the physical symptoms, most of the women reported with low back pain (76%), aching in muscles and joints (83%), leg pain (77%) decrease in stamina (80%)
Study conducted in 2018 by Ganapathy et al. Reported consistent findings of decreased physical energy, generalized weakness.15,16,17 Karmarkar et al. conducted a study in West Bengal reported found that women experiencing musculoskeletal pain (84%), poor physical stamina (88%), low back pain (69%).7
A cross-sectional study on menopausal symptoms and problems among urban women from Odisha 2016 have high prevalence of joint pains (66%),hot flushes(77%), and increase in weight (69%).10
The current study reports experiencing poor memory (67%), anxiety (55%), and feeling depression (44%), under the psychosocial domain. It coincides with study conducted on QOL on post-menopausal women conducted on rural and urban communities with loss of memory, anxiety, feeling lonely, sadness (42%) among urban women.11,12,13,14
A study on QOL among menopausal women by Hoda A.E. Et al 2014 reported hot flushes, and sweating, are the most severe symptoms in postmenopausal women which is contradictory to current study where hot flushes, night sweats are least bothered.8
Finally, current study reveals that scores of physical domain were significantly more in postmenopausal women followed by psychosocial, vasomotor and sexual domains. Symptoms have variable onset in relation to menopause. The clinical studies explains that, hormonal replacement therapy such as estrogen or progesterone would be helpful in menopause and also in premenopausal women.19,20
Conclusion: Finally, Family support should be ensured by creating awareness in the rural community as a whole. The use of appropriate therapy should be encouraged, whenever required. All these require intensive health education for women who are in the post-menopausal phase of their lives, for their family and for the community at large.
Acknowledgment: I would like to thank the faculty in the department, non-teaching staff, and the study participants for their time and responses.
Conflict of Interest: NIL
Funding: No funding was received from any external sources
Englishhttp://ijcrr.com/abstract.php?article_id=4293http://ijcrr.com/article_html.php?did=42931. Nayak G, Kamath A, Kumar P, Rao A. A study of quality of life among perimenopausal women in selected coastal areas of Karnataka, India. J Midlife Health. 2012; 3:71-75.
2. Vijayalakshmi S, Chandrababu R, Eilean Victoria . Menopausal transition among northern indian women. NUJHS. 2013; 3:73-79.
3. Sharma S, Mahajan N. Menopausal symptoms and its effect on quality of life in urban versus rural women: a cross-sectional study. J Midlife Health. 2015; 6:16-20.
4. Mohamed HA, Lamadah SM, Lamil LG. quality of life among menopausal women. Int J Reprod Contracept Obstet Gynecol.. 2014; 3:552-561.
5. Lee M, Kim J, Park M, Yang j, KoYh, Ko S et al. factors influencing the severity of menopause symptoms in Korean postmenopausal women. J. Korean Med. Sci.. 2010; (5):758-765.
6. Qazi Ra. Age, pattern of menopause, climacteric symptoms and associated problems among urban population of Hyderabad Pakistan. J Coll Physicians Surg Pak. 2006; 16: 700-703.
7. Karmakar N, Somak M, Aparajita D, Sulagna D. Quality of life among menopausal women: Community-based study in rural areas of West Bengal.J Midlife Health. 2017; 8(1) :21-27
8. Hoda AE, Sahar ML, Luma GAZ. Quality of life among menopausal women. IJRCOG. 2014; 3(3):78-88.
9. Shilpa k, Amit RU, A comparative study of post-menopausal symptoms in rural and urban women of Kerala. Indian J Community Med.. 2015; 2(4): 604-609
10. Santhi V, Sruthi K. Comparison of postmenopausal symptoms in rural and urban women in Guntur, India. IOSR – JDMS. 2016; 15 (8):753-757.
11. Nidhi P. Prevalence of menopausal symptoms among postmenopausal women of urban Belagavi, Karnataka. IJHSBR. 2018;11 (1): 77-80.
12. Ravikumar, Ayesha SN, Sharan KH, varadarajarao. A study of quality of life among perimenopausal women in rural field practice area of a medical college in Karnataka. NJCM. 2016; 7(3):160-164.
13. Maheshwari p. A study on assessment of quality of life in postmenopausal women, RJPT. 2017; 10(1): 15-17.
14. Jayasheela K. Prevalence of metabolic syndrome among postmenopausal women in South India. IJCR. 2018;7(6): 4393-4398.
15. Jayabarathi B, Judie A. A severity of menopausal symptoms and its relation with quality of life in postmenopausal women. IJPCR. 2016; 8(1): 33-38.
16. Radha S. Prevalence of postmenopausal symptoms its effects on quality of life and coping in rural couple. J Midlife Health. 2108; 9(1): 14-20.
17. Doyal DG, Priyanka k, Subha R, Nandini G. Menopausal symptoms and correlates; A study on tribe and caste population in East India. Current gerontology and geriatrics research. 2015; 7(2): 1-7.
18. Poomalar GK, Bupathy A. The quality of life during and after menopause among rural women. JCDR. 2013; 7(1):135-139.
19. Valvekar U, Viswanathan S. Knowledge of qualified paramedical staffs in understanding the symptomatology and hormonal replacement therapy in menopause. IJCRR. 2016; 8(7):8-12.
20. Ruma D, Lawrence D, Anuradha R, Shivani R, Rashmi MR. Study on menopausal symptoms in rural area of Tamil Nadu. J. Clin. Diagnostic Res. .2012; 6 (2):597-601.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareLiquid Chromatography - Mass Spectrometry Method Development and its Validation for the Estimation of Favipiravir and Remdesivir in the Rat Plasma
English3339K. SanthakumariEnglish K. Prasada RaoEnglish S. MohanEnglishEnglish Favipiravir, HPLC, LC-MS, Remdesivir, Validation, StabilityINTRODUCTION
Gilead Sciences has developed Remdesivir as an antiviral drug by the name GS-5734.1 This drug requires bioactivation within the cells.2 Remdesivir contain various basic molecular characteristics, this is an analogue of adenosine nucleotide, it comprises the RNA synthesis and as a result, it acts against RNA viruses.
The validation method of UHPLC-MS/MS of remdesivir and its GS-441524 quantification has been reported in human plasma in the literature. The evaluation of analyte stability has been done in detail.3 This method has been successfully validated and it states that the sample thermal inactivation is the best choice to improve biosafety.
For treating Nipah virus in African green monkey model the remdesivir shows a practicable and which is having great effect.4, 5 This model explained by performing the experiments by infection with a fatal dose of the virus to the animals which are selected for this purpose with one dose of remdesivir daily for 12 days. The results showed that all the treated animals are saved compared to the untreated animals.
This drug is potent which inhibits selectively influenza viral RNA polymerase,6 also active against various strains and subtypes of viruses of influenza all subtypes and strains of influenza viruses including the ones sensitive to marketed M2 inhibitors and neuraminidase.
Favipiravir, initially used for treating against the SARS-CoV-2 in Wuhan, and as the virus spread to European countries, it has received emergency approval for use this drug received approval for emergency use in some other countries and it received DCGI approval for various levels of Covid-19 infections. There are various clinical trials going on to assess the drug’s efficiency in managing the Covid-19 .7
Favipiravir (T-705) has been discovered initially during the assessment of chemical agents for their antiviral activity and it is effective in treating the influenza virus and reported in the chemical library of Toyoma chemicals. Favipiravir has been obtained with various modifications done on pyrazine moiety of T-1105 chemically.8, 9 Favipiravir exhibits useful anti-viral activities with other RNA viruses’ also.10
The literature review suggests that a few methods for evaluating Favipiravir and Remdesivir had been published. However, have developed a method for the validation of these drugs in rat plasma by using LCMS/MS has been carried out in this paper. The newly developed process has been effectively validated using the guidelines set by International Conference on Harmonization (ICH).11,12,13
MATERIALS AND METHODS
Instrumentation
Chromatography has been carried out with waters 2695 HPLC containing degasser, column oven, high-speed autosampler, and SCIEX QTRAP 5500 mass spectrometer for providing a compact and with class Empower-2 software.
Reagents and chemicals
The reference sample was provided as Favipiravir and Remdesivir samples from Biocon, Bangalore. The chemicals like acetonitrile, and methanol used are of HPLC grade and procured from Merck chemical supplier, Mumbai. Throughout the process the water used of HPLC grade which is obtained from Milli-Q water purification system.
Favipiravir Standard Stock Solution (80 ng/mL)
Weigh 8 mg of Favipiravir and diluted with a diluents in a 100 mL volumetric flask. Further dilute 0.1 mL to 100 mL with diluent.
Remdesivir Standard Stock Solution (80ng/mL)
Weigh 8 mg of Remdesivir standard in a 100 mL flask and diluted it with a diluent. Further dilute 0.1ml of above solution in 100 mL volumetric flask with diluent.
Preparation of Standard Solutions (20 ng/mL of Favipiravir and 20 ng/mL of Remdesivir)
In a centrifuged tube 500 µl of Favipiravir and Remdesivir standard stock solutions are taken. Dilute to volume with Plasma, acetonitrile and diluent.
Preparation of Linearity solution
These solutions are prepared with concentrations from 2 nanogram to 40 nanogram per mL of Favipiravir and Remdesivir prepared in a similar way as above. Centrifuge at 4000 RPM for 15 – 20 min. collect the supernatant solution in LC vial and inject into the chromatograph.
Extraction procedure
The treated and centrifuged plasma samples are labelled as per the time intervals. 200 μL sample of plasma is added with 500 μL diluent and shaken it well. Further add 300 μL of Acetonitrile for precipitation of proteins and thoroughly mix it in a vortex cyclo mixture. It is centrifuged at about 4000 RPM for about 15 – 20 min, and the supernatant solution is collected in a HPLC vial and injected into a chromatograph.
Buffer Preparation
Transfer 1ml of formic acid into a1lt water. Filter by using 0.45µ membrane paper.
Methodology for Analysis
The Linearity solution, the blank, and sample solutions are injected into the chromatograph and their chromatograms have been recorded. The peak areas due to Favipiravir and Remdesivir are measured. The linearity curve obtained from the equation express the concentration of these compounds present in the sample of plasma.
RESULTS AND DISCUSSIONS
System suitability
The instrument efficiency is determined by performing analysis with a set of standard and reference ones prior to the analytical process. The percentage of cumulative variation (% CV) for Favipiravir and Remdesivir was found to be 0.31 and 0.29 and area ratio of ISTD has been observed to be 0.59 %, and 0.44 %. Therefore, the suitability of the system has passed.
Specificity and screening of biological matrix
It was observed that in the samples blank rat plasma there were no interfering peaks of Favipiravir and Remdesivir or ISTD at retention times. The interfering peaks response in the standard (STD) Blank at the analyte retention time should be ≤ 20.00 % of that in LLOQ (Lower limit of quantification). Response of peaks that interfere at retention time in the STD Blank and the ISTD should be ≤ 5.00 % of that in LLOQ. About 80 % of the lots of the matrix (except heparinized, haemolysed and lipemic matrix lots) must be in the acceptance criteria with intended anticoagulant.
Sensitivity
The % CV for Favipiravir and Remdesivir was found to be 1.16 % and 0.71 %. % CV accuracy was 99.3 % and 99.4 %. Hence the sensitivity was passed.
Matrix effect
The matrix effect was determined for rat plasma constituents over ionization of the analyte and compared the post-extracted plasma standard MQC (Medium quality control) samples' response (20 ng/ml of Favipiravir and 20 ng/ml of Remdesivir) (n = 6) with that of the analyte from pure samples at the equivalent concentrations. The intended method of the matrix effect has been assessed with chromatographically screened plasma of the rat.
Precision (% CV) for Favipiravir was found to be 0.39 % and 0.77 % for respectively at HQC (High-quality control) and LQC (Low-quality control). Precision (% CV) for Remdesivir was found to be 0.36% and 0.69 % respectively at HQC and LQC. The percentage mean accuracy of the back-calculated concentrations of LQC, and HQC samples that are prepared with lots of different biological matrix must be within the 85.00-115.00 %. This shows that matrix effect on ionization of the analyte has been shown to be in the limit of acceptance. Figure 1 shows the Matrix Effect Chromatogram of LQC.
Linearity
Over concentration range of2-40 ng/mL the standard curves was linear for Favipiravir and Remdesivir. The correlation coefficient has been found to be 0.992 for Remdesivir and it is 0.9901 for Favipiravir. The calibration curves are found to be linear. By using ratio of peak area of the analyte and that of IS the samples have been quantified. The ratios of the peak area are plotted against concentrations of the plasma. The calibration standards’ peak area ratios were found to be proportional to the concentrations. Linearity results of Favipiravir were shown in table 1 and for Remdesivir were shown in Table 2. Figures 2, and 3 shows the plot of calibration for the concentration vs Area ratio of Favipiravir and Remdesivir respectively.
LOD and LOQ
Table 3 shows the LOD and LOQ results of the compounds. Limit of detection (LOD) and limit of quantification (LOQ) have been determined separately with a method of calibration curve. The compound’s LOD and LOQ have been calculated by progressive injection of standard solutions of lower concentrations with the developed LC-MS method. The concentration of LOD for Favipiravir is 0.2 ng/ml and the S/B value is 7. The concentration of LOQ for Favipiravir is 2.2ng/ml and the S/B value is 27. The LOD concentrations for Remdesivir are 0.2 ng/ml the S/B value is 5. The LOQ concentration for Remdesivir is 2.2 ng/ml the S/B value is 22. The chromatograms for MQC and blank are shown in figures 4 and 5 respectively.
Precision and accuracy
The estimation of precision and accuracy has done by analysis of six replicates with Favipiravir and Remdesivir at four kinds of QC levels. The determination of the inter-assay precision was done by the analysis of four levels QC samples with four different runs. For accepting the data the criteria include, the accuracy in the range 85–115% from actual value and the precision in the range of ±15% RSD except for LLQC, where it should be in the range of 80–120% r accuracy and Englishhttp://ijcrr.com/abstract.php?article_id=4294http://ijcrr.com/article_html.php?did=4294
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Maninder Pal S, Manish K, Kashish W, Prerna. Novel Method Development and Validation for UV–Visible Spectrophotometric Analysis of Methscopolamine Bromide. Int. J Cur. Res. Rev. 2021; 13(12): 112-117
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareThe Role of Pulse Oximetry as a Screening Tool for Early Detection of Critical Congenital Heart Disease in Newborn
English4045M. A. MannanEnglish Amlendra YadavEnglish Tareq RahmanEnglish Ismat JahanEnglish Sadeka Choudhury MoniEnglish Mohammad Abul KhayerEnglish Mohammad Kamrul Hassan ShabujEnglish Sanjoy Kumer DeyEnglish Mohammod ShahidullahEnglishIntroduction: Early diagnosis of critical congenital heart defects (CCHD) may be missed both during prenatal echocardiography and the short stay in the neonatal nursery, leading to circulatory collapse or death of the newborn before readmission to hospital. Pulse oximetry screening (POS) has been proposed as an effective, non-invasive, inexpensive tool allowing earlier diagnosis of critical congenital heart disease (CCHD). Objective: This study was conducted to find out the role of pulse oximetry as a screening tool for early detection of critical congenital heart disease in newborn. Methodology: This prospective study was conducted in department of Neonatology and department of Obstetrics & Gynecology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh a tertiary care hospital over one year. All inborn and outborn newborns stayed in hospital within 24 hours of age were included in this study. After taking written informed consent from parents, a thorough history was taken by investigator. Then pulse oximeter was used in standard way to measure reading from arms and legs. Interpretation and follow-up by Echocardiogram was done in pre-designed criteria. Data were calculated manually. Results: During the study period a total of 1033 newborn babies were screened. Among screened newborn positive screening rate was found 16(1.5%) cases. Newborns with positive screening were advised to do echocardiographic evaluation. Echocarbiography was done in all 16 babies and 4 newborn babies were having critical congenital heart diseases. This present study found sensitivity, specificity, PPV and NPV of pulse oximetry screening 100%, 99.6%, 25% and 100% respectively. On echocardiography critical congenital heart diseases were double outlet right ventricle, tetralogy of fallot, pulmonary stenosis and d-TGA. Conclusion: The present study concluded that with this high sensitivity, specificity and negative predictive value Pulse oximetry is safe, feasible and maybe wont to screen for critical congenital heart condition. It would be an attainable noninvasive method to detect the congenial heart disease along with the physical examination in newborn.
EnglishIntroduction
Critical congenital heart defects (CCHD) occur in 2–3 per 1000 live births, usually require invasive medical intervention within the first month of life and can lead to death or significant morbidity if not diagnosed in a timely manner.1 Early detection is important for reducing mortality and improving the postoperative outcome.2 In United States, a survey by American Heart association found congenital cardiovascular defects were the most common cause of infant death.3 Critical Congenital Heart Disease in neonate may present with cyanosis, respiratory distress, poor peripheral perfusion, difference in pulses (arm vs. leg), hyperactive precordium, abnormally heart sound, prominent heart murmur, Shock and unexplained metabolic acidosis and often these features are difficult to identify underlying cause.4Several tools are regularly used to identify infants who have heart defects. Prenatal ultrasounds performed at 18-20 weeks of pregnancy can reveal anatomical abnormalities. After birth, Physical examination by a clinician helps to diagnose CHD along with additional tests like chest radiographs, echocardiograms and pulse oximetry.5Although prenatal ultrasounds and postnatal physical exams successfully detect many heart defects, they are not sufficient to diagnose all cases of CCHD. Postnatally, 20–30% of CCHD are still missed by physical examination, as symptoms often occur later, when the ductus arteriosus closes.6 Murmurs are not always present with CCHD and may occur in up to 60% of healthy newborns.7 Also, it has been shown that the assessment of cyanosis is unreliable for detecting hypoxaemia.8 So screening is necessary for early detection and early treatment of these conditions. New research suggests that when all infants are screened using pulse oximetry in conjunction with routine practices, CCHD can be detected in over 90% of newborns (American Heart Association updates 2013).3 Pulse oximetry (PO) is a widely available, accurate method to objectively quantify oxygen saturation (SpO2), and thereby identify the clinically undetectable hypoxemia that occurs in the majority of neonates with CCHD.9 Pulse oximetry is a low-cost, non-invasive and painless bedside diagnostic test that can be completed by in as little as 45 to 60 seconds. It can detect mild hypoxemia, which is characteristic for many forms of CCHD, and those may not be recognized by clinical examination.10 When the screening is suggestive of having the possibility of CCHD additional testing can be completed.11 The American Heart Association (AHA), the American Academy of Pediatrics (AAP), and the American College of Cardiology Foundation (ACCF) recently outlined commendations for a standardized pulse oximetry screening approach and diagnostic follow-up for CCHD (American Heart Association Fact Sheet 2013).3 Due to variation in presentation of CCHD, many defects may not be identified and infants may be discharged from the hospitals before signs of disease are detected. So pulse oximetry screening may be helpful for the early detection of CCHD. But there is a paucity of this type of study in Bangladesh. So the study was conducted to see the role of a pulse oximeter as an early screening tool for diagnosing CCHD in newborns.
Materials and Methods
This Prospective study was conducted at the Department of Neonatology and Department of Obstetrics and Gynecology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh from May 2016 to May 2017 approval from the institutional review board. Neonates were excluded with life-threatening congenital anomalies other than cardiac disease, severe cardio-respiratory depression and required surgical management other than cardiac disease. After taking written informed consent from the parents/guardians, there was a face-to-face interview with the mother or caregivers. A thorough history of these newborns including general information, demographic and socioeconomic information as well as information to facilitate follow-up contact was taken. The infant’s medical records were reviewed to identify the risk factors of CHD and recorded in a data collection form. Pulse oximetry screening was conducted by a team of investigators (doctors) in postnatal ward, labor room, post-operative ward and neonatal intensive care unit.
All investigators were demonstrated properly for screening and they were blinded regarding antenatal Echocardiography report. Pulse oximetry testing of the right hand and either any of one foot was performed by the investigator in all infants by using pulse oximeter (model- OxiMax N-560 Guide, Korea). Proper care was taken to rule out any interference with pulse oximetry like agitation of the infant, proper placement the probe, human error or equipment malfunction. The test was performed in infant less than 24 hours of age. If the newborn's oxygen saturation is >95% in either extremity, with a Englishhttp://ijcrr.com/abstract.php?article_id=4295http://ijcrr.com/article_html.php?did=42951. Hoffman JI, Kaplan S et al. The incidence of congenital heart disease. J Am Coll Cardiol 2002; 39:1890–900.
2. American Heart Association, Congenital Cardiovascular Defects, Statistical Fact Sheet 2013 Update.
3. Gomella, TL, Cunningham, MD, Eyal, FG and Tuttle, DJ, 2013, Neonatology Management, Procedure, On-Call Problem, Diseases and Drugs, 7thedn, McGraw Hill education, New York.
4. Fixler DE, Xu P, Nembhard WN,. Age at referral and mortality from critical congenital heart disease. Pediatrics 2014; 134:e98–105.
5. Frank T R, Cornelia W , Schneider P , Mockel A,. Effectiveness of neonatal pulse oximetry screening for detection of critical congenital heart disease in daily clinical routine—results from a prospective multicenter study, Eur J Pediatr (2010) 169:975–981.
6. Gorska-Kot A, Blaz W, Pszeniczna E,. Trends in diagnosis and prevalence of critical congenital heart defects in the Podkarpacie province in 2002–2004, based on data from the Polish Registry of Congenital Malformations. J Appl Genet, 2006; 47:191–4.
7. Meberg A, Andreassen A, Brunvand L,. Pulse oximetry screening as a complementary strategy to detect critical congenital heart defects. Acta Paediatr, 2009; 98:682–6.
8. Valmari P. Should pulse oximetry be used to screen for congenital heart disease? Arch Dis Child Fetal Neonatal Ed 2007; 92:F219–224.
9. O'Donnell CP, Kamlin CO, Davis PG, Clinical assessment of infant colour at delivery. Arch Dis Child Fetal Neonatal Ed 2007; 92:F465–467.
10. Shah F, Chatterjee R, Patel P C, KunkulolR. Early detection of critical congenital heart disease in newborns using pulse oximetry screening, Int J Med Res Health Sci. 2015; 4(1): 78-83
11. Congenital Heart Disease Screening Program Toolkit, 2ndedition, Children’s National Medical Center’s Congenital Heart Disease Screening Program.
12. Thangaratinam S, Brown K, Zamora J,. Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis. Lancet 2012; 379:2459–64.
13. Hoke TR, Donohue PK, Bawa PK, Oxygen saturation as a screening test for critical congenital heart disease: a preliminary study. Pediatr Cardiol 2002; 23: 403–09.
14. Richmond S, Reay G, Abu-Harb M, Routine pulse oximetry in the asymptomatic newborn. Arch Dis Child FetNeonatal Ed 87:F83–F88
15. Ewer AK, Furmston AT, Middleton LJ, Pulse oximetry as a screening test for congenital heart defects in newborn infants: a test accuracy study with evaluation of acceptability and cost-effectiveness. Health Technol Assess 2012; 16: v–xiii, 1–184.
16. Bakr AF, Habib HS, Combining pulse oximetry and clinical examination in screening for congenital heart disease. Pediatr Cardiol 2005; 26: 832–35.
17. Arlettaz R, Bauschatz AS, Mönkhoff M, Essers B, Bauersfeld U,. The contribution of pulse oximetry to the early detection of congenital heart disease in newborns. Eur J Pediatr 2006 Feb 1; 165(2):94-8.
18. Sendelbach DM, Jackson GL, Lai SS,. Pulse oximetry screening at 4 hours of age to detect critical congenital heart defects. Pediatrics 2008; 122:e815–820.
19. Brown K L, Ridout D A, Hoskote A, Verhulst L, Ricci M, Bull C et al. Delayed diagnosis of congenital heart disease worsens the preoperative condition and outcome of surgery in neonates. Heart 2006; 92:1298–302.
20. Cora P, Elizabeth A, Tiffany R C, Matthew E. O, Cynthia H. C, David E. F, Suzan L, Gary M. S, Suzanne M. G et al. Estimation of the Potential Impact of Proposed Universal Screening Using Pulse Oximetry, JAMA Pediatr. 2014-168(4):361-370.
21. IIona N, Nico B, Andrew E, Maximo V, Paolo M, Arjan B T P, et al. Aspects of pulse oximetry screening for critical congenital heart defects: when, how and why? Arch Dis Child Fetal Neonatal Ed 2015; 0:F1–F6.
22. Kochilas LK, Lohr JL, Bruhn E, Implementation of critical congenital heart disease screening in Minnesota. Pediatrics 2013; 132:e587–594.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareEffects of Endocrine Disorders on Bone Mineral Density - A Narrative Review of Literature
English4656Ranjani ThillaigovindanEnglish Vetriselvan AbiramiEnglish Ponsekar AbrahamEnglishIntroduction: Hormones are primary messengers that regulate the physiological and behavioral aspects of the body. Bone, a dynamic connective tissue, forms the framework of the body alongside its contribution in maintaining homeostasis and hosting the bone marrow. Disturbances in hormonal levels disrupt bone health thereby leading to impaired quality of life. Aim: To encapsulate the effects of various endocrine disorders on bone mineral density based on previous clinical studies. Methodology: An electronic search was conducted across PubMed, EMBASE, CINAHL, Google Scholar and Cochrane databases during the period of March to July 2021 by two reviewers independently using Medical Subject Headings (MeSH) terms. Result: The search yielded a total of 208 articles and further screening based on selection criteria resulted in inclusion of 19 studies to elicit the effects of commonly prevalent endocrine disorders on bone mineral density. Studies revealed that most hormonal imbalances have a negative impact on the bone mineral density (BMD) at varying degrees. Conclusion: Endocrine disorders have become highly prevalent at present deteriorating the life standards, especially the middle-aged and elderly population. Any disruption in this normality will lead to altered bone mineral density and further risks of fracture or immobility. Constant monitoring of hormonal levels and bone health is required to enhance the quality of living alongside an increased life expectancy.
EnglishEndocrine disorders, Bone Mineral Density, Parathormone, Diabetes Mellitus, Calcitonin, HormonesINTRODUCTION
The endocrine system is composed of various glands that secrete a set of chemical messengers called hormones, which are instrumental in regulating growth and development, metabolism, electrolyte balance, reproduction and several other important functions.1 The terms endocrine and hormone are derived from Greek words ‘endokrinein’ and ‘hormaein’ respectively. The actual word hormone meant ‘to arouse’ or ‘to excite’, which was later defined by Starling (1905) as “the chemical messengers which speed from cell to cell along the bloodstream, may coordinate the activities and growth of different parts of the body”.2 The endocrine system is principally controlled by the hypothalamus which secretes the releasing and inhibiting hormones that in turn influence the release of stimulating hormones from the pituitary gland.1 These hormones released into the bloodstream may stimulate other glands or directly target distant tissues to bring about cellular changes. Hormonal imbalance, per se, has become a quotidian term in recent times, and is reported with a high incidence rate. Various physical, psychological and social stresses in day-to-day life have had an adverse impact on the endocrine system leading to multiple systemic manifestations.3 It has led to a growing concern to keep a watch over the hormonal levels not only among the elderly but also among the younger age groups. There is a need to reinstate the former ways of living, with appropriate diet balance, adequate exercise and a relaxed state of mind, body and soul in order to maintain a healthy life. This requires serious attention in maintaining good bone health in order to sustain a quality living.
METHODOLOGY
An electronic search was conducted across PubMed, EMBASE, CINAHL, Google Scholar and Cochrane databases during the period of March to July 2021 by the two reviewers independently. The search methodology used a combination of Medical Subject Headings (MeSH) words and keywords such as "Type 2 Diabetes mellitus", "Estrogen disorders", "Vitamin D deficiency", "Osteoporosis", "Parathormone", "Thyroid disorders" AND "Bone mineral density "considering synonyms, alternative spelling, and related terms.
Inclusion criteria
Articles published dating from 1999 to 2020
Clinical trials on humans, cross-sectional retrospective or prospective studies
Studies assessing the effects of Type II Diabetes Mellitus, Estrogen, Vitamin D, Osteoporosis, Parathormone & Thyroid dysfunction on bone mineral density.
Gender neutral as well as gender-specific studies included
Studies done on adult participants alone
Exclusion Criteria
Animal trials, In-vitro studies, Case reports, Literature or Systematic reviews
Population having any comorbidities or multiple factors affecting bone mineral density.
Studies that had methods of measuring bone quality other than Bone mineral density.
Publications made in languages other than English
A structured electronic search was conducted by two reviewers independently using the Keywords and MeSH terms yielding a total of 208 articles. Initial screening consisted of a check for duplication during which a total of 56 articles were excluded based on the titles and authors. This was followed by assessment of title and abstract based on article type which led to the exclusion of 73 articles. The final phase of screening involved full text reading based on selection criteria and exclusion of 60 articles was done. A total of 19 studies were included for the final review. The search methodology has been summarized in Figure 1.
PHYSIOLOGICAL BONE REMODELLING
Bone is a highly dynamic connective tissue that undergoes constant remodeling throughout the lifetime. It serves two crucial roles, provision of skeletal support and maintenance of mineral homeostasis. Bone contains three major types of differentiated cells, namely the osteoblasts or the bone-forming cells, osteocytes and the osteoclast or bone-resorbing cells. Bone rigidity and density depends on the deposition of calcium and phosphorus as hydroxyapatite during mineralization. The inorganic content composed of the minerals sum up to 70% while the remaining 30% consist of organic matter, especially Type 1 collagen. The outer layer consists of a dense cortical bone that provides structural support while the inner trabecular bone forms the reservoir for the bone marrow hosting the active process of bone remodeling.4 Bone remodeling is a sequence of seven phases: quiescence, activation, resorption, reversal, formation, mineralization and termination. This activity of deposition and resorption is influenced by local and systemic factors. The major role is played by the systemic factors that include hormones and growth factors. The list of hormones and growth factors that majorly affect the remodeling of bone is mentioned in (Table 1).
BONE MINERAL DENSITY (BMD)
Bone mineral density, in the literal sense, would mean the mass per unit volume of mineralized bone without the organic portion or adjacent tissue. But clinical investigations simply reveal the apparent bone mineral density inclusive of the bone marrow and the overlying tissues. However, bone mineral density is a reliable and non-invasive biophysical parameter that aids in measuring bone quality. It is one of the major diagnostic tools for bone disorders like osteopenia, osteoporosis etc. Investigatory techniques for determining the BMD include: (i) Dual energy X-Ray absorptiometry (DXA), (ii) Single energy absorptiometry (SXA), (iii) Quantitative Computed Tomography (QCT), (iv) High-resolution peripheral quantitative computed tomography (HR-pQCT), (v) Peripheral quantitative computed tomography (pQCT) and (vi) Quantitative Ultrasonography (QUS). DXA is the most popularly used technique for the assessment of BMD, which operates by propagation of two low dose X-ray that provide the density profiles of hard and soft tissues thereby aiding in determination of BMD. Measurements are commonly done at four sites namely, lumbar spine, femoral neck, trochanteric region and Ward’s triangle.
The most widely accepted parameter for measuring the BMD is the T-score, which is a unitless value that is calculated as a ratio of the difference between the observed bone mineral density (BMD) and the expected young normal value (YN) to the standard deviation of the population. It is used to compare the BMD of an individual with the healthy, young population of the same gender.
According to WHO5, four general diagnostic categories had been established for women as follows:
1. Normal: Value of BMD within 1 SD below the young adult reference mean (T-score ≥ -1)
2. Low bone mass (osteopenia): Value of BMD ranging from 1 to 2.5 SD below the young adult mean (T-score < -1 and > -2.5)
3. Osteoporosis: Value of BMD more than or equal to 2.5 SD below the young normal (T-score ≤ -2.5)
4. Severe osteoporosis: Value of BMD more than 2.5 SD below young adult mean (T-score ≤ 2.5) with the presence of one or more fragility fractures.
While yet another scoring system is the Z-score that compares the BMD of two individuals of the same age and gender. It aids in determining the presence of secondary causes of osteoporosis which is indicated when the score goes below -2.5.
A constant monitoring of the BMD among various age groups that are commonly vulnerable to bone fragility due to endocrine disorders is required in order to prevent disabilities in early stages. Women of perimenopausal age groups and infants lacking adequate nourishment are to be treated with special care to prevent the occurrence of endocrine disorders. Hormones are governed by various internal as well as external factors of which diet, livelihood as well as state of mind plays a crucial role in balancing the homeostasis. Hence, it is necessary to sustain a healthy way of living for a quality life.
ENDOCRINE DISORDERS AND BONE MINERAL DENSITY
PARATHORMONE
There are normally two pairs of parathyroid glands, namely, the superior and inferior parathyroid situated in the posterior aspect of the two lobes of thyroid gland. Although the parathyroid glands are small in size, they secrete parathormone that plays a crucial role in Calcium homeostasis. Parathormone (PTH) acts as a scavenger of Calcium ions thereby maintaining a high serum Calcium level by resorbing the bone, preventing loss of Calcium ion through urine and also increasing the intestinal absorption of dietary Calcium ions. PTH acts by induction of osteoclast formation that is mediated through the osteoblast by stimulation of RANKL and inhibition of OPG mRNA expression.6 The release of Parathormone normally occurs when there is a decrease in normal serum Calcium levels. Increased level of parathormone in blood leads to bone resorption in order to raise the serum Calcium levels thereby decreasing the bone mineral density.
CALCITONIN
Calcitonin is secreted from the parafollicular cells of the thyroid gland that couples with PTH in order to maintain calcium homeostasis in blood. Calcitonin has a hypocalcemic effect that counteracts the activity of parathormone. The normal serum Calcium levels range from 8.5 to 11.5mg/dl. Calcitonin acts by binding to specific receptors located at the sealing area leading to the loss of ruffled border of the osteoclasts required for resorbing bone surface.7 These receptors are known as Calcitonin Receptors (CTR) which cause loss of mobility of osteoclasts (Q-effect) and also lead to retraction (R-effect). Calcitonin acts by two known signaling mechanisms: one using cyclic adenosine monophosphate (cAMP) as the secondary messenger and the other using phospholipase C pathway that aids in influx of serum calcium ions promoting bone deposition.8 Calcitonin is usually absent or deficient in patients who have undergone thyroidectomy, which often leads to decreased serum calcium levels, decreased PTH levels and reduced bone formation rates. Capelli et al. 9 reported that osteocalcin showed decreased bone formation with an increased turnover rate signified by the presence of resorption markers like deoxypyridinoline and N-terminal telopeptide of type I collagen thereby decreasing the bone mineral density.
VITAMIN D
Vitamin D is a fat soluble vitamin that is also categorized under steroid hormones since its active form is synthesized in the body. Vitamin D is obtained from the exposure of skin to Ultraviolet rays of sunlight. It undergoes hydroxylation in the liver initially to form 25-hydroxyvitamin D (25(OH)D) and later in the kidney to form an active metabolite as 1,25-dihydroxyvitamin D (1,25(OH)2D). Vitamin D plays a major role in Calcium and bone homeostasis and has an inverse relation with PTH levels in the blood, thereby counteracting the effects of PTH. Vitamin D binds to the Vitamin D receptor (VDR) on the osteoblasts that increases the Receptor Activator for Nuclear Factor κB Ligand (RANKL) expression which in turn leads to the binding of RANK on the preosteoclasts. This aids in the conversion of preosteoclasts into mature osteoclasts which release hydrochloric acid that demineralize bone.10Chronic vitamin D insufficiency results in hypocalcemia and hyperparathyroidism, thereby a lowered bone mineral density which can contribute to high incidence of osteoporosis and fractures especially in the elderly population. Epidemiological studies by Palacios C et al. 11 show that in the United States having vitamin D deficiency sum up to 35% of the total adult population while Pakistan, India, and Bangladesh show about 80% prevalence. Meanwhile, the prevalence of Vitamin D among the elderly population relates to aboutn61% in the United States, 90% in Turkey, 96% in India, 72% in Pakistan, and 67% in Iran. Hence Vitamin D levels need to be monitored constantly over age. Khadijeh J. Menai et al., in a study assessing the effect of Vitamin D on performance of adult footballers revealing its extended relation on skeletal muscle due the necessity of Vitamin D3 on maintaining serum Calcium levels that aid in adequate contraction of skeletal muscle.12
ESTROGEN
Estrogen is an important sex hormone produced predominantly from the ovaries in females and present in trace amounts in males. Apart from its role in regulating the human reproductive system, it also has its influence on the bone, neuroendocrine and adipose tissues. Estrogen has a down regulatory effect on tumor necrosis factor-α (TNF-α), Interleukin-1 and 6 (IL-1, IL-6), Macrophage Colony Stimulating Factor (M-CSF) and prostaglandin-E2 (PGE2) that leads to decreased resorption. Estrogen acts on the bone by modulating both osteoclast and osteoblast cells, which result in inhibition of RANKL/M-CSF induced activator protein-1-dependent transcription, thereby preventing osteoclast differentiation.6 Vargas et al.13 found that TNF-α is the most important mediator in bone resorption by experimenting on TNF-Receptor 1 (TNF-R1) deficient mice which resulted in normal bone physiology even under estrogen deficiency. Post-menopausal women experience a rapid drop in the levels of estrogen produced by the body often leading to osteoporosis and risks of fracture due to the increased activity of the osteoclast stimulating factors and decreased bone mineral density.
INSULIN
Insulin, a polypeptide hormone secreted by the pancreas plays a crucial role in regulating glucose levels in blood. It is the only hypoglycemic hormone synthesized by the human body. The normal serum insulin level ranges between 6-15µIU/ml. Diabetes mellitus (DM) is of two types: Insulin-dependent DM (Type I DM) and Non-Insulin dependent DM (Type II DM). Type II DM is highly prevalent among the adult population accounting for 85% of the total diabetic population,14 while Type I DM, which is often a hereditary type, has a trail of concrete evidence in causing retinopathy, neuropathy, cardiovascular disorders, periodontal problems and many other complications. However, studies in recent years revealing the effects of insulin on bone metabolism have led to further prospective research to establish the exact correlation. Wang et al. 15 reported that insulin acted by reducing the osteoprotegerin(OPG) to RANKL ratio, thereby decreasing the osteoblastic and osteoclastic activity in bone resorption. Hence a decrease in insulin leads to Further, hyperglycemia may also induce the formation of advanced glycation end-products (AGEs) through non-enzymatic pathways which have a negative effect on bone quality, affecting the extracellular matrix and the vessels by increasing osteocytic expression of sclerostin, a negative regulator of bone formation.16
THYROID HORMONE
The thyroid is a butterfly-shaped gland that is normally bilobed and is connected by an isthmus. Histologically, it consists of the follicular cells that secrete thyroxine (T4) and triiodothyronine (T3) and the parafollicular cells which secrete Calcitonin, the release of which is regulated by the Thyroid Stimulating Hormone(TSH) secreted from the pituitary gland. Thyroid hormones play a major role in maintaining basal metabolism. Its effect on bone density is still a debatable topic till date. Studies have stated that hypothyroidism reduces osteoblast formation and thereby increases the rate of osteoclastic resorption resulting in a slowed bone remodeling process.6 On the other hand hyperthyroidism increases osteoblast and osteoclast activity raising the bone turnover with an impaired bone formation cycle favoring rapid resorption. In adults, hyperthyroidism leads to reduced bone mineral density (BMD), and increased fracture risk, especially in postmenopausal women.
GLUCOCORTICOIDS
Glucocorticoids are a class of steroid hormones that are secreted from the zona fasciculata region of the adrenal cortex. They play an important role in immunosuppression as well as metabolic activities. Excess glucocorticoids decrease the bone remodeling rate primarily by reducing the levels of gonadotropins causing an estrogen-deficient state. This results in elevated levels of tumor necrotizing factor-α (TNF-α), increased RANK-RANKL interaction alongside colony-stimulating factor (CSF-1) stimulating osteoclastogenesis and suppressing osteoprotegerin (OPG), a decoy receptor.17 Glucocorticoids are also known to stimulate the release of matrix metalloproteinases (MMPs) that destroy the collagen matrix of bone leading to further resorption. Weinstein et al.18 reported that increased levels of glucocorticoids also destroy the osteoblast progenitor cells immensely compared to osteoclast precursors.
GROWTH HORMONE
Growth hormone (GH) or somatotropin is a protein hormone made of 190 amino acids and is synthesized and secreted from the adenohypophysis or anterior pituitary gland. It is controlled by Growth hormone-releasing hormone (GHRH) that stimulates the secretion of GH from the pituitary and Somatostatin (SS) counteracts the GHRH by inhibiting the secretion of GH. Ghrelin is yet another peptide hormone secreted by the epithelial cells of the stomach that binds to the growth hormone secretagogue receptor (GHS-R) of somatotroph cells that aids in the synthesis and secretion of GH. GH acts through either direct or indirect mechanisms on the target cells. GH acts on the bone majorly through Insulin-like Growth factor (IGF1& IGF2) that induce chondrocyte proliferation and differentiation as well as increase the formation of osteoblasts thereby, their activity by OPG expression. They also enhance calcium and phosphate absorption by increasing the activity of calcitriol (D3), thereby elevating the rate of reabsorption of phosphate in the renal tubules.19 This in turn increases the bone mineral density by increasing the bone mineralization. Murray et al. 20 conducted a study with 125 adults having growth hormone deficiency (GHD) revealing higher number of younger adults (60 years) denoting that the effect of GHD on BMD was less severe among the elderly. This causes an increased risk of fracture of the long bones as well as vertebral column. While in acromegaly, a state of excess GH production in the adults, the bone turnover rate was higher with increased formation and resorption as well as increased bone mineral density at the femoral neck region compared to insignificant change in lumbar spine region as reported by Maffezzoni et al.21 which also results in high rates of vertebral fractures especially in males with hypogonadism.
DISCUSSION
Endocrine disorders, once widely been considered as hereditary disorders, have now become a common encounter in the medical field with changing lifestyles disrupting the circadian rhythm and basal metabolism of the body. Apart from their effects on growth, development and regulation of homeostasis, their role in balancing the dynamic remodeling of bone tissue and serum Calcium levels which in turn aid in preserving the functional state of the body. The most commonly prevalent endocrine disorders among the general adult population include Type II diabetes mellitus, hypovitaminosis of VITAMIN D, thyroid and parathyroid disorders among the general population and estrogen deficiency disorders and osteoporosis common among post-menopausal women as listed in Table 2.
Type II Diabetes Mellitus (T2DM) has become an ubiquitous metabolic disorder of the present age, threatening the overall health having a long trail of comorbidities affecting most of the organs. Many studies have been done on the adult population assessing the effect of Insulin-resistant diabetes on bone mineral density. Isaiah et al.22 and Gerdhem et al.23 had illustrated a decrease in BMD in patients with T2DM compared to the healthy control groups. In contrast to these results, Bonds et al.24 and Schwartz et al.25 demonstrated an increase in BMD with increased risks of fractures. These are common in both male and female populations though the women of perimenopausal age have a higher predilection for bone disorders with multiple risk factors in play.
The role of sex hormones on bone remodeling has been undoubtedly proven by many. Studies by Ho Pham et al.26 revealed that the effects of Estrogen levels on BMD are more pronounced compared to the Testosterone levels thereby reasserting the risk of decreased BMD with reducing estrogen levels among post-menopausal women when compared to the men of similar age. Cauley et al.27 and Popat et al.28 expressed the direct positive correlation between Estrogen levels and BMD and also proved that supplements of Estrogen combined with Progestin greatly improved the BMD and reduced the risks of fractures.
Hypovitaminosis of Vitamin D3 commonly measured in its active form as Calcitriol that was once a concern among countries that are located at the tropical or temperate zones with insufficient exposure to sunlight has now become common among the population in equatorial regions due to the growing sedentary lifestyles inside closed, non-ventilated rooms. Studies by Arya et al.29 and Grados et al.30 reveal that there is a decrease in BMD with decrease in serum Vitamin D levels and vice versa that is contrary to the findings of Brot et al.31 who stated that there was an increased bone turnover with increase in Vitamin D3 levels thereby decreasing the BMD. Aloia et al.32 and Nieves et al.33 demonstrated that there were no significant changes in the BMD with Vitamin D3 supplements.
Siris et al.34 and Pressman et al.35 demonstrated the inverse relation between the severity and chronicity of osteoporosis with the BMD, with high female predisposition increasing the risks of fracture in long bones among post-menopausal women. Osteoporosis has perturbed the health status among the older population thereby resulting in disabilities. Rathod et al. states that Indian studies show the risk of skeletomuscular disorders in post-menopausal women while vasomotor complications are evident in peri-menopausal women.36
Parathyroid disorders usually occur secondary to the discrepancies occuring in thyroid glands resulting in removal of parathyroids during thyroidectomy. Neer et al.37 and Hodsman et al.38 demonstrated the positive correlation between parathormone levels and BMD. Parathormone replacement therapy has proven highly efficient in improvising bone quality.
Thyroid disorders have been rising over the current age due to stress levels and dietary habits. Not many studies have been done to clearly elicit the effect of thyroid dysfunction on BMD, and there are various schools of thought regarding the correlation of serum thyroxine levels on bone quality. Tuchendler et al.39 illustrated a decrease in BMD level among those with hyperthyroidism compared with the hypothyroid group and control group. Jodar et al.40 demonstrated a mild deleterious effect of endogenous and exogenous thyroid hormone excess in the axial bone mass with an evident decrease in BMD in male subjects. Further Vestergaard et al.41 studied a rise in fracture risk hyperthyroidism and hypothyroidism and also thyroid surgery in hyperthyroid patients revealed a decreased fracture risk.
Various states of hormonal imbalance have led to impediment of regular activities among adults. Endocrine disorders that are acquired with age are a global concern and require constant monitoring of health status that are often neglected until impairments set in. A nation’s progress hugely depends on the accessibility and affordability of health care services to its people. Bone health apart from general health has a greater impact on the quality of living, which needs to be assessed and kept track of. This narrative review asserts the effects of endocrinology on bone health therefore, any disturbance in the hormonal levels requires serious attention. Further studies with wider perspectives are required to determine the exact mechanism of action of each hormone on bone health.
CONCLUSION
Apart from their roles in growth and development, hormones play an undoubtedly important role in maintaining the homeostasis of the body vis-à-vis bone health. The bone health in turn is determined by means of measuring the bone mineral density. Endocrine disorders that were once considered as the diseases of old have now become prevalent among the younger generations due to nutritional deficiency, dietary changes, comfortable standards of living as well as increased levels of stress due to work, education and in sustaining a good living. The focus has diverted from a healthy life to a wealthy life, leaving behind ailments among all age groups. A constant record of bone health is important to avoid bone fragility resulting in morbidities among the population, especially in post-menopausal women.
Acknowledgement:
Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Conflict of Interest: Nil
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareAn Empirical Study of Procrastination Practices at Workplace and their Associated Factors across Institutions: Case of Healthcare Administrative Professionals
English5763Mohamed KhedhiriEnglish Hanan AlthagafiEnglishIntroduction: Little research has explored procrastination in Healthcare Institutions rather than business settings, especially in the Kingdom of Saudi Arabia where the healthcare sector is growing rapidly. Objective: To perform an empirical study of procrastination practices at workplace and their associated factors across institutions in a cross-sectional data setting when the target population is healthcare administrative professionals. Method: A specific questionnaire was prepared to address the stated objective. Two estimation procedures were performed: (i) seemingly unrelated regression was used to determine the effect of routine procrastination practices on project management procrastination; (ii) White’s heteroscedasticity consistent covariance estimator is used to estimate a single model. Results: The main finding is that the routine procrastination practices have a positive impact on project management procrastination 1% level, there is sufficient evidence to support the claim that neuroticism and project procrastination are not related, indicating that people have rational choices and obey to the time-consistent preferences. In addition, we found that people working at the Ministry of Health and University Hospitals were more likely to procrastinate at workplace than any other healthcare institutions. A further finding highlights a more general issue: respondents’ bad habit is an important factor for people to procrastinate at workplace. Conclusion: This paper contributes to past procrastination in project studies; estimating each model separately and ignoring the inter-relation between these models provide biased results, and hence wrong policy decision makings.
EnglishProcrastination, Project, Healthcare, Habits, Neuroticism, QuestionnaireINTRODUCTION
There is a growing literature on procrastination over the past decades. Only few studies have explored procrastination from a management perspective over employees,1 and little research has explored procrastination in Healthcare Institutions rather than business settings, especially in the Kingdom of Saudi Arabia (KSA) where the healthcare sector is growing rapidly. The Kingdom increased the budget of the Ministry of Health by 7.40% during the fiscal year of 2020, the highest increase in more than a decade despite a government deficit of SAR186, 935million, and the highest percentage of the Kingdom’s GDP on healthcare among the GCC countries. The main goal of this increase is to support its healthcare transformation strategy (HTS) proposed in the vision 2030 of the Kingdom. 2 The HTS is the first of three five–year phases. Each phase will put the Kingdom on track to reach the ultimate goals of its vision.2,3
Motivated by the HTS, the focus of this paper is on the negative form of procrastination practices at workplace, when the target population is healthcare administrative professionals working in the Kingdom; that means the irrational delay of behavior.4
Therefore, the goal of this paper is twofold. The first goal is to perform an empirical study of procrastination practices at workplace and their associated factors across healthcare institutions in a cross-sectional data setting. The collection of the data was performed through a survey that was supervised by the principal investigator to ensure the best procedures were adopted. The second goal is to determine the impact of routine procrastination practices on project procrastination practices. This latter is subsequently tested, and the results are compared to a broad single equation model.
Literature review
Langton5 suggests that procrastination is the process of doing more pleasurable things in place of less pleasurable ones, thus delaying tasks to later time. A more in-depth analysis of procrastination defines procrastination as a voluntary delay of an intended course because of, (i) fear of success6 or failure,7 or (ii) fear of being alone or dependent. 8Procrastination may cost employers about $10,000 per employee per year9 and reduce earnings by approximately 30%. 10
There are many types of procrastination: (i) academic procrastination, defined as putting academic assignments until the last minute if at all;11 (ii) life routine procrastination, defined as difficulty in scheduling when to do the many recurring life routines and doing them on schedule12and in some studies they called it ‘Trait Procrastination;’8 (iii)decisional procrastination, defined as the inability to make timely decisions in minor matters13, 14 and in major ones;15and (iv) compulsive procrastination defined as decisional and task procrastination in the same person.
A variety of other studies suggested that all procrastinators lack high action identities. 16, 17The generality of the action identity will be referred to as the level of the action identity. 18, 19 On the Decisional Procrastination side, indecisiveness has been defined20 as a trait-related general tendency to experience decision difficulties across a variety of situations, leading to decision delay, worry, and regret. Indecisive individuals not only show uniformly increased delay relative to others, but rather that their delay behavior may be more striking in its unresponsiveness to risk. 21In another study,22 it has been confirmed that there is strong evidence for that indecisive individual in changed shift behavior from the first to the second half of the task. Anticipated regret and perceived fairness were mentioned as possible mediating processes. 23 An experimental study in a bank in Colombia aimed to send reminders about goal achievements with small in-kind prizes every week to remind employees of their goal achievements found effective for fighting procrastination in the workplace. 24
Projects are aspirational efforts using significant resources to reach a better future state by achieving tangible goals. 25 The value of these projects is very known in the literature by studying cost-benefit analysis approach in a broad sense. 26, 27, 28, 29Recent research indicates30 that projects contribute to approximately one-third of the gross domestic product (GDP) in a typical Western economy transitioning from an industrial to a post-industrial setting.
Past research on project procrastination has shown people are most prone to procrastinate on the highest cost of the project stage. 31 If the cost structure is endogenous, people are prone to choose cost structures that lead them to start but not finish projects.32
A meta-analysis33 contains the correlations of 121 studies examining the relation between procrastination and personality variables (motives, affect, and performance), resulted in a negative effect found in relation to conscientiousness and self-efficacy, and a positive relation was found with self-handicapping. Affect was moderately related, as well as performance outcomes, and motives were weakly correlated.
In the next section, we examine the methods used to perform the analysis of this study. Then, the results are reported and discussed. And finally, the paper concludes with some remarks that may refine and improve the validation of our results.
MATERIALS AND METHODS
Study design and sampling techniques: The target population for this study was the administrative professionals who worked in the healthcare facilities located in Riyadh city, Saudi Arabia. The term “healthcare facility” includes Ministry of Health (MOH) hospitals, private hospitals, military hospitals, and academic hospitals.
A cross-sectional study was conducted based on the following criteria: (i) Individuals who are working at administrative departments in the hospitals; (ii) A minimum of bachelor’s degree diploma and three years of experience in the field; (iii) Saudi citizen or non-Saudi citizen; (iv)English or Arabic as a native or second language.
A subset of the population working in this area was surveyed by using a self-administered questionnaire. Based on MOH, 2019, the total number of health administrators is 3920, with a margin of error of 5%, a confidence level of 95%, and a response distribution of 50%, the estimated sample size was 350. Trained research coordinators at King Abdulaziz Medical City conducted the interviews. The collection of the data was supervised by the principal investigator to ensure the best procedures were adopted. After cleaning and editing the data set, only 245 responses were retained and used for this study (response rate = 70%).
Interview questionnaire: A specific questionnaire was prepared in 2020 that addressed the aims of this study. To best of our knowledge, no existing questionnaire has been found that cover this type of analysis. In this paper, we have three continuous dependent variables (Table 1): The first dependent variable is project management procrastination (item 1 and 2), the second dependent variable is routine procrastination practices (item 3 and 4), and lastly, the procrastination practice at work (items 1, 2, 3,4) which includes project management procrastination and routine procrastination practices as well.
The exogenous variables can be classified in two categories. The first category includes two continuous variables: procrastination habits (5 items) and neuroticism (7 items).
In all these items, employees are asked to rate their responses in – Likert response categories – ranging from 1 “strongly disagree” to 5 “strongly agree”. For each variable, items are summed and converted on to a scale of 100 to minimize measurement errors encountered in this type of analysis. The second category includes respondent's personal characteristics such as sex, nationality, age, and experience. 32
Statistical analysis: SAS 9.2 version33was used for data analysis. The internal consistency 34 of each dimension was checked via Cronbach coefficient “alpha >0.70.”
The Kruskal-Wallis 35 test was used to compare the homogeneity among groups. Two estimation procedures were performed: (i) seemingly unrelated regression36 was used to determine the effect of routine procrastination practices on project management procrastination; (ii) White’s heteroskedasticity consistent covariance estimator37 is used to estimate a single model. And finally, our analyses present test of significance of some important factors affecting procrastination at workplace by using an F-test.
RESULTS
The summary statistics and internal consistency were provided by Table 1. The study sample was comprised of 71% men and 29% women. 79.6% of respondents are Saudi while 20.4% are non-Saudi. Project management procrastination (PMP), routine procrastination practices (RPP), and procrastination practices at workplace (PPW) represented average below 50% (45.5%, 47.4%, and 46.4% respectively), while habits and neuroticism represented average above 50% (51.9% and 69.8% respectively). Finally, experience had standard deviation 74% half the size of the mean, indicating a wide range of experience across the sample.
The reliability of all variables was determined by using Cronbach’s alpha method. In all dimensions, the overall alpha scale was, at least, equal to or greater than 70%, suggesting that all variables exhibit internal consistency at subscale levels.
The validity of instruments was conceptually difficult to prove quantitatively without a standard. However, some evidence may be built over time. One method is to check construct validity. The construct validity was supported by two evidences: (i) the high internal consistency mentioned above; (ii) the quantitative analysis that will be discussed later in this section.
We used Kruskal – Wallis procedure to test whether healthcare institutions differ significantly among these groups. Table 2 provides the results of this test for PMP, RPP, and PPW. Under the null hypothesis that there is no significant difference among all types of healthcare institutions is rejected for all types of practice. For this reason, we generated four dummy variables that considered this difference (Table 1).
Table 3 shows the parameter estimates of the statistical models. The effect of routine procrastination practices on project procrastination practices is showed by cross model correlation estimates (estimates= 0.597, p-value = 0.000), and deemed to have significant positive impact at 1% level. Thus, the estimates of the procrastination practice at workplace model are reported in the last column for comparative purposes only.
In a statistical context, and not surprisingly, the RPP estimates show that habits and neuroticism increase procrastination (estimates are 0.515 and 0.124 respectively). These suggest that habits and, with less degree neuroticism, are important factors that enhance procrastination tendencies. Moreover, and across institutions, we found that professionals working at the Ministry of Health and University Hospitals were more likely to procrastinate at workplace, while Military sector and Private sector did not provide us any effects.
Regarding the PMP estimates, we found similar pattern in terms of sign and significance, except that neuroticism has no significant impact on PMP (the past study also indicates that neuroticism has no direct link to procrastination),38 and the magnitude of the parameters estimates in the PMP model are greater than that of RPP model.
In terms of respondent personal characteristics, we investigated four factors associated with procrastination. These include respondents' sex, age, experience, and nationality. These factors deemed to be related to procrastination but in more diffuse and nonspecific pattern. Professionals' people with long experience have less procrastination practice for both RPP and PMP models, suggesting people with long experience are more organized in setting their goals. For the RPP model, male professionals tend to procrastinate more than female, while age has no significant effect. The opposite pattern holds for the PMP model, that is mean, older professionals procrastinate more than younger professionals, while sex has no significant effect. Finally, the nationality of professional workers has no
significant effect on both models. To better understand the above findings, we conducted several tests of the most important factors, cross the models, that may affect procrastination, and which are then compared to a single equation estimation model (model PPW, last two columns of Table 3). Table 4 contains the results of these tests. Test 1, states that there is no relationship between procrastination and neuroticism; Test 2, states that healthcare administrative professionals working at the Ministry of Health and University Hospitals do procrastinate; and finally, Test 3, states that respondent’s sex and age affect, indeed, procrastination.
Results show, also, that neuroticism cannot affect healthcare administrative professionals to procrastinate when managing projects (p-value = 0.142). This result is a little bit different from the PPW model where neuroticism is significant at 10%. Hence, using a single equation estimation may lead to the wrong result. However, Tests 2 and 3 are rejected by SUR procedure, indicating that healthcare administrative professionals working at the Ministry of Health and University Hospitals do not procrastinate and that sex and age, in general, have a positive effect on procrastination.
DISCUSSIONS AND IMPLICATIONS
Our empirical analysis identifies several results about procrastination practices at workplace when the target population is healthcare administrative professionals. The key intuition that drives our results is that by just estimating the PPW model as a single equation and ignoring the impact of RPP on PMP, the non-significance of neuroticism cannot be detected. The first reason of the absence of neuroticism is that Healthcare Administration requires effective leadership and business expertise in addition to strong analytical and communication skills. A second reason is that healthcare administrative professionals deemed to be rational in their decision makings and they obey to the time-consistent preferences.39Thus, it is possible to state that neuroticism cannot affect healthcare administrative professionals to procrastinate when managing projects. Another finding of the study that deserves to be mentioned is that healthcare administrative professionals working at the Ministry of Health and University Hospitals procrastinate more than any other healthcare institution, although the former is more significant than the latter, in a statistical context.
The results in this study highlight a more general issue: respondents’ habit or the environmental cultural is an important factor for people to procrastinate at workplace. Habit is a very complex dimension to measure and evaluate since some of the habit's components are associated with heredity, 40 teamwork activity, friends, etc. One possible solution for policy decision makings is to implement incentives to combat bad habits at workplace. These incentives may include a significant improvement of the institution's environmental culture by providing people adequate training, a meaningful and challenging workplace, and especially, competency-based performance systems. 41, 42, 43
CONCLUSION
This paper focused on performing an empirical study of procrastination practices at workplace and their associated factors across institutions in a cross-sectional data setting. The target population was healthcare administrative professionals in Saudi Arabia. It is important to openly acknowledge the limitation of the data and the potential bias encountered in cross-sectional data. 44
Three models were developed that distinguish among routine procrastination practices (RPP), project management procrastination (PMP), and procrastination practice at workplace (PPW). A seemingly unrelated regression estimation was used to capture the effect of RPP on PMP. Throughout our analysis, we proposed testable hypotheses across the models and their implications for policy decisions making process. The findings of this study indicate that the routine procrastination practices at workplace have, indeed, a positive impact on project procrastination. In addition, and across the models, neuroticism has no relationship with procrastination, and that age and sex have positive impact on procrastination. Furthermore, we found that professionals working at the Ministry of Health and University Hospitals were more likely to procrastinate at workplace, while Military sector and Private sector did not provide us any significant effects.
We suggest this paper contributes to past procrastination in project studies: estimating each model separately and ignoring the inter-relation between these models provide biased results, and hence wrong policy decision makings. In line with the recognition of the need for more studies on project procrastination in health care sector, we provided models that distinguish among different types of institution.
More research is needed to validate and refine the above findings. A possible strategy for healthcare institutions to curb procrastination would be to increase the sample size at the national level and test how robust the present findings are under different parameterizations and model specifications. We also see a new opportunity on model building on project values28 that allows a more comprehensive understanding of the strategic choices for each institution rather than using project as broad variable. Moreover, additional research on the genetic aspects of procrastination is required to better understand this phenomenon,45 and how these aspects differ across cultures.
Acknowledgement:
Authors acknowledge the support of NGHA for this research. Special thanks to respondents of the questionnaire who provided valuable and constructive information that greatly inspired the research and IJCRR comments on an earlier version of the manuscript.
Source of funding: None
Conflict of Interest: No conflict of interest
Authors’ Contribution:
Mohamed Khedhiri: Manuscript writing, submission, and revision.
Hanan Althagafi: Questionnaire design and literature review.
Englishhttp://ijcrr.com/abstract.php?article_id=4297http://ijcrr.com/article_html.php?did=4297
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareOral Cancer Detection using Machine Learning and Deep Learning Techniques
English6470Nanditha B REnglish Geetha Kiran A Sanathkumar M PEnglishIntroduction: Oral cancer is one of the most dangerous cancers which occurs in the oral cavity. Overuse of tobacco and smoking cigarettes are the primary risk factors for developing oral cancer. Oral cancer diagnosis at an early stage can save the lives of many people with proper treatment. Objective: The proposed work aims at early detection of potentially malignant oral lesions by the development of an automated disease diagnosis system. Building a large dataset of well-annotated oral lesions is a primary key component. A novel strategy to build automatic oral cancerous image classification software is provided in this paper. Methods: In the present work, machine learning models and deep neural networks are used to build an automated diagnosis system. By using the initial data which was gathered in this study, Naive Bayes, KNN, SVM, ANN, and CNN classification models are constructed for the automated detection and classification of oral malignancies. A new CNN network is designed which consists of 43 deep layers, whose network structure is inspired by the standard VGG-16 network. Results: Performance analysis of different machine learning models and deep learning models has been provided. Results demonstrate that the deep learning model has the potential to tackle this challenging task of early detection of oral cancerous lesions. Conclusion: It is observed from experiments that different classifiers can perform well in identifying oral cancerous lesions. Particularly, the deep learning CNN model shows high accuracy in differentiating normal and cancerous images.
EnglishDeep learning, Lesions, Machine learning, Texture features, Oral cancer, Convolution Neural Network, Benign, MalignantINTRODUCTION
According to World Health Organization, nearly six lakh new cases of oral cancer and more than three lakh deaths are reported every year.1 Oral cancer include the main sub-sites of the lip, oral cavity, nasopharynx, and pharynx and have a particularly high burden in South Central Asia due to risk factor exposures.2 A comprehensive approach is needed for oral cancer to include health education and literacy, risk factor reduction and early diagnosis.
Computer vision can greatly assist in the diagnosis of oral cancer compared to a naked human eye examination, which turns out to be more complicated. Diagnosis and classification of oral cancer can be performed by traditional machine learning and deep learning techniques 3. In traditional machine learning techniques, a domain expert needs to identify the applied features and make them more clearly visible to the learning algorithm to work, to reduce the complexity. Literature reveals the use of conventional classification techniques like support vector machines (SVM), naïve Bayes, and k-nearest neighbor (KNN) classifiers for the classification of oral lesions into normal and abnormal lesions.4
SVM is a supervised machine learning algorithm that can be employed for classification.5 A method called the kernel trick is used to modify the data and then an optimal boundary is chosen. Naive Bayes is mainly employed in the classification problem and uses a similar technique which is probabilistic based on different features of different classes.6 K-nearest neighbor is used in predicting the class label of unknown data by taking the majority of the class labels of K-nearest data instances and the distance between the instances is measured by various distance measures 7.
Deep learning is a subfield of machine learning which works on artificial neural networks, which are algorithms inspired by the structure and function of the brain. ANN (Artificial Neural Network) can be trained on numerous images of both benign and malignant lesions. By learning the non-linear interactions, the model can tell itself if the image is malignant or benign. So, in deep learning, there is no need for domain expertise for feature extraction. In the present work, the classification of oral images into benign or malignant images is performed by a deep learning model using CNNs (Convolutional Neural Networks), which is a type of ANN.
CNN's are composed of multiple layers of artificial neurons. The behavior of each neuron is defined by its weights. Every CNN network consists of 4 layers: input layer, convolution layer, pooling layer, and fully connected (FC) layer. The convolutional layer extracts feature maps from the input image using filters and the pooling layer replaces the output of the network at certain locations by deriving a summary statistic of the nearby outputs. This leads to reduction of spatial size and thus reduces computational complexity. Neurons in fully connected layers have full connectivity with all neurons in the preceding and succeeding layers. The FC layer helps to map the representation between the input and the output. To classify the output, generally, a softmax layer is used in image classification. CNN's are trained using labeled datasets given with the respective classes. CNN's learn the relationship between class labels. For the input image shown in Figure 1, the feature maps extracted by the convolutional layer are shown in Figure 2.
LITERATURE REVIEW
Various researchers have tried different machine and deep learning techniques for the classification of images into normal and abnormal images. Licheng Jiao et al.8 present a survey on new-generation deep learning techniques which can be used for image processing tasks. Three series of deep learning models namely, CNN series, GAN series, and ELM series networks and their roles in image processing tasks have been described. These are used extensively in image processing nowadays, where these techniques have different depth and types of networks which makes image processing tasks easier now. Daisuke Komura et al. 9 have applied machine learning techniques like SVM, random forest, CNN, k-means, auto encoder, and principal component analysis for histopathological image analysis. Before applying machine learning methods, feature extraction and classification between cancer and non-cancer patch are performed.
A survey on feature extraction methods that extract meaningful features from the raw images has been presented by Anne Humeau et al.10 Seven classes of texture feature extraction methods, their advantages, disadvantages, and applications are reviewed. A large number of texture datasets that are used by the authors to test and compare the feature extraction algorithms have been described. For very high-resolution remote sensing images, the authors have proposed histogram-based attribute profiles that allow the modeling of texture information from attribute profiles.
A discussion on supervised, unsupervised, and semi-supervised feature selection techniques which reduce computation time, increase accuracy and help in removing redundant and irrelevant data has been presented by Jie Cai et al.11 Their use in many fields like image retrieval, text mining, fault diagnosis, and other areas has been reviewed by the authors.
Skin segmentation using Yellow-Chrominance blue-Chrominance red (YCbCr) and Red-Green-Blue (RGB) color models is presented by Shruti et al.12 The authors have developed a computationally efficient and accurate approach for skin cancer detection which may be used in real-time. Results indicate that the YCbCr model is better than the RGB model in segmenting and classifying skin lesions.
A deep learning model has been developed by the authors for classifying oral malignant lesions by the use of CNN technique.13
DATA COLLECTION
A total of 630 oral images have been used in the present work for oral image classification. Few of these images were downloaded from the internet and few others were collected from different hospitals by consulting oral specialists. From these images, 1200 lesion regions were cropped and as a result, we obtained separate images of lesion regions. Out of those 1200 lesion images, 600 are malignant images and 600 are normal images. Figure 3 and Figure 4 depict different patches of few normal and malignant images from the dataset. The benign patches are labeled as B001, B002, and so on. The malignant patches are labeled as M001, M002, and so on. A feature vector was created by extracting useful features from these lesion images and then the newly obtained dataset is used in machine learning models for testing purposes. For the deep learning model, the lesion images are augmented to generate 9600 images. Then these images are used for training the network.
MATERIALS AND METHODS
The details of the proposed work for oral malignancy detection have been elucidated in Figure 5. The input to the disease diagnosis system is an RGB oral image; this input image is then subjected to a segmentation process in order to select the lesion region. After segmentation, features are extracted from the lesion region; these features are used to classify the image using SVM, KNN, Naive Bayes, and ANN models. CNN takes a segmented lesion image as an input to the network and classifies the image as normal or malignant. The details of this process are elaborated in the following sections.
Segmentation
In this process, the lesion region is extracted from an input image. Firstly, the input RGB image is converted into YCbCr color space and then a mask of lesion region is created based on blue difference chroma (Cb) and red difference chroma (Cr) intensity values. Cancerous oral images have two types of lesion patches-white and red lesion patches.
If the mean Cr value of the input image is less than a predefined threshold value, then that image will have white patches; a mask of white lesion patches is created using Cb intensity, if a region contains a mean Cb value more than the mean Cb value of the whole image then that region is considered as a white lesion patch. If the mean Cr value of the input image is greater than the predefined threshold value, then the input image will have red patches; a mask of red lesion patches is created using Cr intensity, if a region contains a mean Cr value more than the mean Cr value of the whole image then that region is considered as a red lesion patch.
After creating the lesion mask, a region-based active contour segmentation is performed, which selects the lesion regions in the input image based on the mask, and the lesion which has the wider area is considered as the final output lesion and then that lesion is extracted as a separate image. Figure 6 depicts the details of oral lesion segmentation.
Feature Extraction
A feature vector of 44 features is created by extracting Grey-level co-occurrence matrix (GLCM), Grey-level run-length matrix (GLRLM), Fractal features, Gabor features, and Color features from lesion images. The extracted features are Energy, Homogeneity, Contrast, Correlation, Short-run emphasis, Long-run emphasis, Gray-level non-uniformity, Run-length non-uniformity, Run percentage, Low gray-level run emphasis, High gray-level run emphasis, Short-run low gray-level emphasis, Short-run high gray-level emphasis, Long-run low gray-level emphasis, Long-run high gray-level emphasis, Fractal dimension, Fractal lacunarity, Standard deviation, Gabor mean squared energy, Gabor mean amplitude, Mean and Standard deviations of RGB, Hue-Saturation-Value (HSV) and YCbCr color components.
Feature Selection
The irrelevant and redundant features from extracted features have been removed and only the most relevant features are selected by using the statistical feature selection methods: Minimum Redundancy Maximum Relevance (MRMR) and Box plot methods. Based on the rank assigned by these feature selection methods, the top 19 features are selected. The selected features are listed in Table 1.
Classification
The dataset of 19 selected features is used for training machine learning classification models and the ANN model. Segmented lesion images are used for training the CNN model. The classification Techniques employed in this paper are described below:
Support Vector Machine (SVM)
SVM is a supervised machine learning algorithm that can be employed for the classification process. Medium Gaussian SVM model is used for classification which utilizes a method called the kernel trick to modify the data and then based on these changes it identifies an optimal boundary among the possible output.
K-Nearest Neighbour (KNN)
A modified version of KNN i.e., weighted KNN is used to classify the image based on selected features from the lesion region. The performance of this method is completely dependent on the training set and the choice of hyperparameter K. For the current work, a value of 10 is chosen for K.
Naïve Bayes
A Naive Bayes classifier is a simple probabilistic classifier that is based on the Bayes theorem. For the present classification, a Bayesian classifier with different kernel densities is made use of.
Artificial Neural Network (ANN)
A Feed-Forward Artificial Neural Network is used to classify images based on selected features from the lesion image. A dataset of 19 features extracted from lesion images is used to train the network. The network consists of 20 hidden layers and 1 output layer. The ANN network architecture is shown in Figure 7.
Convolutional Neural Network (CNN)
A new convolutional neural network is created for oral disease detection, which has 43 layers. The architecture of the CNN network is shown in Figure 8. This network includes 10 convolutional layers, Batch normalization layer is used to normalize convolutional layer output and the ReLU layer is used activation function. The max-pool layer is used for pooling. 3 fully connected layers are used with 1024, 512, and 2 nodes in respective layers. Output is predicted using softmax layer. This CNN network takes 64x64 RBG images as input and classifies them as benign or malignant images.
RESULTS
Dataset
A dataset that consists of 19 feature values of 1200 lesion images is used to train using SVM, KNN, Naive Bayes, and ANN models. Training and testing dataset details for the used models are given in Table 2. Segmented lesion images are used for training and testing the CNN model and their dataset details are given in Table 3.
Training and Testing results
The training accuracies of the classification models are given in Table 4. The testing performance measures of the classification models are given in table 5.
DISCUSSION
From the obtained results, among machine learning classification models i.e. Naive Bayes, KNN and SVM, the SVM model performs well when compared to the other two models. CNN model performs better when compared to ANN. Though ANN’s performance is nearly equal to CNN, CNN still stands out to be best because of its ability to learn better features by itself by looking at the overall performances of each classification model, CNN outperforms all other models with 99.3% training accuracy and 97.51% testing accuracy. Also ANN and SVM model performs almost equally when considered to the performance of CNN.
CONCLUSION
In this paper, a few machine learning and deep learning classification models for oral cancer detection have been discussed. The results of the classification models for automating the early detection of oral cancer have been demonstrated. Desktop software is built using Matlab to classify whether an image is malignant or normal by using any of the models which are presented in the paper and a report is generated accordingly.
The promising model results demonstrate the effectiveness of deep learning and suggest that it has the potential to tackle these challenging tasks.
FUTURE SCOPE
In future work, it will be possible to gather more images for enriching the dataset and to improve the accuracy of the models using different techniques of fine-tuning and augmentation. The main goal will be implementing a semantic segmentation for selecting lesion region from an input image to improvise accuracy results of the models.
Acknowledgment
The authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals, and books from where the literature for this article has been reviewed and discussed
Source of Funding
No financial support has been obtained for this work
Conflict of interest
Authors have no conflict of interest
Author’s Contribution
All authors have substantially contributed to the conception and design of the manuscript and interpreting the relevant literature. The authors have drafted the manuscript and revised it carefully for important intellectual content.
Englishhttp://ijcrr.com/abstract.php?article_id=4298http://ijcrr.com/article_html.php?did=4298
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareThe Potential Role of Carotenoid Pigment Isolated from a New Rhodotorula Species in Ameliorating Cerebral Ischemic Stroke Experimentally
English7180Neveen A SalemEnglish Ghada S IbrahimEnglish Shaimaa El ShebineyEnglish Mostafa M. Abo ElsoudEnglishAbstract
Objectives: Natural antioxidants particularly carotenoids have been associated with a lowered risk for stroke and cerebrovascular diseases. The present study proposes a new microbial source of carotenoid-rich bio-pigment and investigates its potency in mitigating ischemic stroke in an animal model. Methods: A yeast isolate rich in carotenoid pigment was defined morphologically and physiologically, recognized by 18S rDNA as Rhodotorula mucilaginosa G20with a similarity of 100%, then submitted to Gen Bank (accession number KY271337.1). The extracted pigment was analyzed using high-performance liquid chromatography invitro. Furthermore, an in-vivo rat model was assessed to investigate the effect of the extracted pigment against Endothelin-1 (ET-1) induced focal cerebral ischemia. Rats were assigned into four groups: Group (1) normal control rats received saline. Group (2): sham-operated rats received saline, Group (3): rats received ET-1.Group (4): rats received extracted pigment and ET. Results: HPLC results revealed that the extracted yeast pigment consists mainly of neoxanthin and β-carotene. Invivo, pretreatment with extracted pigment significantly enhanced the grip strength, restored impaired vertical forelimb use induced by ET-1 in rats, halted oxidants biomarkers, and triggered antioxidant mediators. Moreover, it suppressed inflammatory and apoptotic markers. The histological and structural deterioration in the ventral subiculum was deterred. Conclusions: Based on these encouraging results, The extracted microbial carotenoid pigment production can be considered efficient and economical and proves to be a promising approach for ameliorating cerebral ischemic injuries.
EnglishCarotenoid, Endothelin, Neoxanthin, Oxidative Stress, Rhodotorula, StrokeIntroduction
Many synthetic coloring agents were banned by the U.S. Food and Drug Administration (FDA) and the European Food Standards Authority (EFSA) due to their toxicological problems and carcinogenicity. Efforts were made to produce natural pigments not only for their role in industries like cosmetics, food, textile, and plastic but also in medical uses for their antioxidant, anti-inflammatory, anticancer, and anti-microbial activities.1 Micro-organisms are a promising natural color source besides; they are versatile tools in biotechnology. Many bio-pigments were produced using microorganisms including carotenoids, melanins, flavins, or quinines.2 Carotenoids are the most prevalent natural pigment with many significant biological activities and manufacturing applications.3 A growing interest in this class of pigments is directing the search for new.4Rhodotorula sp., Blakeslea trispora, Phaffia sp. Streptomyces chrestomyceticus, Flavobacterium sp, and Phycomyces blakesleeanus are acknowledged for producing carotenoids.5 Rhodotorula yeast strains are efficient in utilizing the whole biomass and produce a high yield of carotenoids.6 The pharmacological value of carotenoids in many diseases involving cardio- and cerebrovascular diseases is due to their lipid-soluble anti-oxidant nature .7
Stroke is a major cerebrovascular disorder leading to acquired adult disability and death.8Only a minority of patients suffering from acute ischemic stroke benefit from thrombolytic intervention with recombinant tissue plasminogen activator since it must be taken within the first 5 hours of ischemic injury onset.9 Stroke mostly results in dysfunction with a permanent or reversible neurological deficit.9 Infiltration of inflammatory cells, oxidative molecules, excitotoxicity, and apoptotic mediators through the ischemia-impaired blood-brain barrier lead to lesion progression and eventual neuronal cell death.10 Dietary intake of antioxidants is considered a modifiable risk factor that can reduce the severity of injury after an ischemic stroke. 11 Neuroprotective treatments during or following exposure to ischemic stroke interrupt the cellular, biochemical, and metabolic elaboration of injury and ameliorate brain injury.12 Severalstudies revealed the beneficial capability of carotenoids such as α- and β-carotene, zeaxanthin, lycopene, and lutein on suppression of stroke risk.13
The present study utilized Rhodotorula species for the production of carotenoid-rich pigment which can be applied in clinical therapeutics. The produced pigment was investigated biologically for its neuroprotective impact on the brain ischemic injury rat model. Focal injection of endothelin (ET)-1 is considered a reproducible model of ischemic stroke.14 Modulating therapeutic effects were investigated behaviorally, biochemically, and histopathologically.
Materials and Methods
Drugs
Endothelin-1 powder ≥97% was obtained from Sigma-Aldrich,(St. Louis, MO, USA) (Lot#102M4762V). Ketamine, xylazine, astaxanthin, α- and β-Carotene, lycopene were purchased from (Sigma-Aldrich Fine Chemicals) (Zeaxanthin, Violaxanthin, Antheraxanthin, Neoxanthin) were obtained from Fluka (Buchs SG, Switzerland
Isolation and identification of carotenogenic yeast
The isolated yeast strain that produces carotenoid, was isolated from the surface of cold yogurt by the particle plating method. The isolated yeast was identified by determining its morphological properties. 15 Also, The produced pigments and shape of colonies of yeast were examined.
Yeast biomass was collected from grown YPD cultures. One ml of broth was centrifuged at 10,000 rpm for 10 min. DNA was extracted using a DNA extraction Kit and its quality was evaluated on 1.2 % agarose gel where a single band of high Mw DNA was observed. The extracted DNA was used as a template for phylogenetic analysis. The 18S rDNA gene was PCR-amplified using ITS1 primer(5'-TCCGTAGGTGAACCTGCGG-3') and ITS4 primer (5'-TCCTCCGCTTATTGATATGC-3') . Then, partial sequencing was performed at Macrogen Company, Korea. Nucleotides sequences were compared with the GenBank database (http://www.ncbi.nlm.nih.gov/) by using the BLASTN program followed by a sequence alignment. A phylogenetic tree was constructed using the Neighbor-Joining algorithm version 5.2 of Molecular Evolutionary Genetics Analysis (MEGA) and 1,000 re-samplings. 16,17
Production of carotenoid-rich pigment
Carotenoids were produced using yeast malt broth medium with the following ingredients: yeast extract, 3 g/L; malt extract, 3 g/l; peptone, 5 g/l, glucose 10 g/lat pH 5. The medium was sterilized at 121°C for 20 minutes. The production of cell biomass was performed in three successive steps. Firstly, 500ml of yeast malt broth medium was inoculated with yeast cells (OD 0.5 at 610 nm) and incubated for 5 days at 30°C and 160 rpm. At the end of the incubation period, the entire 500ml production medium was added to 4.5L of yeast malt broth medium and incubated under the same conditions. Finally, a total of 5L was used for inoculation of 45L of sterile yeast malt broth medium in a 75L total volume bioreactor. The culture was incubated at 30°C for 5 days with aeration at 0.2 v/v/m and 200 rpm agitation speed .18
Extraction of bio-pigment
Yeast cells were harvested by continuous centrifugation using CEPA continuous centrifuge. The cells harvested from the 50L production medium were hydrolyzed with (1N) HCl for one and half hours in a water bath at 70°C. Excess acid-washed away with water and then cells get immersed in acetone: methanol (1:1) overnight. The pigment was extracted from the cells using acetone until all color was removed. The extract of acetone was allowed to dry out in the air.
HPLC analysis of carotenoids extract
Extracted carotenoids were dried and concentrated under nitrogen and re-dissolved in methanol. 10 µL of the carotenoid extract was analyzed using reversed-phase HPLC (C18; 25 cm×4.6 mm, 5 μm) and isocratic mobile phase composed of (dichloromethane: acetonitrile: methanol) (20:70:10, v) at a flow rate of 1.0 ml/min. Beak recognition and λ max values of these components were accepted by their retention times and standard chromatogram characteristic spectra put down with a Shimadzu SPD-10AVP photodiode array detector (Shimadzu, Japan) the spectra were recorded from 400-600 nm scan range.19 The mass spectra were obtained using 130oC heated source APCI, and the probe was held at 500oC. The voltages were optimized for corona (5 kV), HV lens (0.5 kV), and cone (30 V). At 100 and 300 L/h, respectively, nitrogen was used as a sheet and drying gas. In positive mode, the spectrometer was calibrated, and [M+H]+ ions were captured. Mass spectra of carotenoids with m / z 400-700 were acquired and verified with respective standards.
Animals
40 adult female Wistar rats weighing 160±20g (NRC, Egypt) were used in this study. Rats were kept in plastic wire–meshed rodent cages and maintained under standard conditions of humidity, temperature (23 ± 3°C), and light/dark cycle (12/12 h). Rodent chow diet and water were allowed ad libitum. Experiments were carried out following the instructions of the Ethical Committee of National Research Center, Egypt, which are in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals recommendations (NIH Publications No. 8023, revised 1978).
Experimental design
Animals were assigned into 4 groups (n=10) .Group 1(normal control group) rats received saline (1 ml/kg, i.p/ day for 14 days ), Group 2 (sham group) rats received saline (1mg/kg ,ip/day for 14 days ) followed by saline intracerebroventriculary (4 μl, ICV ,once) . Group 3 (Induced group) rats received saline (1mg/kg ,ip/ day for 14 days ) followed by ET-1 (4 μl, ICV , once ). Group 4 (bio pigment group) rats were pretreated with carotenoid extract (50 mg/kg, i.p./day for 14 days) followed by ET-1 administration.
Twenty four hours after ET injection, rats were behaviorally examined for grip strength and activity in cylinder test. Then rats were euthanized, decapitated and brains were harvested and hippocampi were dissected for biochemical and histological examination.
Endothelin-1 (ET-1) induced cerebral ischemia
All rats were anesthetized with a ketamine/xylazine cocktail (1 ml/kg,i.p.).The skin above the skull was sterilized using a 5% povidone-iodine solution. Each rat was mounted on stereotaxic apparatus (Kopf Instruments, Tujunga, CA). At midline, an incision was made to expose the skull. A hole was drilled above the intended lesion site through the skull using a dental burr. The coordinates for the injection were determined based on the rat brain atlas 20 AP-2.7mm, ML +?3.2mm, and DV -3.1mm. (4 μl) 100 pmol/l of ET-1 solution in sterile saline, at the rate of 0.5 μl per minute was delivered. A 10 µl Hamilton syringe was lowered into place and allowed to remain undisturbed. In sham control animals, saline solution was applied instead of ET-1 solution and the same procedures were followed.
Neurobehavioral assessment :
At the end of the experimental period, motor behavioral impairment for all rats was assessed using the wire hanging test and the cylinder test.
Wire hanging test
The wire hang test was carried out to evaluate neuromuscular strength. Each rat was placed with its forelimbs on a 20 cm long wire adjusted horizontally 50 cm above the surface. Latency time to fall was recorded. 30 seconds cut-off time was taken. 21
Cylinder test:
The cylinder test is used to measure locomotor activity and behavioral deficits in the rats by calculating rearing frequency. The spontaneous movement was estimated by inserting each rat in a small transparent cylinder (height, 15.5 cm; diameter, 12.7 cm) for 5 min. The number of rears was recorded after each treatment. A rear was counted when an animal made a vertical movement with both forelimbs removed from the ground .22
Biochemical analysis:
Oxidative stress biomarkers
Lipid peroxidation was evaluated by estimating thiobarbituric acid reactive substances (TBARS) in brain tissues as per.23 Catalase (CAT) and superoxide dismutase (SOD) activities were estimated following 24,25 respectively. Bioassay for xanthine oxidase (XOD) activity was performed according to Gulec et al.26 Glutamine Synthetase (GtSx) activity was evaluated as per Sunil et al.27 and tyrosine hydroxylase (TH) activity was determined using enzyme linked-Immunosorbent technique using (ELISA) kit provided by BioSource, Inc.San Diego, USA.
Brain inflammatory and apoptotic mediators
Matrix metalloprotein-9 (MMP-9), Nuclear factor Kappa B (NF-κβ), and Caspase-3 and Nuclear factor erythroid -2 (NRF-2) were estimated using ELISA kits provided by Biosource Inc., USA according to the manufacturers’ instructions.
Statistical Analysis
Data were displayed as mean±SEM. All experiments were tested for significance using Tukey's post hoc analysis following one-way ANOVA. Differences were considered significant at p< 0.05.
Results
Phylogenetic Analysis and Identification of Carotenogenic Yeast
The isolated yeast strain G20 has rapid growth and the ability to produce a high quantity of pigments. G20 isolate has a mucous, smooth surface and a color that ranges from orange to red on the YPD agar plate. Cells were oval under the microscope. (Figure 1)
The ITS sequence obtained from isolated G20 strain was compared with the sequences in the GeneBank database and presented that the G20 strain possessed 100% similarity to Rhodotorula mucilaginosa. The nucleotide sequence was placed under the KY271337.1 accession number in the GeneBank (http:/www.ncbi.nlm.nih. gov). The phylogenetic tree of Rhodotorula mucilaginosa KY271337.1was constructed with closely related sequences accessed from the GenBank as shown in Figure 2
HPLC-APCI-MS analysis of the carotenoid extract
The results revealed that the extracted yeast pigment consists mainly of neoxanthin (40%) and β-carotene (30%), according to retention time and absorption spectra as compared to respective reference standards. Neoxanthin was eluted at 2.66 min, β-carotene was eluted at3.47 min. Positive ion mass spectra were obtained for the peaks of maximum absorption and [M+H]+ dominant for neoxanthin was 601.2 of and fragments of 509.1 [M+H-18]+, and 491.2 [M+H-18-92]+. The mass spectra for β-carotene was mass peak of 537.2 [M+H]+, 519.2 [M+H-18]+, and 445.2 [M+H-92]+.
Neurobehavioral assessment
Wire hanging test:
As indicated in table (1), ET-1 treated rats exhibited a shorter latency period in the wire hanging test as compared to the sham group, Pretreatment of ET-1 rats with carotenoids extract almost normalized the latency period as compared to the control and sham group
Cylinder test
Data presented in table 1 revealed that ET-1 treated rats had impaired rearing frequency versus sham group, whereas, pre-administration of ET-1 rats with carotenoids extract restored normal rearing frequency as compared to control and sham group
Oxidative stress status
The current data demonstrated a significant elevation in brain MDA level following ET-1 induced ischemia(1.61±0.15nmol/mg protein) as compared to the sham control group (0.75± 0.03nmol/mg protein). Meanwhile, pretreating ischemic rats with carotenoids extract significantly ameliorated brain MDA level as compared to ET-1 injected rats (0.90±0.04nmol/mg protein). XOD could serve as a source for reactive oxygen species (ROS) and was found to be triggered after ET-1 ischemia production (0.19±0.04vs. 0.07±0.03 nmol/mg protein). However, carotenoids extract reduced its content to a normal level (0.07±0.02 nmol/mg protein). In the same manner, GtSx was significantly elevated after ET-1 treatment ( 25.2±4.2 Vs 14.8±2.8 µmol/mg protein)as compared to the sham group, carotenoids extract treatment significantly attenuated the GtSx level ( 15.5±2.1 µmol/mg protein) as compared to ischemic group (Fig.3A)
Brain SOD and CAT activities were significantly down-regulated (68%, 74.3% respectively) in ischemic rats as compared to the sham group. However, rats that received carotenoids extract prior to ET-1 administration exhibited significant enhancement in brain antioxidant enzymes activities (104.2% for SOD, 222.2% for CAT) as compared to ET-1 injected group. Also, A significant depression in TH activity in rat brains was observed following ET-1 administration ( 16.3±4.2 Vs 38.4±6.9 U/mg protein) as compared to the sham group. carotenoids extract pre-administration in ischemic rats significantly ameliorated TH decline in comparison with the ET-1 group. (Fig. 3B)
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareC-reactive Protein and Neutrophil Lymphocyte Ratio Levels as Predictive Biomarkers for Severity of COVID-19 Infection
English8186Prashant BhardwajEnglish Manjari KumariEnglish Esha SinghalEnglishIntroduction: COVID- 19 is a highly contagious viral disease and spectrum of disease presentation range from asymptomatic to severe disease. Early diagnosis and assessment of disease severity is upmost priority to limit the morbidity, mortality and spread of disease. Aims: The aim of present study was to assess predictive values of C- reactive protein (CRP) levels and neutrophil-to-lymphocyte ratio (NLR), to disease severity to provide reference values for clinical treatment. Methodology: It was a prospective observational study in which 143 COVID-19 positive patients categorized into non-severe and severe groups. Clinical parameters, CRP values and NLR of all patients were recorded and analyzed. The receiver operating characteristic (ROC) curve was applied to determine the thresholds for both biomarkers. Result: Out of 143, total 85(59.44%) were males and 58(40.56%) female in our study. 114(79.72%) patients were non-severe and 29(20.27%) patients in severe group. Mean CRP and NLR of non severe group were 12.24(±8.5) mg/l, 2.97(±1.12) and in severe group 58.8(±43.16) mg/l, 7.85(±5.51) respectively. ROC curves analysis showed area under the curve (AUC) of 0.884 (95% CI 0.800-0.967; p valueEnglishCRP, NLR, COVID-19 infection, Predictive biomarkerIntroduction
The current outbreak of pneumonia which is caused by coronavirus was first reported in Wuhan, China, in December 2019.1-5Later this disease has been officially named as “COVID-19” by World Health Organization (WHO).6,7 Within few months COVID-19 disease spread globally, resulting in a worldwide pandemic.8Corona virus belongs to the family Coronaviridae, subfamily Ortho-coronavirinae and Order Nidovirales. SARS-CoV had also caused the outbreak of severe acute respiratory syndrome in 2003.9 The nature of this disease is rapidly progressive, and severely ill patients can develop acute respiratory distress syndrome, sepsis, and multiple organ dysfunction syndromes in very short period of time.10
To improve the patient outcome early diagnosis, clinicopathological monitoring and appropriate treatment protocol are essential. A Chest CT scan has an important role in assessing the disease.11 Chest CT scan is an expensive diagnostic modality and not readily available all places. So we have to consider some laboratory markers that must be inexpensive, within reach for all people and simultaneously sensitive and specific. Two biomarkers CRP and NLR both are immune-inflammatory parameters in COVID-19 infection and are associated with the progression of the infection.
In 1930s Tillett and Francis discovered CRP as an acute phase reactant. It is synthesized by liver by the action of cytokine interleukin 6 (IL- 6). Not only in bacterial infections even in other pathological processes like injuries, cardiovascular events and other inflammatory states CRP rise to very high levels. The high level of CRP is a biomarker of a pro-inflammatory state and it can be used as a prognostic marker for the underlying disease processes.12 For the early diagnosis of pneumonia C-reactive protein (CRP) levels can play important role and patients suffering with severe pneumonia have high CRP levels.13
Few studies suggest that neutrophil/lymphocyte ratio (NLR) is associated with the progression of the infection,14 or an early warning signal of severe COVID-19 infection.15 It can be considered as an independent biomarker for poor clinical outcomes and mortality in COVID-19 infection.16-20 We assessed the predictive ability of CRP levels, NLR to assess disease severity to provide a reference for clinical treatment.
Materials and Methods
This prospective observational study was started after being reviewed and approved by the institutional ethics committee (ethical committee clearance latter no. RMRI/EC/2021/54 dated on 02/04/21). We enrolled those cases that had clinical manifestations of upper respiratory tract infections like cough, shortness of breath and chest pain, which tested positive for COVID-19 by real-time reverse transcription-polymerase chain reaction (RT-PCR) using nasopharyngeal and/or oropharyngeal swabs and radiological findings of consolidation, ground-glass opacities on high-resolution computed tomography (HRCT).
After considering the inclusion and exclusion criteria we collected data of 143 patients admitted in our hospital from mid of April to May 2021 from medical records of patients. Since this was a time-bound observational study, no formal sample size calculation was done. Patients were clinically categorized into mild, moderate and severe disease according to ICMR guidelines.21 Then we sub-categorized the patients into two groups: non-severe and severe. Patients who had mild and moderate symptoms like fever, upper respiratory tract symptoms without breathlessness, SPO2>90% at room air were grouped into non-severe group and severe group had those patients who had severe symptoms like breathlessness and SPO2 0.70 were considered to be clinically significant or relevant for good predictive score. For optimal cut-off values of CRP and NLR respective sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. p value ≤ 0.05 were considered statistically significant along with the 95% confidence interval for the test statistic computed.
Results
A total of 143 patients with age above 18 years and confirmed diagnosis of COVID-19 were included in during the study period. Patients were divided into two comparison groups according to their clinical profile. Among the enrolled study subjects 114(79.72%) patients were in non-severe group and, 29(20.27%) patients in severe group. There were 85(59.44%) males and 58(40.56%) females in our study. As per laboratory findings mean CRP and NLR of non-severe group was 12.24(±8.5) mg/l, 2.97 (±1.12) and 58.8(±43.16) mg/l, 7.85(±5.51) in severe group respectively. (Table 1)
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareA Study to Find the Effect of Short-Wave Diathermy, Cervical Traction and Mobilization on Pain and Range of Motion in Acute Locking of the Cervical Spine - An Interventional Study
English8793Parmar JEnglish Chhatlani REnglish Kakkad AEnglishIntroduction: Acute locking of the cervical spine is a very clearly defined syndrome, occurring most commonly in adolescents. The short-wave diathermy used widely utilise the frequency of 27.12 MHz and wavelength greater than 11m. Cervical traction is a modality of choice for many cervical dysfunctions. It is applicable in a wide range of problems from sprain to fractures and dislocations of the cervical vertebrae. Mobilization is defined as a low-velocity and small- or large-amplitude movement applied anywhere within a joint Range of Motion. Aim: To find the effectiveness of Short-Wave Diathermy (SWD), Cervical Traction (CT) and Mobilization on Pain and range of Motion in Acute Locking of Cervical Spine. Method: 15 male patients with age between 23 to 45 years with the chief complaint of locked neck and difficulty in moving the neck were included in the study. SWD, CT and Mobilization was given to them. VAS and Cervical ROM was assessed before and after the treatment. Result: All Statistical analysis were done by software SPSS 20.0 version. Means and Standard Deviation (SD) were calculated as a measure of central tendency and measure of dispersion respectively. Comparison within group for Visual Analogue Scale (t=30.984), Cervical Flexion (t=-6.671), Cervical Side-Flexion (t=-21.569) and Cervical Rotation (t=-20.601) Range of motion were done by Paired ‘t’ test (pEnglish Short-Wave Diathermy, Cervical Traction, Locking Cervical Spine, Mobilization, Pain, Range of motion, Acute Locking, Visual Analogue ScaleINTRODUCTION:
Acute locking of the cervical spine is a very clearly defined syndrome, occurring most commonly in adolescents.1 It can be described as a condition of sudden onset of ipsilateral neck pain and contra-lateral side flexion of the cervical spine which is primarily caused by abnormal facet joint articulation.2 This syndrome is not to be confused with the locking of joints which can occur as a result of "loose bodies" or torn menisci. The disease has a classic history, preventive deformity and consistent pain. The onset is always sudden and is associated with movement, usually a very quick and often unexpected movement. The result is a sudden, sharp pain accompanied by an inability to return the head to the straight position.1
There are various treatment options available for pain relief including manual and electrical modalities in Physical Therapy. Patients also take various steroid medications for pain relief. 4-10
Short wave Diathermy is a Deep healing modality. Radio waves in the short-wave band have frequencies in the range of 10 MHz-100 MHz. The short-wave diathermy used widely utilize the frequency of 27.12 MHz and wavelength greater than 11m.
There are further 3 methods of applying SWD to the patients:
1. Co-planar: It is also called as the parallel method. The electrodes are placed side by side.
2. Contra-planar. It is also called as through and through the method. Pads are placed on either side of the joints. In this method, deeper tissues are heated.11
3. Crossfire Method: In this technique, half of the treatment is given with the placement of electrodes in one direction, i.e., medial or lateral aspect and another half is used with the placement of electrodes in other direction, i.e., anterior or posterior aspect. This method is commonly used for the treatment of the knee joint, sinuses (frontal, maxillary and ethmoidal) and for pelvic organs.12
Cervical traction is a modality of choice for many cervical dysfunctions. It is applicable in a wide range of problems from a sprain to fractures and dislocations of the cervical vertebrae.
Mainly there are 2 ways in which CT can be given
Static traction: Traction for 20-25 minutes is applied with weight ranging from 10 to 30 lbs with a constant pull. It is indicated when pain does not subside with other conservative treatments, especially in radiating neurological pain.
Intermittent traction: Traction with alternate phases of stretching (pull) and relaxation is the popular mode of traction. It produces the effects of massage on the muscular, ligamentous and capsular structures. It promotes circulation and reduces swelling, thereby reducing inflammation, spasm and pain.13
Mobilization is defined as a low-velocity and small- or large-amplitude movement applied anywhere within a joint ROM. For an immediate effect, mobilization of the cervical spine had shown a superior effect to reduce pain and increase ROM than mobilization with muscle energy technique or positional release therapy.14,15 The MET was done by asking the patients to repeatedly contract their affected muscles isometrically against the manual resistance by the therapist.14
Outcome Measures:
Neck pain was measured via the VAS. It was a 10-cm line with pain descriptors marked “no pain” at 1 end and “the worst pain imaginable” at the other. The patients were asked to point their perceived pain level with a perpendicular mark on the line, both on most painful activity and at rest. VAS is a reliable and valid measure of pain.16,17
Neck mobility was assessed with a Goniometer. The neck ROM of the patients were measured while high-sitting with feet on the ground, their hips and knees positioned at a 90-degree angle, and their back supported on a chair. Theintratester reliability was reported to be high (ICCs range, .76 –.98).17,18
AIMS AND OBJECTIVES:
AIM:
To find the effectiveness of Short-Wave Diathermy, Cervical Traction and Mobilization on Pain and range of Motion in Acute Locking of Cervical Spine.
OBJECTIVES:
To find the effect of Short-Wave Diathermy on Pain and Range of Motion in Acute Locking of Cervical Spine.
To find the effect of Cervical Traction on Pain and Range of Motion in Acute Locking of Cervical Spine.
To find the effect of Mobilization on Pain and Range of Motion in Acute Locking of Cervical Spine.
HYPOTHESIS:
Experimental Hypothesis:
There is a significant difference in Pain and Range of Motion with the application of Short-wave Diathermy, Cervical Traction and Mobilization in patients with Acute Locking of Cervical Spine.
Null Hypothesis:
There is no significant difference in Pain and Range of Motion with the application of Short-wave Diathermy, Cervical Traction and Mobilization in patients with Acute Locking of Cervical Spine.
MATERIALS AND METHODS:
Study Design: Interventional Study
Study Duration: July 2019 to March 2020
Study Setting: Department of Physiotherapy, Marwadi University, Rajkot, Gujarat, India.
Study Population: Patients with Acute Cervical Lock syndrome
Sampling Design: Purposive Sampling
Sample Size: 15 Male Patients
Inclusion criteria:
Age between 23 to 45 years,
Chief complaint of locked neck,
difficulty in moving the neck at desired direction without pain, and
Patients with sudden onset of cervical pain.
Exclusion criteria:
1) Disorders and diseases of the cervical spine such as PIVD, cervical spine stenosis, postoperative diseases of neck and shoulder areas,
2) Torticollis,
3) Any other Cervical Pathology.
The primary physiotherapy screening was done in the OPD. All patients had very similar complaints and signs/symptoms when the assessment was done which is as mentioned here. The diagnosis is made solely on the findings of physical examination and none of the patients were referred for the radiological investigation.
Pain
The patients have pain at the nape of the neck and trapezius muscle of the same side of the neck. All patients were very anxious about the sudden locking of the cervical spine as it would be very difficult to do the Activities of Daily Living (ADL).
Range of Motion
The most commonly seen protective limitation was one of rotation and lateral flexion restriction and sometimes a degree of extension is also limited. Out of all movements at cervical spine rotation was more limited than the lateral flexion and lateral flexion was more limited than the extension. All patients were more concerned about the rotation than the extension of the cervical spine.
METHOD:
Total of 15 patients were taken as per inclusion and exclusion criteria. The procedure and aim of the study were explained to the patients and written consent was taken. Demographic data like Age, onset of the condition, contact details, etc were taken.
SWD for 20 minutes to the trapezius area in supine position. SWD was given in a contra planner manner means one pad was kept on trapezius muscle and the other pad was kept in front of the shoulder. All the necessary precautions were taken before applying short wave diathermy to the patients.
Every patient was given manual cervical traction and checked for the symptoms, if symptoms were increased or gave any discomfort then mechanical cervical traction was not given. If a patient had relief in symptoms then mechanical cervical traction was given to the patients.
If the patient did not have pain and gives comfort to the patient and reduction in pain then the patients were given cervical traction in supine position with 1/7th of the body weight in intermittent mode. At every cycle feedback was taken for any discomfort or pain in the neck. Next day onwards, feedback was not taken while traction was given.
Heat therapy with the hot bag was advised at home for 10 to 15 minutes 2 times in a day.
Next part of the treatment was facilitation of the vertebral rotation while the patient attempts to do the rotation. The patient was in a comfortable sitting position and hands were relaxed on the arms of chair.
The therapist was at backside of the patient. Patients were asked to do the active rotation and when the movement is halted the therapist will help to do the rotation of the cervical vertebra from C4 to C7 and every time patient has to do active rotation maximally. The tip of the right thumb was kept at every level of the cervical spine and pushed to the opposite side of rotation i.e., if the patient was attempting right cervical rotation then the therapist pushed the vertebra towards left side to facilitate the rotation towards right side and vice versa. The gentle oscillatory movement was also performed at each level of cervical spine from C4 to C6 when the active rotation was halted by the patient. The patient was instructed not to do excessive rotation which increased the pain intensively. But at the same time minimal or bearable pain while attempting the movement was allowed.
Thumb kneading was given only for 5 to 7 minutes to the affected trapezius to reduce the spasm. Gentle myofascial release was given from the occiput to the trapezius area with the radial side of the thumb for 5 to 7 minutes to relax the muscle of the same side.
After this, to improve the extension of the cervical spine the position was the same as for rotation. The patient was asked to do the active extension till he can do it without much pain when the active extension was halted due to pain the therapist will be palpating the spinous process of cervical vertebra from C4 to C7 and it was pushed towards the anterior-superiorly with the help of ulnar border of right thumb. Gentle oscillations were also given at each level at the end of active movement which was done by the patient. Oscillations were given for 2 to 3 minutes to the patients.
Patient was advised to do the active movement of the cervical spine at home but in pain free range of motion along with the heat therapy. No other exercises were given at home.
Patient was informed that soreness may occur after some time due to this mobilization and advised not to do anything for that except heat therapy.
RESULT:
All Statistical analysis were done by software SPSS 20.0 version. Means and Standard Deviation (SD) were calculated as a measure of central tendency and measure of dispersion respectively. Comparison within-group for, Cervical Flexion, Cervical Side-Flexion and Cervical Rotation Range of motion were done by Paired ‘t’ test.
Interpretation: The above table shows the mean difference of pre and post cervical Flexion score i.e., 38.333±22.253 (SD). Result shows significant difference for pre & post Cervical Flexion Range of Motion (t= -6.671).
Interpretation: The above table shows the mean difference of pre and post-VAS scores i.e., 8±1 (SD). Result shows significant difference for pre & post VAS score (t= 30.984).
Interpretation: The above table shows the mean difference of pre and post cervical Side-Flexion score i.e., 24±4.309 (SD). Result shows significant difference for pre & post-Cervical Side-Flexion Range of Motion (t= -21.569).
Interpretation: The above table shows the mean difference of pre and post cervical Rotation score i.e., 48±9.023 (SD). Result shows significant difference for pre & post Cervical Rotation Range of Motion (t= -20.601).
DISCUSSION:
From the results it can be commented that significant improvements in terms of pain and increased range of motion at the cervical spine is obtained with the designed protocol.
SWD is considered as a deep heating modality.18 Short-wave diathermy uses an oscillating electromagnetic field of high frequency to heat body surface areas. It heats to a tissue depth of 2 to 3 cm.19 SWD increases temperature of the tissue. SWD effects can be divided mainly into thermal and not thermal. Thermal effects cause vasodilatation, reduction in muscle spasm, elevation of pain threshold, increased soft tissue extensibility, and acceleration of cellular metabolism.21 They include decreased joint pain and stiffness, increased blood flow, faster resolution of oedema, accelerated wound healing, and reduced inflammation.22 Another possible mechanism is activation of A-alpha and A-beta fibres or the cutaneousthermoreceptors which blocks the transmission of pain (A-delta and C fibres) as it enters the spinal cord.23 Diathermy improves cellular healing processes, which produces expression of heat shock proteins (HSP), which causes faster intracellular protein repair and in turn healing process.24,25,26
Cervical traction is commonly used to reduce the spasm at the neck. Cervical traction in a supine lying position gives stretching effects on the neck muscle and gives muscle relaxation which ultimately reduces pain and improved range of motion. Traction was given to only those patients who had improved in symptoms during manual traction. None of the patient had increased pain during or after the cervical traction in supine lying position.27,28
Manual mobilization was given in terms of gentle oscillation, forward glide, rotatory glide which have facilitated the movements in the restricted direction. This had improved the rotation to the affected side along with the forward flexion and extension. Research has shown that mobilization helps initiate local physiological mechanism and also involves central mechanism like facilitation of pain-gait mechanism.29
Limitations:
Small Population size was taken.
Only male patients were taken.
Long term effect of treatment could not be observed due to time constraint.
Further Recommendations:
Study can be conducted with larger sample size.
Male as well as Female patients can be included.
The intervention can be compared to other manual and electrical modalities.
Long term follow-up of patients should be taken.
CONCLUSION:
A combination of Short-Wave Diathermy, Cervical Traction and Mobilization is effective in reducing pain and increasing range of motion in acute locking of the cervical spine.
ACKNOWLEDGEMENT:
Authors acknowledge the immense help received from the scholars whose articles are cited and included in the references of this manuscript. The authors are also grateful to the authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
SOURCE OF FUNDING:
No fund was needed for the study.
CONFLICT OF INTEREST:
There was no personal or institutional conflict of interest for this
AUTHORS’ CONTRIBUTION:
PARMAR J:
Data Collection, Methodology, Research Design, and Framework for the research.
CHHATLANI R:
Referencing, Discussion, and Statistical Analysis
KAKKAD A:
Data Collection, and Cross-referencing
Englishhttp://ijcrr.com/abstract.php?article_id=4301http://ijcrr.com/article_html.php?did=4301
Maitland G. ACUTE LOCKING OF THE CERVICAL SPINE1 1Presented at “Conference on Headache, Neck and Arm Pain”, Western Australian Institute of Technology, Australian Physiotherapy Association, 26th November, 1977. Aus J of Physio. 1978;24(3):103-109.
Langenfeld A, Humphreys B, de Bie R, Swanenburg J. Effect of manual versus mechanically assisted manipulations of the thoracic spine in neck pain patients: study protocol of a randomized controlled trial. Trials. 2015;16(1).
Shanmugam S. Immediate Effects of Paraspinal Dry Needling in Patients with Acute Facet Joint Lock Induced Wry Neck. JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH. 2017.
McCray R, Patton N. Pain Relief at Trigger Points: A Comparison of Moist Heat and Shortwave Diathermy. Journal of Orthopaedic & Sports Physical Therapy. 1984;5(4):175-178.
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Rawe I. The case for over-the-counter shortwave therapy: safe and effective devices for pain management. Pain Management. 2014;4(1):37-43.
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Helpline Electrotherapy for Physiotherapists Vivendra Kr. Khokhar, Bharat BharatiPrakashan, 3rd Edition, pg.49-62
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López-Jiménez C, Rodriguez-Blanco C. Immediate effects on neck pain and active range of motion after a single cervical high-velocity low-amplitude manipulation in subjects presenting with mechanical neck pain: a randomized controlled trial. J Manipulative Physiol Ther 2006;29:511-7.
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Masiero S, Pignataro A, Piran G, Duso M, Mimche P, Ermani M et al. Short-wave diathermy in the clinical management of musculoskeletal disorders: a pilot observational study. International Journal of Biometeorology. 2019;64(6):981-988.
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareCadaveric Study of Branches of Facial Artery in the Face
English9497Ramya PavithranEnglishIntroduction: The facial artery is the anterior branch of the external carotid artery and forms the major source of nourishment to the face and terminates as the angular artery. The variations in the facial artery is highly useful to surgeons and clinicians in facial reconstructions and evaluating various clinical conditions. Aim: To identify and trace the branches of the facial artery in the face. Settings and Design: It is an observational study. Methods and Material: The present study is a descriptive observational study done by dissection method in 50 cadavers. The facial artery branches were identified and traced from their origin to the termination. Care was taken not to damage the vessels. Variations were documented and analyzed. Statistical Analysis Used: The data obtained were entered in a master chart. All qualitative data obtained were quantified according to the frequencies. Frequencies were calculated as percentages. Results: In 73% of cases all the facial branches were present. The facial artery terminated as the angular artery in 82% of cases, as lateral nasal in 12%, superior labial and alar artery in 3% of cases each. 10% of cases showed the presence of the alar branch and pre masseteric was seen in 18%. Conclusions: Variations in the facial artery are useful to anatomists and surgeons alike. These studies provide information that is welcome in this world of cosmetic surgeries of face.
EnglishFacial artery; Premasseteric branch; Angular artery; Lateral nasal artery; Alar artery; Labial arteries; Facial reconstructionIntroduction:
The facial artery forms the main arterial supply of the face along with the superficial temporal artery and branches from the ophthalmic arteries. Facial artery arises from the external carotid artery at the level of greater cornu of the hyoid bone within the carotid triangle. It has a tortuous course throughout and passes onto the face at the anteroinferior border of the masseter muscle. The facial artery supplies branches to the skin and muscles of the face. The branches on the face are the pre masseteric branch, the superior and inferior labial arteries and the lateral nasal artery. Beyond the lateral nasal the facial artery terminates as the angular artery.1 The facial artery may be rudimentary or hypoplastic. It can terminate as the submental artery (not reaching the face), as labial arteries or as nasal arteries. In its absence, it can be replaced by either the nasal branch of the ophthalmic artery at the medial side of the orbit, the transverse facial, or the maxillary artery. The buccal, posterior alveolar, or infraorbital artery can also be larger than usual, compensating for a deficiency of the facial artery.2
The facial artery pulsations can be felt on the base of the mandible at the anteroinferior angle of the masseter. The anaesthetists feel the facial artery pulsations for monitoring the patients during surgeries(facial artery is also known as the Anaesthetist’s artery). The branches of the facial artery anastomose with each other and with other arteries of the face. The deep wounds and incisions involving the face will bleed profusely. The facial wounds will usually heal quickly and rarely necrose. The anatomical knowledge of the facial artery and its branches become important in cosmetic and reconstructive surgeries. FAMM flap (Facial artery myomucosal flap) is an effective means for reconstructing defects in and around the oral cavity. The FAMM flap was first used by Pribaz.3 Francis Henry et al.4, Hui Ling Chia et al.5, Dupoireux et al.6, Tereck Ayad et al.7 have studied the use of the FAMM flap. The Abbe flap used for the reconstruction of the lips, cleft lip, philtrum and palate also depend on the anatomy of the facial artery. Koshy John C et al.8 and Theodore T Nyame et al.9 have conducted recent studies on the same. The masseter muscle is often exploited to correct facial palsies, benign masseteric hypertrophy, neurectomy induced atrophy of muscle traumatic or non-traumatic upper and lower lip defect repairs and also in other maxillofacial surgeries. If the pre masseteric branch is not taken care of, it can lead to profuse bleeding during the procedure.10
Proper anatomical knowledge of the facial artery and its variations would help the clinicians and surgeons alike.
Materials and Methods:
The present study was done on 100 hemi-facies from 50 properly embalmed and formalin fixed cadavers in the Department of Anatomy, Government Medical College, Kozhikode used for the undergraduate teaching of MBBS and BDS students as a part of the thesis work on the variations of the facial artery. The study protocol was approved by the Institutional Ethics Committee. The facial artery was identified and traced from its origin to the termination. Care was taken not to damage the vessels. Mutilated bodies were excluded from the study.
Results:
In 73% of the specimen the facial artery showed the presence of all branches in the face, in 27% the artery lacked one or the other branch. Angular artery was absent in 7 specimen (14%), of which 6 specimen showed bilateral absence of the angular artery. Out of the 50 cadavers dissected, lateral nasal artery was not seen in 13 cadavers (26%). In 4 cases, there was bilateral absence of the lateral nasal artery, in 6 cases it was absent on the right and in 3 on the left. The absence of the inferior labial artery was seen in 1 case on the right side. Unilateral absence of the superior labial was seen in 4%, one on right and left side each. Pre masseteric branch was noted in 18% (figure 1), 2 cases showed bilateral pre masseteric branch, unilateral right and left pre masseteric were noted in 5 and 2 cases respectively. The presence of the alar artery directly from the facial artery was seen in 10%. Bilateral alar artery was seen in 2 cases, unilateral right side was seen in 3 cases. Left-sided alar branch from facial artery was noted found in the present study. Sometimes one or the other branch of the facial artery may arise as a common trunk and then divide to form separate arteries. In one of the specimen (1%), the left facial artery gave a common trunk for the labial arteries near the angle of the mouth (figure 2). This common trunk then bifurcated into the superior and the inferior labial arteries, which coursed upper and lower lip areas respectively. In another case, the superior labial and the lateral nasal originated as a common trunk from the facial artery on the left side(figure 3). The facial artery then continued as the angular artery.
Discussion:
In the study by Midy et al.11, facial artery gave angular artery in 27.5%, superior labial in 40% and nasal type in 30%. In 2.5% abortive type was seen. In the study by Niranjan NS12, facial artery terminated as angular artery in 68%, lateral nasal artery in 26%, superior labial artery in 4%. In 2% cases artery terminated at the alar base. Koh KS et al.13 noted 44% lateral nasal and 36.3% angular artery. YA Pinar et al.14 noted that facial artery terminated as angular artery in 22%, as nasal facial in 60%, alar in 12%, superior labial in 4%. Hypoplastic type was seen in 2%. Orhan Magden et al.15 noted that the pre masseteric artery originated as a separate trunk in 14 cadavers studied. Bayram et al.16 classified facial artery into 3 types based on termination. They noted Type I (Facial artery terminated as angular artery) in 76%, type II(facial artery terminated as superior labial) in 12% and type III(Facial artery terminated as inferior labial) in 12%. Ashish S Kulkarni and Geetha KN17 noted that the facial artery terminated as the angular artery in 36%, lateral nasal in 44% and superior labial artery in 20%. In 95% they noted the presence of the pre masseteric artery.
According to George Dickson et al.18, the facial artery had been grouped into 6 types based on termination, as
Type I: facial artery terminating as the superior labial artery
Type II: facial artery terminating as the inferior labial artery
Type III: facial artery terminating as the lateral nasal artery
Type IV: facial artery terminating as the superior alar artery
Type V: facial artery terminating as the inferior alar artery
Type VI: facial artery terminating as the angular artery
Angular artery was seen in 27.5%, lateral nasal in 15%, superior labial in 27.5%, inferior labial in 15% and alar type 15%.
Facial artery terminated as the angular artery in 56%, lateral nasal in 12%, superior labial in 12% and was abortive in 2% in the study by Vasudha et al.19. The premasseteric branch was found in 6% of cases. The percentage of occurrence of various branches of the Facial artery with that of previous studies have been compared in table 1.
Conclusion:
The facial artery forms the major arterial supply of the face. Proper anatomical knowledge of the facial artery and its variations would help the clinicians to diagnose various pathological conditions and also avoid various complications during the procedures. The knowledge of the branching pattern of the facial artery becomes important in various flap surgeries and other procedures of the face, parotid region etc. It also has importance in face lift procedures, dermal filler injections etc. which are cosmetically challenging.
Acknowledgement:
“Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.”
Source of funding: Nil
Conflict of Interest: Nil
Authors’ Contribution:
Dr Ramya Pavithran- Collection of data, compilation and presentation.
IEC Letter No: GMCKKD/ RP 2016/EC/215
Figure 1: Right side of the face showing the pre masseteric branch of the facial artery
FA- facial artery, PM- pre masseteric branch, TFV- transverse facial vessels
FA- facial artery, PM- pre masseteric branch, TFV- transverse facial vessels
Figure2: Left facial artery with a common trunk for the labial branches.
FV- facial vein, FA- facial artery, IL- inferior labial artery, SL- superior labial artery
Figure 3: Left facial artery with a common trunk for the superior labial and the lateral nasal
List of abbreviations:
FAMM- Facial artery myomucosal flap
AN- Angular artery
LN- Lateral nasal
SL- Superior labial
IL- Inferior labial
AL- Alar artery
PM- Premasseteric branch
H- Hypoplastic
Englishhttp://ijcrr.com/abstract.php?article_id=4302http://ijcrr.com/article_html.php?did=43021. Standring S. Gray’s anatomy: the anatomical basis of clinical practice. 2016.
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5. Chia H-L, Wong C-H, Tan B-K, Tan K-C, Ong Y-S. An algorithm for recipient vessel selection in microsurgical head and neck reconstruction. J Reconstr Microsurg. 2011 Jan;27(1):47–56.
6. Dupoirieux L, Plane L, Gard C, Penneau M. Anatomical basis and results of the facial artery musculomucosal flap for oral reconstruction. Br J Oral Maxillofac Surg. 1999 Feb;37(1):25–8.
7. Ayad T, Kolb F, De Monés E, Mamelle G, Temam S. Reconstruction of floor of mouth defects by the facial artery musculomucosal flap following cancer ablation. Head Neck. 2008 Apr;30(4):437–45.
8. Koshy JC, Ellsworth WA, Sharabi SE, Hatef DA, Hollier LH, Stal S. Bilateral cleft lip revisions: the Abbe flap. Plast Reconstr Surg. 2010 Jul;126(1):221–7.
9. Nyame TT, Pathak A, Talbot SG. The abbe flap for upper lip reconstruction. Eplasty. 2014;14:ic30.
10. Kumar N, Nayak SB, Shetty S, Guru A. Unusual posterior (premasseteric) branch of facial artery–a case report. IJAV. 2011;4:161–3.
11. Midy D. A contribution to the study of the facial artery, its branches and anastomoses. Application to the anatomic vascular bases of facial flaps. Surg Radiol Anat. 1986;8(2):99–107.
12. Niranjan NS. An anatomical study of the facial artery. Ann Plast Surg. 1988 Jul;21(1):14–22.
13. Koh KS, Kim HJ, Oh CS, Chung IH. Branching patterns and symmetry of the course of the facial artery in Koreans. Int J Oral Maxillofac Surg. 2003 Aug; 32(4):414–8.
14. Pinar YA, Bilge O, Govsa F. Anatomic study of the blood supply of perioral region. Clin Anat N Y N. 2005 Jul;18(5):330–9.
15. Ma?den O, Göçmen-Mas N, Senan S, Edizer M, Karaçayli U, Karabekir HS. The pre masseteric branch of facial artery: its importance for craniofacial surgery. Turk Neurosurg. 2009 Jan;19(1):45–50.
16. Bayram SB, Kalaycioglu A. Branching patterns of facial artery in fetuses. NJ Med. 2010;27:227–30.
17. K.N G, Kulkarni A. Variations in Branching Pattern of Facial Artery: An Anatomical Study in 50 Indian Adult Cadavers. 2011.
18. Dickson G, Clark SK, George D, Mackenzie F, Mann NA, Wright K, et al. The variability of the facial artery in its branching pattern and termination point and its relevance in craniofacial surgery. Eur J Plast Surg. 2014 Jan;37(1):1–8.
19. Vasudha TK, DivyashanthiD’Sa, Gowda S. A STUDY ON COURSE AND VARIATIONS OF FACIAL ARTERY ON THE FACE. Int J Anat Res. 2018 Feb 5;6(1.2):4928
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareUtility of Fluorescence Immunoassay in Early Diagnosis of Dengue
English98103Das RashmitaEnglish Joshi SuvarnaEnglish Palewar MeghnaEnglish Karyakarte RajeshEnglishIntroduction: Early and prompt diagnosis of dengue infection can help in improving the clinical outcome of patients by ensuring early initiation of supportive treatment. Non-structural glycoprotein-1 (NS-1) is a useful biomarker for the early diagnosis of dengue as it is abundantly present in the serum during the early stages of infection. Several rapid diagnostic tests targeting NS-1 antigen are commercially available and many more are being developed. The present study evaluated a newly developed fluorescence immunoassay (FIA), NS-1 QUANTI CARD test, to determine its effectiveness in the early diagnosis of dengue. Methods and Material: A total of 85 serum samples from clinically suspected dengue patients were tested for NS1 antigen by ELISA, FIA and rapid immunochromatography test (ICT). The performance characteristics of FIA and ICT were calculated considering ELISA as the gold standard test. Sensitivity, specificity, predictive values, likelihood ratios and Cohen’s Kappa value for the level of agreement were calculated using MedCalc® Statistical Software version 19.6.4. Results: The overall sensitivity, specificity, positive and negative predictive values of FIA and ICT were found to be 96.5%, 96.4%, 93.3%, 98.1% and 65.5%, 83.9%, 67.8%, 82.4%, respectively. There was almost a perfect level of agreement between the ELISA and QUANTI CARD test whereas ELISA and ICT results had a moderate level of agreement. Conclusion: Owing to its shorter turnaround time (TAT), the NS1 Ag QUANTI CARD test can be a better alternative to ELISA for dengue diagnosis in resource-limited settings and critically ill patients for prompt diagnosis.
EnglishIntroduction
Dengue, the most common arboviral infection worldwide, has spread rapidly to more than 129 countries. World over, about 3.9 billion people are at risk of acquiring dengue infection, 70% of these people at risk are from Asia. Over the last two decades, the number of reported cases has increased by eight-fold from half a million cases in 2000 to 2.4 million cases in 2010 and 4.2 million cases in 2019. Similarly, the reported deaths have increased from 960 to 4032 over 15 years, from 2000 to 2015.1
The virus causes a wide spectrum of disease manifestations ranging from subclinical infection to severe disease that leads to bleeding, organ impairment and death. Therefore, early diagnosis of infection can help improve the clinical outcome of the disease by ensuring early initiation of supportive therapy and close follow-up, thus lowering the fatalities to less than 1%.2 The major obstacle in early diagnosis is the non-specific clinical presentation that may lead to delay and misdiagnosis of the disease. Therefore, all clinically suspected cases must be confirmed by laboratory tests for efficient and accurate diagnosis.3
A range of laboratory diagnostic tests have been developed for dengue diagnosis. Definitive diagnosis of dengue includes isolation of virus by culture, viral genomic RNA detection by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), detection of viral products like Non-Structural (NS1) protein or detection of host immune response to the virus by measuring the specific IgM/IgG antibodies against dengue virus using rapid immunochromatography test or Enzyme-Linked Immunosorbent Assay.2
Virus isolation by culture is the gold standard test for dengue diagnosis. It is time-consuming as it takes days and weeks to complete. The RT-PCR test requires specialized reagents and technical expertise. Both the tests are useful in the first five days of illness and thereafter the sensitivity of the tests decreases as the viremia decreases over time.4 Serological diagnosis is not helpful during acute illness as the antibodies remain undetectable until 3-4 days post-symptom onset and require a second sample within 14-21 days for definitive diagnosis. NS-1 protein is released during the infection and is accumulated in human serum in very high concentrations. It is detectable early during the infection. Therefore, NS1 antigen has become an attractive target for diagnostic assay development as it is more specific and shows high specificity. However, the choice of diagnostic method depends on the time of sample collection, laboratory facilities the technical expertise available, and the purpose of testing, i.e., clinical diagnosis, epidemiological studies, or vaccine development.5
The most widely used test for diagnosis of dengue is Enzyme-Linked Immunosorbent Assay (ELISA) which is used for the detection of viral antigen and anti-DENV IgM/IgG antibodies in patient serum. It has high specificity and sensitivity, but at the same time, it is time-consuming, labor-intensive and requires skilled manpower and equipment.4 Therefore, in the past two decades, with the growing demand for point-of-care diagnostics, many Rapid Diagnostic Tests (RDTs) have flooded the market. However, the available diagnostic tests vary in their sensitivity and specificity.6
With the above background, the current study aims to evaluate the diagnostic accuracy and utility of a newly developed rapid fluorescence immunoassay test, i.e., Dengue NS1 Ag QUANTI CARD test with a commercially available NS1 antigen rapid immunochromatography test and NS1 ELISA for early diagnosis of dengue infection.
Material and Methods
The present study was carried out in the Department of Microbiology at Byramjee Jeejeebhoy Government Medical College, Pune, Maharashtra.
Study Design: A diagnostic evaluation study
Specimen collection
A total of 85 serum samples from patients suspected of dengue infection with fever for less than or equal to five days were collected and tested. Following all standard precautions, 5 mL of blood sample was collected in a clean plain vacutainer. The blood was allowed to clot at room temperature for 45 minutes and then serum was separated. 10 serum samples were also collected from healthy individuals to evaluate the specificity of the newly developed test.
Methodology
The collected serum samples were tested for NS1 antigen (NS1 Ag) using fluorescence immunoassay (FIA), Rapid Immunochromatography test (ICT) and ELISA test.
Dengue NS1 QUANTI CARD (J. Mitra & Co. Pvt. Ltd., New Delhi, India) is a fluorescence immunoassay test based on the principles of sandwich immunoassay. It is a cartridge-based test for the qualitative detection of Dengue NS1 Ag in human serum/plasma. On a nitrocellulose membrane, the test region is coated with specific anti-dengue NS1 antibodies. When a sample containing NS1 Ag is added, the antigen forms a complex with a conjugated antibody directed against the NS1 Ag. The antigen-antibody complex migrates along the nitrocellulose membrane to the test region and binds to immobilized antibodies forming an antibody-antigen-antibody immunocomplex. The results are read after 30 minutes using iQuant analyser. The results obtained were interpreted in terms of NS1 Ag units as reactive (> 1.1 U), equivocal (> 0.9 to < 1.1 U) or non-reactive (< 0.9 U).
Dengue NS1 rapid antigen test (RAT) was performed using Dengucheck, a rapid qualitative immunochromatographic test for detection of NS1 Ag in serum/ plasma (Zephyr Biomedicals, a division of Tulip diagnostics (P) Ltd, Goa, India) according to the manufacturer’s instructions.
Similarly, Dengue NS1 Ag ELISA was performed using Dengue NS1 antigen Microlisa (J. Mitra & Co. Pvt. Ltd., New Delhi, India) according to the manufacturer’s instructions. It is a solid phase Enzyme-Linked Immunosorbent assay based on the principles of direct sandwich ELISA.
Reproducibility of the test results of the newly available fluorescence immunoassay test, NS1 QUANTI CARD, was evaluated by testing four samples (two weak positive samples and two negative samples for NS1 Ag) at four different times by the same technician.
Statistical analysis
The data obtained was compiled using Microsoft® Excel. Sensitivity, specificity, predictive values, likelihood ratios and Cohen’s Kappa value for the level of agreement were calculated using MedCalc® Statistical Software version 19.6.4.
Results
Characteristics of the study population
A total of 85 samples were collected from suspected patients of dengue. The mean age of the study population was 20.98 years and the sex ratio (male: female) was 1.7:1.
Characteristics of the diagnostic tests
A comparison of several functional attributes of NS1 QUANTI CARD test, NS1 rapid immunochromatography and NS1 ELISA test is shown in Table 1.
Correlation between results of fluorescence immunoassay and rapid immunochromatography with NS1 ELISA test.
Out of 85 samples tested, NS1 ELISA was positive in 29 (34.1%) and negative in 56 (65.9%) samples; dengue NS1 QUANTI CARD test was positive in 30 (35.3%) and negative in 55 (64.7%) samples, and NS1 rapid immunochromatography test was positive in 28 (32.9%) and negative in 55 (67.1%) samples. The correlation between the results of NS1 ELISA, NS1 QUANTI CARD test and rapid immunochromatography test is shown in Table 2 and 3, respectively.
Performance characteristics of fluorescence immunoassay and rapid immunochromatography test considering ELISA as the gold standard test.
The performance characteristics of the Dengue NS1 QUANTI CARD test, Dengue NS1 Ag rapid immunochromatography test was calculated considering Dengue NS1 ELISA as the gold standard test as shown in Table 4.
To test the specificity of the newly developed test, 10 serum samples collected from healthy individuals were tested. The specificity and NPV of the Dengue NS1 QUANTI CARD test were found to be 100% and 80%, respectively.
Reproducibility testing of Dengue NS1 QUANTI CARD test.
The dengue NS1 QUANTI CARD test results were reproducible with all dengue samples (two dengue NS1 Ag positive and two dengue NS1 Ag negative) in four different runs as shown in Table 5.
Discussion:
Dengue infection usually presents with non-specific symptoms, mimicking any other viral infection. However, due to a wide spectrum of disease presentation, early diagnosis and prompt treatment are of paramount importance.1 Detection of NS1 antigen has emerged as a popular diagnostic method for early diagnosis of dengue as it becomes detectable from day 1 to day 9 after the onset of disease in both primary and secondary dengue cases.5 Therefore, many diagnostic tests have been developed using NS1 as a target and are being assessed for early diagnosis of dengue.
One such newly developed test, the Dengue NS1 Ag QUANTI CARD test, a fluorescence immunoassay test based on the principles of sandwich immunoassay was evaluated in this study. In the present study, the QUANTI CARD test produced results comparable to that of ELISA. The sensitivity, specificity, PPV and NPV of the FIA test were found to be 96.5%, 96.4%, 93.3% and 98.1%, respectively. The Cohen’s Kappa value was found to be 0.92, indicating almost total agreement between ELISA and QUANTI CARD test results. The test showed reproducible results when tested at four different times. Our findings are similar to those of Pohekar et al. where the sensitivity, specificity, PPV and NPV were 100%, 98.3%, 97.4% and 100%, respectively.7
The need for a simple point-of-care diagnostic test has led to the large-scale production of Rapid Diagnostic Tests (RDTs) using the immunochromatographic format. In this study, the sensitivity, specificity, PPV and NPV of RDT were 65.5%, 83.9%, 67.8% and 82.4%, respectively. The Cohen’s Kappa value was 0.499, indicating a moderate level of agreement between ELISA and rapid ICT test results. The performance of the RDT kit was lower as compared to other studies in India as various studies have reported a sensitivity of 88% to 100% and a specificity of 90% to 98%.8-11 In a study by Yow et al. (2021), the sensitivity and specificity of six RDT kits were found to be 68.5% to 87% and 100%, respectively.12 Similarly, Pal et al. (2014) in their study have highlighted that the sensitivity of NS1 antigen rapid tests that have been reported in the literature varies from 58% to 99%.4
After comparing the characteristics of the three tests, it is observed that the ELISA test requires technical expertise, is time-consuming and requires a constant power supply for its operations. It requires approximately 2-3 hours of assay time. RDTs based on the principle of FIA and ICT, on the other hand, are easy to perform with very little expertise and require 15 to 30 minutes of run time. However, the interpretation of results in the case of an ICT is subjective. This is of particular importance while interpreting tests with weak positive bands. Whereas the results of the FIA test are read using iQuant Analyser. This provides a numerical value to every test, thereby ruling out any subjectivity during the interpretation of results. The inbuilt memory of the iQuant analyser can store results that can be used for future reference. It also has a 1-hour battery backup which keeps the machine operational in case of power failure.
Conclusion
To conclude, the performance of the newly developed Dengue NS1 Ag QUANTI CARD test was superior to the rapid immunochromatographic test and was comparable to the performance of the ELISA test. Due to its superior sensitivity, the ELISA test will remain the recommended choice of test in laboratories with trained manpower and equipment. On the other hand, in resource-limited settings such as in semi-urban and rural areas, with restricted availability of skilled manpower and equipment, the fluorescence immunoassay with high sensitivity and lesser TAT can be a better alternative to ELISA. It would be a valuable tool for prompt diagnosis of dengue infection in critically ill patients as it may impact patient management by early initiation of appropriate therapy.
Acknowledgement:
We acknowledge Mrs Shobha Sabale and Mrs Sonal Kalbhor for their technical support during the study.
Source of funding: Nil
Conflict of Interest: Authors have declared that no conflict of interest exists.
Authors’ Contribution:
This work was carried out in collaboration among all authors. Authors Rashmita Das, Suvarna Joshi, Meghna Palewarand Rajesh Karyakarte have conceptualised and designed the study. Authors Rashmita Das, Suvarna Joshiand Meghna Palewar performed data acquisition and managed the literature searches. Authors Rashmita Das, Suvarna Joshi performed the data analysis and author Rashmita Das wrote the first draft of the manuscript. Authors Rashmita Das, Suvarna Joshi, Meghna Palewar and Rajesh Karyakarte performed manuscript editing. All authors reviewed and approved the final manuscript.
Englishhttp://ijcrr.com/abstract.php?article_id=4303http://ijcrr.com/article_html.php?did=43031. Dengue and severe dengue [Internet]. WHO 2021. [cited 29 July 2021]. Available from: https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue
2. Dutta A, Dighade R, Malpekar K, Bisure K. Comparison of Diagnostic Modalities in Early Dengue in a Tertiary Hospital in Mumbai. Ann. Int. Med. Den. Res. 2021;7(1):MB01-MB05.
3. Chong Z, Sekaran S, Soe H, Peramalah D, Rampal S, Ng C. Diagnostic accuracy and utility of three dengue diagnostic tests for the diagnosis of acute dengue infection in Malaysia. BMC Inf Dis. 2020;20(1):1-11.
4. Pal S, Dauner AL, Mitra I, Forshey BM, Garcia P, Morrison AC, Halsey ES, Kochel TJ, Wu SJ. Evaluation of dengue NS1 antigen rapid tests and ELISA kits using clinical samples. PLoS One.2014;9(11):1-8.
5. National Vector Borne Disease Control Program. National Guidelines for Clinical Management of Dengue Fever. New Delhi: Government of India; 2015:15.
6. Raafat N, Blacksell S, Maude R. A Review of Dengue Diagnostics and Implications for Surveillance and Control. Trans. R. Soc. Trop. Med. Hyg. 2019;113(11):653-660.
7. Pohekar J, Bhalchandra M, Ghogre H, Pathrikar T. Evaluation and Comparison of Currently Available Fluorescence Immunoassay (FIA) Test with Rapid Immuno-Chromatographic Test (ICT) Considering NS 1 ELISA as a Reference Test. Int J Curr Microbiol Appl Sci. 2017;6(11):506-513.
8. Reddy R, Sahai K, Malik A, Shoba S, Khera A. Comparative Analysis of Rapid Dengue Testing and ELISA for NS1 Antigen and IgM in Acute Dengue Infection. Int J Curr Microbiol Appl Sci. 2016;5(10):931-937.
9. Naidu A, Venkateswarlu P, Umadevi S, Sailaja M, Praveena B, Devi A. Detection of Dengue NS1 by a Comparative Analysis of Panbio Elisa and Rapid Diagnostic Test. Sch. J. Appl. Med. Sci. 2017;5(3B):816-820.
10. Hassan S, Khare V, Singh M, Asghar S. Comparison of Rapid Immuno- Chromatographic Card Test with ELISA in Diagnosis of Dengue Fever at Tertiary Care Centre. Indian J Microbiol Res. 2018;5(2):284-287.
11. Gill M, Kaur A, Kukreja S, Chhabra N. Comparative Evaluation of a Rapid Test with ELISA for the Detection of Dengue Infection. Indian J Microbiol Res. 2016;3(4):405-407.
12. Yow K, Aik J, Tan E, Ng L, Lai Y. Rapid Diagnostic Tests for the Detection of Recent Dengue Infections: An Evaluation of Six Kits on Clinical Specimens. PLoS ONE. 2021;16(4):1-11.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcarePost Covid Lower Limb Axonal Neuropathy - A Case Report
English104105Yashasvi ShuklaEnglish Dhara SharmaEnglish Khanjan PatelEnglishIntroduction: The spectrum of neurologic complications subsequent to novel coronavirus 2 (SARS-Cov-2) infection is broad. COVID-19, caused by the infection with the SARS-Cov-2, is a pandemic affecting the whole globe with periods of exacerbations and remissions. Neurological manifestations occur in about 36.4% of patients infected with SARS-Cov-2. Case Report: Here reported case is of 37- year- old female who was clinically diagnosed with post covid lower limb axonal neuropathy after 50 days of covid 19 infection. A survey on neurological manifestations was specially designed to address 10 neurological manifestations of COVID-19: headache, altered sensation, nausea and vomiting, sudden hemiparesis (stroke), numbness and paresthesia, vertigo, ataxia, seizure, encephalitis/meningitis, Guillain-Barré Syndrome (GBS), and myelitis. Conclusion: Physical rehabilitation playing a significant part in treating balance, strength and returning to independence is known worldwide.
English Axonal Neuropathy, Post Covid Complication, Physiotherapy, Nerve Conduction Velocity test, Balance, StrengthINTRODUCTION
COVID-19, caused by the infection with the SARS-Cov-2, is a pandemic affecting the whole globe with periods of exacerbations and remissions. The spectrum of neurologic complications subsequent to novel coronavirus 2 (SARS-Cov-2) infection is broad. Neurological manifestations occur in about 36.4% of patients infected with SARS-Cov-2 and span several domains within the central and peripheral nervous system.1,2 One of those is sub-acute peripheral neuropathy. Here reported case is of 37-year-old female who was clinically diagnosed with post covid lower limb axonal neuropathy after 50 days of covid 19 infection.
CASE REPORT
This healthy 37-years-old female got tested positive with covid 19 in early May 2021. After 25 days of infection, she felt swelling over right eye for which she consulted an ophthalmologist who gave her 5 dose of methylprednisolone IV daily for choroidal thickening. After 2 weeks she felt sudden numbness in her both lower limbs which not only made her ambulation difficult but also lead to domestic fall once. Consequently, she consulted an orthopedic surgeon who further commented L5-S1 disc bulging with haemangioma based on MRI. Blood reports were suggestive of reduced haemoglobin 9.5gm/dl along with reduction in P.C.V, M.C.V., M.CH. M.C.H.C. with values 30.8%, 60.5%, 18.7%, 30.8% respectively. Furthermore, NCV finding concluded axonal motor neuropathy.
The patient had no co-morbidity hence diabetic neuropathy was ruled out. Furthermore, since the patient developed manifestations after covid 19 infection, Guillain Barre Syndrome was first on our differential list. Ascending flaccid paralysis, areflexia but in contrast our patient had involvement of lower back, lower limb till distal thigh. Moreover, patient had an acute presentation which goes against the chronic course of multiple sclerosis with no demyelinating lesions on MRI- brain and spinal cord. Considering nutritional neuropathy, a classic B12 deficiency scenario presents with chronic fatigue and neurological symptoms like tingling, numbness and loss of balance, Despite the Methylcobalmine injections of 1000mcg/ml for 5 doses there was no relief in pain, but the numbness went down to 50% as stated by patient. Hyperreflexia in knee can be seen due to corticospinal tract involvement, vibration, and proprioception is involved too, which was absent in this case. Cauda Equina can present with lower limb hyperreflexia, radiating pain and fecal incontinence which is classic in cauda equine but was absent in this patient, neither the MRI spine suggested any nerve root damage or compression.
On assessment, the patient had pain that was sharp and stabbing in nature and radiated posterolaterally downwards originating from the buttocks that giving her a sensation of heavy limb. According to Oxford grading for Manual Muscle Testing, on right side grade 1 in tibialis anterior, grade 2 in hamstrings, grade 1 in gluteus and the rest had grade 3, whereas on left side these muscles were grade 3. The clinical picture came out to be of post covid lower limb axonal neuropathy. Physiotherapy was aimed to reduce pain, stimulate paretic muscles, strengthen them and hence make the patient independent. Exercises were started in form of mechanical strengthening of bilateral lower limbs in form hip flexion, extension, abduction and back extension, electrical muscle stimulator and fast brushing for weak muscles like tibialis anterior
On progression after 15 days of exercise patient did all the above-mentioned exercises with 1kg of weight along with dynamic and static balance training, gait training with verbal and audio cueing from a therapist and visual biofeedback from a mirror while training. Furthermore, pain was reduced to NPRS 2 at rest which was 8 initially.
DISCUSSION
Peripheral neuropathy represents a spectrum of diseases with different etiologies, of which the commonest are certain co-morbidities like diabetes and can also be genetically inherited. Survey on neurological manifestations was specially designed for COVID-19 patients by researchers which addressed 10 neurological manifestations of COVID-19: headache, altered sensation, nausea and vomiting, sudden hemiparesis (stroke), numbness and paresthesia3,4 vertigo, ataxia, seizure, encephalitis/meningitis, Guillain-Barré Syndrome (GBS), and myelitis. Neurological manifestations were later confirmed by a thorough review of all available patient records.5 Peripheral neuropathies are the commonest neurological conditions having an incidence of 77/100,000 per year and a prevalence of 1–12% in all age groups and up to 30% in older people.3 Physical rehabilitation playing a significant part in treating balance, strength and returning to independence is known worldwide.
CONCLUSION:
This case study of post-Covid Axonal Neuropathy gives an insight into the disease, its complication and challenges. It as well demonstrates the contradictions of diagnosis, the detailed prognosis and its management. Persistent monitoring, early interventions and meticulous plan of management are the key components to expedite the recovery.
ACKNOWLEDGEMENT:
Authors sincerely thank the patient for her cooperation and adherence towards rehabilitation throughout the entire period of assessment and Khyati College of Physiotherapy for aiding with specific instruments when needed. The authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to the authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed
SOURCE OF FUNDING:
Self-funded
CONFLICT OF INTEREST:
Authors declare they have no conflict of interest.
AUTHORS’’ CONTRIBUTION:
Dr Yashasvi and Dr Dhara conceived and conceptualized the idea. Dr Yashasvi, Dr Dhara and Dr Khanjan were involved with the analysis of the facts, differential diagnosis and backing it up with a theoretical framework. Dr Yashasvi drafted the manuscript. Dr Dhara reviewed the manuscript.
Englishhttp://ijcrr.com/abstract.php?article_id=4304http://ijcrr.com/article_html.php?did=4304
Bureau B, Obeidat A, Dhariwal M, Jha P. Peripheral Neuropathy as a Complication of SARS-Cov-2. Cureus. 2020Nov 12;12(11)
Iltaf S, Fatima M, Salman S, Salam J, Abbas S. Frequency of Neurological Presentations of Coronavirus Disease in Patients Presenting to a Tertiary Care Hospital During the 2019 Coronavirus Disease Pandemic. Cureus. 2020 Aug 12(8)
Lehmann H, Wunderlich G, Fink G, Sommer C. Diagnosis of peripheral neuropathy. Neurological Research and Practice. 2020;2(1).
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurology. 2020;77(6):683.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. JAMA. 2020;323(11):1061.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareEffect of Watching Animated Cartoon Film on Level of Pain during Venipuncture among Children Admitted in Ministry Hospital Ras Al Khaimah
English106111Safiya U.K.English Sneha PitreEnglish Eman Abdelaziz Ahmed Rashad DabouEnglish Shukri AdamEnglishIntroduction: Venipuncture is one of the commonest painful stimuli children are exposed during hospitalization. Improper management of pain has long lasting effect on psychosocial behavior of children. Many non-pharmacological methods are useful in minimizing procedural pain. Objective: To assess the effect of distraction in form of animated cartoon film on level of pain among hospitalized children during venipuncture. Methodology: Study was conducted among sixty children between 3-10 years of age by using Quasi-experimental posttest only control group design. FLACC or Wong Baker Scale was used for the assessment of pain during venipuncture as per the age of the child. Animated cartoon film in Arabic or English depending on the child’s interest, were used as an intervention. It was started five minutes prior to venipuncture and results were documented immediately after the procedure. Results: Majority (66.6%) of the children were between age group of 3-6 years and had (70%) history of previous experience in venipuncture procedure. Distraction in form of cartoon film during venipuncture had shown statistically significant reduction in level of pain among study group. Conclusion: Acute pain associated with venipuncture is an unavoidable traumatic experience for hospitalized children. If not managed appropriately can lead to a long-lasting effect on the psychosocial behavior of the children. Animated cartoon film is an effective and user-friendly method that is well accepted by children and can be implemented by nursing personnel independently.
EnglishDistraction, Pain, Animated Cartoon, Venipuncture, Effect, FLACC, Wong BakerIntroduction
Pain is a spiteful sensation associated with or approaching the actual or potential tissue damage.[i] Pain sensation is a complex of all stimuli, which depends on age, cognitive development, and ability to express the pain severity in any individual. It is a common observation that all individuals during their childhood are exposed to painful stimuli right from birth in form of immunization and thereafter for diagnostic or therapeutic purposes if hospitalized.
Venipuncture is one of the commonest procedures that children usually get the encounter, during hospitalization.[ii] This procedure was associated with fear of mutilation among children between 3-12 years of age.[iii] Though it is a fundamental right of every child to receive appropriate preparation and intervention to reduce pain during venipuncture[iv], it is not usually practiced as a routine.2,[v] For instance, when the frequency of painful stimuli and interventions adopted to minimize the level of pain was assessed among 2987 hospitalized children, only 844 (28.3%) receive pain management interventions specifically for the painful procedure.2
Fear of needle is a common phenomenon observed in children, which plays an important role in the experience of pain.[vi] It was evident from findings reported by parents while witnessing the invasive procedure for their children. The level of fear scored higher than the pain level among the children following the application of EMLA cream during the insertion of a needle into a subcutaneously implanted intravenous port. It was also suggested that along with anesthetic cream additional intervention, which will distract the attention from painful stimuli, should be used to minimize fear in children.[vii]
In the process of atraumatic care, lots of non-pharmacological strategies have been used by health care professionals to decrease procedural pain in children such as the use of distraction cards and kaleidoscopes, video games (Canbulat, Inal & Sönmezer, 2014)[viii], Dolls and puppets (Silva et al., 2016).[ix]
Cartoon film was used by Susan et.al to distract the attention of children aged between 4-6 years old during venipuncture. A significant difference in pain scores was observed in the study (6.63 ± 0.80) and control (9.43±0.62) groups at pEnglishhttp://ijcrr.com/abstract.php?article_id=4305http://ijcrr.com/article_html.php?did=4305[1]. Eisenberg E, Marinangeli F, Birkhahn J, Varrassi G. International Association For The Study Of Pain (IASP). PAIN. 2005.https://www.iasp-pain.org/.
[2]. Blount RL, Piira T, Cohen LL, Cheng PS. Pediatric procedural pain. Behavior modification. 2006 Jan; 30 (1):24-49.
[3]. Kortesluoma RL, Nikkonen M. ‘I had this horrible pain’: the sources and causes of pain experiences in 4-to 11-year-old hospitalized children. J. Child Health Care. 2004 Sep; 8 (3):210-31.
[4]. Czarnecki ML, Turner HN, Collins PM, Doellman D, Wrona S, Reynolds J. Procedural pain management: A position statement with clinical practice recommendations. Pain Management Nursing. 2011 Jun 1;12(2):95-111.
[5]. Berberich FR, Schechter NL. Pediatric office pain: crying for attention. Pediatrics. 2012 Apr 1;129(4):e1057-9.
[6]. Uman LS, Birnie KA, Noel M, Parker JA, Chambers CT, McGrath PJ, et al. Psychological interventions for needle-related procedural pain and distress in children and adolescents. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD005179. DOI: 10.1002/14651858.CD005179.pub3.
[7]. Hedén L, von Essen L, Ljungman G. The relationship between fear and pain levels during needle procedures in children from the parent's perspective. Eur J Pain. 2016 Feb;20(2):223-30.
[8]. Canbulat N, Inal S, Sönmezer H. Efficacy of distraction methods on procedural pain and anxiety by applying distraction cards and kaleidoscope in children. Asian Nursing Research. 2014 Mar 1;8(1):23-8.
[9]. Soares da Silva JR. Using Therapeutic Toys to Facilitate Venipuncture Procedure in Preschool Children. Pediatric nursing. 2016 Mar 1; 42(2).
[10]. Maharjan S, Maheswari BU, Maharjan M. Effectiveness of the animated cartoon as a distraction strategy on level of pain among children undergoing venipuncture at selected hospital. Int J Health Sci Res. 2017;7(8):248-52.
[11]. Noel M, McMurtry CM, Chambers CT, McGrath PJ. Children's memory for painful procedures: The relationship of pain intensity, anxiety, and adult behaviors to subsequent recall. J. Pediatr. Psychol. 2009 Nov 4;35(6):626-36.
[12]. Wlassoff V. Gate Control Theory and pain management. Retrieved, May. 2014; 12: 2017.
[13]. Kochman A, Howell J, Sheridan M, Kou M, Ryan EE, Lee S, et al. Reliability of the faces, legs, activity, cry, and consolability scale in assessing acute pain in the pediatric emergency department. Pediatric emergency care. 2017 Jan 1;33(1):14-7.
[14]. Wong-Baker FACES FOUNDATION. Wong. (n.d.). https://wongbakerfaces.org/wong-baker/.
[15]. Rattray JE, Johnston M, Wildsmith JA. Predictors of emotional outcomes of intensive care. Anesthesia. 2005 Nov;60(11):1085-92.
[16]. Abd El SM, Elsayed LA. Effect of interactive distraction versus cutaneous stimulation for venipuncture pain relief in school-age children. J Nurs Educ Pract. 2015 Apr 1;5(4):32.
[17]. Uman LS, Chambers CT, McGrath PJ, Kisely SR. Psychological interventions for the needle-related procedural pain and distress in children and adolescents. Cochrane Database of Systematic Reviews. 2006(4).
[18]. Akgül EA, Karahan Y, Ba?olu F, O?ul A, Öztornaci BÖ, Yetim P, et al. Effects of watching cartoons on pain scores in children undergoing venepuncture. Nursing children and young people. 2021 May 6;33(3).
[19]. Bantick SJ, Wise RG, Ploghaus A, Clare S, Smith SM, Tracey I. Imaging how attention modulates pain in humans using functional MRI. Brain. 2002 Feb 1; 125 (2):310-9.
[20]. Kuo HC, Pan HH, Creedy DK, Tsao Y. Distraction-based interventions for children undergoing venipuncture procedures: a randomized controlled study. Clinical nursing research. 2018 May; 27 (4):467-82.
[21]. Windich-Biermeier A, Sjoberg I, Dale JC, Eshelman D, Guzzetta CE. Effects of distraction on pain, fear, and distress during venous port access and venipuncture in children and adolescents with cancer. J. Pediatr. Oncol. Nurs. 2007 Jan;24(1):8-19.
[22]. Balanyuk I, Ledonne G, Provenzano M, Bianco R, Meroni C, Ferri P, et al. Distraction technique for pain reduction in Peripheral Venous Catheterization: randomized, controlled trial. Acta Bio Medica: Atenei Parmensis. 2018;89(Suppl 4):55.
[23]. http://www.Sundaytimes.3/2015, 2015
[24]. Stuber M, Hilber SD, Mintzer LL, Castaneda M, Glover D, Zeltzer L. Laughter, humor and pain perception in children: a pilot study. Evidence-based complementary and alternative medicine. 2009 Jun 1; 6 (2):271-6.
[25]. Shaker NZ, Taha AA. Effectiveness of distraction therapy on children’s pain perceptions during peripheral venous cannulation at a pediatric teaching hospital in Erbil City. Erbil Journal of Nursing and Midwifery (ENJM). 2018 Nov 30; 1 (2):75-84.
[26]. Bergomi P, Scudeller L, Pintaldi S, Dal Molin A. Efficacy of non-pharmacological methods of pain management in children undergoing venipuncture in a pediatric outpatient clinic: a randomized controlled trial of audiovisual distraction and external cold and vibration. J. Pediatr. Nurs. 2018 Sep 1; 42: e66 -72.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareA Cross-sectional Study on Menstrual Coping among Reproductive Age Group Women in Chengalpattu, Tamil Nadu
English112118Chitharaj Rajan RushenderEnglish Vijayakrishnan GEnglish Ameenah Anwar Hussain SirajaEnglishContext: Menstruation is one of the important indicators of women’s reproductive health. As menstruation-related problems are becoming increasingly common both globally as well as in India, dealing with problems during menstruation has become a challenge in the life of women belonging to the reproductive age group. Aims: The present study is designed to assess menstrual coping and various coping mechanisms adopted by women during menstruation. Setting and Design: This study was conducted amongst adolescents/women of reproductive age (Women who are currently menstruating) who visited SRM medical college hospital and its field practice areas (both rural and urban) Materials and Methods: A questionnaire was developed specifically for this study, comprising of questions about the socio-demographic characteristics of the study population as well as menstrual history, emotional coping during menstruation & perception about menstruation. Statistical Analysis: Descriptive statistics and chi-square analysis were used to analyze the data. Results: More than 2/3rd of the participants (87.38%) reported regular menstrual cycles with a majority of women (90.03%) experiencing 3-5 days cycles. Some of the prominent symptoms experienced by the participants during menstruation were pain (80.73%), backache (29.90%), and headache (23.59%). Conclusions: In the present study, 40% of the women were having emotional problems during menstruation and factors like frequency of symptoms, commitments during menstruation, taking off during menstruation, and responsibility-sharing during menstruation were found to have a significant effect on emotional problems during menstruation.
EnglishMenstrual coping, Emotional problems during menstruation, Menstrual coping mechanisms, Menstrual coping amongst women in Chengalpattu, Emotional coping during menstruation, Emotional coping mechanisms during menstruationIntroduction
Menstruation is one of the important indicators of women's reproductive health. The adolescent period is the transition between puberty and adulthood and menarche happens to be one of the most important markers of puberty. For most girls in the country, menarche happens between the ages of 10 to 16 years, however, this shows a remarkable range of variation. The normal range for ovulatory cycles is between 21 and 35 days. While most periods last from 3 to 5 days, the duration of menstrual flow normally ranges from 2 to 7 days1. The pattern of menstruation can be affected by various factors such as ethnicity, family history, smoking, stress, physical activities, and dietary habits2. Globally 75% of girls are experiencing problems associated with menstruation. The World Health Organization reports that 18 million women aged 30–55 years perceive their menstrual bleeding to be excessive3. The major abnormalities are dysmenorrhea, premenstrual syndrome (PMS), and menstrual irregularities. These disorders may lead to problems in daily activities such as academic excellence, achievements in sports, and loss of self-confidence4 which in turn may lead to mental and emotional stress amongst women.
Dysmenorrhea is one of the most prevalent menstrual problems during adolescence and can even cause women to become bedridden. Dysmenorrhea is an important public health problem among various ethnic groups and is associated with loss of school days and poor quality of life5. Menstrual disorders such as menorrhagia, abnormal uterine bleeding, and polymenorrhea contribute to almost 12% of gynecology referrals and are usually associated with a very high chance of surgical intervention2. Premenstrual syndrome (PMS) is a collection of emotional symptoms with or without physical symptoms related to a woman’s menstrual cycle, the prevalence of PMS has been reported in 20 to 32 % of premenopausal and 30-40% of the reproductive female population. Premenstrual syndrome (PMS) affects women’s quality of life, economic productivity, and social performance to a degree that affects their daily lives6. Irregular menstruation is an indicator of health in women, the prevalence of irregular menstruation varies from 5% to 35.6% depending on age, occupation, and country of residence. Irregular menstruation can occur as a result of hormone imbalances and stress. Irregular menstruation is related to a mental health condition such as depression7.
As menstruation-related problems are becoming increasingly common both globally as well as in India, dealing with problems during menstruation has become a challenge in the life of women belonging to the reproductive age group. Addressing the physical and psychological needs related to menstruation is the need of the hour as far as the reproductive health of women is concerned. Although various researchers have been conducted in the areas of menstrual disorders and their prevalence, very little is known about how women cope with menstruation-related problems and how to help women improve to adapt to menstrual changes both physically and psychologically. Hence the present study is designed to fill in the gaps related to menstrual coping and various coping mechanisms adopted by women during menstruation.
Materials and Methods
This study was a cross-sectional study. The sample size was calculated to be 264 using a prevalence of 22% for emotional stress and absolute precision of 5%. To account for non-participation amongst the participants a non-participation rate of 10% was considered. Hence, 27 participants (10%) were added and the final minimal sample size was estimated to be 291. The study population included adolescents/women of reproductive age (Women who are currently menstruating) who visited SRM medical college hospital and its field practice areas (both rural and urban). Data were collected between May 2020 to August 2020. Women who are currently pregnant, women who are on oral contraceptive pills & IUDs, women with premature surgical menopause & physiological menopause were excluded from the study.
A questionnaire was developed specifically for this study, comprising of questions about the socio-demographic characteristics of the study population as well as menstrual history, emotional coping during menstruation & perception about menstruation. Questions such as age, residence, education, SES, Marital status, occupation, and type of family were asked related to the socio-demographic characteristics. Questions such as age at menarche, regularity and duration of cycles, symptoms experienced and commitments during menstruation were some of the questions included in the questionnaire. Regarding the emotional coping and perception about menstruation, questions such as coping methods, a distraction from symptoms, communication with others during menstruation, and family support were included in the questionnaire. Data were entered and analyzed using a Microsoft Excel spreadsheet. Descriptive statistics and chi-square analysis were used to analyze the data. Each study subject was approached individually and written informed consent was obtained for the study. Institutional ethical committee approval was obtained (Institutional Ethical Committee clearance number –1898/IEC/202) and confidentially of the study participants was maintained thought the study.
Results
For the present study, a total of 301 women who are in the reproductive age group and presently menstruating were included. The mean age of the participants was 27.90 (±8.01) yrs (Refer Table-1). The majority of the participants (55.48%) were currently married and less than a half of the participants (43.52%) were single. Minorities of the study participants were divorced (0.33%) and widowed (0.66%). More than half of the participants were living in urban areas (54.15%) and the rest (45.85%) of the participants were living in rural areas. As far as the educational qualifications of the women are concerned, a majority of the participants (39.87%) had qualified for an undergraduate degree followed by the participants who had a secondary school education (15.61%).
A proportion of (13.29%) women had completed higher secondary school education followed by participants who had qualified a postgraduate degree (8.64%). Of the 301 participants, a proportion of (11.63%) were illiterates. A majority of (82.39%) of the participants belonged to a nuclear family and the rest (17.61%) were from joint families. Most of the participants (33.22%) were housewives and were not employed which was followed by the proportion of students (33.2%) and working women (32.89%). A majority of (80.73%) of the participants belonged to the Hindu religion which was followed by Christians (14.62%) and Muslims (4.65%). The social economical class was classified according to BG Prasad's scale, the highest proportion of women belonging to the middle class (32.56%) followed by upper lower class (20.27%) and upper class (17.28%).
Regarding the menstrual history of the participants, the mean age at menarche of the participants was 12.61(±1.79) yrs (Refer Table-2). More than 2/3rd of the participants (87.38%) reported regular menstrual cycles with a majority of women (90.03%) experiencing 3-5 days cycles. Some of the prominent symptoms experienced by the participants during menstruation were pain (80.73%), backache (29.90%), and headache (23.59%). The majority of the participants (35.22%) had a moderate frequency of symptoms followed by women who had symptoms often (33.89%). Most of the participants (77.74%) happened to be tracking their cycles regularly. The majority of the participants (86.38%) followed hygienic practices like the usage of sanitary pads during menstruation. Of all the commitments that participants had during menstruation, family commitments constituted the major proportion (38.21%).
Regarding the emotional coping mechanisms adopted by the participants during menstruation, it was found that more than half of the participants (53.16%) had some form of emotional problems during menstruation. A proportion (32.22%) of the women had an outburst as a method of coping during menstruation. The majority of the participants (44.85%) had mobile phones as a means to distract from these symptoms. More than 2/3rd of the participants (75.75%) had family support during menstruation.
Regarding the association between socio-demographic and menstrual factors with self-perceived emotional problems during menstruation, we found the frequency of symptoms during menstruation (‘p’= 0.000), commitments during menstruation (‘p’= 0.042), taking off from work during menstruation (‘p’= 0.012) and responsibility-sharing (‘p’= 0.017) to be statistically significant, Refer (Table.4).
Discussion
The present study was conducted amongst 301 women participants, all the participants included were in the reproductive age group and presently menstruating. The mean age of the participants was 27.90 (±8.01) yrs and the mean age at menarche of the participants was 12.61(±1.79) which was similar to the study done amongst adolescent girls by Omidvar S et al.12018. The majority of the participants had graduated with an undergraduate degree (39.87%) and belonged to the middle class (32.56) nuclear families (82.39%) as the majority of the participants were residents of urban areas (54.15%). According to the results of the present study (12.62%) of women were having menstrual irregularities which are close to the study findings of Kwak Y et al. 2019 which was conducted amongst women aged (19-54) on the prevalence of menstrual irregularities in South Korea that reported that (14.2%) women were having menstrual irregularities. This minor variation could be due to the differences in country of residence7.
Regarding the duration of the menstrual cycle, the present study results show that a majority of the women had a duration of 3-5 days cycle (90.03%) followed by >5 days cycle (5.98%) and Englishhttp://ijcrr.com/abstract.php?article_id=4306http://ijcrr.com/article_html.php?did=4306
Omidvar S, Amiri FN, Bakhtiari A, Begum K. A study on menstruation of Indian adolescent girls in an urban area of South India. J Family Med Prim Care. 2018;7(4):698–702.
Rafique N, Al-Sheikh MH. Prevalence of menstrual problems and their association with psychological stress in young female students studying health sciences. Saudi Med J. 2018;39(1):67–73.
Karout N, Hawai SM, Altuwaijri S. Prevalence and pattern of menstrual disorders among Lebanese nursing students. East Mediterr Health J. 2012 Apr;18(4):346-52.
Negi P, Mishra A, Lakhera P. Menstrual abnormalities and their association with lifestyle pattern in adolescent girls of Garhwal, India. J Family Med Prim Care. 2018;7(4):804 808.
Abu Helwa, H.A, Mitaeb, A.A, Al-Hamshri, S. et al. Prevalence of dysmenorrhea and predictors of its pain intensity among Palestinian female university students. BMC Med. Women's Health(18),18-32.
A DM, K S, A D, Sattar K. Epidemiology of Premenstrual Syndrome (PMS)-A Systematic Review and Meta-Analysis Study. 2015 Jul;9(7):ZZ05]. J Clin Diagn Res. 2014;8(2):106-109.
Kwak Y, Kim Y, Baek KA. Prevalence of irregular menstruation according to socioeconomic status: A population-based nationwide cross-sectional study. PLoS ONE 14(3):e0214071. Available from: https://doi.org/10.1371/journal.pone.0214071. [Last accessed on 2020 Sep 26].
Bellad G.C, Guru M. Association between body mass index and dysmenorrhea among medical students: A cross-sectional study. Obs Rev: J Obstet Gynecol 2020;6 (2):38-43.
Kural M, Noor NN, Pandit D, Joshi T, Patil A. Menstrual characteristics and prevalence of dysmenorrhea in college-going girls. J Family Med Prim Care. 2015 Jul-Sep;4(3):426-31.
Shaikh Z, Panda M, Gaur D. Acceptability of low-priced, socially-marketed sanitary napkins amongst non-users of sanitary napkins in a slum population of Delhi. Int J Community Med Public Health 2019;6:1754-9.
Mathiyalagen P, Peramasamy B, Vasudevan K, Basu M, Cherian J, Sundar B. A. descriptive cross-sectional study on menstrual hygiene and perceived reproductive morbidity among adolescent girls in a union territory, India. J Family Med Prim Care. 2017Apr-Jun; 6(2):360-365.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareComparison of Ultrasound-Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries
English119123Shanthan Kumar RepalleEnglish B Srinivas RaoEnglish Sudhalaxmi Anusha ParimiEnglishIntroduction: Brachial plexus block is an integral part of the regional anesthetic technique employed in orthopedic surgeries of hand, arm, and shoulder. It is used to circumvent the need for general anesthesia. Aim: The present study aimed to compare the efficacy of ultrasound guidance and nerve stimulation technique for supraclavicular brachial plexus block. Methods: Based on the inclusion criteria and exclusion criteria n=60 patients were identified and selected for the study. They were randomly allocated in two groups of n=30 each by computer-generated random allocation. Group A (US group) will receive ultrasound-guided supraclavicular brachial plexus block and Group B (NS group) will receive nerve stimulator-guided supraclavicular brachial plexus block. Results: The average number of attempts taken to locate supraclavicular brachial plexus in Group A (US) was 1.33 and in Group B (NS) was 5.56 which is statistically significant (pEnglishIntroduction
Brachial plexus block is an integral part of the regional anesthetic technique to circumvent the need for general anesthesia and its side effects as well as safe in patients with comorbidities making them unsuitable for general anesthesia. It is a frequently employed technique in orthopedic surgeries of hand, arm, and shoulder by using an appropriate and accurate needle location in the vicinity of the nerves of the brachial plexus. Thorough knowledge of applied anatomy, pharmacological properties of local anesthetics, working principles of the equipment, and importantly dexterity required for the performance of the safe block. The commonly employed techniques to position the needle accurately in a brachial plexus block are transarterial, eliciting paresthesia, use of a peripheral nerve stimulator/ locator, or an ambulatory sonological device.1 The initial technique of Brachial plexus blocks was blindly hitting the first rib by a wandering technique or using the adage "No Paresthesia-No Anesthesia" before the availability of Nerve locators. 2 The introduction of peripheral nerve locator was a landmark achievement in the field of regional anesthesia providing objective evidence of needle proximity to target nerves. Their main advantages being lightweight and compact, visual and audible signals with a bright display, providing a safe circuit between the stimulator, needle and the patient with an adjustable impulse duration of 0.1 and 1 millisecond with an adjustable current from 0 to 5 mA at increments of 2 Hz impulse frequency.
The nerve stimulation technique using nerve locator carried doubt regarding its sensitivity, particularly while detecting the needle position in the intraneural space (requiring high current intensity to elicit a motor response) and keeping the needle extra neural posed more challenging for nerve injury. Ultrasonography is a useful state-of-the-art tool in the armament of regional anesthesia. 3, 4 By comparison with nerve stimulation techniques, ultrasound guidance offers some advantages of direct visualization of anatomic structures, helping to minimize vascular punctures, and a dynamic vision of needle advancement and local anesthetic spread in the per neural area. 5 Although no signi?cant differences in the incidence and severity of postoperative neurological symptoms have been reported, 6 ultrasound guidance has been shown to reduce the number of needle redirections 7 and to enhance block success rate, particularly when performing inter scalene block. 8 US guidance has also been shown to improve peripheral nerve block onset times when compared with a neurostimulation technique, 9 although very few studies showed up speci?cally when this issue was addressed for inter scalene block. 10 Hence, we conducted a prospective randomized study to test whether Ultrasonography (USG) guidance can improve the success rate and can shorten the onset time of supraclavicular brachial plexus block as compared with nerve stimulation guidance.
Material and Methods
This prospective controlled study was done in the Department of Anesthesiology, Mahatma Gandhi Medical Hospital Warangal, Telangana from June 2018 to August 2019. Institutional Ethical committee permission was obtained for the study (No.2003035D 24/06/2018) after following the due protocol. Written consent was obtained from all the patients in the study.
Inclusion criteria
American Society of Anesthesiologists grades I, II, and III physical status.
Patients of either sex between 18-60 years.
Elective upper limb surgery
Exclusion criteria
Those who do not fit in inclusion criteria
Preexisting nerve damage (sensory or motor) in the extremity to be blocked
Peripheral neuropathy
Significant cardiovascular disease
Body Mass Index (BMI) > 35
Uncontrolled diabetes
Renal Impairment (Creatinine> 2.0 mg/dl)
Based on the inclusion criteria and exclusion criteria n=60 patients were identified and selected for the study. They were randomly allocated in two groups of n=30 each by computer-generated random allocation. Group A (US group) will receive ultrasound-guided supraclavicular brachial plexus block and Group B (NS group) will receive nerve stimulator-guided supraclavicular brachial plexus block.
In the US group (Group A), A 10 MHz Transducer probe covered with a sterile Tegaderm was placed in a transverse plane just superior to the clavicle and tilted appropriately to locate the subclavian artery. After local anesthetic skin infiltration of skin with 2% lignocaine 2 ml one cm lateral to the transducer to reduce discomfort to the patient, a 25G, 5cm, the needle was inserted and 20 ml of 0.75% Ropivacaine solution was injected all around the nerve trunks in a lateral to medial direction by hydro locating the tissue layers, with intermittently aspirating ruling out intravascular accidental entry.
In the neurostimulation group (Group B), patients were positioned similarly as described in the US group, and a 25 G, 5 cm insulated tip-free needle was used. Polarity is maintained using an appropriate electrode in proper places. The needle connected to a nerve stimulator was set to deliver a current of 1 mA the needle was inserted at an angle of 45° 2-3 CMSs depth above the clavicle with palpating fingers firmly pressed between anterior and middle scalene muscles and brachial plexus approached. Position of needle confirmed by looking for muscle contraction in the digits, hand, forearm, arm, and pectoralis with a minimal current of 0.5 mA. 0.75% Ropivacaine 20 ml was injected with intermittently aspirating ruling out accidental intravascular injections and the pressing finger pressure released finally.
Patients were kept for one hour in the post anesthesia recovery room and assessed every half an hour by the recovery nurses for the Visual Analogue Scale (VAS) for pain, the motor power for elbow flexion, and any late side effects of local anesthetics.
Statistics: All the available data was entered in MS Excel spreadsheet and descriptive statistics such as Mean, Standard Deviation, Student's T-test, ANOVA were performed (pEnglishhttp://ijcrr.com/abstract.php?article_id=4307http://ijcrr.com/article_html.php?did=4307
Winnie, AP. Perivascular techniques of brachial plexus block. Plexus anesthesia: perivascular techniques of brachial plexus block I (2nd ed.). W.B. Saunders Company Philadelphia 1990; pp. 261.
Perlas, Anah, Chan, Vincent W.S, Simons, martin. ultrasound-guided supraclavicular brachial plexus block. Reg Anesth. 2003; 12:178-79.
Marhofer P, Harrop-Grif?ths W, Kettner SC, Kirchmair L. Fifteen years of ultrasound guidance in regional anesthesia: part 1. Br J Anaesth. 2010; 104:538-46.
Marhofer P, Harrop-Grif?ths W, Willschke H, Kirchmair L. Fifteen years of ultrasound guidance in regional anesthesia: Part 2-recent developments in block techniques. Br J Anaesth. 2010; 104:673-83.
Baciarello M, Danelli G, Fanelli G. Real-time ultrasound visualization of intravascular injection of local anesthetic during a peripheral nerve block. Reg Anesth Pain Med. 2009; 34:278-79.
Liu SS, Zayas VM, Gordon MA,. A prospective, randomized, controlled trial comparing ultrasound versus nerve stimulator guidance for interscalene block for ambulatory shoulder surgery for postoperative neurological symptoms. Anesthesia Analg. 2009; 109:265–71.
Orebaugh SL, Williams BA, Kentor ML. Ultrasound guidance with nerve stimulation reduces the time necessary for resident peripheral nerve blockade. Reg Anesth Pain Med. 2007; 32:448-54.
Kapral S, Greher M, Huber G,. Ultrasonographic guidance improves the success rate of interscalene brachial plexus blockade. Reg Anesth Pain Med. 2008; 33:253-58.
Liu SS, Ngeow J, John RS. Evidence basis for ultrasound-guided block characteristics onset, quality, and duration. Reg Anesth Pain Med. 2010; 35:S26-35.
Soeding PE, Sha S, Royse CE, Marks P, Hoy G, Royse AG. A randomized trial of ultrasound-guided brachial plexus anesthesia in upper limb surgery. Anaesth Intensive Care. 2005; 33:719-25.
Singh G, Mohammed YS. Comparison between conventional technique and ultrasound guide supraclavicular brachial plexus block in upper limb surgeries. IJSS. 2014; 2(8):169-76.
Orebaugh SL, Williams BA, Kentor ML. Ultrasound guidance with nerve stimulation reduces the time necessary for resident peripheral nerve blockade. Reg Anesth painted. 2007; 32:448-54.
Williams SR, Chouinard P, Arcand G,. Ultrasound guidance speeds execution and improves the quality of supraclavicular block. Anesth Analg. 2003; 97:1518-23.
Kapral S, Greher M, Huber G,. Ultrasonographic guidance improves the success rate of interscalene brachial plexus blockade. Reg Anesth Pain Med. 2008; 33:253–58.
Liu SS, Zayas VM, Gordon MA,. A prospective randomized controlled trial comparing ultrasound versus nerve stimulator guidance for interscalene block for ambulatory shoulder surgery for postoperative neurological symptoms. Anesth Analg. 2009; 109:265–71.
Leslie C. Thomas, Sean K. Graham, Kristie D. Osteen, Heather Scuderi Porter, Bobby D. Nossaman. Comparison of Ultrasound and Nerve Stimulation Techniques for Interscalene Brachial Plexus Block for Shoulder Surgery in a Residency Training Environment: A Randomized, Controlled, Observer- Blinded Trial. Ochsner J2011;11: 246-52.
Fawzy M, Nevan M. Mekawy, Ahmed Abd Elaziz Aref, GomaaZahry Hussin, Mohamed Mourad. Interscalene brachial plexus block (a comparative study between nerve stimulator and ultrasound guidance in shoulder surgery). Ain-Shams Anesthesiology J. 2012;5-2:238-42.
Ullah H, Samad K, Khan FA. Continuous interscalene brachial plexus block versus parenteral analgesia for postoperative pain relief after major shoulder surgery (Review). Cochrane Database of Systematic Reviews 2014; 2:CD007080.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241141EnglishN2022January3HealthcareIdentification of the Organic Volatile Impurities in Telmisartan Active Pharmaceutical Ingredient and Its Pharmaceutical dosage forms by using Head Space Gas Chromatography Technique
English124131J. Krishna KishoreEnglish K. Prasada RaoEnglishIntroduction: Residual Solvents or Organic Volatile Impurities are potential risk for quality and stability of drug products as well as human body if intake exceeds the permitted daily exposure. They do not provide any therapeutic benefit and must be removed to the maximum possible level Objective: The work presented in this paper explains the simple and rapid Head Space Gas Chromatography (HS-GC) technique for the Quantitative estimation of Three Organic Volatile Impurities (OVIs) in Telmisartan Active Pharmaceutical Ingredient (API) and its Pharmaceutical dosage forms. Methods: Organic solvents such as methanol, acetone, and n-butanol are frequently used in the manufacturing of Telmisartan. The process for quantification of OVIs in Telmisartan API has been done with Head Space Gas Chromatographic method with detector of Flame Ionization and utilizing the Shimadzu GC- 2010 with a capillary column of FID (DB-624, 30 m × 0.53 mm, 3 μ), with a carrier gas nitrogen at 4.0 mL/min flow rate. The experimental parameters like injection temperature, oven temperature, make-up flow, zero air, injection temperature; split ratio, headspace conditions, and the diluent selection have been considered and were optimized. Results: Retention times are 2.23 min for methanol, 3.04 min for acetone, and 7.20 min for n-butanol respectively. The proposed technique has been statistically validated based on standard International Conference on Harmonization guidelines (ICH). The % Relative Standard Deviation (% RSD) for the system precision of six injections was should be not more than 10.0 %. The percentage recovery was found between 85-115 %. The correlation coefficient (R2) is not less than 0.99. Limit of Detection (LOD) was found as 19 ppm (methanol), 26 ppm (acetone), and 21 ppm (n-butanol). The Limit of Quantification (LOQ) was found as 58 ppm (methanol), 77 ppm (acetone), and 64 ppm for n-butanol. The intermediate precision and method precision were found to be within the limit of acceptance. Conclusion: From the obtained validation results the proposed technique has been fruitfully applied for quantification of organic volatile impurities in Telmisartan Active Pharmaceutical Ingredient as well as its pharmaceutical dosage forms.
EnglishMethod development, Organic volatile impurities, Telmisartan API, Validation, Chromatography, QuantificationINTRODUCTION
Organic solvents are commonly used in the synthesis of various drugs, excipients and in the formulation of the drug. The presence of these solvents in the final product should not be present as they are highly harmful and they impact the drug substance stability and even impart taste and odour and which would be harmful. In the literature there are various procedures and technologies being reported to eliminate these organic solvents.1 Some drugs contain even small amounts of these organic solvents after carrying out several operations to remove them and such minute concentrations of these solvents are regarded as residual chemical solvents. The major challenge faced by the pharma industries is to find various analytical activities to detect these residual solvents in the medicinally important compounds and drug products. The use of various active ingredients of medicinal importance and their formulations into pharmaceutical drug compounds under good conditions of industrial practice needs necessary quality control of these ingredients used in the synthesis. Hence, before the synthesis of medicinal compounds by any useful process these solvents need to be regulated and the compound purity has to be maintained.2 The reports of the regulatory guidance shows the required amounts of various organic solvents.3-5 Chemically the Telmisartan is 2-(4-{[4-methyl-6-(1- benzodiazol-1-yl] methyl} phenyl) benzoic acid. This is an Angiotensin Receptor Blocker and exhibits great affinity towards receptors of angiotensin II type 1, and its duration of action is long, and have higher long life than any other ARB.6-8 The following scheme shows its synthetic route (Scheme-I).
In the preparation of the Telmisartan, the organic solvents like methanol, acetone, and n-butanol are used. These solvents are grouped with class-3 according to ICH Q3C (R6) guidance.9 These organic solvents of this class have toxic effects on humans as a result we need to regulate the presence of these solvents in Telmisartan.
The main objective of this work is to develop and validate a fast, simple, and reliable Quantitative identification of these OVIs (methanol, acetone, and n-butanol) in Telmisartan API and its Pharmaceutical dosage forms.10 The various prominent aspects and novelty of the method described include short elution time, easy sample treatment at ambient temperature with sonication of little amount of powder, good precision, and more recovery rate (>100±15%). The applicability of the method designed and validated as per guidelines of ICH for determination of above said organic solvents in the bulk as well as in the tablet dosage form.
Methanol, acetone, and n-butanol are the generally used chemical solvents during the synthesis of many pharmaceutical drug compounds. These chemicals must be controlled in the finished product to minimum level and based on their toxic effects their limits are fixed according to ICH guidelines for residual solvents.
The level of these organic volatile impurities has to be determined and controlled. There is no literature available to simultaneously determination of methanol, acetone, and n-butanol in this Telmisartan. These structures are followed in (Figure 2).
MATERIALS AND METHODS
Chemicals and reagents
Telmisartan API was taken from local well-known laboratory. GC grade Methanol, Acetone, n-Butanol and Di methyl sulfoxide (DMSO) were obtained from Merck -Mumbai. The structures of the compounds are shown in figure 1.
Instrumentation
Chromatography was carried out on Shimadzu chromatography equipped with GC-2010 system with FID (Shimadzu). The samples have been injected by Teledyne tekmar HT3TM Headspace and acquisition and integration of data was done using GC-solution software.
Chromatographic condition
Column: DB-624 (30 m, 0.53 mm ID, 3 μm); Carrier gas: Nitrogen with a rate of flow of 3.6 mL/min; temperature of the Injector: 180 ºC; split ratio: 1:20; Oven program: initial 60 ºC hold for 5 min, increase @ 8 ºC/min up to 140 ºC, hold for 0.0 min, increase @ 30 ºC/min up to 200 ºC, hold for 13 min; temperature of the Detector (FID): 240 ºC; Flow of the air gas: 400 mL/min; flow of the hydrogen, 40 mL/min; overall run time: 30 min.
Condition of the Headspace sampler
Temperature of the Vial: 90 ºC; The needle temperature: 100 ºC; Temperature Transfer line: 115 ºC; Conditioning time of vial: 30 min; Pressurize time of Vial: 3.0 min; Volume of the Injection: 1.0 mL; Inject time: 1.0 min; Cycle time of GC: 45 min.
Preparations
Specifications for Organic volatile impurities
Methanol is 3000 ppm, Acetone is 5000 ppm and n-Butanol is 5000 ppm.
Standard Solution preparation
Weighed and transferred about each 750.35 mg of methanol, 1250.95 mg of acetone and 1250.85 mg of n-butanol along with 70 mL of diluents into 100 mL volumetric flask and it is diluted with the diluents. Further into 50 mL of volumetric flask 5 mL of the above solution is taken and diluted to a volume with the diluent.
Meanwhile with 2 mL of standard solution the standard Headspace vials have been prepared and sealed it aluminum closure. (The standard solution has been prepared as per the sample concentrations of Telmisartan).
Preparation of Telmisartan API sample solution (250 mg/mL)
About 500 mg of Telmisartan pure sample weighed accurately into a 10 mL of the vial and 2.0 mL of diluents is added and sealed it with aluminum closure immediately.
Preparation of Telmisartan Tablet solution
Twenty tablets of Telmisartan were weighed and they were powdered. An amount of powder equivalent to 500 mg Telmisartan was exactly weighed and transferred to a 10 mL of headspace vial, and add 2 mL of the diluent and sealed immediately with aluminum closure.
Calculation:
Organic volatile impurity content was calculated from,
RESULTS AND DISCUSSION
Development of the Method
The development of the method was done by following the principles of Quality-by-Design along with column selection and diluents. During the development of HS-GC method, we have selected the appropriate system parameters in order to obtain the best separation, time efficiency and sensitivity the three organic volatile impurities mixtures were injected under various types of conditions. Example, at different GC Columns (DB-5, VF-1, DB-624), HS Vial temperature (70-90 ºC), HS Needle temperature (80-110 ºC), HS Transfer line temperature(90-130 ºC), GC-FID temperatures (200-300 ºC), GC Injector temperatures (100-220 ºC), GC gradients (40-200 ºC, at the rate of 5–40 ºC /min), carrier gas flow rates (2.0-5.0 mL/min), different diluents (NMP, DMSO and DMF) etc. The final HS-GC conditions were used for the validation of the method was obtained on the basis of GC parameters. These solvents were individually injected once separately in order to find the specificity of the method and sensitivity of the signal response.
Method validation
The validation of the method was studied by evaluating repeatability, specificity method, limit of quantification (LOQ), method precision, limit of detection (LOD), and accuracy, linearity, ruggedness, and stability if the solution Organic volatile impurities according to the guidelines given by ICH.11
Specificity
Table 1 shows the specificity data for three organic volatile impurities Specificity was studied by injecting blank, sample preparation, and Standard solution and showing resolution between all peaks are in both sample solution and Standard Solution and there was no interference from the blank at the retention times of analyte peaks those were obtained from standard solution and resolution of more than 2.0 was obtained between two closely eluting peaks which meet the acceptance criteria. Typical Chromatograms for Specificity is shown in figure 2.
System precision
The system precision has been determined by injecting the six replicate injections of the standard solution respectively and analyzed as per ICH guidelines. The precision of the system is expressed in terms of % RSD. The RSD was found out to be less than 10 %. A typical overlay chromatogram for System precision is shown in figure 3.
Precision Method
Table 2 shows method precision data for three OVI’S. The method precision is shown in terms of % RSD. The precision method was demonstrated by separately analyzing of sample six preparations as per the method. RSD was found to be less than 10. Typical overlay chromatogram for Method precision is shown in figure 4.
Linearity (Low level) for LOD and LOQ
Linearity of the technique which was proposed is found out over 1-10 % concentration range for three organic volatile impurities. At each level two replicates have been conducted. The correlation coefficient (R2), LOD, SLOPE, LOQ, and STEYX have been measured by this data and the results are have been recorded. Tables 3 contain the linearity data for three organic volatile impurities. Correlation graph for three OVI’S is shown in figure 5.
Linearity with LOQ
Linearity has been measured by injection of each organic volatile impurity over 50-150 % range and LOQ level. Two replicates were varied out at every level. By averaging the peak area ratio of these two replicates we obtain calibration curves. The correlation coefficient values (r2) of all organic volatile impurities were observed to be greater than 0.99 and found that in this range the calibration curves are linear.
LOD and LOQ
Table 4 shows the LOD and LOQ data of OVI’S. The Limit of Detection and the Limit of Quantification for the method proposed have been measured by using calibration standards and calculations were done using respectively by 3.3 σ /s and 10 σ/s formulae, in which 's' indicates slope of the calibration curve and 'σ' indicates the standard deviation of y-intercept. Typical LOD and LOQ Chromatograms for three OVI'S is shown in figure 6.
The System precision at LOQ
This method's system precision has been shown in terms of % RSD. At the LOQ concentration, the system precision at LOQ concentration was denoted with six replicate injections of the standard solution. The percentage RSD (% RSD) is found out to be less than 10 %. A typical overlay chromatogram for LOQ precision is shown in figure 7.
Accuracy
With the application of the standard addition technique, the method accuracy has been assured. The % recovery has been measured. Mean percentage recovery of each solvent at 50 %, 100 %, 150 % and LOQ levels must not be less than 85.0 and not more than 115.0. The obtained results in this method were lain within the given limits indicate that this process is accurate. Table 5 shows accuracy data for three OVI’S.
Robustness
The study of robustness was carried by making variations that are small in parameters of this method. Changes in flow of the column (±0.4 mL/min) and the temperature of vial condition (±5°C) have been carried out. The results obtained lie within the criteria of acceptance that indicates this process is robust in the specified range. The values of % RSD are less than 10.
Ruggedness
The evaluation of the method's ruggedness was carried out by doing analysis of the sample in six replicates by various analysts on various days. The obtained results lie within the limit of criteria of acceptance which indicates that the process is rugged in the given range. The values of % RSD are less than 10.0. Table 6 shows the ruggedness data for three OVI’S.
Application of the proposed method (Analysis of Telmisartan tablet)
The method proposed has been evaluated by commercially available Telmisartan tablet for quantification of organic volatile impurities present in this. Results obtained for organic volatile impurities have been compared with specified limits of given guidelines and are recorded. It shows the concentrations of organic volatile impurities in Telmisartan tablet in ppm which was less than the limit specified.
Solution stability
The six organic volatile impurities standard and Telmisartan API sample solutions were prepared in Dimethyl sulfoxide as a diluent. So we have to check whether these standard and sample solutions are stable or not. To prepare the standard and sample solutions for Three-time intervals (Initial hours, after 12 h and after 24 h) on the first day and kept at room temperature. These solutions are injected at Initial hours, after 12 hours and after 24 h. Then, we calculated the percentage of solution stability for the area at each time interval. We got a % of solution stability is 100±5%. Based on these data, six organic volatile impurities standard and Telmisartan API solutions were stable up to 24 h. Table 7 shows the solution stability data for three OVI’S.
CONCLUSION
The HS-GC method which is single, rapid and highly selective one has been developed and validation was carried out for the quantification of three organic volatile impurities present in Telmisartan API with the knowledge of the synthetic process, solvents nature, and kind of column stationary phase. The process that has been developed has to evaluate the reliability and the economical result in the determination of Methanol, Acetone and n-Butanol as organic volatile impurities present in Telmisartan. The results obtained in different validation parameters shows that this process is Specific, Limit of Detection, System Suitability, Limit of Quantification, and Accurate (% of recovery studies) as per the guidelines of ICH. The process was found to be applicable for the routine analysis of the Telmisartan API and its pharmaceutical dosage forms in pharmaceutical industry.
ACKNOWLEDGEMENT
Dr. K. Prasada Rao supervised the manuscript preparation and reviewed the manuscript. I am grateful to the college management and faculty of the department for their support in completing my work.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interests regarding the publication of this article.
Funding: NIL
Author’s Contribution: First author has developed methods and validated the proposed methods. Second author guided in entire work.
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