Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcareSituational Analysis of WASH Facilities in Maternity Units of a District of Central India     English0107Pal REnglish Shukla AEnglish Galhotra AEnglish Gaikwad UEnglishIntroduction: Pregnancy and childbirth remain to be one of the leading factors of mortality worldwide, among women of reproductive age despite the advancement of modern medicine. As per current situation of LMICs it is found only 50% deliveries are safe. The reason is minimal improvement is done for awareness and hence adherence to the given guidelines. Many of these service-providing facilities, do not have enough of trained health workers. Aims: To investigate the Infection Prevention Control practices & policy in the maternity units in Raipur districts. Methodology: A cross-sectional study was carried out that utilized quantitative methods to collect data from secondary and tertiary care of Raipur district from June 2019 to November 2019. Results: Training in Infection prevention control for healthcare providers and non-medical staff was reported by 66.7% & 55.6%. Proper Personal protective equipment are worn by staff in all healthcare facilities. Syringes and gloves used once in all delivery units, Standard color coded waste bins were kept in all delivery units. During discharge women are given advice regarding dangerous sign for which they should seek treatment in all healthcare facilities and in majority oral instruction. Standard IPC was observed in six of nine HCFs. Staff vaccination was reported in eight of nine HCFs. Conclusions: There is a need to dedicate more resources to the provision of monitoring of IPC in the labor rooms to further reduce the mortality in mother and neonate. Although, training and retraining of staff towards various aspects of WASH is critical; it is of utmost importance that IPC practices & infrastructure facilities be improved upon in all HCFs. EnglishIntroduction: Pregnancy and childbirth remain to be one of the leading factors of mortality worldwide, among women of reproductive age despite the advancement of modern medicine.1The question of safe motherhood has been widely recognized as an issue of social inequity and is not merely a public health concern anymore.2,3 The target to reduce the maternal mortality ratio (MMR) to less than 70 per 100,000 live births by 2030 and to provide universal access to reproductive healthcare globally has been mentioned under the Sustainable Development Goals (SDGs), however, India remains to be the second-highest contributor worldwide, when it comes to maternal deaths.4 There has been a decline of approximately 4.6% in the Maternal Mortality Ratio (MMR).5 India has improved much and is on the path to achieve its SDG goal no 3 by reducing MMR to 113 Per 100,000 in 2016-2018 from 122 in 2015-17 and 130 in 2014-2016.6 Genital tract infections and sepsis can be contracted due to poor sanitation of hand, unhygienic and contaminated surfaces, where the deliveries have taken place and it contributes to eight percent of the postpartum deaths. With the help of the Janani Shishu Suraksha Yojana (JSSY) establishment, safe deliveries have popped up by improving the hygiene standards and practices in the healthcare facilities (HCFs). These practices will help in stepping toward the change and in reducing the maternal & neonatal mortality and morbidity statistics.7 Approximately 10.7% of postpartum, neonatal mortality, and morbidity is still related to sepsis.8  Up to 70% of deliveries in Chhattisgarh state take place in HCFs and it has increased the pressure on the facilities, which has impacted both the quality of the care provided and the birth environment; in terms of infection, prevention, and control (IPC) and HCAIs.9 As per the current situation of LMICs it is found only 50% of deliveries are safe if we draw comparison with the WASH and IPC standard guidelines. The reason is minimal improvement is done for awareness and hence adherence to the given guidelines.10 Many of these service-providing facilities, do not have enough of trained health workers and neither do they have the capacity to cope up with the increased demand of the service. Hence, the health of the mother and her child is ignored, leading to a rise in infection-related deaths of the mothers and their babies.11 There are not many studies to prove the relation between safe institutional deliveries in LMICs, IPC, and infections in mothers and babies. But, there are numerous facts suggesting that the lack of sanitation, WASH, and IPC have an adverse effect on the health of the mothers and their babies.12,13 The State Government and other key supporting divisions in the state are supportive of a focus on infection control, and the work fits in with a state-level initiative for a hospital accreditation scheme, which requires the guidelines and standards to be met on various aspects of health service provision. As the State does not have a plan and guidelines for controlling the infection and infectious disease of its own, the guidelines used for this study were based on the principles of the World Health Organization’s Global Patient Safety Challenge. This effort on the healthcare-associated infections, provides guidelines for clean practices, clean equipment, a clean environment, and the availability of diagnostics and treatment.14 We hope that the conclusion of this research will provide an insight into specific areas lacking infection, prevention, control practices, water availability, newborn & postpartum care thereby improving subsequent interventions to reduce the rate of infections and associated Infant & maternal mortality. Materials & Methods: Study settings & design: A cross-sectional study was carried out that utilized quantitative methods to collect data from secondary and tertiary care of Raipur district from June 2019 to November 2019. Raipur district is divided into four blocks. The study was restricted to the all Maternity units of all the 8 Community Health Centres (CHC) and 1 District hospital (DH) of Raipur district. The permission from Chief Medical & health officer (CMHO) of Raipur district was taken for data collection and the list of Block Medical Officers (BMOs) along with their phone numbers was obtained from the CMHO office. A suitable day & time along with their consent was agreed upon for the data collection. The data collection was done, using a Semi-structured questionnaire to assess the Infection Prevention Control Practices & policy in these maternity units. In charge of the maternity unit (i.e., Staff nurse) and cleaners were also interviewed. Specific objectives of the data collection tool are shown in Figure no 1: It can be observed from table no 1 that the Orientation program had information on IPC for new Healthcare providers and was conducted in four of the nine HCFs.  Training in IPC for all the HCP were given in six of the nine HCFs. There is also a training program in IPC for non-medical staff (maintenance, cleaning, and kitchen staff), which were given in five out of nine HCFs. From Table no 2 shown that practice of disinfecting the premises is performed routinely, and walls and ceilings are cleaned and sanitized regularly in 8/9 (88.9%) of the healthcare facilities. Regular OT fumigation practices are performed in 3/9 (33.3%) of healthcare facilities, and segregation of soiled linen contaminated with blood practices are routinely performed in 5/9 (55.6%) of the healthcare facilities. Personal protective equipment such as caps and masks are worn by staff in all the healthcare facilities studied. The practice of changing dress and footwear is routinely performed in all of these healthcare facilities. Dusting and sanitizing doors, door handles of delivery unit & OT, is also practiced by all these healthcare facilities. Disinfection using UV lamps was not performed in any of the healthcare facilities. 4/9(44.4%) of Healthcare facilities were using a cloth mop, 3/9(33.3%) were using Jute mop and 2/9(22.2%) are using a ready-to-use mop for the cleaning of Delivery unit premises. Separate Mop for different departments is available in 7/9(77.8%) healthcare facilities and Mops were changed as per the requirement in 5/9(55.6%) of healthcare facilities. As shown in Figure no 2. It was observed that needles, syringes & gloves used in the delivery unit were used only once in all of the healthcare facilities. Contracted disposal of contaminated waste is a practice in 7/9 (77.8%) healthcare facilities, 2/9(22.2%) healthcare facilities practice disposal in the hospital campus in a specific waste disposal area. Sharp disposal boxes & Standard color-coded waste bins are kept in the delivery unit of all the healthcare facilities. Contaminated waste is stored separately from routine waste in the delivery unit of all these healthcare facilities (100%) shown in Figure no 3. Patient practices in the delivery units were not good. No routine cleansing of perineum is done in 8/9(88.9%) facilities. Betadine 8/9(88.9%) prior to clamping and cutting of the umbilical cord, is routinely used in all of these healthcare facilities. Prophylactic antibiotics are used in delivery units (Table no 3), irrespective of indication was observed in 4/9(44.4%) healthcare facilities. Another indication used of prophylactic antibiotics in labor with spontaneous rupture of membranes four hours or more, no fever or other signs of infection in labor with rupture of the membrane was observed in 3/9(33.3%) healthcare facilities. In addition, prophylactic antibiotics was also used in the Elective and emergency C section in 1/9(11.1%) healthcare facilities Gloves are always worn for vaginal exams & deliveries in all these healthcare facilities and gloves were changed after examining the patient. Overall, the average length of stay for normal delivery is more than 24 hours and the average length of stay for an emergency C section is more than 4 days in 3/9(33.3%) healthcare facilities. In all the healthcare facilities, patients are advised regarding the alarming signs for which they should seek treatment during their discharge. The verbal instruction is given in 8/9 (88.9%) along with the written instruction from 1/9 (11.1%) healthcare facilities.(Figure 4) Usage of Sterile clamps is routinely practiced and disposable cord clamps are used in all the healthcare facilities. In 3/9(33.3%) of the healthcare facilities, a blade is used only once to cut the cord and the newborn is cleaned after the delivery in all of these healthcare facilities. The type of cleaning material used for cleaning the newborn baby was sterile and the towel is reusable in 4/9 (44.4%). The cloth brought by the patient is used in 5/9(55.6%) healthcare facilities. 4/9(44.4%) Hospitals provide sanitary pads free of cost after the delivery and the Disposable sanitary pads used by the women after the delivery is 4/9(44.4%), sterile cloth pads is 1/9 (11.1%) and the Cloth pads brought by the patients is 4/9(44.4%). One of the healthcare facilities provides JSSK (Janani Shishu Suraksha Karyakram) kits which include sanitary pads, towels, Protein powder, Multi-vitamin drops, iron, and calcium tablets. Separate wards for the mother or the newborn with infections are available in 2/9(22.2%) healthcare facilities and designated staff for these wards in 1/9(11.1%). Table no 4. Summary of Quantitative findings related to key IPC policies and procedures, training to the Healthcare providers.  Availability of policies and procedures in the delivery unit shows that the Standard IPC, Decontamination of body fluids, Microbiological surveillance for LR policies and procedures is at 6/9 HCFs, Hand-washing protocols are in place for 8/9 HCFs, and a protocol for Sterilization, sharps disposal, waste disposal is in place at 7/9 HCFs. Microbiological surveillance for OT policies is available at 4/9 HCFs and changing of the mops and buckets policies is not available in any of the HCFs. Specific personnel responsible for looking after infection controls is present in 6/9 HCFs, personnel responsible for IPC such as Staff Nurse, Labor room in-charge, Block Program Manager (BPM), Lab assistant is present in six HCFs. It was reported that five HCFs had a Formal/Informal Infection control committee and a monthly meeting of infection control committee was reported in only one HCFs. There is also a provision for staff vaccination as a preventive measure in 8/9 HCFs and the vaccination for Hepatitis B, TT, Flu is provided to the staff.  Discussion: Patient safety and infection control is a very challenging issue and it's very complex when it comes to the Labor room, given the critical nature of the healthcare services being delivered. The Janani Suraksha Yojana Program implementation in Chhattisgarh had a huge spike in Institutional deliveries. The high case load of maternal care services in Chhattisgarh, highlights the importance of improving the quality of care in health facilities. One of the markers of quality care is the prevention and treatment of infections, so the focus on infection control during the provision of maternity services is of utmost priority to achieve India’s SDG goal of number 3. Common issues of IPC include Microbiological Surveillance of OT, policies were absent in the majority of the healthcare facilities, A study done in Gujarat state on Infection Control in labor and delivery units in Gujarat state, India reported significant shortcomings in the current practices and procedures. For example, a standard IC procedure was only available in 5% of facili­ties. Another study from LMIC countries shows that 74% lack guidelines for standard precautions.15 Reuse of surgical gloves for vaginal examinations in the labor room was commonly practiced in over 70% of facilities and in only 15% of facilities cleaning of surfaces was done immediately after each delivery.16Changing of Mops and Buckets policies is absent in all the healthcare facilities. Other gaps are identified, formal/informal infection control committees are present in half of the healthcare facilities & Mops are changed in the labor room as per the requirements observed in the majority. Antibiotics are widely and irrationally used and the assessment presented here offers evidence about the actual conditions and need for improvement in the IPC.  Conclusion: There is a need to dedicate more resources to the provision of monitoring of IPC in the labor rooms to further reduce the mortality in mothers and neonates. Although, Training and retraining of staff in various aspects of WASH is critical. It is of utmost importance that IPC practices & infrastructure facilities be improved upon in all HCFs. Limitation: The selection of sites is limited to the Raipur district only and does not generalized to entire HCFs in Chhattisgarh. Additional studies are needed. Due to logistics and financial constraint, it was not feasible to cover all the healthcare facilities and that’s the reason for its restriction to the Maternity units of all CHC & DH. Funding: Non-funded Conflict of Interest: There is no conflict of interest Author Contribution: Dr Rahul Pal (Conceptualization, Manuscript preparation, Data collection, Design, Literature search) Dr Arvind Shukla (Data analysis, Design, Manuscript Preparation) Dr Abhiruchi Galhotra (Conceptualization, Design, Manuscript review) Dr Ujjwala Gaikwad (Manuscript review and preparation) Englishhttp://ijcrr.com/abstract.php?article_id=4317http://ijcrr.com/article_html.php?did=4317 Alkema L, Chou D, Hogan D, Zhang S, Moller AB, Gemmill A, et al. Global, regional, and national levels and trends in maternal mortality between 1990 and 2015, with scenario-based projections to 2030: a systematic analysis by the UN Maternal Mortality Estimation Inter-Agency Group. The lancet. 2016 Jan 30;387(10017):462-74. Rosenfield A, Maine D. Maternal mortality-a neglected tragedy: Where is the M in MCH. The Lancet. 1985 Jul 13;326(8446):83-5. World Health Organization. Reduction of maternal mortality: a joint WHO/UNFPA/UNICEF/World Bank statement. World Health Organization; 1999.  World Health Organisation. MDG 5:Improve maternal health Geneva, 2015. Available: https://www. who. int/ topics/ millennium_development_ goals/ maternal_ health/ en/ [Accessed 07 Feb 2020].) World Health Organization. Trends in maternal mortality: 1990-2015: estimates from WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division. World Health Organization; 2015 MMR bulletin- 2016-2018. Special Bulletin on Maternal Mortality in India 2016-18 Sample Registration System, Office of Registrar General, India. Available from: https://censusindia.gov.in/vital_statistics/SRS_Bulletins/MMR%20Bulletin%202016-18.pdf. Accessed on 4 January 2021. Water Aid. Assessments of WASH in Healthcare Facilities in India. 2016; Available from: https://www.worldpulse.com/en/system/files/post/37271/73425/post_document/68cf2fe4389c3733ff13f377b4172fcf/introduction-1_1.pdf Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J, Gülmezoglu AM, Temmerman M, Alkema L. Global causes of maternal death: a WHO systematic analysis. The Lancet global health. 2014 Jun 1;2(6):e323-33. National Family Health Survey (NFHS 4) 2015-16: Factsheets India and 29 states- (2017) Government of India- Ministry of Health and Family Welfare, Mumbai International Institute for Population Sciences. Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C, Heuton KR, et al. Global, regional, and national levels and causes of maternal mortality during 1990_2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014; 384: 956. Hussein J, Mavalankar D, Sharma S, D’Ambruoso L. A review of health system infection control measures in developing countries: what can be learned to reduce maternal mortality. Global Health 2011; 7: 14. Campbell O, Benova L, Gon G, Afsana K, Cumming O. Getting the basics right _ the role of water, sanitation, and hygiene in maternal and reproductive health: a conceptual framework. Trop Med Int Health 2015; 20: 252_67. WHO. WHO / UNICEF Report: ?World Health Organization. WASH in health care facilities: global baseline report 2019.Available from: www.who.int/water_sanitation_health/publications/ wash-in-health-care-facilities/en Pittet D, Allegranzi B, Storr J, Donaldson L: `Clean care is safer care’: the global patient safety challenge 2005-2006. Int. J. Infect. Dis. 2006, 10(6):419-424. Cronk R, Bartram J. Environmental conditions in health care facilities in low-and middle-income countries: coverage and inequalities. Int. J. Hyg. Environ. Health. 2018 Apr 1;221(3):409-22. Mehta R, Mavalankar DV, Ramani KV, Sharma S, Hussein J. Infection control in delivery care units, Gujarat state, India: A needs assessment. BMC Pregnancy and Childbirth. 2011 Dec;11(1):1-8.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcareGeospatial Mapping of Genetic Diseases in the Southern Karnataka, India: A Novel Approach in Medical Technology     English0816Mohandas AparnaEnglish Kumar Sunil DEnglish Bhat DeepaEnglish Murthy Narayana MREnglish Gopi ArunEnglishIntroduction: India records almost all known genetic disease, however surveillance activities and services are limited. Geographical information system (GIS) can act as a useful tool for surveillance. Aims: The aim of the study was to assess the geospatial distribution of genetic diseases in Southern Karnataka, India and to describe their clinico-epidemiological profile. Methodology: A cross-sectional study was conducted among 101 genetic disease patients attending the Genetic clinic of a tertiary care hospital. Data regarding the socio-demographic and clinico-epidemiological profile of the patients were collected using a semi-structured questionnaire. The geographical co-ordinates of the patients’ addresses were recorded. Statistical analysis was performed using SPSS Version 22 and QGIS software Version 3.16.3 “Hannover” was used to create the maps. Qualitative variables were represented using proportions. Association between qualitative variables were inferred using Chi-square test. Results: Geospatial mapping showed that functional genetic diseases were more compared to structural genetic diseases. Among the 101 patients, 66(65.34%) were males, 34(33.66%) were females and 1(0.99%) belonged to the other gender. 17.82% were born of a 2nd degree and 25.74% from a 3rd degree consanguineous marriage. 3(2.97%) of mothers were above the age of 35 years. 75(74.25%) had gene defects, 13(12.87%) had chromosomal diseases, 7(6.93%) had mitochondrial diseases and 6(5.94%) had multifactorial diseases. Conclusion: It is evident from the geospatial mapping that both structural and functional genetic diseases have a widespread distribution in the population and is no longer a “rare disease”. It is the need of the hour to expand surveillance activities. EnglishCongenital anomaly, Genetic diseases, Geographical information system, Geospatial mapping, Rare diseases, SurveillanceIntroduction Annually, 7.9 million children suffer from a grave congenital anomaly of genetic etiology which contributes to 3.3 million deaths. The major contributors of genetic diseases being a family history of such diseases, carrier state in the parents, consanguineous marriage, advanced maternal age, and maternal exposure to teratogenic drugs, radiations or chemicals, and infections like syphilis, rubella and use of recreational drugs, tobacco and alcohol.1 Chromosomal disorder add to 6% of birth defects, Down syndrome being the most common of them.1,2 The next major group are the single gene defects which account for 1 in 1000 live births, the two most predominant diseases being Sickle cell anemia and Thalassemia.3,4 It is estimated that about 5% of the global population carries trait for hemoglobin disorders and 3 to 5 lakh children who are delivered annually suffer from them.4,5 India as such has a high burden of Down syndrome, inborn errors of metabolism and hemoglobin disorders like Sickle cell anemia and Thalassemia.6 In India, Down syndrome affects 1 in every 900 children.7 As far as hemoglobin disorders are concerned, at one point of time there are about 1.5 lakh cases of Sickle cell anemia and 1 lakh cases of beta Thalassemia. It is more predominant amongst the scheduled subpopulation of the country, the prevalence of Thalassemia ranging between 4-17% amongst them.4 Another important group are the inborn errors of metabolism and in India, 5-15% of newborns, yearly, suffer from these. Newborn screening is a simple method of identifying the affected children to initiate early treatment and to prevent disabilities and also to offer prenatal diagnosis in the future pregnancies, however the services offered in India are limited.8  Over the years, the burden of genetic diseases has increased, also the advancement in various dimensions has increased survival, adding on to the morbidity and impairment due to genetic diseases. While some countries, like in the United Kingdom have already incorporated neonatal and antenatal screening for hereditary diseases in their health system, the economically backward countries which contribute to nearly 94% of the infants with genetic defects, lack in public health policies for care and prevention of genetic diseases.9 Reducing the burden of genetic diseases should begin with active and passive surveillance in the community and at the hospital setting with the partnership of laboratories and research institutes. This shall help to lay the foundation by assessing the burden and trends in various geographic locations across the country. It is high time that genetic screening and counseling be incorporated into the existing health care delivery system. Expansion of diagnostics with adequate treatment and rehabilitative services also becomes a prerequisite.10,11 Geographical information system (GIS) is a tool that combines spatial information with attributable data and assembles them as layers. GIS helps to build up these layers into visualizations using maps, which reveal patterns and relationships between spatial data and attribute data.12 With regard to genetic diseases, GIS can be used to investigate the spatial form of distribution of these diseases and the associated spatial determinants which can play an important role in estimating the prevalence of genetic diseases across the country and also assessing the gaps in the existing service delivery system.13 With this background, the present study was conducted to assess the geospatial distribution of genetic diseases in Southern Karnataka, India and to describe their clinico-epidemiological profile. Materials and Methods Study design and population This cross-sectional study was conducted for one and half years from January 2019 to July 2020 among patients attending the genetic clinic of a tertiary care hospital, in Southern Karnataka, India. Consecutive sampling was used to select the participants. Participants with genetic diseases who were willing to participate in the study were included and those who were not confirmed as having genetic diseases by laboratory diagnosis were excluded from the study. Ethical statement The study was commenced after presenting the protocol and obtaining ethical clearance from the institutional ethics committee. IEC NO: JSS/MC/PG/4623/2018-19 Before beginning the collection of data, the study details were explained to the patients or parents as relevant. Verbal assent was taken from children below 18 years and written informed consent was taken from parents/patients as appropriate. Data collection Data was collected by interview method using a semi-structured questionnaire regarding the sociodemographic factors (age, gender, religion, address, occupation, type of family) and family history, previous obstetric history and antenatal history. Relevant birth history, clinical and investigation history and diagnosis of the patient was recorded. Final diagnosis of the patient was obtained and categorized as a structural or functional genetic disease. Structural diseases- Refers to defects in body structure including skeletal system and organs. It includes external as well as internal defects. Includes neural tube defects, cleft lip, cleft palate, congenital heart diseases, Down syndrome, Edward syndrome, cystic kidney disease, skeletal and limb deformities and indeterminate sex. Functional diseases- Functional defects in the neurological, muscular immunological or endocrine system. Includes metabolic disorders, cystic fibrosis, muscular dystrophy, behavioral disorders and neurological disorders.14 Statistical analysis Data was entered into Microsoft Excel 2013 spreadsheet and analyzed using SPSS V.22 (Licensed to JSS AHER). Qualitative variables like gender, religion, place of residence, etc. were represented using proportions. Association between qualitative variables was inferred using the Chi-square test. A p value less than 0.05 was considered statistically significant. Geospatial analysis Freely accessible online sources were used to geocode the address of the study participants. The latitude and longitude were entered in Microsoft Excel and converted into CSV file (comma separated values) and exported into a free and open-source software version QGIS 3.16.3 “Hannover” (released on 15.01.2021) to create maps. Results Figure 1, depicts the map of southern Karnataka, India and the distribution of the study participants based on gender. The majority were males in the present study. Among the 101 study participants, the majority of the parents gave a history of non-consanguineous marriage (Figure 2). Figure 3, gives the classification of study participants based on the type of genetic diseases. In the study, functional genetic diseases were more, compared to structural genetic diseases. Among the 101 study participants, 10(9.9%) were below 6 months, 40(39.60%) were between the age of 6 months to 1 year, 21(20.79%) were between 1 to 5 years, 13(12.87%) were between 5 to 10 years and 17(16.83%) were above the age of 10 years. 3(2.97%) of the mothers were above the age of 35 years at the time of conception. Among the 101 genetic disease patients, 56.43% were born of a non-consanguineous marriage, while 18.81% and 24.75% were born of a 2nd and 3rd degree consanguineous marriage, respectively. Among the mothers, 27.72% gave a history of previous abortions/neonatal death/stillbirths while 72.27% did not have such a history. 2(1.98%) of the mothers gave a history of fever during pregnancy. 73(72.27%) of the participants were of normal birth weight while 28(27.73%) had low birth weight. 89.10% of the study participants were term babies and 10.89% were preterm babies. In 11.88% of the cases, siblings had similar diseases. In the 101 study participants, 65(64.35%) had functional genetic diseases and 36(35.64%) had structural genetic diseases (Table 1). On the classification of genetic diseases, 75(74.25%) had gene defects, 13(12.87%) had chromosomal diseases, of which Down syndrome (9.9%) was the majority, 7(6.93%) had mitochondrial diseases and 6(5.94%) had multifactorial diseases (Table 2). Table 3, represents the association between socio-demographic and clinical-epidemiological factors with genetic diseases. There was a significant association between gender and socioeconomic class with genetic diseases. 3 (2.97%) of the mothers were above the age of 35 years and all of them had children with structural anomalies. There was a significant association between maternal age at conception and paternal medical conditions with genetic diseases in the children. 3(2.97%) of fathers had Diabetes Mellitus and they had children with structural anomalies. Discussion Geocoding is an important GIS tool used in public health for surveillance activities.15 Disease surveillance tracks data related to the incidence/ prevalence of the disease, its spread and possible risk factors which shall give the pattern and trend of the disease.16 In the present study, the locations of the patients were mapped. Functional genetic diseases accounted for the majority compared to structural genetic diseases. It is evident from the visualization that genetic diseases are not ‘rare’ as thought to be earlier, but rather have a widespread distribution across the population. GIS has an important role in scenarios wherein it can be utilized to study the distribution of genetic diseases, associated gene mutations and their trend over the years. This shall help to identify cluster areas as well as develop causal relationships.17In the study we have considered all genetic diseases, and it would require disease-specific genetic studies to make such conclusions. Among 101 study participants, 65.34% were males, 33.66% were females and 1(0.99%) belonged to another gender. Similar findings were reported by Lavanya et al. and Jayasree et al.. in institutional-based studies in south India. It is suggested that females are affected more with lethal defects and cannot survive till term gestation.18,19 Genetic diseases were more among the lower socioeconomic class in our study. This can be attributed to the predominance of consanguineous marriage and poor maternal health, added with higher exposure to environmental risk factors among them.1,20 In the present study 97.02% of the mothers were below the age of 35 years at conception. The majority of the studies suggest the same, bulk of genetic diseases are reported among mothers less than 35 years, owing to the fact that in India, major proportion of deliveries take place before the mother reaches 35 years.18,19 However among the 3% mothers above the age of 35 years, all had children with structural anomalies. This is consistent with the findings that advanced maternal age is associated with a higher risk of chromosomal abnormalities.1 Among 101 study participants, the majority were born out of non-consanguineous marriage. Structural and functional genetic disease proportions were similar in non-consanguineous and consanguineous marriages. Jayasree et al. reported that only 1% of children with congenital anomalies were born out of a consanguineous marriage.19 Rama devi et al. suggest that in the background of various other environmental factors contributing to the burden of genetic diseases, the role of consanguinity may have been masked.20 27.72% of the mothers in our study gave a history of previous abortion/neonatal deaths and stillbirths. Jayasree et al. in a study in Kerala reported that 25.1% of the women who gave birth to a child with congenital anomaly had a previous history of abortions or intrauterine deaths (IUD) or neonatal deaths.19 This can be due to the fact that many genetic diseases are lethal and cause fetal death and hence women with bad obstetric history are at higher risk.21 In our study, 2.97% of fathers had Diabetes Mellitus and all of these children had structural genetic diseases. However, Mills et al. reported that children born to diabetic fathers had the same risk of developing malformations compared to non-diabetic fathers.22 11.88% of the cases had similar conditions in the sibling. El Kowmi et al. reported that 6% of the affected children in their study had a history of an anomaly in the family, signifying that genetic diseases tend to recur and requires evaluation so as to prevent the same conditions in future pregnancies.23 In the present study, 12.87% had chromosomal abnormalities, 74.25% had single gene defects, 6.93% had mitochondrial diseases and 5.94% had multifactorial diseases. Rama devi et al. in a study in Karnataka reported the prevalence of single-gene disorders to be higher followed by multifactorial disorders.20 The most common chromosomal abnormality in our study was Down syndrome (9.9%). Similar findings were reported by Kaur et al., where the prevalence was 11% and Wojnik et al. who reported a prevalence of 30% among chromosomal disorders.24,25 Among the single-gene disorders, the most common were the inborn errors of metabolism-organic acidemia (12.87%) and Lysosomal storage disorders (8.91%). Similar findings were quoted by Verma et al. from a multi-center study where the prevalence of organic acidurias were maximum (27.5%).21 The proportion of Duchenne muscular dystrophy was 5.94% and other common dystrophy was Limb-girdle musculodystrophy (1.98%) in this study. 2.97% had spinal muscular atrophy. Kaur et al. reported an overall proportion of muscular dystrophies to be 0.8% and Wojnik et al. reported the prevalence of spinal muscular atrophies to be 16% which is quite higher compared to our study, probably because of the difference in size of the sample and study setting.24,25 1.98% of study participants had sickle cell anemia and Thalassemia in this study. The prevalence of the Beta-Thalassemia trait being 3-4% and Sickle cell anemia allele being 2-20% in India.6 5.94% had multifactorial diseases in our study. Verma et al. quote a prevalence of 4.64%. The most common ones being cleft lip/cleft palate and multiple anomalies.21 Kaur et al. reported a proportion of 0.1% in her study while Rama devi et al. reported 2 in 12 cases of polygenic inheritance for cleft lip/cleft palate.20,24 Limitations Since this was a hospital-based study, the address provided by the patients were used for geocoding their locations and we could not confirm their accuracy of it. The sample was limited, hence we have given proportions for the various parameters assessed. It would require a community-based study to assess the prevalence of genetic diseases. Conclusion It is evident from the geospatial mapping that both structural and functional genetic diseases have a widespread distribution in the population and is no longer a “rare disease” as described earlier. Genetic diseases being a rising cause of childhood morbidity and mortality in India, it is the need of the hour to expand surveillance activities, incorporate newborn screening into the routine biochemical testing and to provide adequate diagnostic services to the suspected with preventive services like carrier screening and counselling. Acknowledgement We thank the study participants and their families for their time and co-operation. Financial support None Conflict of interest None Author’s contribution Mohandas Aparna: Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing-original draft, writing-review and editing Kumar Sunil D: Conceptualization, Methodology, Supervision, Data curation, writing-review and editing Bhat Deepa: Conceptualization, Methodology, Investigation, writing-review and editing Murthy Narayana M.R: Methodology, Supervision, Data curation, writing-review and editing  Gopi Arun: Methodology, Data curation, Formal analysis, writing-review and editing Englishhttp://ijcrr.com/abstract.php?article_id=4318http://ijcrr.com/article_html.php?did=4318 Christianson A, Howson CP, Modell B. March of Dimes: global report on birth defects, the hidden toll of dying and disabled children. New York: March of Dimes Birth Defects Foundation; 2006.84p. Bhavani V, Paulose D. Spinal Anaesthesia in Down's syndrome-A Case Report. Int J Cur Res Rev 2015 May;7(9):33. National Human Genome Research Institute. Genetic Disorders [Internet]. Bethesda: National Human Genome Research Institute; [updated 2018 May 18; cited 2020 Sep 30]. Available from: https://www.genome.gov/For-Patients-and-Families/Genetic-Disorders Colah R, Italia K, Gorakshakar A. Burden of thalassemia in India: The road map for control. Pediatr Hematol Oncol J 2017 Dec;2(4):79–84. Kadri AM. Genetics and health. In: Kundapur R, Maroof A.K, editors. IAPSM’s Textbook of Community Medicine. 1st ed. Haryana: Jaypee Brothers Medical Publishers (P) Ltd; 2019. p. 836-839.  GUaRDIAN Consortium, Sivasubbu S, Scaria V. Genomics of rare genetic diseases—experiences from India. Hum Genomics 2019 Dec;13(1):1-8. Pankaj G, Avani K, Salil V. Prevalence of Down syndrome in Western India: A Cytogenetic Study. Br J Med Med Res 2015 Jan;5(10):1255–1259. Kapoor S, Thelma BK. Status of Newborn Screening and Inborn Errors of Metabolism in India. Indian J Pediatr 2018 Dec;85(12):1110–1117. World Health Organization. Congenital anomalies [Internet]. Geneva: World Health Organization; [updated 2020 Dec 1; cited 2020 Sep 30]. Available from: https://www.who.int/news-room/fact-sheets/detail/congenital-anomalies Burton H, Jackson C, Abubakar I. The impact of genomics on public health practice. Brit Med Bull 2014 Dec;112(1):37–46. Wang G, Watts C. The Role of Genetics in the Provision of Essential Public Health Services. Am J Public Health 2007 Apr;97(4):620–625. Environmental Systems Research Institute. What is GIS? [Internet]. California: Environmental Systems Research Institute; [cited 2020 Nov 19]. Available from: https://www.esri.com/en-us/what-is-gis/overview Ananth M, Rajesh R, Amjith R, AL A, Valamparampil MJ, Harikrishnan M, et al.. Contamination of household open wells in an urban area of Trivandrum, Kerala State, India: a spatial analysis of health risk using geographic information system. Environ Health Insights 2018;1-9. Birth Defect Research for Children. Structural and Functional Birth Defects [Internet]. Florida: Birth Defect Research for Children; 2020[cited 2020 Oct 27]. Available from: https://birthdefects.org/structural-and-functional-birth-defects/ Chang KT. Geocoding and Dynamic Segmentation. Introduction to geographic information systems. 9th ed. New York: McGraw-Hill Education; 2018.p.363-364. Shaw N.T, McGuire S.K. Understanding the use of geographical information systems (GISs) in health informatics research: a review. J Innov Health Inform 2017 Jun;24(2):228–233. Hockham C, Bhatt S, Colah R, Mukherjee MB, Penman BS, Gupta S, et al.. The spatial epidemiology of sickle-cell anaemia in India. Sci Rep 2018 Dec;8(1):1-10. Lavanya S, Seethalakshmi V. A two-year study of patterns and prevalence of congenital malformations. Int J Reprod Contracept Obstet Gynecol 2018;7(1):114-118. S. Jayasree, D’Couth S. Prevalence of congenital anomalies in a tertiary care centre in North Kerala, India. Int J Reprod Contracept Obstet Gynecol 2018 Mar;7(3):864-869. Devi AR, Rao NA, Bittles AH. Inbreeding and the incidence of childhood genetic disorders in Karnataka, South India. J Med Genet 1987 Jun;24(6):362–365. Verma IC, Puri RD. Global burden of genetic disease and the role of genetic screening.  Semin Fetal Neonatal Med 2015 Oct;20(5):354-363 Mills JL. Malformations in infants of diabetic mothers. Birth Defects Res A Clin Mol Teratol 2010 Oct;88(10):769–778. El Koumi MA, Al Banna EA, Lebda I. Pattern of congenital anomalies in newborn: a hospital-based study. Pediatr Rep 2013 Feb;5(1):20-23. Kaur A, Singh JR. Chromosomal Abnormalities: Genetic Disease Burden in India. Int J Hum Genet 2010 Mar;10(1 Suppl 3):1–14. Wojcik MH, Schwartz TS, Thiele KE, Paterson H, Stadelmaier R, Mullen TE, et al.. Infant mortality: the contribution of genetic disorders. J Perinatol 2019 Dec;39(12):1611–1619.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcareImpact of COVID-19 on RPE & Functional Status of Patients Using PCFS Scale: A Cross-Sectional Survey     English1722Reema JoshiEnglish Shilpa KhandareEnglish Madhuri RaiEnglish Mrunal RasaneEnglish Roopali BanerjeeEnglish Sajitha HarilalEnglish Ruturaj SalviEnglishEnglishPost COVID-19 Patients, PCFS, Functional Status,SARS-CoV-2, RPE, DyspnoeaINTRODUCTION                                                                                                                                                                                         The Novel Corona virus disease (COVID-19) is an emerging respiratory infectious disease caused by severe acute respiratory syndrome-Coronavirus-2. The SARS COV-2 is known to be the causative agent of a potentially fatal disease that is of enormous global public health concern. In December 2019, there as a cluster of pneumonia cases of unknown etiology in Wuhan, Hubei Province, China. The virus has spread globally to infect over 180 countries. SARS-CoV-2 has infected humans in all age groups, of all races, both males and females while spreading across communities at an alarming rate. The symptoms range from asymptomatic, to most common symptoms like fever, dry cough, fatigue, headache, sore throat, diarrhea, anosmia, ageusia to severe symptoms like pneumonia and acute respiratory distress syndrome.6 SARS infections have revealed a considerable impact on the respiratory system, and musculoskeletal system which includes skeletal muscle, neurological, bone, and joint disorders. Extensive ventilator use also causes elevation of cytokines and C-reactive protein (CRP) causing pro-inflammatory sequelae inducing muscle de-conditioning in the recovery period. There was a subsequent reduction in the health indices hampering the quality of life due to depletion in the functional capacity of these patients.13 The Borg Rating of Perceived Exertion (RPE) is a method of measuring physical activity intensity level. RPE is a personalized exertion grading since it gives a good estimate of heart rate during physical activity. The RPE scale runs from1-10. Physical activity and exercise is imperative in maintaining the muscle mass and to stay healthy. Impaired physical function caused by SARS-COV2 infection is multidirectional due to an extended period of immobilization leading to muscle de-conditioning and infection resulting in disturbance in mitochondrial homeostasis. Physical inactivity is correlated with deleterious effects comprising of decreased levels of aerobic performance and reduction in VO2 peak and depletion in musculoskeletal and cognitive function. It is also linked to several metabolic disturbances involving changes in Insulin signaling. This causes rise in peripheral insulin resistance and growth of inflammatory mediators along with adipose tissue lipolysis and changes in the function of mitochondria. Physical inactivity produces increased insulin sensitivity in the skeletal muscle which causes the dissemination of energy substrates to surround tissues leading to central fat accumulation.16, 17The Post COVID-19 functional status scale (PCFS) is an ordinal tool to measure the full spectrum of functional status in a recovered post-COVID-19 individual. F.A. Klok, G.J.A.M. Boon and B. Siegerink drafted the first version of the manuscript. This scale is a tool to keep a track on function independence of post-COVID patients and also can be used as a full range of functional outcomes. It focuses on constraints in day to day activities and changes in lifestyle. It comprises of 6 grades according to the functional capabilities of the individual post-recovery. The proposed “Post- COVID-19 Functional Status (PCFS) scale” could be assessed upon discharge from the hospital, at 4 and 8 weeks post-discharge to monitor direct recovery, and at 6 months to assess functional sequelae.18 Hence it is necessary to identify the magnitude of the impact of COVID- 19 infection on functional status and rate of perceived exertion in recovered post-COVID-19 patients.                                                 METHODS:                                                                                                                                                          A Cross-Sectional Study was conducted in Pune City. During the period of October 2020 till March 2021 around 500 patients, contacts were received from the COVID ward of the hospital those who were recovered 4 weeks back from COVID-19 were interviewed on the telephone and the study intention was explained about Post COVID functional status of COVID patients. Out of those who were interested were called with appointment to OPD of Dr D. Y. Patil College of Physiotherapy, Pune.  Both male and female above the age of 25 years were included whereas any patient with any acute symptoms, fever, excessive fatigue, recent injury, severe cardiovascular complications were excluded from survey.    The Borg Rating of Perceived Exertion (RPE) was used to measure the physical activity intensity level.14 RPE is a personalized exertion grading since it gives a good estimate of heart rate during physical activity. 6-minute walk test was performed and after that patient's RPE level was graded based on the Modified Borg scale grading 1-10 with 1 as “nothing”, 2 as “very easy” 3 as “Easy “,4 as “comfortable”,5 as “somewhat difficult”,6 as “difficult”,7 as “hard", 8 as "very hard",9 as “extremely hard”,10 as “maximal exhaustion” 15. All the subjects were also assessed with Hindi & English versions of Post COVID-19 Functional Status Scale (PCFS) to evaluate the magnitude of functional limitations in the recovered post-COVID-19 patients. The PCFS is an ordinal scale with kappa’s of 0.75 and 1.0 developed by Klok and his colleagues incorporating six components based on basic activities of daily living, instrumental activities of daily living, participation in social roles and symptom checklist. The functional limitations were graded according to Grade-0 (with no functional limitations), Grade 1 (with negligible functional limitations), Grade 2 (with significant functional limitations), Grade 3 (with moderate functional limitations) and Grade 4 (with severe functional limitations).               Statistical Analysis:                                                                                                                                          Data was analyzed using the statistical package SPSS 22.0 (SPSS Inc., Chicago, IL) and level of significance was set at P0.05). Statistically, significant difference was observed between the BMI categories with respect to PCFS scale where the highest mean was reported in OBESES CLASS 1(1.066) and Underweight ( 1.062) and the least mean was observed in Underweight class 1(0.375). PEnglishhttp://ijcrr.com/abstract.php?article_id=4319http://ijcrr.com/article_html.php?did=4319 Lai CC, Chih-Cheng L, Tzu-Ping S, Wen-Chien K, Hung-Jen T, Po-Ren H et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges Int. J. Antimicrob. Agents 17:105924. HuipengGe, Xiufen Wang, Xiangning Yuan, Gong Xiao, Chengzhi Wang, Tianci Deng et al.The epidemiology and clinical information about COVID-19. 2020 Apr 14:1.  Ghosh A. Srijita N, Tapas KM How India is dealing with COVID-19 pandemic. Sensors International. 2020 Jan 1; 1:100021.  Adeknule S, Chuku O, Aleksandra M, Risha P, Kokab Y, Priyank D et al. Comorbidity and its Impact on Patients with COVID-19. SN comprehensive clinical medicine. 2020 Jun 25:1-8.  Husain R, Siddappa B. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of autoimmunity. 2020 Feb 26:102433 https://www.who.int/emergencies/diseases/novel-coronavirus-2019 Bandyopadhyay D, Tauseef A, Adrija H, Manasvi G, Avash D, Sandipan C et al. COVID-19 pandemic: cardiovascular complications and future implications. Am. J. Cardiovasc.2020 Jun 23:1-4.  Shereen MA, Suliman K, Abeer K, Nadia B, Rabeea S. COVID-19 infection: Origin, transmission and characteristics of human coronaviruses. J. Adv. Res. 2020 Mar 16.  Bohn M, Hall A, Sepiashvili L, Jung B, Shannon S, Khosrow A. Pathophysiology of COVID-19: mechanisms underlying disease severity and progression. Physiology. 2020 Sep 1;35(5):288-301.  https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/what- coronavirus-does-to-the-lungs?amp=true Varkey B, Bhattacharjee S. Neurological complications with COVID-19: A contemporaneous review. Annals of Indian Academy of Neurology. 2020 Jul 1;23(4):468. Qing Ye, Wang B, Zhang T, Xu J, Shang S. The mechanism and treatment of gastrointestinal symptoms in patients with COVID-19. An J Physiol Gastrointest Liver Physiol  Aug 1;319(2): G245-52.  Disser N, Micheli A, Schenk M, Konnaris M, Piacentini A, Daniel LE et al. Musculoskeletal consequences of COVID-19. JBJS. 2020 Jul 15;102(14):1197-204. https://www.cdc.gov/physicalctivity/basics/measuring/exertion.htm       15. .https://www.nursing center.com/journalarticle?Article_ID=2695880&Issue_ID=4388241 Rooney S, Webster A, Paul L. Systematic Review of Changes and Recovery in Physical Function and Fitness after Severe Acute Respiratory Syndrome–Related Coronavirus Infection: Implications for COVID-19 Rehabilitation. Physical Therapy. 2020 Sep 28;100(10):1717-29.  Woods J, Hutchinson NT, Powers SK, Roberts WO, Gomez-Cabrera, Radak Z et al. The COVID-19 pandemic and physical activity. 2020 June 2(2) Pant P, Joshi A, Basnet B, Shrestha B, Bista N, Bam Net al. Prevalence of Functional Limitation in COVID-19 Recovered Patients Using the Post COVID-19 Functional Status Scale. JNMA 2021 Jan;59(233):7. Klok FA, Boon G, Barco S, Endres M, Geelhoed J, Knauss S et.al. The Post-COVID-19 Functional Status scale: a tool to measure functional status over time after COVID-19. Eur. Respir. J.2020 Jul 1;56(1). Sattar N, Mclnnes I, McMurray J. Obesity is a risk factor for severe COVID-19 infection: multiple potential mechanisms. Circulation. 2020 Jul 7;142(1):4-6. Mohammad S, Aziz R, Mahri S, Malik S, Haji E, Khan A et al. Obesity and COVID-19: what makes obese host so vulnerable? Immunity & Ageing. 2021 Dec; 18 (1):1-0. Taboada M, Morano E, Carinena A, Rey T, Romero R, Leal S et al. Quality of life, functional status, and persistent symptoms after intensive care of COVID-19 patients. British journal of anaesthesia. 2021 Mar 1;126(3):e110-3. Callender LA, Curran M, Bates S, Mairess M, Weigandt J, Bettes C et al. The impact of pre-existing co-morbidities and therapeutic interventions on COVID-19. Frontiers in Immunology. 2020;11. Ejaz H, Alsrhani A, Zafar A, Javed H, Junaid S, Abdalla A et al. COVID-19 and co-morbidities: Deleterious impact on infected patients. Journal of Infection and Public Health. 2020 Aug 4. Thaweerat W. Current evidence on pancreatic involvement in SARS-CoV-2 infection. Pancreatology. 2020 May 27. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? The Lancet. Respiratory Medicine. 2020 Apr;8 (4):e21.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcareCommunity Perception of Chronic Kidney Disease in Supebeda, Chhattisgarh     English2328Vinay RathoreEnglish Rahul PalEnglish Abhiruchi GalhotraEnglish Saurabh NayakEnglish SnehalataEnglish Vivekanand JhaEnglish Nitin M NagarkarEnglishIntroduction: An unusual number of Chronic kidney disease (CKD) cases have been reported from the village of Supebeda of district Gariyaband in Chhattisgarh. Recent studies have shown that the clinical profile of CKD patients in this village fits into the profile of CKD of Unknown Origin (CKDu). Objectives: We conducted this study to explore the perception of the community about CKD in Supebeda. Material & Methods: This study was undertaken as a part of the outreach initiative of the Health Department of the Government of Chhattisgarh from October 2019 to January 2020. We conducted six In-depth Interviews (IDI) on a purposive sample of CKD patients and one Focus Group Discussion (FGD) with 11 mitanins (ASHA workers). Interviews were audio-recorded and transcribed verbatim. Data was analyzed manually using discourse analysis. Results: All six respondents of IDI were farmers and had nonspecific symptoms of body aches, loss of appetite & weakness. They sought treatment from private practitioners from the nearby state of Odisha because of proximity and preferred to go to Raipur only when they needed advanced treatment. The majority of these patients had received analgesics, herbal and ayurvedic drugs from rural practitioners. The study also revealed stigmatization of the village because of this disease. The participants of FGD were of opinion that CKD in the village was due to consumption of contaminated water and that it has led to ostracization of the village and reduced opportunity to get employment for the people of Supebeda. Conclusion: We document community perception and health-seeking behavior of a remote village in Chhattisgarh state with a high prevalence of CKD. The study revealed a strong influence of socio-economic determinants, the influence of local myths, difficulties in accessing healthcare and stigma associated with kidney disease. EnglishChronic kidney diseases, Supebeda, CKDu, Perception, Community, VillageIntroduction: The public health importance of chronic kidney disease (CKD) due to its increasing burden and high cost of treatment has been recognized in recent years. The Global burden of disease study has shown that while the main drivers of CKD around the world are diabetes, hypertension and glomerular disease,1 a large proportion of CKD in low and low middle-income countries are caused by indiscriminate use of nephrotoxic drugs, herbal medications, toxins and infections. A high prevalence of CKD, primarily amongst rural communities engaged in agricultural work, has been observed in select geographical areas in several countries (El Salvador, Nicaragua, Costa Rica, Egypt, Sri Lanka and India) over the past two decades. 2 CKD in these select demographics cannot be attributed to the known/traditional risk factors. The generic term “Chronic Kidney Disease of Unknown Etiology (CKDu)” has been used to describe this entity since the early 2000s.3 In India, this condition has been described from coastal villages of the Srikakulam district in Andhra Pradesh and parts of Odisha.4 A variety of hypotheses, including prolonged dehydration leading to heat stress, heavy metal toxicity, pesticide exposure, snake bite and genetics, have been proposed.2             Recent media reports have highlighted the high burden of CKD in Supebeda village of Gariyaband district, Chhattisgarh state in central India (Figure1), with reports of many deaths since 2009. One report estimated that over 100 people out of the total population of 1182 had advanced CKD in the village.5 The issue of deaths suspected to be due to CKD in this village has been highlighted in media and has been raised in state assembly.6 A recent study has shown that the clinical profile of CKD patients in this village fits into the profile of CKDu.7The reports also talk about anxiety, fear and sense of uncertainty in the minds of people about the nature of this disease and its causative factors. With the global nephrology community increasing the focus on patient-centric approaches, this study was carried with the aim to understand the perception of the people of Supebeda regarding kidney diseases. Material &Methods: This qualitative study was conducted between October 2019 and January 2020 as a part of the outreach initiative of the Health Department of the Government of Chhattisgarh to provide support to the people affected with CKD in Supebeda. Focus group discussion (FGD) and in-depth interviews (IDI) were conducted to understand the community perspectives about the disease, its cause and its impact on people's health and livelihoods. Participants were selected using a purposive sampling method and included patients diagnosed with kidney disease, community leaders and frontline health workers (Mitanin). Semi-structured interviews were used to collect data. Initially, participants were explained the purpose of the visit. All interviews were conducted face to face. Each interview began with an open-ended question. The content of these interviews explored the causes of kidney diseases, symptoms, food habits, means of livelihood, addiction history, pesticide use, preventive and control measures of the disease, complications of the disease, health-seeking behaviour and the response of the government. The interviews were conducted in the local language (Hindi), audio recorded, and transcribed verbatim. Transcripts were checked to ensure that they did not contain any mistakes. The transcripts in Hindi were subsequently translated into English by bilingual interviewers and reviewed by the research team. The data was analyzed manually (as the small number of transcripts did not require qualitative data analysis software), using the discourse analysis, which involves naturally occurring talks and all types of written texts. The themes identified are mentioned in table 1 Results: A total of six IDIs were conducted with six patients with CKD (5 males and one female) and a focus group discussion was conducted with 11 Mitanins. In-depth Interview: The findings of IDI are summarized in tables 1 and 2. The interviews revealed that all the respondents perceived that CKD is caused due to contaminated water. All the respondents were of the opinion that the village faces stigmatization because of media highlights. We describe the perception of one of the patients as narrated.             “Sir, the main problem of kidney diseases is due to contaminated water and media highlight has led to stigmatization of village. People of other villages are afraid of marrying their sons and daughters due to stigma of kidney disease in the village.”  (CKD patient in his 50s) Most of the patients had nonspecific symptoms like loss of appetite, weakness and body aches. “I have had regular body aches, and itching all over the body, for almost a year” (A male CKD patient in his 40s) “I have loss of appetite, episodes of vomiting & fatigue most of the time” (A female patient of CKD in her 40s). “ Most of the respondents were regular consumers of tobacco, while some gave a history of frequent consumption of locally distilled alcohol. “I have been chewing gudakhu for last 20-25 years”. (A CKD patient in his 60s) “I have been smoking bidi and sometimes drink locally brewed alcohol but now quit alcohol for last three months” (A CKD patient in his 30s). “ All respondents were farmers by occupation. Most of them were not able to work because of the illness. Many patients used analgesics for body aches.  “I am not working due to my illness, previously worked as a farmer for 15 years (A male CKD patient in his 50s) Most of the respondents took herbal medications and ayurvedic drugs from local practitioners since the nearest medical facility is quite far.  Some patients took treatment from the local community health centre. For specialized care, including dialysis, they travelled to the hospitals in Raipur, the state capital. “I had been taking treatment from the hospital at Dharamgarh because the distance was hardly 2 km from Supebeda (A CKD patient in mid 50s.) (Dharamgarh is a town located in Odisha)” “I went to Ramkrishna hospital (private hospital in Raipur) 250 km from our village because it requires dialysis. There is no facility of dialysis nearby and the dialysis machine at CHC, Deobhog, is not working.”(A female patient in her 40s requiring dialysis). Focus group discussion findings: The key issues discussed were sorted into three major themes of interest: Food and water, health-seeking behaviour and occupation. Food and water: The participants were of the firm belief that kidney damage is because of the consumption of contaminated drinking water sourced from borewells. They felt it might be contaminated because they perceived its taste to be somewhat different, almost metallic. People felt that water should be drawn from a river close by – the ‘Tel River’ which contained 'pure water’. They also believed that the Alexandrite mine located near the village might also be responsible for kidney disease. Some unique eating habits were reported; breakfast generally consisted of a sweet dish (gulgula) in the morning. The previous day's cooked rice soaked in plain water overnight, known locally as "Maadh” was alsotaken as a meal. Occupation: About two-thirds of the population of the village depend on agriculture or cattle grazing. A majority of people worked as unskilled farm labourers for daily wages. However, an increasing number were not able to work due to illness and were busy seeking treatment. Health-seeking behaviour: Most of the villagers prefer going to private physicians in a nearby town, which is in a different state, Odisha. They did not see a reason to seek care in the state public health system because the closest facility was quite far – they would need to spend more time and money to get there. They often sought prescriptions for over-the-counter analgesics for body aches that would develop as a result of heavy manual labour. Interruptions in treatment were common, both because of temporary relief in symptoms and the high cost of treatment. They would take some ayurvedic medicines from local health practitioners. Several myths were prevalent – for example, pregnant women did not take folic acid and iron supplements, as it was perceived that these lead to big babies. They thought that a bigger-sized baby might create difficulties for normal delivery. They pointed out that the water plant (fluoride-free water) set up by the state government two years ago was often not working because of a series of technical issues. The villagers narrated several social problems, including ostracization of the village and reduced opportunity to get employment that involved manual labour. Interestingly, kidney disease was perceived to affect the 'marriage ability’ of the local population, as families from outside the village were unwilling to enter into a matrimonial relationship with local residents because of perceived health issues. Discussion: Through this qualitative study, we describe the perception of the community of village Supebeda regarding the growing burden of CKD in the village and understand the health-seeking behaviour. Most of the reported issues were related to lack of access to essential needs – like clean drinking water, secure employment and essential healthcare. We confirmed the presence of social practices that give insights to their perceptions and health-seeking behaviour. A majority of the patients belonged to the agricultural occupation- they are directly exposed to chemical pesticides.  Our findings suggest that while some patients raised serious concerns about the rising burden of CKD in the communities, the majority had a lack of awareness of its risk factors and adverse consequences. Although there was a strong suggestion that they blamed poor groundwater quality or local mining activity when asked for the basis, they were unable to provide supporting arguments. Studies from other regions of the world have reported poor knowledge and awareness of CKD amongst healthcare providers and patients, which aligns with our findings.9-11 Our findings also identify the major impact of socio-economic determinants on health-seeking behaviour and reasons for the delay in seeking medical advice. Lack of public health facilities nearby, the high cost of travel and treatment combined with the loss of income related to taking time off for medical treatment came out as important reasons for delayed diagnosis. Interruptions in treatment due to financial reasons and misperception that lack of symptoms indicate the absence of disease may also contribute to disease progression. The stigma associated with the diagnosis of kidney disease, which leads to social exclusion and loss of job opportunities, creates a vicious cycle of ill-health and poverty.             A number of social practices that can affect human health adversely, especially in the presence of other risk factors, were found to be common. This included tobacco use, use of over-the-counter pain killer medicines and consumption of herbs therapy. Our study showed an overall lack of awareness about the adverse health impact of these practices.           Finally, we found a general apathy and fatalistic attitude towards their health in the villagers, with the focus on livelihoods and social stigma leading to a neglect of health issues. Conclusion: we document community perceptions and health-seeking behaviour of a village with a high prevalence of CKDu. The study revealed a strong influence of socio-economic determinants, the influence of local myths, difficulties in accessing healthcare, and stigma associated with kidney disease. Multi-pronged action is needed to influence awareness, change behaviour and develop a resilient healthcare system that can respond to the needs of the community Limitation: Since this is a qualitative study with a limited sample size, the findings cannot be generalized unless they are combined with population-based quantitative research. Since, this study was done as a part of service delivery the sample size of our study for IDIs and FGDs was limited. Ethical Approval: AIIMSRPR/IEC/2020/700 dated 19.12.2020. Source of Funding: Nil Conflict of Interest: The authors have no conflicts of interest associated with the material presented in this paper. Acknowledgement: We appreciate the collaboration of all participants, State health authorities Dr Netram Navratna (CMHO), Dr.SK Binjwar additional director and nodal officer Gariyabandh, Dr Sunil Bharti (BMO Deobhog CHC), Dr Jay Patel (PG MO, Gariyaband) other Senior Health officers as well as all the supports extended from the Directorate Health services, Raipur ORCID: Vinay Rathore: https://orcid.org/0000-0003-4315-5072 Rahul Pal: https://orcid.org/0000-0003-3542-1959 AbhiruchiGalhotra: https://orcid.org/0000-0001-6169-8527 VivekanandJha: https://orcid.org/0000-0002-8015-9470 Authors’ Contribution: Dr Vinay Rathore, Dr Rahul Pal, Dr Abhiruchi Galhotra, Dr Saurabh Nayak,  Ms Snehalata, Prof Vivekanand Jha, Prof  Nitin M Nagarkar. Englishhttp://ijcrr.com/abstract.php?article_id=4320http://ijcrr.com/article_html.php?did=4320 GBD Chronic Kidney Disease Collaboration Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. Lunyera J, Mohottige D, Von Isenburg M,Jeuland M, Patel UD, Stanifer JW. CKD of Uncertain Etiology: A Systematic Review. Clin J Am Soc Nephrol. Correa-Rotter R, Wesseling C, Johnson RJ. CKD of unknown origin in Central America: the case for a Mesoamerican nephropathy. Am J Kidney Dis. Anupama YJ, Sankarasubbaiyan S, Taduri G. Chronic kidney disease of unknown etiology: Case definition for India - A perspective. Indian J Nephrol [Epub ahead of print] [cited 2020 Jul 23]. Available fromhttp://www.indianjnephrol.org/preprintarticle.asp?id=266081 Supebeda Village Population - Deobhog - Raipur, Chhattisgarh. [Internet]. Census2011.co.in. n.d. Available at: [Accessed 27 September 2020] Indian express. Chhattisgarh government to examine genetic cause of kidney ailments that claimed 71 lives. Available at: https://www.newindianexpress.com/nation/2020/jan/16/chhattisgarh-government-to-examine-genetic-cause-of-kidney-ailments-that-claimed-71-lives-2090433.html Chowdhary, P., Rathore, V., Jain, K., Galhotra, A., Verma, N., Kale, S. et al., (2020). CKD of Unknown Origin in Supebeda, Chhattisgarh, India. Kidney international reports, 6(1), 210–214. Ravishankar PL, Nadkerney P, Pramod V, Soni A, Jaiswal R, Kumar A, et al., Effect of Gudakhu (Smokeless Tobacco) on Periodontal Health: A Case-control Study. Int J Oral Care Res, 2017;5(2):87-90 Choukem, S. P., Nchifor, P. K., Halle, M. P., Nebongo, D. N., Mboue-Djieka, Y., Kaze, F. F. et al., (2016). Knowledge of physicians on chronic kidney disease and their attitudes towards referral, in two cities of Cameroon: a cross-sectional study. BMC research notes, 9, 29. Plantinga LC, Tuot DS, Powe NR. Awareness of chronic kidney disease among patients and providers. Adv Chronic Kidney Dis. Lunney, M., Alrukhaimi, M., Ashuntantang, G. E., Bello, A. K., Bellorin-Font, E. et al.(2018). Guidelines, policies, and barriers to kidney care: findings from a global survey. Kidney international supplements, 8(2), 30–40

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcareInfluence of Mini-Scleral Contact Lens Wear on Cornea in Ectatic Corneal Disorders     English2935Simi AfrozEnglish Khowal RiteshEnglish Dubey GauravEnglish Jamshed AliEnglish Yadav JuhiEnglish Das PrasenjitEnglish Manik K. R.EnglishIntroduction: Scleral lenses are gaining popularity in places where contact lenses are fitted. MSCL’s sub-group of scleral contact lenses with a total lens diameter between 14 and 18 mm, which rest entirely upon the sclera. Aim: The study aims to evaluate the influence of mini-scleral contact lens (MSCL) wear on corneal shape, thickness, and higher-order aberration after the lens settled on the eye for 4 to 6 hours in non-inflammatory ecstatic corneal disorders. Purpose: The study aims to check the change in corneal curvature and thickness after settling the lens on the eye for 4 to 6 hours. Also, check if there is any change in corneal aberration just after insertion and after settling the lens for 4 to 6 hours. Methods: This study was a prospective Cross-sectional experimental study to prove what was hypothesized in advance. Scheimpflug imaging was done for 15 subjects (mean age 26.4(±6.57)), first before insertion of mini-scleral contact lens. Second, just after wearing the mini-scleral contact lens. Third, after 4 to 6 hours of wearing of mini-scleral contact lens. Fourth, just after removal of MSCL in non-inflammatory ecstatic corneal disorder patient. Natural diurnal variations were considered by measuring separate control groups. Results: Small but significant increase in corneal thickness was observed just after removal of the lens after 4 to 6 hours of wearing (from 447.2(±46.8) to 457.8(±50.35) µ) P=0.023. After 4 to 6 hours of wearing, significant flattening of steep and steepest corneal curvature was observed having mean (0.0524(±0.085) mm, 0.933(±1.6) D respectively (P=0.032). Conclusion: Increase in corneal thickness, and significant flattening of steep corneal curvature was observed immediately after removing the lens after 4 to 6 hours of wearing. Modern MSCL decreases both higher and lower order aberration immediately after wearing the lens. Modern mini scleral lenses influence the corneal shape and induce small but significant corneal oedema after 4 to 6 hours of wearing. English Mini scleral contact lens (MSCL), Corneal Aberrations, Corneal thickness, Ecstatic cornea, Keratoconus, RGP Contact LensIntroduction Scleral lenses are gaining popularity in places where contact lenses are fitted. MSCL’s a sub-group of scleral contact lenses with a total lens diameter between 14 and 18 mm, which rest entirely upon the sclera, is sealed to the anterior eye with minimal movement upon blinking or ocular versions (Sindt, 2008).1 They are primarily used to correct irregular corneal optics commonly encountered in Keratoconus, Keratoglobus, Post LASIK Ectasia, as the post-lens tear layer (the fluid reservoir between the posterior lens and anterior cornea) effectively neutralizes most of corneal astigmatism. More recently, scleral lenses have also been utilized as a therapeutic intervention in cases of ocular surface disease (e.g., Exposure Keratopathy, Sjogren&#39;s syndrome, Steven–Johnson&#39;s Syndrome) as they provide hydration to the cornea during lens wear without evaporation. Previously, scleral lenses were larger in diameter, and the fitting was empirical and primarily relied upon practitioner interpretation of haptic (landing zone) vascular compression of the bulbar conjunctiva. Newer technology and advancements in anterior eye imaging with corneal topography and optical coherence tomography have resulted in a more reliable and accurate fitting process. Improved lens design led to the increase in the prescription of scleral lenses. This has led to a subsequent increase in the scleral contact lens prescription. Scleral lenses are significantly thicker (up to 1300 µ central thickness for full scleral lenses) than corneal rigid gas permeable (RGP) lenses to avoid the eye and handling flexure. Consequently, to counteract this increased thickness, modern scleral lenses are manufactured from highly permeable materials to maximize oxygen transmission to the cornea (Vincent, 2014).2 This is particularly important since scleral lenses do not move upon blinking to allow freshly-oxygenated tears to replenish the post-lens tear layer.Post-lens tear thickness varies from lens to lens, cornea to cornea and practitioner to practitioner. It may act as an additional barrier to the corneal oxygen reaching the atmosphere. The increased lens thickness, poor tear exchange and the presence of a thick post-lens tear layer are all possible hypoxia variables, however clinical reports of substantial corneal oedema associated with current scleral lens usage are rare. There have been several investigations into the corneal response to scleral lens wear in an attempt to quantify it. In an early study using full scleral lenses, Bleshoy and Pullum reported corneal edema in a single subject following 5hrs of sealed scleral contact lens wear using an RGP material with a Dk of 24. Central lens thickness was varied from 180 to 500 µ, and corneal swelling increased slightly with increasing lens thickness from 3.6% to 4.8% centrally and 4.6–5.3% in the periphery (although these central and peripheral zones were not defined). More recently, Pullum and Stapleton assessed central corneal swelling for four subjects following 3 hours of sealed scleral lens wear while varying lens thickness and oxygen permeability. Sclera lenses with a thickness of 1200 and a Dk of 32 showed up to 8% corneal edema, although this decreased as the lens thickness was reduced and the Dk increased. Other studies have looked at how well scleral contact lenses fit (such as apical clearance) and how they affect vision and ocular health (such as enhanced acuity, lens tolerance, and problems).This study assessed the physiological changes in corneal characteristics (biometrics and optical properties including anterior higher order aberrations) associated with modern MSCL wear. Scheimpflug imaging was used to investigate the influence of MSCL wear on the irregular cornea, young subjects with the ecstatic non- inflammatory irregular cornea (i.e., keratoconus or corneal abnormalities including ocular surface disease) over a substantially larger corneal region than previously examined. There are some drawbacks to correcting higher-order aberrations in normal eyes, including the fact that the eye is a dynamic optical and biological system. Consequently, the optical aberrations measured and corrected one day may not yield the same level of visual improvement on another day (Jinabhai, 2009). 3 Jinabhai study also reports that aberration measurements can come from accommodation fluctuations, tear film fluctuations, small eye movements and pupil size changes (Jinabhai, 2009). 3Simply said, correcting aberrations in normal eyes is like correcting a little fluctuating value. Despite the disadvantages for normal eyes, higher-order aberration contact lenses could improve vision in ecstatic eyes due to the huge magnitudes of optical aberration present in these patients. The practicality of ecstatic eye contact lenses with aberration control is being studied. Correction of these optical imperfections would greatly improve joyful eyes&#39; visual performance. The first step is to precisely measure sick optical defects. To explain the optical distortions, present in the ecstatic cornea. It will also assess the progress made in correcting them with micro scleral contacts. Currently, these tailored lenses only partially correct higher-order aberrations in keratoconus eyes. The use of aberration-controlling contact lenses in non-inflammatory ecstatic eyes is investigated in this research. Currently, aberration-controlling contact lenses seem realistic. If designers can create bespoke lenses with precision and movement stability. The study aims to estimate the change in corneal curvature and thickness after settling the MSCL on eye for 4 to 6 hours and to evaluate the change in aberration after settling the lens for 4 to 6 hours.The Stephen study concludes that Modern mini-scleral contact lenses that vault the cornea may slightly influence corneal shape and power but do not induce clinically significant corneal oedema during short-term wear. (Stephen J. Vincent, 2014).3,4 Pullum says in his study that the calculations of oxygen transmissibility, with varying tear layer and lens thicknesses, ranged from 10 to 36.7 at the scleral lens centres and from 17.4 to 62.6 at the peripheries. Their calculations of maximum central lens thicknesses show a practical range of 250–495 µm, in conjunction with a post-lens tear layer thickness of 100–250 µm. He also used the Holden–Mertz Dk/t criteria of 24 Fatt units for the central cornea. The Harvitt–Bonanno criteria of 35 Fatt units for the limbal area were used as reference points (Pullum, 1997).5 Article by customized lenses is found to correct only partially the higher-order aberrations found in keratoconic eyes. Suppose contact lens designers can manufacture customized lenses with accuracy and good movement stability. In that case, aberration-controlling contact lenses could prove to be a very useful tool for those involved in managing keratoconus patients (keratoconus, 2015).6 Jinabhai said the use of MSCL correcting higher-order aberrations may still be extremely beneficial in improving visual function in keratoconic eyes due to the enormous magnitudes of optical aberration observed in these patients. (Jinabhai, 2009). 3 Alio J. L., in his study, shows that the eyes with the lenses have a statistically significantly thicker cornea compared to the non-lens wearing eye after wearing either lens for 8 hours, lying within clinically and physiologically acceptable limits. Their clinical findings contradict existing theoretical estimates, which predict an increase in corneal edema as the tear layer thickness increases.It has to be evaluated if the effect on corneal oedema changes with longer wearing periods, larger samples, or other influences (Alió J. L., Corneal higher order aberrations: a method to grade keratoconus, 2006).6,7 Christiane Arlt&#39;s Despite current theoretical estimates, clinical evidence show that increased tear layer thickness does not increase corneal edema.It has to be evaluated if the effect on corneal oedema changes with longer wearing periods, larger samples, or other influences (Christiane Arlt, 2015). 8 As far as my knowledge ours is the only study done on young, healthy corneas but not on irregular or ecstatic corneas. Also, there is no study on aberration change after settling the lens for 4 to 6 hours. The study&#39;s main objective is to estimate the change in corneal curvature and thickness after settling the lens on eye for 4 to 6 hours and to check the change in aberration before and after insertion of the lens. Methodology  This study was a prospective Cross-sectional experimental study to prove what was hypothesized in advance. The author collected the data according to the hypothesis. The prevalence of the ecstatic corneal disorder is very low. (2300/100,000 for keratoconus) (Jonas, 2009).9 So sample size collection was based on convenient sampling. This study&#39;s inclusion criterion was Irregular cornea (ecstatic non-inflammatory corneal disorders); all subjects were between the ages of 18 yrs. to 50 yrs. with both males and females, and Post collagen cross-linking were also included. All kinds of Systemic Diseases, Presence of ocular disease except for non-inflammatory ecstatic corneal disorders), Age Group above 50 years, Age Group below 18 years, those who were absent on the day of the study, those who did not consent to participate in the study were excluded from this study All the patients presented in the visual aids centre Lajpat Nagar New Delhi were included in our study. They all took part voluntarily and without a financial refund. Ten subjects were included in the study. The average age within the sample was 34.5 years, with a standard deviation of 11 06 years at the time of the measurements. The consent form was signed, which shows their voluntary participation in my study. All the subjects had to pass the pre-fitting evaluation; the ideal diameter and base curve were chosen using the provided fitting set. If evaluation with fluorescein at the slit lamp did not look as expected, modifications were made in cooperation with the manufacturer. After finalizing the lens parameters, the lens was ordered with final refractive power incorporated in the lens. The vault used in the study is 300±25 micron. To avoid diurnal variation, the subject had to wear the lens in the morning at about 10:00 am and remove after 4 to 6 hours, about 3:00 pm. Only if all requirements were fulfilled, the lens could be used in the study. Data were coded and recorded in the MS Excel spreadsheet program. SPSS v16 was used for data analysis. Shapiro-Wilk normality test, paired-sample t-test, and Wilcoxon sign ranked test were used according to suitability and analysed data. The level of significance was taken as p < 0.05. Various graphs were used for showing the pre vs post changes of each parameter. The prior approval was taken by the hospital authority to conduct this. Table-1 Four scans were taken in the following Sequence of the Measurement: First, before fitting the mini-scleral contact lens. Second, just after fitting the mini-scleral contact lens. Third, after 4 to 6 hours of wearing of mini-scleral contact lens. Fourth, just after removal of the mini- scleral contact lens. Above mentioned parameters were measured. Visual acuity was measured five times using a log MAR chart in the following way First unaided visual acuity was measured before fitting the contact lens and also without any refractive error. Second, just after fitting the final lens. Third after 4to 6 hours of wearing the lens. Fourth unaided visual acuity was measured just after removal of the lens.   RESULT Fifteen (15) subjects (12 male and 3 Female) of mean age 26.4(±6.57). The mean apex pachymetry (micron) increased from 447.2(± 46.476) before insertion of MSCL to 457.8(±50.35) after removal of the lens after approx. 5hours. This change was statistically significant (Paired Sample-Test), ‘p’ = 0.023 (Figure- 1). The mean of Thinnest corneal thickness before insertion of MSCL increase from 431(±38.46) to 443(± 44.34) after approx. 5 hours. This change was significant paired-sample t-test), ‘p’= 0.013 (Figure-2). There is no significant change in the flat corneal curvature before insertion of mini scleral and just after removal of MSCL. But there is a significant change in steep corneal curvature before insertion, and just after removal of MSCL with ‘p’ = 0.032, mean value of steep corneal curvature before insertion of MSCL and just after removal of mini sclera contact lens is 6.55(±0.78) and 6.61(±0.082) respectively (Figure-3). There is no significant change in the flat corneal curvature before insertion of mini scleral and just after removal of MSCL. But there is a significant change in steep corneal curvature before insertion, and just after removal of MSCL with ‘p’ = 0.032, mean value of steep corneal curvature before insertion of MSCL and just after removal of mini sclera contact lens is 6.55(±0.78) and 6.61(±0.082) respectively (Figure-3). There was also a significant change in the steepest corneal curvature before insertion and just after removal of MSCL with‘p’= 0.049(Figure-4). There is a flatting of approximately 0.933(±1.6) in the steepest corneal curvature. The mean value of the steepest corneal curvature before insertion of MSCL and just after removal of MSCL are 58.57(±7.76) and 57.64(±7.85), respectively. There were no significant changes in Pmax, variance index, and irregularity index with ‘p’= 0.158, 0.619 and 0.426, respectively (Table-1). Relation between before insertion and just after insertion of MSCL: RMS of total aberrations before insertion of MSCL decreases from 10.397(±3.70) to 4.67(±3.05) (mean value) just after insertion of MSCL with ‘p’= 0.001, which is highly significant (Figure-5). RMS of LOA aberration before insertion of MSCL also decreases from 10.08(±3.57) to 4.87(±2.70) (mean value) just after insertion of MSCL, which is statistically significant with ‘p’= 0.000. RMA of HOA decreases before insertion of MSCL from 2.75(±1.16) to 1.3873(±0.92) (mean value) just after insertion of MSCL, which is statistically significant with ‘p’=0.001. Spherical aberration before insertion of MSCL decreases from 0.756(±0.76) to 0.392(±0.34) (mean value) just after insertion of MSCL with ‘p’ = 0.017, which is statistically significant. Secondary astigmatism before insertion of MSCL decreases from 2.88(±2.21) to 2.013(±2.76) just after insertion of MSCL with ‘p’ =0.020, which is statistically significant. Defocus before insertion of MSCL decreases from 3.362(±2.95) to 1.33(±1.30) just after insertion of MSCL with significant ‘p’= 0.003. Trefoil aberration before insertion of MSCL decreases from 0.408(±0.29) to 0.332(±0.35) just after insertion of MSCL with ‘p’ =0.001, which is highly statistically significant. Coma aberration before insertion of MSCL decreases from 0.85(±1) to 0.627(±0.74) just after insertion of MSCL with ‘p’= 0.036, which is statistically significant.  Quadra foil, Penta foil, and hexafoil did not show statistically significant results with ‘p’ =0.394, 0.443and 0.609 (Figure-6). Relation between just after insertion and before removal after 4 to 6 hours: RMS of HOA further decreases from 1.387(±0.92) to 1.17(±0.87) (mean value) with ‘p’=0.047 which is statistically significant. RMS of LOA further decreases from 4.87(±2.7) to 3.847(±2.29) with a ‘p’=0.036 which is statistically significant (Table-2). Secondary astigmatism further decreases from 2.013(±2.76) to 1.107(±0.95) with a ‘p’ =0.044 which is statistically significant. Spherical aberration, Defocus, Trefoil, Coma, Quadra foil, Penta foil and Hexa foil did not show any statistically significant result having ‘p’ = 0.82, 0.394, 0.334, 0.191, 0.307, 0.307and 0.293, respectively (Figure-7).   Before insertion and just after removal of MSCL: There is no statistically significant change in any aberration before insertion and just after removal of MSCL after 4 to 6 hours of wearing. Discussion Our best knowledge is the only Indian study that reveals statistically significant corneal oedema following 4 to 6 hours of wearing of MSCL. There is an increase in central corneal thickness following 4 to 6 hours of wearing MSCL with the mean percentage change of 0.0236, whereas Stephen Vincent et al. study says the opposite. The increase in corneal thickness is either due to hypoxia or the imbibition of saline used in MSCL or it may be a combination of both. To minimize saline imbibition, we use near equivalent composition, osmolarity, pH, and refractive index as that of tear layer. (Michaud, 2012)10 in his study concluded that scleral contact lens with Dk of 100 and lens thickness of 300 µm and corneal vault of 400 µm would yield a predicted Dk/t of 12.5, which do not satisfy Holden and Merts criteria for successful daily wear, so the clinically or statistically significant corneal swelling was observed (Michaud, 2012). 10 There is a flatting of steep corneal curvature following 4 to 6 hours of MSCL wear. Still, no significant change was noted in flat corneal curvature, whereas Vincent et al. study says overall flatting of corneal curvature. There is also a flatting of steepest corneal curvature (0.035(±0.1)) following 4 to 6 hours of MSCL wear. Analysis of change in individual Zernike coefficient up to 6th order aberration was done. But only up to 4th order aberration shows a significant change in before and immediately following MSCL wear.  When we take individual aberration into account, there is no further change after wearing 4 to 6 hours of MSCL except RMS of HOA, RMS of LOA, and secondary astigmatism shows a statistically significant decrease. RMS to LOA shows a highly statistically significant decrease in aberration. There is numerous higher-order aberration of which only spherical aberration, coma and trefoil are of clinical interest. Spherical aberration is commonly increased in myopic LASIK, surface ablation and keratoconus (non-inflammatory ecstatic corneal disorder (Michaud, 2012).10 Spherical aberration results in halos around the point image. It is statistically decreased in the ecstatic cornea after wearing MSCL. Coma is common in patients with decentred corneal graft, keratoconus, and decentred laser ablations (Michaud, 2012).10 Our study shows a statistically significant decrease in coma aberration after wearing MSCL. Trefoil produces less degradation in image quality compare with coma. It causes glare, ghost images and loss of contrast. They make up to about 15% of the total number of aberrations in an eye. (Vessel, 2020).11 LOA account for approx. 85% of the overall wave aberration in the eye. It includes positive defocus, negative defocus, and regular astigmatism. LOA mainly accounts for visual acuity, i.e., Measure of form sense. Our study shows a highly significant decrease in RMS of LOA (p-value=0.000) and the same we get by measuring visual acuity before and after insertion of MSCL (‘p’=0.001). There is a statistically significant decrease in defocus before insertion and just insertion of MSCL (‘p’=0.003).  RMS of LOA and RMS of HOA further decrease 3 hours after lens wear. Individual aberration remains content and no further change, showing that MSCL did not affect the corneal aberration after wearing short-term MSCL  (Vessel, 2020). 11There is no evidence of change in corneal aberration before insertion of MSCL and just after removal of MSCL after 4 to 6 hours of wear, which indicates that the lens does not cause any significant change in LOA. There is no evidence of change in corneal aberration just after insertion of MSCL and before removal of MSCL after 4 to 6 hours of wearing, which indicates mini scleral. This particular type of lens provides stable constant vision. Different lens materials and designs should be taken into consideration (Vessel, 2020).11 Conclusion Corneal thickness has changed and increased after settling the MSCL on the eye for 4 to 6 hours. There is flattening of steep corneal curvature and the steepest corneal curvature (Kmax) after settling the MSCL on the eye for 4 to 6 hours. There is no evidence of change in flat corneal curvature. There is a decrease in total aberration after wearing the lens, and there is no evidence of a change in aberration after settling the lens for 4 to 6 hours of wearing. There is an increase in visual acuity just after wearing the lens. Modern MSCL decreases both higher and lower order aberration immediately after wearing the lens. Modern mini scleral lenses influence the corneal shape and induce small but significant corneal edema after 4 to 6 hours of wearing.   Limitations This study was a prospective Cross-sectional experimental study; further research on a more diverse group in terms of keratoconus, PMCD, post LASIK is required to arrive to reach a strong conclusion and recommendation.  Smaller sample size. Lack of human resources and lack of awareness among practitioners and patients. Recommendation We recommend a similar study with larger sample size, and a more diverse group should be considered to ascertain that similar findings will be revealed. Acknowledgment The authors would like to thank the higher authorities of the visual aids centre in Lajpat Nagar New Delhi for providing all possible support for the smooth conduction of this research. The authors acknowledge the immense help received from the scholars whose articles are cited and included in references to 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 This research did not receive any outside funding or support Source of funding-None Ethical Statement-  The prior approval was taken by the hospital authority to conduct this. Authors’ Contribution: Abbreviations:         1.    MSCL- mini scleral contact lens 2.    MAR- minimum angle of resolution 3.    SPSS-  Statistical Package for the social sciences 4.    RMS- root mean square 5.    LOA- lower order aberration 6.    HOA-higher order aberration 7.    PMCD- pellucid marginal corneal degeneration 8.    LASIK- laser-assisted in situ keratomileusis Englishhttp://ijcrr.com/abstract.php?article_id=4321http://ijcrr.com/article_html.php?did=4321 Sindt C. Basic scleral lens fitting and design. Contact Lens Spectrum. 2008; 23(10), 10. Vincent S. J.-C.Corneal changes following short-term mini scleral contact lens wear. contact lens and anterior eye.2014; 37(6), 461-468. Jinabhai A. R. Higher-order aberrations in keratoconus: A review. optom. pract.2009 Stephen J. Vincent, D. A.-C.  Corneal changes following short-term mini scleral contact lens wear. Contact Lens & Anterior Eye.2014 37, 461–468. Pullum, K. W. Scleral lens-induced corneal swelling: what is the effect of varying Dk and lens thickness? The CLAO journal: official publication of the Contact Lens Association of Ophthalmologists, Inc.1997; 23(4), 259-263. Keratoconus, O. E.  The Epidemiology and etiology of keratoconus. International journals of keratoconus and ectatic corneal disease.2015; 7-15. Alió, J. L. Corneal higher-order aberrations: a method to grade keratoconus. Journal of Refractive Surgery.2006; 22(6), 539-545. Christiane Arlt, P. P.Clinical Effect of Tear Layer Thickness on corneal edema during scleral lens wear. alien university.2015; 1-79. Jonas, J. B.  Prevalence and associations of keratoconus in rural Maharashtra in central India: the central India eye and medical study. Am. J. Ophthalmol.2009;148 (5), 760-765. Michaud, L. V. Predicting estimates of oxygen transmissibility for scleral lenses. Contact Lens and Anterior Eye.2012; 35(6), 266-271. The vessel, M.2020 AAV Media, LLC. Retrieved from www.allaboutvision.com:https://www.allaboutvision.com/conditions/aberrations.html

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcareDevelopment and Evaluation of Temperature Mediated In-Situ Mucoadhesive Gel of Lamotrigine for Intranasal Administration English3641Rathi TejasEnglish Khetade RoshanEnglish Dhande PayalEnglish Das RenukaEnglish Umekar MilindEnglish Taksande JayshreeEnglishIntroduction: Epilepsy a neurodegenerative disease causes spontaneous and repetitive seizures. Treatment requires instantaneous pharmacotherapy to prevent further the condition of status epilepticus. Aim: The present study was aimed at developing temperature-sensitive in situ gel for intranasal administration of lamotrigine, an anticonvulsant drug used to treat generalised and partial seizure. Methodology: Pluronic 127, chitosan and β-glycerophosphate were used for the preparation of gel in varying concentrations by cold method. These systems were characterized for physical properties such as pH, gelling temperature, gelling time, drug content, in vitro drug diffusion studies, ex-vivo drug permeation and histopathological studies. The drug polymer compatibility was studied using Fourier transform infrared spectroscopy. Results: All the prepared formulations gelled immediately below 25 sec at the nasal pH and temperature. Addition of chitosan with Pluronic 127 increases the mucoadhesion and contact time of formulation in nasal cavity. The result of in-vitro drug release study revealed 93% of Lamotrigine and 75.33% of drug release in ex-vivo permeability study from the optimized formulation in about 210 min. Result of histopathological studies suggests the suitability of prepared formulation for intranasal administration. Conclusion: In-situ intranasal gel of lamotrigine prepared by using Pluronic 127 and chitosan demonstrated gelation at body temperature and exhibited satisfactory release of drug from its dosage form. It can be concluded that the prepared formulation has potential for the intranasal administration of lamotrigine in the treatment of epilepsy. English In-situ gel, Mucoadhesive, Intranasal administration, Lamotrigine, Temperature-sensitive, EpilepsyINTRODUCTION Epilepsy is a neurological disorder of brain characterized by sudden recurrent episodes of sensory disturbances causing seizures. Increased and unusual nerve cell activity in the cortex of the brain results in epileptic seizures.1 Some occur as a result of tumour of brain, brain injury and brain defect stroke.2 About 3-10 per 1000 people have epilepsy worldwide.3 Selection of AED for a patient depends upon the affected individual’s condition and side effects of drug.4 The nasal mucosa is highly vascularised responsible for the transfer of drug through the mucus layer leads to the absorption.5 A drug molecule can be transferred quickly across the single epithelial cell layer directly to the systemic blood circulation without first-pass hepatic and intestinal metabolism. Nowadays nasal delivery has been focused as an alternative route of drug administration. The advantages of the nasal administration include rapid absorption, higher bioavailability, fast onset of therapeutic action, avoidance of presystemic metabolism, non-invasive administration and improved patient compliance.6 The poor bioavailability and therapeutic response exhibited by the conventional nasal solution due to short residence time is the basic problem of highly efficient nasal route. Mucoadhesive in situ gelling formulation is one of the approaches to enhance the residence time of the drug in the nasal cavity leading to improved drug absorption and its therapeutic effect with rapid onset of action. Mucoadhesive system aims in targeting and localization of the dosage forms and provide an intimate contact between dosage form and absorptive mucosa resulting in high retention time and greater absorption of drug.7, 8 In situ liquid polymeric formulations once administered undergo in situ gelation. Various approaches used for in situ gelling system include physiological stimuli, osmotic stimuli, chemical stimuli, pH-triggered system, and temperature-dependent system.9 Temperature is most widely used stimulus in environmentally responsive polymer system. In these systems, gelling of the solution is triggered by change in temperature. These hydrogels are liquid at room temperature (20–25oC) and undergo gelation with increase in temperature when in contact with body fluid (35–37oC).10 The polymers which show temperature-induced gelation include chitosan, pluronics, tetronics, xyloglucans, and hydroxyl propyl methyl cellulose.11 Lamotrigine, an antiepileptic drug regularly used to treat partial seizures and tonic-clonic convulsions.12 Lamotrigine has relatively few side effects and does not require therapeutic drug monitoring. Lamotrigine is available as tablet and intravenous formulation. In view of the potential pharmacological application of lamotrigine in the treatment of epilepsy, the present work was designed to formulate its mucoadhesive temperature-sensitive in situ gel for treating acute and emergency epileptic condition. MATERIAL AND METHODS Materials Lamotrigine was obtained as a generous gift sample from Lupin pharma, Pune, India. Chitosan, pluronic127, β-glycerophosphate, benzalkonium chloride were purchased from Sigma Drug Laboratory Pvt. Ltd. All the chemicals used in experiments were of analytical grade. Methods Formulation of In-Situ Gel Table 1 depicts the concentration of lamotrigine, chitosan and pluronic F 127 used for the preparation of various batches of formulations. The concentration of Pluronic F127 was selected based on initial studies so as to obtain gel at minimum possible concentration below 34°C and pH of 4.8. Chitosan was used as mucoadhesive polymer to increase the gel strength. Benzalkonium chloride was added as preservative and β-glycerophosphate was used as antioxidant to protect the formulation from microorganisms and oxidation. Distilled water was used as vehicle. The gel was prepared by cold method. Initially 2% w/v chitosan solution was prepared in 0.1M HCl in ice bath, to it 10% w/v of glycerophosphate solution was added dropwise with continues stirring. Separately, pluronic F127 solutions of different concentration was prepared and kept these solutions in ice bath for removal of foam. Further chitosan solution was added to pluronic F127solution with continues stirring.13, 14 Calibration curve of Lamotrigine A solution of 100 µg /ml of lamotrigine was scanned in the range of 400 to 200 nm for the determination of λ max. The calibration curve of lamotrigine was plotted for the concentrations 2-20 µg/ml in phosphate buffer pH 6.6. Physicochemical Characterization Formulated in-situ intranasal gel was critically analysed for physicochemical properties such as clarity, pH, gelation time and gelation temperature.  Clarity is one of the most important characteristics features of gel formulation. All the prepared gel formulations were evaluated for clarity by visual observation against black and white background.15 pH of each formulation was determined by using digital pH meter which was previously calibrated using buffer of pH 4 and pH 7. The pH values were recorded immediately after preparation of gel. Gelation temperature and gelation time of various gel preparations were determined by taking a formulation equivalent to 10 mg of drug in a test tube and immersed in a water bath. The temperature of water bath was increased slowly and left to equilibrate for 5 min at each new setting. The sample was then examined for gelation, which was said to have occurred when the meniscus would no longer move upon tilting through 900C. Gelation time was measured as the time at which gel does not flow at 370C on immersing the solutions in a thermostatic water bath. Fourier Transform Infrared Spectroscopy (FTIR) FTIR spectra of the pure drug, physical mixture of drug with polymers were obtained using FTIR (Thermo Nicolet, Avatar 370). The samples were prepared as potassium bromide (KBr) disks on an FTIR spectrophotometer (2 mg sample in 200 mg KBr ratio) and scanned in a range 400-4000/cm as described earlier.16FTIR spectra were taken to investigate compatibility between the drug and the polymer. Differential Scanning Calorimeter (DSC) Differential scanning calorimetric (DSC) was used to evaluate the thermal behaviour of pure drug and physical mixture of the drug and excipients. The thermal profile of mentioned samples was recorded on DSC (Mettler Toledo DSC 822e). The thermograms were obtained by heating the microspheres at rate of 10°C/min from 30°C to 300°C using nitrogen purge of 50 ml/min.17 X-ray Diffraction Studies (XRD) X- ray diffractogram analysis provides information about the crystalline and amorphous nature of the substances. Diffractograms were recorded for the pure drug and formulation on X-ray diffractometer (Brucker AXS D8) to evaluate its crystallinities. Diffractograms were scanned in the range from 3°C to 80°C (2θ) with resolution of 0.02°C and scanning speed of 2.0°C/min. An accelerating voltage of 40 kV was applied at the current intensity of 35 mA. The XRD pattern of in situ gel formulation was compared with that of the pure drug.4 Drug Content Drug content of prepared formulations was determined by dissolving 1 ml gel formulation into 50 ml of pH 6.6 phosphate buffer solution. The resultant solution was analysed for the drug content by ultraviolet (UV)-visible spectrophotometer at 306 nm (Shimadzu 7800, Tokyo Japan). pH 6.6 phosphate buffer was used as blank. The data were collected by repeating the procedure in triplicate. In vitro drug diffusion studies The in vitro drug diffusion study of gel formulations was carried out using Franz diffusion cell across dialysis membrane (Av diameter 21.5 mm, Av flat width 32.34 mm) as diffusion barrier. The membrane was equilibrated overnight with pH 6.6 phosphate buffer before the application of gel onto the donor compartment. The receptor compartment was filled with phosphate buffer solution (pH 6.6) that was within the pH range in the nasal cavity. The donor compartment was placed in such a way that it just touched the diffusion medium in the receptor compartment. The temperature was maintained at 37°C ± 1°C using circulating water bath. 300 µl of sample was withdrawn at predetermined time points from the receptor compartment, replaced with the same amount of fresh pre-warmed buffer solution and analysed for lamotrigine using UV-visible spectrophotometer at 306 nm.18 Ex Vivo Permeation Studies For the purpose of this study, fresh nasal tissue of goat was obtained from the local slaughterhouse. The nasal mucosa was separated from septum and the connective tissue as well as most of the adhering cartilaginous tissue was carefully removed with forceps and scissors without damaging or scratching the nasal mucosa. The specimen was individually placed on Franz diffusion cell and clamped between the donor and receptor compartments. 18 ml of pH 6.6 phosphate buffer was maintained at 370 was placed in the receptor compartment. Formulation equivalent to 10 mg of lamotrigine was placed in the donor compartment. Sampling was done in a similar manner as for in vitro release studies. The amount of lamotrigine diffused into the receptor phase from the formulations was determined by UV spectrophotometry at 306 nm. The method was found to be sensitive enough for detecting the amount of drug permeated.18 Ex vivo biocompatibility study The histopathological studies were accomplished to confirm the biocompatibility of lamotrigine intranasal in-situ gel formulation with goat nasal mucosa. The freshly excised nasal mucosa of goat was collected and cleaned with saline solution as mentioned in vitro drug diffusion study. After application of predefined amounts of lamotrigine in-situ gel (1 mg), mucosal tissues were fixed in 10% formalin solution and implanted in paraffin. Paraffin sections (7.5 µm) were stained with Hematoxylin Eosin and observed under digital Motic microscope (Model no B1-223SP). The untreated mucosa incubated with phosphate buffer solution (pH 6.6) was used as a control.19 Statistical analysis  All the results are reported as mean ± standard deviation (SD) or mean ± standard error mean (SEM) RESULT AND DISCUSSION In-situ temperature-sensitive intranasal mucoadhesive gel of lamotrigine was prepared by cold method. Initially, various concentrations of Pluronic F127 were used to obtain a formulation that forms gel at a temperature near 34°C and pH of 4.8.  Formulations showed adequate gelation in proper time at concentration of 32% w/v and 34% w/v. Chitosan concentration was also varied to obtain gel having suitable viscosity. Based on these studies’ concentration of chitosan and Pluronic F127 was selected for the further formulations. The purity of lamotrigine was checked by determining its melting point of it by capillary method which was found to be 2160 C -2180 C. The drug exhibited the λ max at 306 nm and showed reproducibility. Calibration curve of lamotrigine obeyed Beers-Lambert’s law in the concentration range 2-20 µg/ml (Figure 1). Physicochemical Characterization All the formulations showed the pH in the range of 4.87 ±0.16 to 5.37 ±0.08, which is suitable according to the nasal pH. All the formulations were clear in appearance in sol form. The gelling temperature of the prepared formulations were in the range 32.23 ±1.87 to 35.30 ±1.22 °C. In the present study, all the formulations showed gelation temperature within the acceptable range. The gelling temperature suitable for temperature-sensitive in-situ nasal gel ranges between 30–36 °C. The gelation point refers to the temperature when the meniscus of the formulation would no longer move upon slanting the test tubes at 90°, with gradual increase in the temperature. The gelling time of all the formulations was found in the range of 15.06 ±0.90 to 25.33 ±4.48 sec. All the formulations exhibited satisfactory gelation time for intranasal administration for lamotrigine (Table 1). Fourier Transform Infrared Spectroscopy FTIR spectra of lamotrigine showed characteristic absorbance at 3448 cm-1 specifying NH stretching of an amino group (Aromatic), 3209 cm-1 shows aromaticity (aromatic CH stretching), 1620 cm-1, 1486 cm-1 indicates C=C ring stretching and 962 cm-1. In FTIR spectra of physical mixture characteristics peak of both lamotrigine and excipients were observed. It suggests no significant interaction between drug and excipient.   However, the characteristic absorbance peaks of lamotrigine were found to be shifted to the lower values and decreased in intensity also, suggesting the incorporation of lamotrigine within in-situ gel prepared with Pluronic F127 and chitosan as carriers (Figure 2). X-ray Diffraction Studies The X-ray diffractogram of lamotrigine shows a sharp and intense peak indicating the crystalline nature of the drug in pure form. The X-ray diffractogram of the physical mixture was observed to determine if there is a loss or modification of the pure drug&#39;s crystal structure. Figure 3 indicates that there is virtually no difference in crystallinity between physical mixture of drug with excipients and pure lamotrigine proposed compatibility between the lamotrigine and the excipients. Drug content  Drug content of the formulations was found to increase with the increase in concentration of pluronic F 127 and chitosan. The drug content of the formulations was ranging from 48.35 ±3.55% to 69.12 ±2.77%, indicating maximum entrapment of drug in the formulation (Table 2).  The maximum amount of drug content 69.12 ±2.77% was obtained for in-situ gel formulation with 34% of Pluronic F127 and 8% of chitosan concentration.  In vitro drug diffusion study The release of lamotrigine from the in situ intranasal formulations was determined using Franz diffusion cell. The receptor compartment was filled with phosphate buffer pH 6.6 as the dissolution medium. In vitro drug diffusion study revealed that the release rate is dependent on Pluronic F127 and chitosan concentration. The higher the pluronic F127 concentration, the greater the rate of drug release was observed from the formulations. However, formulations with greater chitosan concentration decreased the rate of drug release might be due to increased viscosity of the gel formulation. The concentration of chitosan 2% and 4%, showed a greater release of lamotrigine. The Bioadhesive property of chitosan is responsible to retain the formulation at the administration site helps to increase the retention time, also increases the transmembrane permeability of drug and thereby exhibit better absorption of the drug. The formulation F6 containing 34% w/v of Pluronic F127 and 4% w/v of chitosan concentration showed 93% of drug release in 270 min (Figure 4). The same formulation was selected further for the ex- vitro permeation study and histopathological study. Ex-vivo permeation study The ex-vivo permeation study of formulations F6. Ex-vivo permeation study was performed for the significant batch using goat nasal mucosa. The percent drug permeated after 210 min was found to be 85.18±2.28% (Figure 5) from nasal gel formulation showing the significant release of drug from the formulation. Ex vivo biocompatibility study The epithelium layer was intact and there were no alterations in basal membrane and superficial part of submucosa as compared with PBS treated mucosa (Figure 6). Thus, in-situ gel formulations seem to be safe with respect to nasal administration. CONCLUSION In this study we have formulated intranasal mucoadhesive in-situ temperature-sensitive gel of lamotrigine. Physicochemical characterization exhibited satisfactory gelation of formulation in 25 sec. In-vitro and ex-vivo drug permeation studies have shown that in situ gels act as potential drug delivery system for lamotrigine. Histopathological study revealed the safe intranasal administration of in-situ gel formulation. Present study highlighted the importance of intranasal administration of lamotrigine as mucoadhesive in-situ temperature-sensitive gel for emergency conditions of epileptic seizures. However, in vivo studies are required to be carried out to confirm the potential of these formulations. ACKNOWLEDGEMENT The authors are thankful to the Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee management for providing research facilities and support for carrying out this study. FUNDING INFORMATION There is no financial support received any government or non-government funding agency. CONFLICT OF INTEREST The author stated no conflict of interest for the publication of this research article. Rathi Tejas- Data collection, methodology, formal analysis and investigation. Khetade Roshan- Data collection, methodology, formal analysis and investigation. Dhande Payal- Data collection, methodology, formal analysis and investigation. Taksande Jayshree- Supervision, validation, writing original draft and editing. Das Renuka- Supervision, validation, writing original draft and editing. Umekar Milind- Supervision, validation, writing original draft and editing. Englishhttp://ijcrr.com/abstract.php?article_id=4322http://ijcrr.com/article_html.php?did=4322 Tan L, Yu JT, Guan HS. Intranasal anticonvulsive treatment: prospective management of intractable epilepsy? Med Hypotheses 2008; 71: 542-5. Kumar S, Mohanty BB, Agrawal D, Nayak P, Patnaik S, Patnaik J, Mahapatra SK. Antiepileptics and Pregnancy: A Review. Int. J. curr Res Rev 2012;4(21):132-43. Taksande V, Burbare N, Chaure K, Deogade N, Deshmukh S, Dhole J. To Assess the Effectiveness of Planned Teaching on the Knowledge Regarding Epilepsy in Children Among the Anganwadi Workers. Int. J. curr Res Rev 2000;12(24):151-54. Paul A, Fathima KM, Nair SC. Intra Nasal In situ Gelling System of Lamotrigine Using Ion Activated Mucoadhesive Polymer. The open medicinal chem J 2017; 11: 222-44. Chitra Karthikeyini S, Kavitha K. Nasal Drug Delivery-A Pre Hospital Therapy in Status Epilepsy-Review. IOSR J. Pharm. 2016; 11(3): 39-46. Soane RJ, Hinchcliffe M, Davis SS, Illum L. Clearance characteristics of chitosan-based formulation in the sheep nasal cavity. Int J Pharm 2001; 217: 183-191. Kukudkar P, Rahate S, Trivedi R, Umekar M, Taksande J. Intranasal Topiramate Polymeric Nanoparticles for Epilepsy: In Vitro And Ex-Vivo Investigation. Int J App Pharm 2020; 12(5): 258-64. Agrawal V.A, Rajurkar R.M, Mahle A.M, Thonte S.S. Sustained Intranasal Drug Delivary System For The Treatment Of Gastroparesis. International Journal of Current Research and Review 2011; 03 (02): 4-12. Caramella CM, Rossi S, Ferrari F, Bonferoni MC, Sandri G. Mucoadhesive and thermogelling systems for vaginal drug delivery. Advanced Drug Delivery Reviews 2015: 92, 39–52. Karavasili C, Fatouros DG. Smart materials: in situ gel-forming systems for nasal delivery. Drug Discovery Today 2016; 21(1): 157–66. Jagdale S, Shewale N, Kuchekar BS. Optimization of Thermoreversible In Situ Nasal Gel of Timolol Maleate. Scientifica (Cairo). 2016; 2016: 6401267. Schiller Y, Krivoy N. Safety and efficacy of lamotrigine in older adults with epilepsy and co-morbid depressive symptoms. Clin Med Ther 2009; 1: 825-33. Nazar H, Fatouros DG, Van der Merwe SM, Bouropoulos N, Avgouropoulos G, Tsibouklis J, Roldo M. Thermosensitive hydrogels for nasal drug delivery: The formulation and characterization of systems based on N-trimethyl chitosan chloride. European J. P’ceutics & Biopharmaceutics 2011; 77: 225-32. Altunta? E, Yener G. Formulation and Evaluation of Thermoreversible In Situ Nasal Gels Containing Mometasone Furoate for Allergic Rhinitis. AAPS Pharm Sci Tech 2017;18(7): 2673-82. Saudagar RB, Deore SB, Gondkar SB. Formulation development and evaluation of in-situ nasal gel of lisinopril dihydrate. Sch Acad J Pharm 2016; 5(7): 277-83. Gangurde H, Chavan N, Mundada A, Derle D, Tamizharasi S. Biodegradable chitosan-based ambroxol hydrochloride microspheres: Effect of cross-linking agents. J Young Pharm 2011; 3: 9-14. Patil PR, Salve VK, Thorat RU, Shahi SR. Formulation and evaluation of ion-sensitive in-situ gel of zolmitriptan. Int J Pharmacy and Pharm Sci 2014; 7(1): 478-86. Naik A, Nair H. Formulation and evaluation of thermosensitive bio gels for nose to brain delivery of doxepin. Hindawi Pub Co Scientifica BioMed Research International 2014; Volume 2014, Article ID 847547, 10 pages. Pardeshi CV, Belgamwar VS, Tekade AR, Surana SJ. Novel surface-modified polymer-lipid hybrid nanoparticles as intranasal carriers for ropinirole hydrochloride: In vitro, ex vivo and in vivo pharmacodynamic evaluation. J Mater Sci Mater Med 2013; 24: 2101-15.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcareEvaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers English4246Maryam Mohammed JeburEnglish Alaa Hussein J Al-qaisiEnglish Nazar Sattar HarbiEnglishIntroduction: Rheumatoid Arthritis (RA) is a joint-damaging chronic inflammatory disease that affects the synovium and articular cartilage. RA is characterized by symmetric arthritis that primarily affects the tiny joints of the hands and feet. Adipokines play a role in the etiology of a variety of metabolic, vascular, and inflammatory diseases. The goal of this study is to compare the levels of inflammatory adipocytokines (chemerin and visfatin) and their ratios, as well as certain related biomarkers, in RA patients and healthy controls to see if they can help diagnose Rheumatoid Arthritis. Methods: A total of 70 (25 males and 45 females) RA patients’ group with ages ranging from 45-65 years and 30 (10 males and 20 females) as the control group with ages ranging from 40-70 years old were involved in the study. All individuals had their biochemical parameters, demographic profile and serum chemerin and visfatin concentrations analyzed. Results: Our findings indicated that serum levels of Visfatin and Chemerin were significantly higher in individuals with rheumatoid arthritis than in healthy controls. Chemerin had moderate positive correlations with C-reactive protein (CRP) and total cholesterol (TC) while, it had weak negative correlation with high-density lipoprotein cholesterol (HDL). Conclusion: The variations in adipokine levels that we observed could play a role in diagnose of Rheumatoid Arthritis. English Rheumatoid arthritis, Chemerin, Visfatin, Adipokines, C-reactive protein, High-density lipoproteins INTRODUCTION Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting the joints principally. If left untreated, it is the most prevalent inflammatory disease of the joints, characterized by cartilage and bone degradation, leading to functional deterioration and disability. As a result, increasing cartilage and joint degeneration occurs, as well as impairment.1 According to data, women have a 3:1 chance of developing this condition. Any age group can be affected; however, the onset is most common between the ages of 40 and 60 .2 Rheumatoid arthritis has no recognized etiology. Clinical signs and symptoms can be caused by a mix of genetic predisposition and environmental triggers. RA is characterized by symmetric arthritis that primarily affects the tiny joints of the hands and feet. General discomfort and swelling of joints (often symmetrically), morning stiffness, and movement limitations that last more than one hour and can be eased by mild motions are all common indications and symptoms of RA. However, RA can affect any organ, with the most prevalent symptoms being interstitial lung disease, renal amyloidosis, skin vasculitis, episcleritis, and poly-neuropathy of numerous mono-neuropathies. Better diagnostic biomarkers for the early detection of RA are always needed.3 Adipose tissue not only serves as a passive energy storage reservoir, but it also serves as an endocrine gland, producing and secreting a variety of bioactive peptides called adipokines.4Adipokines play a role in the etiology of a variety of metabolic, vascular, and inflammatory diseases.5 Adiponectin, resistin, leptin, visfatin, plasminogen activator inhibitor type 1 (PAI-1), tumor necrosis factor alpha (TNF- α), interleukin (IL)-6, and IL-8 are all adipokines .6 One of the future proteins in inflammatory biomarkers might be chemerin, a 16 kDa protein originally discovered in ovarian cancer patients&#39; ascitic fluids and synovial exudates from rheumatoid arthritis patients&#39; synovia as a result of the Tazarotene-induced gene 2 (Tig2).7,8 RA patients have increased levels of Chemerin and ChemR23 expression in their fibroblast-like synoviocytes (FLS) .9 Another pro-inflammatory adipokine that has the potential to help with RA diagnosis is Visfatin was first identified as a cytokine involved in early B-cell development, but it was renamed visfatin since it is mostly released by visceral fat. Visfatin is a peptide that is mostly secreted by the liver. The plasma level of visceral adipose tissue correlates with the amount of visceral fat in humans .10Visfatin levels in the blood are higher in RA, as is its expression in synovial fluids and inflamed synovium. The degree of inflammation, the severity of the disease, and joint destruction were all linked to visfatin serum and synovial fluid levels .10 This study aimed to evaluate RA patients&#39; serum levels of chemerin and visfatin to those of healthy controls. MATERIALS AND METHODS Study participants: The current study was conducted in Al-Baghdad teaching hospital, during the period from October 2020 to March 2021. The present study included 70 (25 males and 45 females) RA patients from 45 to 65 years old and 30 (10 males and 20 females) healthy control group ranging from 40-70 years old. This study was approved by the Department of Chemistry, College of Science, Al-Nahrain University, Baghdad, and by the Research Ethics Committee of the Iraqi ministry of health, Iraq, with ethical clearance letter no.3122. Exclusion criteria: History of hypertension, smoking, heart failure, diabetes mellitus, hypothyroidism, and hepatic or renal disorders, patients taking any medication, and drug used were all eliminated from the current study. Sample collection: Patients and healthy individuals provided seven milliliters of venous blood placed into gel tubes for 15 minutes to coagulate. Serum was isolated from blood samples by centrifugation at 1840 x g for 15 minutes at room temperature. The serum was separated into aliquots and kept at -70°C until testing. Measurement of Body Mass Index: BMI was measured by dividing weight (in Kilograms, Kg) by height squared (in meter, m) for each participant. Biochemical analysis serum levels of chemerin, and visfatin were measured using enzyme-linked immune-sorbent assay (ELISA) provided by (MyBioSource, USA). The photometric method was used to evaluate the serum lipid profile total cholesterol (TC), triglyceride (TG) and high-density lipoprotein cholesterol (HDL) provided by (Linear, Spain). The fluorescence Immunoassay (FIA) method was used to evaluate the CRP level (ichroma, Korea). Statistical Analysis of Parameters: Demographic and biochemical data in the present study were performed using GraphPad Prism software version 8.0.2 (San Diego, California, USA). T-test unpaired was performed to assess mean ± standard deviation (STD) and significant differences (P-value) among means of the two studied groups. Correlations between parameters in the present study were estimated with Pearson’s correlation coefficient. P ≤ 0.05 was considered statistically significant. RESULTS Table (1) shows the demographic data of the two studied groups (Rheumatoid arthritis and control). The results obtained from the preliminary analysis shown in table (1) indicated that there was no significant difference in BMI (P = 0.0993) between RA and control groups. There were no significant differences between RA group and the control group regarding age (P=0.5563). Table (2) shows laboratory data from the blood analysis among the two groups. Our findings indicate there were significant differences between the RA or control groups regarding serum levels of CRP and TC and there were significantly higher in HDL (P< 0.0001) among two groups Table (3) shows the different adipokine concentrations among the two groups. Statistical analysis revealed that serum levels of VSF were significantly higher (p< 0.0001) among two groups, as shown in figure (1). Furthermore, serum levels of Chem were significantly higher (P< 0.0001) in RA group compared to controls, as shown in figure (2). We determined Pearson’s correlation coefficient among the different variables in the study. There were three significant correlations appeared in RA group. Chemerin had moderate positive correlations with CRP (r=0.452, P=0.031) and TC (r=0.504, P=0.014) while, it had weak negative correlation with HDLc(r=-0.245, P=0.041). DISCUSSION Rheumatoid arthritis has been linked in several studies to adipokines.11 The majority of prior research have focused on pre-existing atherosclerotic diseases or symptoms to narrow down their patient group. In our research, we looked at the serum levels of Visfatin and Chemerin in patients with RA to see what role adipokines have in the disease&#39;s etiology. In the current study, the RA patients were obese (30.2 ± 3.4), the marked inflammation encountered in them CRP (30.8 ± 3.9) agreed with Jonssonetal.12 who reported that RA patients explained this finding by the increase in inflammatory cytokine production. Adipocytokines are currently thought to play a role in the etiology of a variety of metabolic and inflammatory diseases, including rheumatoid arthritis. To examine its significance in the pathophysiology of these disorders, we urged researchers to look at the amounts of the adipocytokine in serum samples from patients with inflammatory and non-inflammatory rheumatic diseases, as well as healthy controls .13 serum levels of chemerin is significantly higher (P valueEnglishhttp://ijcrr.com/abstract.php?article_id=4323http://ijcrr.com/article_html.php?did=4323 1. Yap H-Y, Tee SZ-Y, Wong MM-T, Chow S-K, Peh S-C, Teow S-Y. Pathogenic role of immune cells in rheumatoid arthritis: implications in clinical treatment and biomarker development. Cells. 2018;7(10):161. 2. Al-Rubaye AF, Kadhim MJ, Hameed IH. Rheumatoid Arthritis: History, Stages, Epidemiology, Pathogenesis, Diagnosis and Treatment. Int J Toxicol Pharmacol Res. 2017;9(2):145–55. 3. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham III CO et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–81. 4. Jakovljevi? B, Paunovi? K, Stojanov V. Adipose tissue as an endocrine organ. Srp Arh Celok Lek. 2005;133(9–10):441–5 5. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85–97. 6. Giralt M, Cereijo R, Villarroya F. Adipokines and the endocrine role of adipose tissues. Metab Control. 2015;265–82. 7. Bonomini M, Pandolfi A. Chemerin in renal dysfunction and cardiovascular disease. Vascul Pharmacol. 2016;77:28–34. 8. Ernst MC, Haidl ID, Zúñiga LA, Dranse HJ, Rourke JL, Zabel BA, et al. Disruption of the chemokine-like receptor-1 (CMKLR1) gene is associated with reduced adiposity and glucose intolerance. Endocrinology. 2012;153(2):672–82. 9. Ha Y-J, Kang E-J, Song J-S, Park Y-B, Lee S-K, Choi ST. Plasma chemerin levels in rheumatoid arthritis are correlated with disease activity rather than obesity. Jt Bone Spine. 2013;81(2):189–90. 10. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science (80- ). 2005;307(5708):426–30. 11. Del Prete A, Salvi V, Sozzani S. Adipokines as potential biomarkers in rheumatoid arthritis. Mediators Inflamm. 2014;2014. 12. Jonsson MK, Sundlisæter NP, Nordal HH, Hammer HB, Aga A-B, Olsen IC, et al. Calprotectin as a marker of inflammation in patients with early rheumatoid arthritis. Ann Rheum Dis. 2017;76(12):2031–7. 13. Otero M, Logo R, Gomez R, Logo F, Dieguez C, Gómez-Reino JJ, et al. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis. 2006;65(9):1198–201. 14. Ali DMM, Al-Fadhel SZ, Al-Ghuraibawi NHA, Al-Hakeim HK. Estimation of Serum Chemerin, Visfatin Levels and Their Ratio as A Possible Diagnostic Parameters of Rheumatoid Arthritis. 2019; 15. Ernst MC, Sinal CJ. Chemerin: at the crossroads of inflammation and obesity. Trends Endocrinol Metab. 2010;21(11):660–7. 16. Bozaoglu K, Curran JE, Stocker CJ, Zaibi MS, Segal D, Konstantopoulos N, et al. Chemerin, a novel adipokine in the regulation of angiogenesis. J Clin Endocrinol Metab. 2010;95(5):2476–85. 17. Fontes VS, Neves FS, Cândido APC. Chemerin and factors related to cardiovascular risk in children and adolescents: a systematic review. Rev Paul Pediatr. 2018;36:221–9. 18. Maghsoudi Z, Kelishadi R, Hosseinzadeh-Attar MJ. Association of chemerin levels with anthropometric indexes and C-reactive protein in obese and non-obese adolescents. ARYA Atheroscler. 2015;11(Suppl 1):102. 19. Lu B, Zhao M, Jiang W, Ma J, Yang C, Shao J, et al. Independent association of circulating level of chemerin with functional and early morphological vascular changes in newly diagnosed type 2 diabetic patients. Medicine (Baltimore). 2015;94(47). 20. Ali DMM, Al-Fadhel SZ, Al-Ghuraibawi NHA, Al-Hakeim HK. Serum chemerin and visfatin levels and their ratio as possible diagnostic parameters of rheumatoid arthritis. Reumatologia. 2020;58(2):67. 21. Alkady EAM, Ahmed HM, Tag L, Abdou MA. Serum and synovial adiponectin, resistin, and visfatin levels in rheumatoid arthritis patients. Z Rheumatol. 2011;70(7):602. 22. Sglunda O, Mann H, Hulejová H, Kuklová M, Pecha O, Pleštilová L, et al. Decreased circulating visfatin is associated with improved disease activity in early rheumatoid arthritis: data from the PERAC cohort. PLoS One. 2014;9(7):e103495. 23. Institutet K, Hambardzumyan K. Predictive Biomarkers in Rheumatoid Arthritis. 2018. 24. Arogbodo , J. O. ., Faluyi, O. B. ., &Igbe, F. O. . (2021). In vitro Antimicrobial Activity of Ethanolic Leaf Extracts of Hibiscus Asper Hook. F. and Hibiscus Sabdariffa L. on some Pathogenic Bacteria. Journal of Scientific Research in Medical and Biological Sciences, 2(3), 1-12. https://doi.org/10.47631/jsrmbs.v2i3.304 25. Brentano F, Schorr O, Ospelt C, Stanczyk J, Gay RE, Gay S, et al. Pre–B cell colony?enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix?degrading activities. Arthritis Rheum Off J Am Coll Rheumatol. 2007;56(9):2829–39. 26. Mirfeizi Z, Noubakht Z, Rezaie AE, Jokar MH, Sarabi ZS. Plasma levels of leptin and visfatin in rheumatoid arthritis patients; is there any relationship with joint damage? Iran J Basic Med Sci. 2014;17(9):662–27. Makhlouf, A.-M. A. ., Mahmoud, A. M. ., Ibrahim, R. G. ., & Abdel Aziz, Y. S. . (2021). Effects of Vitamin D and Simvastatin on Inflammatory and Oxidative Stress Markers of High-Fat Diet-Induced Obese Rats. Journal of Scientific Research in Medical and Biological Sciences, 2(3), 39-50. https://doi.org/10.47631/jsrmbs.v2i3.297

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16Healthcare“Computer-Assisted Learning (CAL), a Teaching-Learning and Assessment Tool for CBME Curriculum in Practical Pharmacology for 2nd MBBS Students” English4753Meena ShrivastavaEnglish Anjali Ravindra ShindeEnglish Suraj PatilEnglishEnglish CAL- teaching-learning and assessment, 2nd MBBS students, CBME curriculum-practical PharmacologyIntroduction The importance of practical Pharmacology is to encourage, build up and apply the theoretical knowledge about basics of drug actions, their mechanisms and adverse reactions. It must help the undergraduate students to choose right drug for right patient and put a step forward to practice rational therapeutics while prescribing the medicines. Live animal experiments have the problems of availability, procurement, cost, and maintenance, use of animals and ethics regulations. The basis is &#39;3 R&#39; i.e. Reduction, Refinement and Replacement in animal experiments, with the 4th‘R’(Rehabilitation) added as an added measure for animal care. 1,2 There have been debates and objections at different levels about using animals in research and repetitive experiments. 2, 3 The new curriculum of NMC and MUHS for Pharmacology is based on competency-based medical education (CBME). It has tremendously changed the viewpoint of practical Pharmacology for undergraduate medical students. Skill building and its clinical application is now important as never before.CPCSEA rules and regulations have been adopted in this new curriculum of National Medical Commission (old MCI) and Maharashtra University of Medical Sciences (MUHS). 1, 4,5It is now mandatory to stop the older methods of teaching-learning and assessing the students through live animal experiments or animal experiments in form of static graphs, data tables, instruments &photographs. Instead, such skill will be developed by animal simulation experiments in Computer Assisted Learning (CAL), which almost mimics reality. This is a welcome change after a wait of many years and will be immensely important in learning systemic Pharmacology, especially of autonomic, cardiovascular and central nervous system.6,7It has computer-based packages, which focus on interactive animal experiments. Such software versions of CAL are good tools for experimental Pharmacology. Being user-friendly, they allow active participation of learner, making it interactive and interesting. Such an alternative approach of teaching-learning and assessment to the “theoretical” practical sessions on animal Pharmacology, acts as a great motivation for students and teachers alike.2, 8, 9The animal simulation has a great advantage of repeated practice as self-learning tool. This improves the performance of the students in OSPE.10One such CAL software has been developed for CAL in practical Pharmacology by medimation Education Pvt Ltd, Mumbai.11 Present study was planned to see the students’ response animal simulator as CAL in teaching-learning and assessment using the software of Meditation Education Pvt Ltd. This was done as per the regulatory requirements of NMC and MUHS curriculum in practical pharmacology. This study is based on one of the 3R (replacement of animal experiments) of CPCSEA directives. Objectives Use of CAL as a teaching-learning and assessment tool, as per the Curriculum of MUHS for practical Pharmacology for 2nd MBBS students Evaluate feedback responses of 2nd MBBS students to the software of CAL Methods Ethical consideration: Prior permission to conduct this study was obtained from the departmental academic committee since it was a part of regular academic activity in practical Pharmacology. It was a prospective mixed (qualitative & quantitative) open-ended observational study. Inclusion Criteria: 2nd MBBS Students of the institute, present on scheduled days of practical (N-71) participated in the study. 2nd MBBS Students of the institute, present on scheduled days of 1stIA(N-71) participated in the study. Exclusion criteria: Students not willing to sign an informed written consent form Students absent on scheduled dates of the practical session on CAL and 1st IA Study population  Students- Students of 3rd semester of 2nd MBBS present on scheduled days of practical and scheduled dates of 1stInternal Assessment (N-71) participated in the study. Study venue: Department of Pharmacology and Digital Library of tertiary care medical college of central India Study tools: 40 computers with broadband connection facility and CAL software of Animal simulation in Pharmacology“Wonderland Experimental Pharmacology interactive Assessment modules by Meditation Education Pvt Ltd Mumbai”, installed in all 40 computers Documents used: Informed written consent forms, pre-test/ post-test sheets and feedback questionnaire, practical registers, answer sheets and mark sheet of 1stIA of CAL Study period-May- June 2021 CAL sessions were deliberately planned after large group teaching-learning sessions on the Pharmacology of the autonomic nervous system and ocular Pharmacology. This created a good theoretical background for this module.    Steps of Procedure were as follows(Fig 1) A) An introductory session of 2 hours was conducted in lecture hall for 2nd MBBS students (71) who participated in study. This session was conducted one day prior to the CAL practical session. They were explained to their satisfaction the contents of the informed written consent form, which was signed by all. Thereafter, the investigators conducted Pre-test of 10 marks with a set of 10 pre-validated single best response MCQs. The time allotted was 10 minutes. They were meticulously selected to cover the methodology, actions of the drugs, their ADR and drug choices, all in relation to CAL experiment of “Effect of drugs on rabbit eye”. This was followed by a 20 minutes video of provided by the Mediation Company. It demonstrated the effect of autonomic nerves and related drugs on eye. It also elaborated the procedure and precautions about the experiment. This created a good background for the students to work on the said software.       The investigators then explained at length the procedure again step by step and any doubt regarding the procedure to be adopted was clarified to the students. Before this introductory session of CAL investigators and other faculty members of the department had trained themselves in CAL simulation exercise by repeated use of practice and examination mode of the said software. B) Two practical sessions of CAL of 2 hours each were conducted. The software of CAL as animal simulator was "Wonderstand Experimental Pharmacology interactive Assessment modules by Medimation Education Pvt Ltd Mumbai” installed on all 40 computers with BB connection facility. The Experiment of “Effect of drugs on Rabbit Eye” in the software was available in “practice mode” and “examination mode”. In these two sessions, the students worked in “practice mode” Maximum no of students allowed in each session was 36. Each student worked on separate computer. They performed all by themselves, the CAL-animal simulator experiment in “practice mode” as per the stepwise procedure in the flow chart shared with them on WhatsApp group(a common flow chart was prepared by departmental faculty to facilitate students to perform experiments with all drugs). They worked with all 4 drugs provided in the software. The list of the drugs is given in table 1. The time of 1 hour and 45 minutes was adequate for them to record effects of drugs as given in software. They carefully recorded the observations for all 4 drugs in the computer as well as in their practical journals, as per the format of tables provided in software. Though the recorded observations of each student were available in the respective computers, the journal record helped them as a reference to prepare for assessment of CAL. Faculty members of the Pharmacology department were available at all times of the sessions but intervened only of students asked for help. In all sessions of CAL, practice or assessment, the IT professionals of the institute were also present and were a tremendous support in addition to our departmental support staff. This Practical was followed by Post-test(same 10 MCQS as in pre-test), of 10 minutes. The last activity of 2-hour session for the students was to fill up the feedback questionnaires. It had 7 pre-validated structured Questions7 responses of which had to be recorded in form of a Likert scale.2 It also had 5 open-ended questions too. Revealing of identity in the questionnaire form was optional. But many students wrote their roll numbers and names on the feedback form. The students completed the form in approximately 10 minutes. C) Two Repeat Practice sessions of CAL-(Teaching-learning) of 2 hours each were conducted in the following week. Maximum 36 students were included in each session. Here all of them completed questions related to drugs in their journals and they were initiated by the faculty of department. The students had to write answers to following questions separately for all 4 drugs: i) Write the mechanism of ocular actions of the drug ii) Write its ocular adverse reactions iii) Write its ocular therapeutic uses D) Three assessment sessions were conducted on the dates as scheduled in 1st IA practical examination. Maximum 25 students worked on each day. Here they worked separately on each computer, in the “Examination mode” of the software. The unknown drugs were randomly allocated by default in the software itself. They had to identify 1 unknown drug and write 3 questions related to it(as above). They recorded observations and answers in an answer sheet, they were corrected and marks allotted by departmental faculty according to the correct identification and other answers. This was kept as departmental record, additionally, observations and identity of unknown drug were available as per students’ roll no on the respective computers. Statistical Analysis “Paired Two Sample for Means” was used for differences in score of pre and post MCQ tests and “Two Sample Proportion Test” was applied for differences in range of scores in pre and post-tests. Microsoft Office Excel 2007 was used for these tests. Probability (p) value Englishhttp://ijcrr.com/abstract.php?article_id=4324http://ijcrr.com/article_html.php?did=43241. Committee for the purpose of control and supervision of experiments on animals (CPCSEA)GUIDELINES ON THE REGULATION OF.SCIENTIFIC EXPERIMENTS.ON ANIMALS.Ministry of Environment & Forests. (Animal Welfare Division). Government of India: 9-91 http://cpcsea.nic.in/WriteReadData/userfiles/file/SOP_CPCSEA_inner_page.pdf 2. Meena S., Computer Assisted Learning in Practical Pharmacology for 2nd MBBS students: perception of Students and Faculty. IJCRR 2018; 10 (22): 7-13 3. Manish K, Manish K, Hitesh M, Pramod KM, Akash C, Lalit M, et al Undergraduate medical students’ perception regarding computer-assisted learning in experimental pharmacology Practical. Internat.J.of Basic & Clinical Pharmacol 2018;7(3):541-547 4. Medical Council of India, Competency-based Undergraduate curriculum for the Indian Medical Graduate, 2018; Vol. 1:136-159 https://www.nmc.org.in/information-desk/for-colleges/ug-curriculum/ 5. Pharmacology syllabus. https://www.muhs.ac.in/Department UG Circular No 44_030621dated 03-06-2021.pdf 6. Lisha J. A review of computer-assisted learning in medical undergraduates. J Pharmacol Pharmacother. 2013; Apr-Jun; 4 (2): 86–90 7. Veena R. M, Kalpana L, Lavanya S. H, Bharat Kumar V. D, Manasa C. R.Impact of using Computer Assisted Learning in II MBBS Pharmacology Teaching-Perceptions of Students in a Medical College. J Evolution of Med and Dental Sc 2015; (4) :15209-15214, DOI:10.14260/jemds/2015/216 8. Badyal DK, Modgill V, Kaur J. Computer simulation models are implementable as replacements for animal experiments. Altern Lab Anim 2009;37: 191-5. 9. Chitra G, Heethal JP, Chandramouli A, Sharmila SV. Computer-assisted learning: Perceptions and Knowledge, Skills of Undergraduate Medical Students in a Malaysian Medical School. Nat J. of Physiol., Pharmacy &Pharmacol.  2011; 1(2): 63 – 67 10. Kuruvilla A, Ramalingam S, Bose AC, Shastri GV, Bhuvaneshwari K, Anudha G. Use of computer-assisted learning as an adjuvant to practical pharmacology teaching. Advantages and limitations. Ind J Pharmacol 2001;33:272-5. 11. Brochure “Wonderstand Ex” the product by Medimation Education Pvt Ltd Mumbai 12. Kopal S, Pushpawati J, Shipra J, ChandrabhanC. Evaluation of Computer-assisted Learning Module for Undergraduate Pharmacology Practical Classes. J of Mahatma Gandhi University of Medical Sciences and Technology May-August 2017, 2, (2) P 61-64 13. Amirtha R, Rachna G, Harmeet SR, Lalit Kumar G. Impact of Computer Assisted Learning Teaching Modality on Learning & Understanding of Pharmacology Among Undergraduate Medical Students. Ind J Physio Pharmacol 2017, 61(2): 202-207 14. Diwanshu S, PavanM A comparison of computer-assisted learning and practical animal experiment for undergraduate medical students in pharmacology curriculum - a questionnaire-based study conducted in a medical college of North India. Internl J of Basic & Clinical Pharmacol 2016 Dec;5 (6):2581-2584 15. Santhanalakshmi P, Oommen S, Alwar MC, Arya J. Effectiveness of computer-assisted learning as a teaching method in experimental pharmacology. Natl J Physiol Pharm Pharmacol 2018;8 (Online First).Doi: 10.5455/ njppp.2018.8.0723926072018 16. Tikoo D, Gupta M. Student’s perception and experience of computer-assisted learning as a teaching method in experimental pharmacology. Int J Basic& Clin Pharmacol 2015;4:1168-74. 17. Taruna S, Suman B, Richa G, JuhiK. Use of Computer Assisted Learning as an Alternative to Experimental Pharmacology Teaching: Student&#39;s Opinion. www.jkscience.org 2016; 18(2): 116-119 18. Nettah S. Computer-assisted learning (CAL) as a teaching-learning method in teaching experiment pharmacology. Int J Basic Clin Pharm 2014;3:63-5.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcareA Prospective Study of Risk Malignancy Index in Adnexal Masses English5459Neha KumariEnglish Mamta SinghEnglishThis scoring system is based on serum CA-125, menopausal status, ultrasonographicfinding. This scoring method yield much better results than individual parameters. Methods: Present study conducted between July 2017 to June 2019.Parameter like menopausal status, ultrasoundfeatures, and serum level of tumor marker like CA-125 for calculating RMI 3. Then RMI was compared with the histopathological report which was taken as gold standard. Results: RMI 3 had a sensitivity of 100%, a specificity of 91.67%, a positive predictive value of 97.50% and negative predictive value of 100%. Conclusions: This scoring system due to its simplicity and applicability can be used by the general gynaecologists at the periphery to refer suspected ovarian cancer to oncologicalcenters and thereby improving the survival and prognosis of women undergoing surgery for ovarian tumors. EnglishAdnexalmass, Benign ovarian tumor, CA-125, Malignantovarian tumor, Menopausalstatus, Risk Malignancy IndexINTRODUCTION Ovarian cancer is one of the leading causes of mortality in females.1 The annual percentage of increase in age-standardized incidence rates ranged from 0.7% to 2.4%.2 Gynecological cancer constitutes about 30% of the total cancers among women in India and ovarian cancer contributes about 19.8% of the total cases.3 Risk malignancy index (RMI) is a simple scoring system based on serum CA 125, USG score & menopausal status. It is useful in predicting a malignant ovarian mass and in differentiating malignant from benign ovarian mass. Most of the ovarian tumors are diagnosed at a later stage since the onset and progression of this tumor makes early diagnosis difficult. There is a significant difference in the management of malignant and benign tumors. Pre-operative knowledge is necessary to determine the nature of adnexal mass for optimal and appropriate primary treatment. RMI-1 was developed by Jacobs et al. in 1990 and RMI-2 was developed by Tingulstad et al. with slight modification in the score value of menopausal status and ultrasound score. It was modified to RMI-3 in 1994.4 Cut-off value of Risk of malignancy index is taken 250 to increase the detection rate of true negativecases.5 Preoperative determination of the nature of adnexal mass is necessary for optimal and appropriate primary treatment. RMI is a simple scoring system which can be applied in less specialized centers. MATERIAL AND METHODS The present study was conducted in the Department of Obstetrics & Gynaecology in collaboration with Department of Pathology and Department of Radiodiagnosis, Institute of Medical Sciences, Banaras Hindu University from July 2017 to June 2019. This is a prospective study on 100 patients with clinically diagnosed ovarian masses attending either outdoor or admitted in the gynecology ward of SSH, BHU, Varanasi. Written informed consent was obtained from all the participants prior to the enrolment for the study. Confirmed adnexal masses cases were selected purposively from outdoor and those hospitalized in the Gynaecology ward, SSH, BHU. Inclusion criteria Women with clinically detected ovarian mass of any age group. In premenopausal women, the criteria for ovarian masses sizeare more than 8 cm. Postmenopausal status defined as more than 1 year of amenorrhea or, who underwent hysterectomy and criteria for ovarian mass size is more than 5 cm. Exclusion criteria- Women having an ovarian tumor with other conditions like endometriosis, fibroid, pregnancy, PID, women in menstruating phase and associated with concurrent malignancy. Patients who were unfit for major surgery, inoperable cases, or previous major pelvic surgery. Intraoperatively, any other mass other than ovary was also excluded from study. Women with already diagnosed cases of ovarian malignancy receiving chemotherapy, masses arises from GI tract or urinary bladder, pregnancy and its complications like ectopic,  molar and post-abortive were excluded. Clinical history was taken including Age, Parity, menstrual history, socioeconomic status and symptoms. Personal, family and history of any medical illness were also obtained. Premenopausal and Postmenopausal status was certain in each subject. Serum CA125 level was estimated in all subjects. Risk of malignancy index (RMI) RMI – U x M x value of CA-125 (Table 1) USG scoring Transabdominal scans were done using a 3.5MHz and transvaginal scan were done with a 7.5Mz transducer. The lesions were evaluated according to size, shape and multiplicity, the thickness of wall and septa and ascites. Scoring system based on sonographic findings. Morphological evaluation was done using ultrasonography.USG score was done within 2 week prior to laparotomy. SerumCA-125 levelestimation A peripheral venous sample was taken from each patient, prior to surgery for the estimation of serum CA-125 levels by radioimmunoassay. Abnormal CA-125 level is defined as serum levels > 35 U/ml, (considered a high risk for ovarian malignancy). Menopausal scoring (M)-  Menopausal status was defined as one or more years of amenorrhoea or women who had undergone a hysterectomy. All other women were considered premenopausal. For premenopausal women score 1 was given and for postmenopausal women score 3 was given. Risk of malignancy index was calculated for each subject by multiplying USG score, absolute values of CA-125 serum levels and menopausal score.  Operative finding during laparotomy of all cases were noted. An operative specimen or tissue was sent for histopathological examination. Ascitic fluid or peritoneal washing was sent for cytological examination. Histopathological diagnosis was considered as gold standard for defining outcome. Therefore RMI is a simple, valuable, highly reliable and clinically applicable scoring system, in the preoperative evaluation of ovarian mass for differentiating malignant from benign lesion. Interpretation of risk malignancy index (RMI) If the score was < 25, considered as low risk. If the score was 25-250, considered a moderate risk. If the score was >250,considered a high risk. STATISTICAL ANALYSIS Chi-square, Fisher&#39;s exact tests are used to compare proportion of benign and malignant cases with different ultrasonographic parameters. A p-value Englishhttp://ijcrr.com/abstract.php?article_id=4325http://ijcrr.com/article_html.php?did=4325 1. Spencer JA. A multidisciplinary approach to ovarian cancer at diagnosis. The British J Radiol. 2005;78(2005): S95-102.rmi 17. 2. Murthy NS, Shalini S, Suman G, Pruthvish S, Mathew A. Changing trends in incidence of ovarian cancer - the Indian scenario. Asian Pac J Cancer Prev. 2009;10(6):1025-30. 3. Kanan AYSonali SD, Sandip SN, Sanjaykumar BP. Evaluation of the validity of risk malignancy index in clinically diagnosed ovarian masses and to compare it with the validity of individual constituent parameters of risk malignancy index. Int J Reprod Contracept Obstet Gynecol. 2016 Feb;5(2):460-464 4. Tingulstad S, Hagen B, Shjerdestad FE, Onsrud M, Kiserud T, Halorsen T, et al. Evaluation of a risk of malignancy index based on serum CA 125, USG findings and menopausal status in the preoperative diagnosis of pelvic masses. Br J Obstet Gynaecol. 1996:103:826-31 5. RCOG Guideline No. 34 October 2003, Reviewed 2010. 6. Bouzari Z, Yazdani S, Ahmadi MH, Barat S, Kelagar ZS, Kutenaie MJ et al. Comparison of three malignancy risk indices and CA-125 in the preoperative evaluation of patients with pelvic masses. BMC Res Notes. 2011;4:206. 7. Javdekar R, Maitra N. Risk of Malignancy Index (RMI) in Evaluation of Adnexal Mass. The Journal of Obstetrics and Gynecology of India (March–April 2015) 65(2):117–121. 8.   Santosh KD, Atal BD, Benudhar P and Jatindra PH. A prospective study to evaluate the risk malignancy index and its diagnostic implication in patients with a suspected ovarian mass. Dora et al. Journal of Ovarian Research (2017)10:55. DOI 10.1186/s13048-017-0351-2 9. Tahereh A, Mahdieh R. Risk of malignancy index in preoperative evaluation of pelvic masses. Asian Pac J Cancer Prev. 2011;12:1727-30. 10.Kanan AY, Sonali SD, Sandip SN, Sanjaykumar BP. Evaluation of the validity of risk malignancy index in clinically diagnosed ovarian masses and to compare it with the validity of individual constituent parameter of risk malignancy index. Int J Reprod Contracept Obstet Gynecol. 2016 Feb;5(2):460-464 11. Mayer AR, Chambers SK, Graves E, Home C, Tseng PC, Nelson GE, et al. Ovarian cancer staging: does it require a gynecologic oncologist? Gynecol Oncol. 1992; 47:223–7. 12. Simsek HS, Tokmak A, Ozgu E. Ole of a risk of malignancy index in clinical approaches to adnexal masses. Asian Pac J Cancer Prev. 2014;15(18): 7793–7. 13.  Rao JH. Risk of malignancy index in assessment of pelvic mass. Int J Biomed Res. 2014;5(3):184-6. 14. Geomini P, Kruitwagen R, Bremer GL, Cnossen J, Mol BWJ. The accuracy of risk scores in predicting ovarian malignancy: a systematic review. Obstet Gynecol. 2009;113(2):384–94. 15. Tahereh A, Mahdieh R. Risk of malignancy index in preoperative evaluation of pelvic masses. Asian Pac J Cancer Prev. 2011;12:1727-30. 16.   Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG. A risk of malignancy index incorporating CA125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol. 1990;97(10):922-9. 17. Yamamoto Y, Yamada R, Oguri H, Maeda N, Fukaya T. Comparison of four malignancy risk indices in the preoperative evaluation of patients with pelvic masses. Eur J Obstet Gynecol Reprod Biol. 2009;144(2):163–7. 18.Geomini P, Kruitwagen R, Bremer GL, Cnossen J, Mol BWJ. The accuracy of risk scores in predicting ovarian malignancy: a systematic review. Obstet Gynecol. 2009;113(2):384–94. 19. Ulusoy S, Akbayir O, Numanoglu C, Ulusoy N, Odabas E, Gulkijik A. The risk of malignancy index in discrimination of adnexal masses. Int J Gynaecol Obstet. 2007;96(3):186–91.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcareHealth Problems of Low Skilled Indian Male Migrants Living in Gulf Countries: A Cross-sectional Study English6067Mohammed RafiuddinEnglish Kosalram KalpanaEnglishIntroduction: Due to an increase in migrant’s movement, health has become a key issue. Moving across different ecological conditions may expose migrants to new diseases and promote disease transmission. Aims: The present study aimed to determine among low-skilled male migrants health problems and their access to health services in gulf countries. Methodology: This cross-sectional study involved only male migrants from six countries. The study took place at Warangal district, Telangana, India. The survey questionnaire was interviewed. The questionnaire consisted of items pertaining to general health, illness, treatment and diseases including access to health care services in the host countries. Data were analyzed using frequencies, percentages and the chi-square test was used for comparison. Results: A total of 410 participated with a response rate of 82.32%. The majority of sampled respondents were from Saudi Arabia 183(44.63%) and UAE 101(24.63%). The greater number of respondents were employed as construction labour (25.4%), re-tail salesperson (10.2%) and driver (10.5%). The health problem frequently occurring reported are headaches (62.0%), difficulty concentrating (50%), stomach or digestive problems (58.5%) pain or a tight feeling in the chest (42.4%), irritated eyes (57.6%) and dry skin (50.5%). High blood pressure (41%), Cardiovascular diseases (33%), Insomnia (35%), Muscular or joint problems (53%) and Neck problem (60%) are the major illness are ailments reported. Hypertension (196), metabolic arthritis (159), cardiovascular (133) and diabetes (114) are the sufferings of the current disease. The majority of the participants reported having access to health care (77%) in their respective countries of employment provided by the employer. The biggest obstacles are no transportation availability, travelling issues, no time, language problem and lack of finance to access the healthcare services. Conclusions: The findings showed that a substantial portion of health problems were attributed to prolonged working conditions among low-skilled migrants. It emphasizes implementing various strategies or policies to protect the health and well-being and improve their access to essential health services to all types of migrant workers in the host countries government and Indian government by tracking them. English Gulf countries, Health problems, Healthcare, Low skilled workers, treatment and Migrants.Introduction Nearly, 8.5 million Indian migrants are present and working under various employment categories in the gulf nations. Thus, it has the largest population of migrants in the world.1 Due to the rejection of jobs by local workers, low skilled workers work under risk-prone jobs that lead to serious health problems among Indians. Further, these migrants are forced to work under (3Ds) dangerous, dirty and degrading jobs.2 Due to an increasing number of people moving from one country to another, migrant’s health has become a key global public health issue. At present not only the US, UK, Canada and the Gulf, but also a larger number of countries like members of European Union, Africa and Asia are emerging major destinations for Indians.3 Majority of them go to gulf countries as temporary unskilled or semi-skilled workers and work until the expiry of the contract.4 The state of Kerala is considered as the ‘migration hub’ or central node of the India-Gulf migration corridor.5 These migrants are employed either directly by the employer or through the consulted agency. The study reported that while about two-thirds of the migrant workers were semi-skilled or unskilled and only 14% were employed in professional technical and managerial occupations.6 Due to the restrictive immigration policies in the Gulf countries, most of the Gulf migrants return to India.7 It is documented that the reasons for returning are due to low income, poor work conditions, health problems and factors related to the situation at home.8 Moving across different ecological conditions may expose migrants to new diseases and promote disease transmission. Further, a couple of studies showed that social, cultural and economic factors are influenced among men and women during the migration process in different groups and locations.9, 10 There is evidence that many migrants when arriving to the host country were healthy but that good health can deteriorate over time in the receiving society.11 It is noted that across European countries there is high rate of depression and anxiety among asylum migrants including Indians compared to the national population.12 In another study, migrants showed health symptoms such as back pain, abdominal pain, headaches, dizziness, gynecological infections, depression and anxiety.13 Several studies showed that rates of schizophrenia (Mental Disorder) were higher among migrant’s groups compared to native white population.14 In addition, migrants usually have poor access to healthcare services.15 However, the labour markets in the destination countries often do not provide enough services for the low paid workers, despite accepting long working hours for low pay. It is reported that, most of the migrant workers in dangerous jobs, low skilled and manual work are vulnerable and pose an increasing risk for psychosocial health issues and mental health problems.16 An extensive review of the literature did not yield any result of health problems of Indian migrants in gulf countries. Therefore, the present context of this study is intended to examine the health problems among low skilled Indian migrants working in gulf countries. Further, explore the use of health care services and barriers in the host countries. Methods This research design utilized a cross-sectional approach using random sampling procedure and received ethical approval (2965/IEC/2021) from SRM University, Tamil Nadu, India. This study took place in Warangal District, Telangana State, India. The participants of 410 migrants from six countries (Saudi Arabia, United Arab Emirates (UAE), Qatar, Oman, Bahrain and Kuwait). The study only recruited male participants who had at least one year of working experience. The informed consent of the participants was obtained and ages between 20 to 60 were included. Females are excluded because most of them are homeworkers and are not allowed to work. The data was collected from April to August 2019; Ramzan and Bakrid as most of the migrants returned to India on a vacation to celebrate the festivals with their families. Prior to data collection a list of participants was made by contacting the known person and his relatives or friends who are living gulf countries. These participants were contacted through mobile phones and discussed the current study in detail. Those who were interested were interviewed by the researcher at their residence. The researcher checked the copy of participant’s employment identification card of respective countries and employment status to make sure as per the inclusion criteria. Researchers filled the questionnaires based on the response of the participants. All the questions were interview and no physical examination of the participants were taken. The validated study questionnaire was designed and modified from the previous literature review.17-19 The questionnaire was adopted in English only. The questionnaire consisted of four main sections. These are demographic; characteristics of general health; illness and treatments and access to healthcare. To measure various outcomes three options never, sometimes and often and dichotomous variables such as yes or no were also used wherever applicable. In addition, few generalized questions were used to know the perspective of the migrants. All parameters were summarized to compute frequencies, means and percentages using SPSS. Chi-square and Fisher’s exact test was performed to estimate the significance among study variables. Pearson&#39;s χ2 test was used and differences were considered statistically significant at p < 0.05. Results General Results A total of 410 participated, yielding an overall response rate of 82.32%. The majority were from Saudi Arabia 183(44.63%) and UAE 101(24.63). Half of the sampled were educated up to secondary level of education (46.8%). The greater number of respondents were employed as construction labour (25.4%), retail salesperson (10.2%) and driver (10.5%) respectively. It is worth noting that respondents with regards to the status of health were poor (13.9%) in gulf countries compared to 25.4% of poor health before arrival. Interestingly more than one-third of the majority reported that they should be tracked and protected by Indian government and signed international labour conventions in protecting the rights of the workers (Table 1). Characteristics of general health The health problem frequently occurring reported are headaches (62.0%), difficulty concentrating (50%), stomach problems (58.5%) pain or a tight feeling in the chest (42.4%), irritated eyes (57.6%) and dry skin or skin rashes (50.5%) and found slightly significant compared between the countries. Respondents reported often suffering posture movements such as pain in hip, leg or foot (50.0%), neck pain (58.5%) and found it slightly significant. Nevertheless, reported sometimes (88.5%) suffered pain either middle or top of their back (Figure 1). Illness, treatment and access to health care High blood pressure (41%), Cardiovascular diseases (33%), Insomnia (35%), Muscular or joint problems (53%) and Neck problem (60%) are the major illness reported that have been treated during the last five years (Figure 2). The study also reported a lower percentage of industrial accidents and found significance when compared with different countries. Hypertension (196), metabolic arthritis (159), cardiovascular (133) and diabetes (114) are the current diseases reported (Figure 3). Majority of the participants reported having access to health care (77%). To seek medical health, (90%) visit the health center for the treatment of illness. The biggest obstructs are no transportation availability, travelling issues, no time, language problem and lack of finance to access the healthcare services (Table 2). Discussions Indian migrants are world’s top recipient of remittances as well largest supplier of international migrants.20 These migrants pose unprecedented health and livelihood challenges for the millions of Indians working in the middle east regions. The study found that half of the migrants completed their secondary education level. This led to a drop in the Emigration Check Required (ECR) to only those job applicants whose educational qualifications are Class 10th failed or uneducated.21 These outcomes indicate that the middle east countries are approaching the migrants of at least secondary or university level of education in the category of unskilled or skilled workers.  This study supports previous findings that a close correlation exists between the level of education and job performed by the migrants.22 The study found a greater number of migrants were employed as construction labour, retail sales and drivers. The current study strongly supports the similar findings in which report that 70% of Indian migrants work as the driver, domestic servant or as labor at the construction sites.23 This evidence that Indian workers became the pillars for the development of the construction work in the Gulf countries. In the current study the status of migrant health was poor in India (25.4%) compared to staying in Gulf countries (13.9%). The reason for the poor condition of health in India could be due to poverty, poor access to health care, unemployment, psychological stress, work-related injuries and communicable and non-communicable diseases. In addition, behavioral risks such as the use of tobacco and alcohol are reported.24,25 The health condition is little improved in gulf countries probably due to availability of health insurances from the employer, advanced health care’s system, personal finance due to employment and environmental factors perhaps influence the health status. One of the most significant findings is that 90% of the migrants reported that they should be tracked and protected by Indian government in protecting the rights of the workers. These results are prompting greater attention needed by the Government of India and the host governments to diaspora affairs and worker welfare issues. The vast majority of migrants are blue collar workers who have paid highly excessive recruitment fees to sell their labor through uncertain existence due to a foreign labor sponsorship system that formalizes their lack of assurance.26  This system known as Kafala system of foreign labor sponsorship, that binds workers to their employers is common widespread in the many gulf countries and has contributed to labor migrants&#39; uncertainty.27  Many of them criticized the system as unfavorable called as "modern-day slavery" or a maze of exploitation by human rights groups due to poor living conditions of the migrant workers.28 These are contributing factors that lead them to need to track the migrants for better living conditions under the convention of labor agreements between the governments. There are evidence that both countries governments are now committed to managing their contract labour arrangements in such a way as to provide mutual benefit, and to avert the risk of exploitative practices at variance with international standards of human and labour rights.29 However, not a single of them has amended the convention which binds itself to this international treaty. The gulf countries have to take the reforms seriously so that they can make a suitable environment for the migrant laborers. The most common general health issues among them are headache, digestive problems, irritated eyes, skin rashes, concentration difficulties and ailments of the heart (Figure 1). These percentages of health problems reported such as headache and digestive problems among Indian migrants are much higher compared to similar studies reported among Indian subcontinent and Nepalese migrants.19,30 Further, results are consistent with a similar type of health study that reported cardiopulmonary, gastrointestinal (GI), and pseudo neurologic and medical symptoms are higher among migrants in Qatar and found statistically significant.31 Half of the respondents reported often suffering posture movement such as pain in hip, leg or foot and neck pain. High blood pressure, Cardiovascular diseases, Insomnia, Muscular or joint problems and Neck problems are the major illnesses reported (Figure 2). This is clearly evident in the health of the Indian migrant getting through different health crises pertaining to longer employment and longer duration of stay in these gulf countries.19 In contrast, reported a lower percentage of industrial accidents and found significance. This lower percentage is much lower when compared with a similar study where construction workers reported having experienced injuries or accidents at their workplace.19 The explanation for these health reasons that the migrants are neglecting to participate in preventive care or possible delay in treatment process. In addition, low wages, dangerous working conditions, long working hours, poor housing and overcrowded accommodation are detrimental to the quality of life of migrants, which resulted in their health crisis.32 The overall reported diseases currently suffering among migrants are hypertension, metabolic arthritis, cardiovascular, diabetes and the least reported gastric ulcer (Figure 3). These diseases reported are similar as well as higher in the general population and migrants.33,34 Despite the high burden, prevention and management did give any prioritized consideration in the host countries. The current study reported that 77% of them have access to health care in their respective countries of employment provided by the employer through insurance. This is the element contributing the authors believe the health of the migrants shown in this study are much better when compared to their health in India.  The curiosity is that 90% of them visit the health center for the treatment of illness other than regular physicians or hospitals. The authors believe that the extremely low rates of health insurance coverage to health centers instead of hospitals was hindering access to better health care services. Only 23% of them do not have health insurance and reported biggest obstacles are no transportation availability, travelling issues, no time, language problem and lack of finance to access the healthcare services (Table 2). The current study findings support what previous studies found concerning barriers to healthcare.35,36 These barriers lead to consequences of their health and well-being, both in terms of the actual treatment and other possible health-related consequences among migrants. Limitations The study was performed in a single district and the results cannot be attributed to the completely migrant population. Although the current study focuses on migrants from different gulf countries, the majority of respondents were from Saudi Arabia. The responders in the current study have nothing to gain or to fear by reporting their health problems. Thus, the authors believe that such interests have not affected our results. Additional studies are needed to observe factors besides those reported in this study. Despite these limitations, the study sheds light on the issues of migrant health to greater extent considering messages for the migration policy makers in India and the hosting government in conjugation to improve the health services.  Conclusions In conclusion, the present findings demonstrate that the status of health problems were occupying wide space among migrants and reported suffering more than one type of health problem. Despite having the majority of migrants&#39; access to healthcare provided by the employer, still a larger number of them suffer health issues continuingly. It is noted that a substantial portion of health problems were attributed to prolonged working conditions among migrants. It is recommended to provide adequate information for the migrants making them aware of their health risks in the hosted countries. This study emphasizes implementing various strategies or policies to protect health and improve their access to essential health services to all types of migrant workers.  Recommends different government agencies must engage with the Ministry of Health to create a migration platform of tracking and adopt different health policies including easy working environments. Acknowledgment The authors acknowledge the immense help received from all the gulf migrants who participated in this study. The authors also thank Mr. Elamin kheir for his statistical analysis in the current study. Conflict of Interest: None Financial Support: None Author Contribution: First Author: Developing questionnaire survey, data collection and analysis including manuscript writing. Second Author: Reviewed literature and editing the manuscript. Englishhttp://ijcrr.com/abstract.php?article_id=4326http://ijcrr.com/article_html.php?did=4326  India-Gulf Migration. Available from:https://www.mei.edu/publications/india-gulf-migration-testing-time.[Last accessed on 2021 June 15] Benach J, Muntaner C, Chung H, Benavides FG. Immigration, employment relations, and health: developing a research agenda. Am J Ind Med.2010;53:338–43 Khadria B. Skilled labour migration from developing countries: study of India. Geneva: International Labour Office; 2002 (International Migration Papers, No. 49) Irudaya RS, Kumar P. 2010. Historical overview of international migration. In Governance and Labour Migration. India Migration Report 2010, Irudaya RS (ed.). Routledge: London, New York and New Delhi;1–29 Czaika, M. Internal versus international migration and the role of multiple deprivations: some evidence from India. Asian Population Studies, Asian Population Studies.2012; 8(2),125-149 Eevit Z, Zachariah KC. (1978). International labour migration. Finance and Development. 1978;15(4) Shah, Nasra, “Recent Immigration Policies in the Oil-Rich Gulf: How Effective are they likely to be?” ILO Asian Regional Programme on Governance of Labor Migration, WP No. 3, 2008 Czaika M, Varela M. V. Labour market activity, occupational change and length of stay in the gulf. Migration Studies.2014;3,315-342 Castelli F. Drivers of migration: why do people move? J Travel Med 2018;25(1) Bhugra D, Becker MA. Migration, cultural bereavement and cultural identity. World Psychiatry.2005;4(1):18-24 Spencer (ed) S, Johnson MRD, Phillips D, Rudiger A, Somerville W, Wintour P, Refugees and other new migrants: a review of the evidence on successful approaches to integration,(2004)iii-39 Raphaely N: Understanding the health needs of migrants in the South East Region. London: Health Protection Agency and Department of Health,2010 Zimmerman C, Hossain M, Yun K., The health of trafficked women: a survey of women entering post trafficking services in Europe. Am J Public Health. 2008;98(1):55–59 Bhugra D, Jones P. Migration and mental health. Advances in Psychiatric Treatment.2001;7:216–222 Mou J, Cheng J, Zhang D, Jiang H, Lin L, Griffiths SM: Health care Utilisation amongst Shenzhen migrant workers: Does being insured make a difference? BMC Health Service Research 2009,9:241 Mucci N, Traversini V, Giorgi G, Tommasi E, De Sio S, Arcangeli G. Migrant workers and psychological health: a systematic review. Sustainability. 2019;12(1):120 Mehlum IS, Kjuus H, Veiersted KB, Wergeland E. Self-reported work-related health problems from the Oslo Health Study. Occup Med (Lond) 2006;56:371–379 de Castro AB, Gee GC, Takeuchi DT. Job-related stress and chronic health conditions among Filipino immigrants. J Immigr Minor Health.2008;10(6):551–558 Joshi S, Simkhada P, Prescott GJ: Health problems of Nepalese migrants working in three Gulf countries. Bmc Int Health Hum R. 2011,11:3-10.1186/1472-698X-11-3 World Bank, “Migration and Remittances Recent Developments and Outlook; 2019. Available from:https://www.knomad.org/sites/default/files/2019-04/Migration and Development Brief_31_0.pdf.[Last accessed on 2021 June 19] Arabian Business. Indian workers migrating to Gulf region dropped 21% in 2018. Available from:https://www.arabianbusiness.com/politics-economics/411281-indian-workers-migrating-to-gulf-region-dropped-21-in-2018.[Last accessed on 2021 June 20] ILO 2012 Global estimate of forced labour Executive summary. Available from:https://www.ilo.org/wcmsp5/groups/public/---ed_norm/---declaration/documents/publication/wcms_181953.pdf.[Last accessed on 2021 June 22]. The plight of Indian migrant workers in Gulf countries; 2020. Available from:https://blog.ipleaders.in/plight-indian-migrant-workers-gulf-countries/.[Last accessed on 2021 June 22] Kusuma YS, Babu BV. Migration and health: a systematic review on health and health care of internal migrants in India. Int J Health Plann Manag.2018;33(4):775–93 Rafiuddin M, Kalpana K. Psychosocial Workplace Factors and Health Problems among Indian Migrants in Gulf Cooperation Council Countries.Indian J Public Health Res Dev. 2022;13(1)290-300 Kamat A, “The Men in the Middle,” Dissent 62,2(2015):65-72 Diop A, Johnston T,  Le KT. Migration policies across the GCC: Challenges in reforming the Kafala. In P. Fargues and N. Shah (Eds.), Migration to the Gulf: Policies in Sending and Receiving Countries.2018;(pp. 33–60. Unpaid and abandoned: the abuse of Mercury MENA workers. Available from:https://www.amnesty.org/en/latest/research/2018/09/mercury-mena-abuses-qatar/.[Last accessed on 2021 June 23] Plant, Roger,“Temporary Contract Labour in the Gulf States: Perspectives from Two Countries of Origin”, paper presented at the Gulf Forum on Temporary Contractual Labor, 23–24 January 2008. Beshwari M, Bener A, Ameen A, Al-Mehdi A, Ouda H, Pasha M: Pesticide-related health problems and diseases among farmers in the United Arab Emirates. Int. J. Environ. Health Res..1999,9:213-221 Bener A. Health status and working condition of migrant workers: major public health problems. Int J Prev Med.2017;8:68 Fargues, Philippe, Shah, Nasra M., Brouwer, Imco. “Working and Living Conditions of Low-Income Migrant Workers in the Hospitality and Construction Sectors in the United Arab Emirates”, Gulf Labour Markets, Migration and Population Programme (2019):1-79 Petrie JR, Guzik TJ, Touyz RM.Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms. Can J Cardiol 2018;34:575–584 Mishra SR, Ghimire S, Joshi C, Gyawali B, Shrestha A, Neupane D, et al. Cardio-metabolic disease risk factors among South Asian labour migrants to the Middle East:a scoping review and policy analysis. Global Health. 2019;15(1):33 Asgary R, Segar N. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcareComparative Evaluation of Haemodynamic Changes in Patients Undergoing Surgical Removal of Bilateral Impacted Lower Third Molars using 2% Lidocaine vs 4% Articaine with 1:100000 Epinephrine Concentration: A Double-Blind Randomised Study     English6873Shenoy K VandanaEnglish Dutta RonEnglish G GayathriEnglish Mohamed AfradhEnglish Kumar K SenthilEnglishIntroduction: Impacted mandibular third molars are one of the most common findings in the field of dentistry which requires surgical removal. Local Anaesthetics plays a major role to perform the procedure pain-free although the anesthetics may exhibit some haemodynamic changes. Aim: This study aimed to assess and compare the hemodynamic changes during the surgical removal of lower bilateral impacted third molars using local anaesthetic agents 2% Lidocaine or 4%Articaine both in conjunction with 1:100000 epinephrine concentration. Methodology: Forty-one patients with a mean age of 32.6 were enrolled to bilateral surgical removal of lower impacted third molars with an interval of three to four weeks between each surgery. Clinical parameters like Heart Rate, Systolic Blood Pressure, Diastolic Blood Pressure, Mean Arterial Pressure, Peripheral Saturation of Oxygen, Temperature and calculated parameters like Rate Pressure Product and Pressure Rate Quotient were assessed at three different time points: baselilne (Pre-operatively), Osteotomy/Odontosection/Luxation (Intra-operatively) and five minutes after completion of suture (Post-operatively). Result: Forty-one patients underwent thorough clinical examination, among which 33 patients fulfilled the criteria as they participated in both the surgical procedures. The present study found significant difference in the haemodynamic changes when comparing between the three-time intervals in each group during the surgical procedure Conclusion: No significant differences were found when comparing the hemodynamic behavior between both the groups (2% lidocaine and 4% articaine) although significant differences were noted when comparing between the time points within each group. EnglishLidocaine, Articaine, Epinephrine, Anaesthetic, HaemodynamicINTRODUCTION The surgical removal of third molars is the most common and routine procedure in the field of Oral and Maxillofacial Surgery. Local anesthetic plays a major role in limiting pain and providing a pain-free procedure. Most of the local anesthetics are generally used in conjunction with a vasoconstrictor to delay the absorption of the local anesthetic prolonging the duration of the anesthetic and also providing a bloodless field. In the literature by Neves et al.1,2007and Elad et al.2,2008 have confirmed the safety of using a local anaesthetic with a vasoconstrictor. Other few kinds of literature by Vasconcellos et al.3,2008 and Sancho-Puchades et al.4,2012 have reported that patients who undergo surgical removal of third molars showed significant variations in blood pressure and heart rate. Articaine is an amide local anesthetic that contains a ‘thiophene’ ring instead of an aromatic ring thereby increasing liposolubility and potency. The aim of the study is to assess and compare the hemodynamic effects on patients undergoing surgical removal of lower third molar using 2 % lidocaine hydrochloride with 1:100000 concentration of epinephrine and 4 % articaine hydrochloride with 1:100000 concentration of epinephrine. MATERIALS AND METHOD Study design: This retrospective, randomised, controlled double-blinded split-mouth study is approved by the Ethical Committee of the author’s University. All of the participants enrolled in the study read and signed an informed consent confirming their acceptance to take part in the study. The study composed of two groups: Group A (procedure done under 2% Lidocaine with 1:100000 Epinephrine) and Group B (procedure done under 4% Articaine with 1:100000 Epinephrine) Sample Design 41 healthy individuals aged between 18-40 years from September 2019 to March 2020 undergoing surgical removal of bilateral lower third molar impaction with a time interval of 3-4 weeks between the two surgical extractions were included in this study based on clinical examinations and radiographs. Impactions grading moderately difficult according to Pederson Scale was included in the study. The following exclusion criteria were applied: Patients with general health issues like hypertension, diabetes and cardiac disorders, patients with hypersensitivity to the drugs used in research, pregnant or lactating women, patients on blood thinners and mentally challenged patients. Blinding Details Both surgeon and patient were blinded on what anaesthetic solution is been used. Blinding technique was done by covering the cartridge with two colored tapes to separate the two study groups. Only the assistant had access to the colour codes. On initial examination, the patient was directed to select from two sealed envelopes referring to the site of surgical removal (i.e. impacted 38 or impacted 48) along with the color-coded cartridge containing the anaesthetic agent (i.e. either 2% Lidocaine or 4% Articaine) both of which used in conjunction with 1:100000 Epinephrine concentration. As soon as the assistant opened the envelope, the surgeon was informed about the site of surgery and the colour-coded anaesthetic cartridge was given. The second surgery was carried out on the contralateral side with the other type of anaesthetic agent after 3-4 weeks. Study Variables Clinical parameters like Heart Rate (HR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Peripheral O2 Saturation (SpO2) and Temperature (Temp.)(?C) and calculated parameters as Mean Arterial Pressure (MAP), Rate Pressure Product (RPP) and Pressure Rate Quotient (PRQ) at three different time points during the surgical procedure:(1) Baseline at rest (Preoperative), (2) incision, flap elevation, osteotomy after administration of local anaesthetics (Intraoperative) and (3) five minutes after completion of suture (Postoperative). All of the clinical parameters were recorded using a Multi-Para Monitor (Contec 12.1) Procedure Patients who satisfied the criteria underwent detailed clinical examination. All the procedures were performed by the same operator. No premedication were pescribed to any of the participants. All the clinical parameters (HR, SBP, DBP, SpO2 and Temp.) were assessed prior to the surgery (Preoperative). The patient was asked to do mouthwash with 2% Povidone-Iodine Germicide Gargle prior to the surgery. Inferior Alveolar Nerve Block (IANB) along with long buccal nerve block was administered using 2% Lidocaine with 1:100000 Epinephrine concentration (Henry Schein) 1.7mL cartridge or 4% Articaine with 1:100000 Epinephrine concentration (Septodont) with 1.7mL cartridge, using a volume of 3.4mL (2 cartridges). The method used was standard for all of the surgical procedures. Ward&#39;s/Modified ward&#39;s incision was placed and the mucoperiosteal flap elevated and reflected and osteotomy was done. The parameters were recorded once again (Intraoperative). In few patients, odonto section had to be done and extracted. The tooth socket was cleaned by copious saline irrigation and curretage. The flap was sutured and approximated using 3-0 silk and hemostasis was achieved. After five minutes the clinical parameters were recorded again (Postoperative). After all surgical procedures, the patients received post-extraction instructions and were prescribed with the appropriate medications for the controlled of the post operative management. Statistical Analysis: The data analysis was conducted using EPI INFO statistical software (version 7.2.2.6, CDC, Atlanta, Georgia US). The normality of the data was confirmed by Shapiro-Wilk test. Homogeneity of variances was assessed using levene&#39;s test. Descriptive statistics, Independent t-test and Paired t-test was used Results: Forty-one patients underwent thorough clinical examination, but eight of them did not complete all stages as they did not undergo surgical removal of lower impacted third molar on the contralateral side. Therefore 33 patients (19 men and 14 women) with a mean age of 30.8 years and (SD = 12.52), participated in both the surgical procedures. All the haemodynamic parameters were found to have no significant difference between the mean values for HR (Fig 1), SBP (Fig 2), DBP (Fig 3), MAP (Fig 4), SpO2(Fig 5), Temp, RPP (Fig 6) and PRQ when comparing the two anaesthetic groups (i.e 2% Lidocaine and 4% Articaine) both in conjunction with 1:100000 Epinephrine concentration at Preoperative, Intraoperative and Postoperative time intervals. The present study found significant difference in the haemodynamic changes when comparing between the three-time intervals in each group which can relate to patients anxiety and stress during the surgical procedure. HR and RPP showed significant differences in both groups. In the Lidocaine group (i.e. Group A) both HR (p=0.01) and RPP (p=0.006) showed a significant increase from the Preoperative to Intra-operative time interval. In Articaine group (i.e Group B) following significant differences were found: HR (p=0.017), SBP (p=0.00), DBP (p=0.016), MAP (p=0.00), SpO2(p=0.007), RPP (p=0.001) showed significant increase when comparing Preoperative and Intra-operative time intervals. (Table I) DISCUSSION: The present study confirms that no significant difference in the hemodynamic parameters between 2% Lidocaine and 4% Articaine both in conjunction with 1:100000 Epinephrine concentration. Even though there was no significant difference between the two groups, the present study assessed and found significant differences in three different time points throughout the surgical procedure. To eliminate any individual bias, a split-mouth design was used and also to minimize any bias based on the volume of anesthetic solution used, a cartridge each containing 1.7mL was used which doesn’t correlate with earlier studies by Columbini et al.5,2006, Santos et al.6, 2007, Vasconcellos et al.3,2008 and de Morais et al.7,2012 A Multiparametric Vital Signs Monitor (Contec 12.1) was used to assess the hemodynamic parameters and made it possible to record the parameters during the surgical procedure so that a thorough assessment of the haemodynamic variation could be performed unlike earlier studies by Vasconcellos et al.3, 2008; Mestre Aspa et al.9, 2001; Sancho-Puchades et al.4, 2012; de Morais et al.7,8, 2012 A previous study by Stella et al.10, 2018 compared the same two local anesthetic drugs as our study using a similar multi-parametric monitor where the author assessed seven different time points throughout the procedure on 12 patients. The author reported no variation in the hemodynamic status of the patients undergoing lower third molar extraction when comparing between 2% Lidocaine and 4% Articaine but the author reported significant differences when comparing the different time points during the procedure within each group which correlates with our study. Our present study comprised of larger population comprising of 41 patients with three-time intervals, the results are almost similar and also similar to other previous literature as well (Oretel et al.11 1999, Malamed et al.12 2001, Ogunlewe et al.13 2011, Silvestre et al.14 2011, de Morais et al.7,8 2012). Malamed et al.12 in 2001, studied the safety of an amide local anaesthetic agent (4% Articaine). The author compared with 2% Lidocaine (controlled group) to measure the postprocedural pain, headache, facial edema, infection, gingivitis and paresthesia on 1325 participants. The study included various dental procedures ranging from single extraction to multiple extractions but did not include surgical removal of impacted molars. Also the volume of local anaesthetic drug used varied according to the amount of anesthesia needed for achieving pulpal and soft tissue anesthesia which did not correlate to our study. Vital signs were recorded (Systolic Blood Pressure, Diastolic Blood Pressure, Heart Rate and Respiratory Rate) at one and five minutes post-administration of the drug and completion of the procedure. The author found no statistical difference between the two groups similar to our present study. A Study by Ogunlewe et al.13 in 2011, checked only 2% Lidocaine with and without vasoconstrictor on hypertensive patients. The study was conducted in 33 patients indicated for dental extraction and evaluated on Systolic Blood Pressure, Diastolic Blood Pressure and Heart Rate in both groups. The study did not include any surgical removal of impacted molars to assess the hemodynamic changes in the two groups but results are similar to our present study with the group containing 2% Lidocaine with a vasoconstrictor (epinephrine). Silvestre et al.14 in 2011 studied on 97 hypertensive patients having the maximum Systolic Blood Pressure of 139mmHg and Diastolic Blood Pressure of 84mmHg between two anaesthetic agents 4% Articaine with vasoconstrictor vs 3% Mepivacaine without vasoconstrictor. The hemodynamic parameters included in the study are Blood Pressure, Heart Rate and SpO2 and checked at three-time points on the participants who were undergoing single tooth extraction and extraction of erupted third molars. No Multi-parameter monitor was used in the study which couldn’t accomplish monitoring the hemodynamic changes during the procedure. de Morais et al.7 in 2012did a similar split-mouth design study comparing the same two local anaesthetic agents on patients undergoing surgical removal of bilateral impaction of lower third molars. In this study the author included only those patients who had similar type of impaction, as in our present study impaction with a moderate Pederson score was included. The author excluded all surgical procedures exceeding more than 30 minutes and the procedure were done by different operator,s unlike our study where all procedures were done by a single operator. The hemodynamic changes revealed significant differences in Pressure Rate Quotient (PRQ) between the two groups but showed similar results when comparing the different time points in each group, whereas in the study conducted by the present author Pressure Rate Quotient (PRQ) was found to have no significant differences. CONCLUSION The study was conducted to evaluate and compare the two local anesthetic agents with similar concentrations of epinephrine on patients while recording the clinical hemodynamic parameters. Either of the local anaesthetic did not show any major advantage over the other. 4 % Articaine with 1:100000 concentration of epinephrine provides similar quality of anaesthesia to 2 % Lidocaine with 1:100000 concentration of epinephrine. Hence use of both types of local anaesthetic can be considered for minor oral surgical procedures. 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 the authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed Funding: No funding was received Conflict of interests/ Competing interests: The author declares that they have no conflict of interest Ethical Approval: This study was approved by the research ethics committee of Dr. M.G.R. Educational and Research Institute (Ref: Dr.M.G.R/DU/TMDCH/EC/2020-21/334) Englishhttp://ijcrr.com/abstract.php?article_id=4327http://ijcrr.com/article_html.php?did=4327 Neves RS, Neves ILI, Giorgi DMA, Grupi CJ, César LAM, Hueb W, et al. Efeitos do uso da adrenalina na anestesia local odontológica em portador de coronariopatia. Arquivos Brasileiros de Cardiologia. 2007 May;88(5):545–51.https://doi.org/10.1590/S0066-782X2007000500008  Elad. S, Admon. D, Kedmi. M, Naveh. E, Benzki. E, Ayalon. S, Tuchband. A, Lutan. H, Kaufman. E, et al. The cardiovascular effect of local anesthesia with articaine plus 1:200,000 adrenalin versus lidocaine plus 1:100,000 adrenalin in medically compromised cardiac patients: a prospective, randomized, double-blinded study. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod.,105(6):725-30, 2008. doi: 10.1016/j.tripleo.2008.02.005. de Holanda Vasconcellos RJ, do Egito Vasconcelos BC, Genú PR. Influence of local anesthethics with adrenalina 1: 100.000 in basic vital constants during third molar surgery. Med Oral Patol Oral Cir Bucal. 2008;13:E431–7. PMID: 18587307 Sancho-Puchades M, Vílchez-Pérez MA, Valmaseda-Castellón E, Paredes-García J, Berini-Aytés L, Gay-Escoda C et al. Bupivacaine 0.5 % versus articaine 4 % for the removal of lower  third molars. A crossover randomized controlled trial. Med Oral Patol Oral Cir Bucal. 2012 May;17(3):e462–8. doi: 10.4317/medoral.17628 Colombini BL, Modena KCS, Calvo AM, Sakai VT, Giglio FPM, Dionísio TJ, et al. Articaine and mepivacaine efficacy in postoperative analgesia for lower third molar removal: a double-blind, randomized, crossover study. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2006 Aug 1;102(2):169–74. doi: 10.1016/j.tripleo.2005.09.003 Santos. C. F, Modena. K. C, Giglio. F. P, Sakai. V. T, Calvo A. M, Colombini. B. L, Sipert. C. R, Dion.sio. T. J, Faria. F. A, Trindade. A. S. Jr, Lauris. J. R, et al. Epinephrine concentration (1:100,000 or 1:200,000) does not affect the clinical efficacy of 4% articaine for lower third molar removal: a double-blind, randomized, crossover study. J. Oral Maxillofac. Surg.,65(12):2445-52, 2007. doi:10.1016/j.joms.2007.04.020 de Morais HHA, de Santana Santos T, da Costa Araújo FA, de Freitas Xavier RL, Vajgel A, de Holanda Vasconcellos RJ et al. Hemodynamic Changes Comparing 2% Lidocaine and 4% Articaine With Epinephrine 1: 100,000 in Lower Third Molar Surgery. J Craniofac Surg. 2012 Jul;23(4):1204–1211. DOI: 10.1097/SCS.0b013e31824f66a0 de Morais HHA, de Santana Santos T, Araújo FA da C, Vajgel A, de Holanda Vasconcellos RJ. Hemodynamic Changes Comparing Lidocaine HCl With Epinephrine and Articaine HCl With Epinephrine. J Craniofac Surg. 2012 Nov;23(6):1703–1708. DOI: 10.1097/SCS.0b013e31826bec3b Mestre Aspa. R, Carrera Gra. I Berini Ayt.s. L, Gay Escoda. C, Pulsioxymetry monitorization during lower third molar extraction. A comparative study of three local anesthetics with epinephrine 1:100,000. Med. Oral, 6(3):195-204, 2011. PMID: 11500637  Stella PEM, Falci SGM, Coelho VS, dos-Santos CRR. Hemodynamic Behavior in Third Molar Surgeries Using Lidocaine or Articaine. Int J Odontostomat. 2018 Mar;12(1):76–85. DOI: 10.4067/S0718-381X2018000100076 Oertel, R.; Ebert, U.; Rahn, R. & Kirch, W. The effect of age on pharmacokinetics of the local anesthetic drug articaine. Reg. Anesth. Pain Med., 24(6):524-8, 1999. doi: 10.1016/s1098-7339(99)90043-3. Malamed SF, Gagnon S, Leblanc D. Articaine hydrochloride: a study of the safety of a new amide local anesthetic. J Am Dent Assoc. 2001;132(2):177–185. https://doi.org/10.14219/jada.archive.2001.0152 Ogunlewe MO, James O, Ajuluchukwu JN, Ladeinde AL, Adeyemo WL, Gbotolorun OM et al. Evaluation of haemodynamic changes in hypertensive patients during tooth extraction under local anaesthesia. 2011 Jan 1 [cited 2020 Dec 2]; Available from: https://ir.unilag.edu.ng/handle/123456789/6459 Silvestre FJ, Salvador-Martínez I, Bautista D, Silvestre-Rangil J. Clinical study of hemodynamic changes during extraction in controlled hypertensive patients. Med Oral Patol Oral Cir Bucal. 2011 May 1;16(3):354-8.  doi: 10.4317/medoral.16.e354

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcareA Comparative Study on Maternal Outcome in Emergency LSCS Versus Elective Lscs in a Tertiary Care Hospital in Karnataka English7479Saniyah Khan GalzieEnglish Smitha B. RaoEnglishIntroduction: Caesarean section is the delivery of a baby, alive or dead, through an abdominal uterine incision after the period of viability. RCOG proposed a classification relating the degree of urgency to the presence or absence of maternal or fetal compromise. The nature of the caesarean section performed as emergency (category 1&2) or elective (category 3&4) is predicted depending on the indication. This study was conducted to study the indications and compare the maternal intrapartum and postpartum complications in both groups. Materials and Methodology: A prospective observational study on maternal outcome in an emergency (RCOG category 1&2) and elective (RCOG category 3&4) caesarean section was carried out in Yenepoya Medical College Hospital. Sample size was 100 with 50 participants in each group. Relevant antenatal, intranatal data, indications of LSCS, intraoperative and postoperative complications, were collected from the patients. Results: Out of the 100 participants, primigravidas accounted for 24 % of the total caesarean sections & 46% of those who underwent emergency LSCS. Whereas gravida 2 comprised 41% of the total caesarean sections and 56% of those who underwent elective caesarean section. This difference in the obstetric score was highly significant (p= 0.000). The most common indication of LSCS in the elective group was previous 1 LSCS not willing for VBAC, accounting for 68%, whereas most common indication for emergency LSCS was fetal distress, accounting for 32%. Conclusion: Primigravidae are more prone for emergency caesarean section. Fetal distress was the most common indication of emergency caesarean section mainly in primigravidae; meticulous labor management may help in decreasing the same. Elective caesarean section rates may be brought down by decreasing the rate of primary caesarean section, as most women in this group had undergone caesarean section due to previous LSCS. English Caesarean complications, Caesarean outcome, Emergency LSCS, Elective LSCS, Maternal outcome, Previous caesarean sectionINTRODUCTION: Caesarean section is the delivery of a baby, alive or dead, through an abdominal uterine incision after the period of viability.1RCOG2 proposed a classification relating the degree of urgency to the presence or absence of maternal or fetal compromise. Category 1: Immediate threat to life of woman or fetus; maternal or fetal compromise present. Category2: No immediate threat to life of woman or fetus, maternal or fetal compromise present. Category 3: Requires early delivery; without maternal or fetal compromise. Category 4: At a time to suit the woman and maternity services; absence of maternal or fetal compromise. The nature of the caesarean section performed as emergency (category 1 & 2) or elective (category3 & 4) is predicted depending on the indication of the caesarean section. Emergency caesarean section is defined as when the procedure is performed due to unforeseen complications, arising either during pregnancy or during labor without wasting time following the decision. Some common indications of emergency caesarean section are fetal distress, secondary arrest of dilatation, failed induction, etc. Elective caesarean section means when the operation is done at a prearranged time during pregnancy to ensure the best quality of obstetrics, anaesthesia, neonatal resuscitation and nursing services prior to the onset of labor.3Common indications of elective caesarean section are malpresentation, previous multiple caesarean section, previous 1LSCS not willing for VBAC etc. This study was conducted to study the indications and compare the intrapartum and postpartum complications in mothers in both groups. MATERIALS AND METHODS: A prospective observational comparative study on maternal outcome in Emergency (RCOG category 1 & 2) and Elective (RCOG category 3 & 4) caesarean section was carried out in Yenepoya Medical College Hospital, Department of Obstetrics and Gynaecology, after obtaining clearance from the Institutional Ethics Committee. Sampling method: Convenience sampling method. SAMPLE SIZE: Sampling size calculation: Calculated using G – power software with level of significance. Alpha= 5%, power 1- Beta = 80% with 95% confidence interval. The minimum sample size required in each group is 50.The total sample size is 100. SPSS22 was used for statistical analysis. Methodology: Relevant antenatal, intranatal data, indications of LSCS, intraoperative and postoperative complications, were collected from the patients presenting to the Department of Obstetrics and Gynecology at Yenepoya Medical College Hospital as per the inclusion criteria. Written informed consent was taken. In this study two groups of pregnant females were studied. Group1: Women undergoing elective caesarean sections. (RCOG Category 3&4) Group 2: Women undergoing emergency caesarean section (RCOG Category 1 & 2) Inclusion criteria: All pregnant women with singleton pregnancy, irrespective of parity status Without pregnancy-associated complications Without any medical risk. Without surgical high risk With any gestational age Irrespective of their registration status (patients who are referred at the time of delivery and those registered in the antenatal period). Exclusion criteria: All high-risk pregnancies Multiple pregnancies Placenta praevia Abruptio placenta Diabetes in pregnancy Severe anaemia (haemoglobin 24 hrs, More than 2 previous LSCS RESULTS: A total of 100 participants were included in the study. They were divided into two groups, those who had an elective caesarean section (50) and those who had an emergency cesarean section (50). OBSTETRIC SCORE: (TABLE 1) Out of the 100 participants, primigravidas accounted for 24 % of the total caesarean sections & 46%of those who underwent emergency LSCS. Whereas gravida 2 comprised 41 % of the total caesarean sections and 56% of those who underwent elective caesarean section. This difference in the obstetric score was highly significant (p= 0.000). AGE DISTRIBUTION: (TABLE 2) Age groups between 18 – 25 years accounted for 50% of the participants who underwent emergency LSCS. Whereas the age group between 26 – 30 years accounted for 54% of those who underwent elective caesarean section. TYPE OF ANAESTHESIA: TABLE 3 Out of the 100 participants, 99 were done under spinal anaesthesia (SA). Only 1 participant was given general anaesthesia from the elective LSCS group, after attempts to give spinal anaesthesia failed in the participant. INDICATIONS OF CAESAREAN SECTION: TABLE 4 The most common indication of LSCS in the elective group was previous 1 LSCS not willing for VBAC, accounting to 68%, whereas most common indication for emergency LSCS was fetal distress, accounting to 32%. This difference was statistically significant (p=0.000). INTRAOPERATIVE COMPLICATIONS: TABLE 5 The most common complication was same in both the groups, i.e. primary hemorrhage > 500 ml with the use of additional oxytocic agents for management of uterine atony. POSTOPERATIVE COMPLICATIONS: TABLE 6 Postoperative complications were more in emergency caesarean section group. This difference was not statistically significant (p=0.400). The most common complication in emergency caesarean section group was fever. In the elective caesarean section group, blood transfusion was needed in 2 patients accounting for 4% in the elective caesarean section group. HOSPITAL STAY: TABLE 7 2 participants who belonged to the emergency caesarean section group had prolonged hospital stay due to fetal morbidity, i.e. Respiratory distress syndrome and sepsis. DISCUSSION: In our study primigravidae accounted for 24% (24 participants) of the overall study population who underwent caesarean section out of which 95.8% (i.e. 23 participants) underwent emergency LSCS for various indications. Multigravidas comprised 76% of the study population, however 65% had previous caesarean section, (previous 1&2 LSCS) which was a major factor contributing to the repeat caesarean section, either Emergency or Elective. Therefore the primary caesarean section rate in a primigravida was higher (24%), than a multigravida (11%). This was similar to the study conducted by Shrutee et al. 4 in which total 4981 deliveries were observed, of which 2179 were primigravida and 2802 were multigravida. The incidence of primary caesarean section was much higher in primigravida(21.80%) than multigravida (9.81%) (p-value 500 ml with the use of additional oxytocics for management of uterine atony. In study by K Gandhi et al.12, intraoperative complications were 10.25% and 4% respectively in the emergency cesarean section group and elective caesarean section group. Hemorrhage was most common intraoperative complication of both the groups, which was similar to our study. Postoperative complications were 4% in elective cesarean section group and 10% in emergency caesarean section group in the study. The most common complication in emergency cesarean section group was fever, which in total comprised 6% of the total complication rate in emergency caesarean section. Blood transfusion was required in 2 patients accounting for 4% in the elective caesarean section group. However this difference was not statistically significant. K Gandhi et al.12 found in their study that postoperative complications were also more in emergency caesarean sections (33.4%) than elective cases (21.6%). Fever was observed in 10.51% and 7.2% in emergency and elective caesarean sections respectively. Partha P et al.13, observed in their study that overall, maternal morbidities were more in the emergency caesarean section (82/773,10.60%) than planned caesarean section (15/230,6.52%) with p= 0.066. Pyrexia and blood transfusion were significant (p=0.000) in the emergency caesarean section group. There were no cases of maternal mortality in our study. A study conducted by Subeidi et al.14, also did not report any incidence of maternal mortality in their study. Of the 100 participants 99 % had usual hospital stay (5-7 days). However, 2participants (4%) had prolonged hospital in the emergency caesarean section group. This was not statistically significant. Al Nuaim et al.15 reported that 36.5% of emergency group stayed for more than 7 days and 39.8% of elective cases stayed for more than 7 days also, which was not statisEnglishhttp://ijcrr.com/abstract.php?article_id=4328http://ijcrr.com/article_html.php?did=4328 Misra R. Ian Donald’s Practical Obstetric Problem, Caesarean birth. 8th ed.New Delhi:Wolters Kluwer (India) PvtLtd; 2020. p.615. RCOG and RCOA. Classification of Urgency of Caesarean Section – A Continuum of Risk. Good Practice No. 11. 2010:2 Sebastian G, Ghose S, Soundarara Jan P. Comparison of maternal and neonatal outcome in elective lower segment cesarean section done at 38 and 39 weeks. IJRCOG. 2017;6(4):1604-9. Birla S, Gupta M, Birla P, Sharma J. Comparison of incidence, indication and complication of primary cesarean section in primigravida and multigravida. IJMS. 2016;3(3):311-7. Kaur S. Increasing Caesarean Rates: Analysis of Indications and Possible Interventions. JMDS. 2018 Aug 13;7(2):1663-6. Soren R, Maitra N, Patel PK, Sheth T. Elective versus emergency cesarean section: maternal complications and neonatal outcomes. IOSR J Nurs Health Sci. 2016;5(5):2320. Suwal A, Shrivastava VR, Giri A. Maternal and fetal outcome in elective versus emergency cesarean section. JNMA. 2013 Oct 1;52(192). Yeoh SB, Leong SB, Heng AS. Anaesthesia for lower-segment cesarean section: Changing perspectives. IJ. Anaesth. 2010 Sep;54(5):409. Van de Velde M. Anaesthesia for cesarean section. Current Opinion in Anesthesiology. 2001 Jun 1;14(3):307-10. Gurunule AA, Warke HS. Maternal and fetal outcome in elective versus emergency cesarean sections. IJRCOG. 2017 Apr 1;6(4):1222-9. Thakur V, Chiheriya H, Thakur A, Mourya S. Study of maternal and fetal outcome in elective and emergency cesarean section. IJMRR.2015;3(11):1300-5. Gandhi K, Dahiya K, Gandhi K. Maternal and neonatal outcome in 1000 cesarean sections. IJHBR. 2017 Apr;5(03):123-34. Sharma PP, Giri DK, Bera SN. Planned versus emergency cesarean delivery with previous one cesarean section: a prospective observational study. IJRCOG. 2018 Oct 1;7(10):4223-9. Subedi A, Shrestha J, Adhikari KM, Shrestha A, Gurung S. Comparison of Maternal and Perinatal Outcome in Elective and Emergency Cesarean Section in a Tertiary Care Centre. BJHS. 2019 May 3;4(1):616-20. Al Nuaim L, Soltan MH, Khashoggi T, Addar M, Chowdhury N, Adelusi B. Outcome in elective and emergency cesarean sections: a comparative study. ASM. 1996 Nov;16(6):645-9.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcareComparison of Effects of Quadriceps Versus Short Foot Exercises on Pain and Navicular Drop-in Patients with Anterior Knee Pain English8084Khan SeemabEnglish Agrawal RonikaEnglish Siddiqui MisbahEnglishIntroduction: Pronation of foot and reduced medial longitudinal arch (MLA) can result in patellar tracking dysfunction causing anterior knee pain. The treatment protocol commonly includes hip and knee muscle strengthening and patellar taping etc. correcting the biomechanical alignment of the foot by maintaining the MLA height is of great importance in treatment of anterior knee pain. Aim: To compare the effects of quadriceps exercises versus foot exercises on pain and Navicular drop in patients with anterior knee pain. Methodology: The 60 subjects were divided into two groups - A and B, where group A was given foot exercises while group B was given knee exercises. Outcome measures were Visual analog scale (VAS), Navicular drop and KOS-ADL score taken before and after six weeks of intervention. Results: Both the interventions were effective in reducing pain and navicular drop in patients with anterior knee pain. Conclusion: Better result in Navicular drop was found in subjects given short foot exercises while VAS score and KOS-ADL score improved more in subjects who were given quadriceps exercises. EnglishAnterior knee pain, Medial longitudinal arch, Navicular drop, Quadriceps exercise, Short foot exercises, Visual analog scaleINTRODUCTION Anterior knee pain is known as knee pain caused by the aberrant motion of the patella in the trochlear groove, which results from biomechanical and/or physical changes within the patellofemoral joint. 1   There is a strong correlation between pronated foot and reduced MLA therefore anterior knee pain can be prevented by maintaining the integrity of the arch. Many studies suggest the use of weight-bearing as well as non–weight-bearing quadriceps exercises in the rehabilitation programme of anterior knee pain.2 Thus the purpose of this study is to compare the effects of quadriceps exercises versus short foot exercises on pain and navicular drop in patients with anterior knee pain. METHOD After the approval from ethics committee of the institute, subjects having knee pain were screened, 60 subjects meeting the inclusion criteria as having anterior knee pain for at least past 3 months and reported pain in 2 or more daily activities like ascending and descending stairs, squatting, kneeling, jumping and long sitting. pain on palpation of the medial and/or lateral facet of the patella and Navicular drop test more than or equal to 15mm. patients with any knee pathology, recent injury of lower limb and on any other treatment for anterior knee pain were excluded.  All the subjects were asked to fill a consent form after a thorough explanation of the testing procedure, protocol and training and their doubts and queries were cleared. Subjects were then randomly allocated by chit method in two groups namely- Group A and Group B. The measurements of the variables i.e. the Visual analogue scale, Navicular drop test and KOS-ADL Scale were taken at the beginning and after 6 weeks of intervention for both the groups. Outcome measures Visual Analogue Scale: The pain severity was documented using the visual analogue scale (VAS). Test-retest reliability is 0.77 and the Validity of it is 0.76 3 Navicular Drop test:  Navicular drop can be used to measure the amount of pronation of foot  The ICC validity value for Navicular drop is 0.745 and intra- and inter-rater reliability is 0.76- and 0.84 4 KOS-ADL the Knee Outcome Survey-Activities of Daily Living scale (KOS-ADL) is an instrument that helps to determine the functional ability and disability of the patient. Validity is 0.89 and Test-retest reliability is 0.94. 5 Intervention Both the groups received the intervention for six sessions per week for 6 weeks. Ultrasound of 1 MHz with intensity of 1W/cm2, continuous mode was given around the anterior knee to both the groups for 6 mins during the first week of the treatment. 6 Subjects in the Group A were given the short Foot exercises. 7, 8 Subjects in Group B were given Quadriceps exercises.9, 10 Statistical analysis and results Statistical analyses were carried out using the Statistical software R studio version 3.6.2. Microsoft word and Excel were used to generate graphs, tables etc. Results of continuous measurements were presented on Mean ± SD. Level of significance was fixed at p=0.05 and any value less than or equal to 0.05 was considered to be statistically significant. Within-group comparison of visual analogue scale, navicular drop test and knee outcome survey questionnaire was done using Wilcoxon Signed Rank Test, while between-group comparison was done using the unpaired t test. The above table shows pre and post-intervention differences in Group A. As p-value is < 0.05 for all the three variables, it indicates that the VAS Score and Navicular drop have reduced significantly, while KOS.ADLS score has increased significantly after the treatment. The above table shows that p-value < 0.05 for all the three variables in Group B, it indicates that the VAS Score and Navicular drop have reduced significantly, while KOS.ADLS score has increased significantly after the treatment in Group B. The above table shows the intergroup comparison of group A and B. This shows that Knee Exercises given to Group B was more effective in reducing pain and improving function as seen in the VAS Score and KOS-ADL Scale. While foot exercises given to Group A was more effective in improving the Navicular Height. DISCUSSION This study aimed to compare the effects of quadriceps exercises versus foot exercises on pain and navicular drop in patients with anterior knee pain. Both group showed improvement in measures after 6 weeks of intervention. The statistical significance was also due to the healing effects of ultrasound. One of the main effect of ultrasound is acoustic streaming which enhances the flow of particles from one side of a cell membrane to the other, increasing the cell permeability which enhances healing and  reduces pain and inflammation. 6 According to table 3 there was statistically significant improvement in VAS, Navicular drop and KOS-ADL score in subjects of Group A. Exercises like the short foot exercises and toe-curl exercises have shown to improve the strength of intrinsic foot muscles which may help in controlling the excessive pronation at the subtalar joint position during the weight-bearing by maintaining the inner arch. This may be useful in reducing pain in PFPS by correcting the malalignment and the biomechanics that were altered due to pronated foot. 2 Strengthening of intrinsic foot muscles (IFM) by giving short foot exercises increases their activation while walking, which works like an elastic spring to support and maintain the MLA. It is therefore suggested that effective neuromuscular control of the intrinsic foot muscle is important so as to stabilize the tarsal and metatarsal bones and also to control the pronation of foot. This fine-tune control is required for static as well as dynamic control of the MLA during the gait cycle. 11 Previous study also describes the treatment of anterior knee pain by controlling foot movements, which reduces the pronation in the stance phase of gait, thus reducing internal tibial rotation and improving lower limb biomechanics. Thus the foot exercise were helpful in controlling the pronation of foot and hence correct the mechanics of lower extremity and was effective in reducing pain in subjects with anterior knee pain6. According to Table 4 and there was significant changes seen in VAS score, Navicular drop and KOS-ADL Score in subjects of Group B as well. One of the major contributors to anterior knee pain is Muscle dysfunction due to improper firing pattern and quadriceps weakness. Alteration in the contact area and pressure distribution is associated with an increase in strength which relieves the excessive stresses over the sensitive areas and helps in relieving pain. This may be due to changes in the muscle because of strength training, which further reduces the future tissue damage. 9 Similar study was done by another author who suggests that reduction in lateral tracking of patella during postural loading and dynamic actions is important to improve functions, which is achieved by resistance training of VMO 14 When the mechanics at the knee is corrected by correcting the patellar tracking with the help of quadriceps muscles activation, weight-bearing throughout the lower extremity improves and the pronation at the foot is also reduced. In a study by Danny M . Pincivero the recruitment efficiency from 10-90 degrees was more for Vastus lateralis, Vastus medialis was  from 70-90 degrees and that of Quadriceps femoris is greatest at 90 degrees .12 Thus the quadriceps exercise helps in controlling the patellar tracking and is helpful in reducing pain in subjects with anterior knee pain. When the results of both the groups were compared it was seen that foot exercises that were given to group A was more effective in improving the navicular drop in the subjects as seen in table 5. MLA is supported by many structures like plantar calcaneo-navicular ligament, extrinsic foot muscles such as tibialis posterior, intrinsic foot muscles (IFM) and plantar fascia. the main function of the MLA is to act as a shock absorber and distribution of the forces during walking. 13 Janda and VaVrova found that Short Foot exercise helped in strengthening intrinsic muscles of the foot which increased the inner arch of the foot, thereby shortening the longitudinal arch.14 Also in a study by Kyoung A Chunga, the navicular drop showed a significant decrease of 5.47 mm in the group that were given Short foot exercises and 3.93 mm in the Toe curl exercises15 When summarizing the findings of this study, it can be seen that both Short Foot Exercise and Toe Curl Exercise can be used in intrinsic foot muscle training and a significant improvement can be seen in navicular drop in subjects who have been given both these exercises and there was more improvement in Navicular drop in subjects of group A. Also in table 5, it is evident that there was more significant improvement in VAS score and KOS ADL score in Group B that were given quadriceps exercises.  Quadriceps exercises increases knee muscle strength, which reduces the mechanical stress in the joint, in turn reducing pain and improved functions in subjects with anterior knee pain. Also the strengthening lead to better motor control which helps in correcting the malposition of patella and improves the biomechanics of the lower limb during functional activities. Many authors have studied the association between increasing strength, reduction in pain and improvement in function.16,17 This is supported by another author who found a strong correlation between restoring quadriceps muscle strength to improving the function in patients with anterior knee pain.18 Most of the weight-bearing activities like walking, stair climbing, squatting, etc. are affected because of anterior knee pain which requires the action of quadriceps muscles, thus improving the strength helps in improving the functions of the individuals having anterior knee pain.19,20 Hence a better result in Visual Analogue scale and KOS-ADL scale was seen in Group B in which the subjects were given Quadriceps exercises as the improvement in the strength of quadriceps lead to improvement in the pain and function of the subjects with anterior knee pain. Limitations Hip musculature tightness and strength was not taken into consideration which can alter the biomechanical alignment of the lower limb and cause anterior knee pain. Implications Treatment programs for patients with anterior knee pain should incorporate strengthening of the foot muscles as well. Conclusion Both foot exercise and knee exercise are effective on pain, Navicular drop and KOS-ADL score in subjects with anterior knee pain. But a better result in Navicular drop was found in subjects given foot exercises while more improvement was seen in VAS and KOS-ADL score in subjects that were given knee exercises. Acknowledgment We are grateful for the support provided by all the subjects, we would also like to acknowledge the scholars whose articles are cited. Ethical Issue: Ethical clearance was taken from the institutional ethics committee, MARCOPT, Pune. Letter no-MARCOPAR/05/2771A Conflict of interest-Nil Source of funding -Nil Englishhttp://ijcrr.com/abstract.php?article_id=4329http://ijcrr.com/article_html.php?did=43291. Green ST. Patellofemoral syndrome. J Bodyw Mov Ther. 2005 Jan 1;9(1):16-26. 2. Cheung RT, Ng GY, Chen BF. Association of footwear with patellofemoral pain syndrome in runners. Sports Medicine. 2006 Mar 1;36(3):199-205. 3.Boonstra AM, Schiphorst Preuper HR, Reneman MF, Posthumus JB, Stewart RE. Reliability and validity of the visual analogue scale for disability in patients with chronic musculoskeletal pain. Int J Rehabil Res. 2008 Jun;31(2):165-9. doi: 10.1097/MRR.0b013e3282fc0f93. PMID: 18467932 4.Rathleff MS, Nielsen RG, Kersting UG. Navicula drop test ad modum Brody: does it show how the foot moves under dynamic conditions? J. Am. Podiatr. Med. Assoc. 2012 Jan;102(1):34-8. 5. Collins NJ, Misra D, Felson DT, Crossley KM, Roos EM. Measures of knee function: International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS?PS), Knee Outcome Survey Activities of Daily Living Scale (KOS?ADL), Lysholm Knee Scoring Scale, Oxford Knee Score (OKS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Activity Rating Scale (ARS), and Tegner Activity Score (TAS). Arthritis care & research. 2011 Nov;63(S11): S208-28. 6. John AT, Rai HR, Kumar V, Jimshad TU. Effect of ultrasound on pain in amateur squash players with patellofemoral pain syndrome. Int. J. Curr. Res. 2015 Oct 1;7(19):26.. 7. Chung KA, Lee E, Lee S. The effect of intrinsic foot muscle training on medial longitudinal arch and ankle stability in patients with chronic ankle sprain accompanied by foot pronation. Physical Therapy Rehabilitation Science. 2016 Jun 30;5(2):78-83. 8. Howitt S, Jung S, Hammonds N. Conservative treatment of a tibialis posterior strain in a novice triathlete: a case report. J Can Chiropr Assoc. 2009 Mar;53(1):23. 9. Eapen C, Nayak CD, Zulfeequer CP. Effect of eccentric isotonic quadriceps muscle exercises on patellofemoral pain syndrome: an exploratory pilot study. Asian J Sports Med. 2011 Dec;2(4):227. 10.Chiu JK, Wong YM, Yung PS, Ng GY. The effects of quadriceps strengthening on pain, function, and patellofemoral joint contact area in persons with patellofemoral pain. Am J Phys Med Rehabil. 2012 Feb 1;91(2):98-106. 11. Jam B. Evaluation and retraining of the intrinsic foot muscles for pain syndromes related to abnormal control of pronation. Advanced Physical Therapy Education Institute. 2006 May;21:1-8. 12. Pincivero DM, Salfetnikov Y, Campy RM, Coelho AJ. Angle-and gender-specific quadriceps femoris muscle recruitment and knee extensor torque. J. Biomech. 2004 Nov 1;37(11):1689-97. 13. Jam B. Evaluation and retraining of the intrinsic foot muscles for pain syndromes related to abnormal control of pronation. Advanced Physical Therapy Education Institute. 2006 May;21:1-8.  14. Shashi Kumar CG, Syed N, Mohan N. Comparative study of efficacy of vastus medialis obliquus vs rectus femoris using open kinematic and closed kinematic exercises in the patellofemoral pain syndrome. Int J Cur Res Rev | Vol 10 .Issue 03 .October 2011, pg 47-54                                                            15. Chung KA, Lee E, Lee S. The effect of intrinsic foot muscle training on medial longitudinal arch and ankle stability in patients with chronic ankle sprain accompanied by foot pronation. Physical Therapy Rehabilitation Science. 2016 Jun 30;5(2):78-83. 16. Stiene HA, Brosky T, Reinking MF, Nyland J, Mason MB. A comparison of closed kinetic chain and isokinetic joint isolation exercise in patients with patellofemoral dysfunction. J Orthop Sports Phys Ther. 1996 Sep;24(3):136-41. 17. Sharayu Agre, Ronika Agrawal, Memon F, Ammarah Ravi, Comparing the Effect of Fast Tempo Music and Slow Tempo Music During Aerobic Exercise on Cardiovascular Endurance in Overweight Adolescents. Int J Cur Res Rev March 2021| Vol 13 • Issue 05 •pg 163-166 18. Heintjes EM, Berger M, Bierma?Zeinstra SM, Bernsen RM, Verhaar JA, Koes BW. Exercise therapy for patellofemoral pain syndrome. Cochrane Database of Systematic Reviews. 2003(4). 19. Agrawal R, Alirajpurwala A. To Study the Additional Effect of Aerobic Exercises on Cognitive Behavioral Therapy in Depressed Diabetics. Int J Cur Res Rev| Vol. 2021 Feb;13(03):132. 20. Witvrouw E, Lysens R, Bellemans J, Peers K, Vanderstraeten G. Open versus closed kinetic chain exercises for patellofemoral pain. Am. J. Sports Med. 2000 Sep;28(5):687-94 0

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcareA Neuropharmacological Review of Alzheimer’s Disease English8592Shubham S. BagadeEnglish Laxmikant B. BorseEnglish Atul R. BendaleEnglish Anil G. JadhavEnglishAlzheimer is one of the most frequent diseases that affect nerve cells in various sections of the brain. Pathologically, it occurs due to intracellular neurofibrillary tangles and extracellular amyloid protein depositions that result in the obstruction of neural transmission, culminating in this neurodegenerative illness. Additionally, food and nutrition are essential for developing and preventing Alzheimer’s. The biomarker utilized for detecting the disease should be able to differentiate between different causes of dementia and detect it early. Use of Induced Pluripotent Stem Cells shows to be a successful treatment for the condition mentioned. There are three main hypotheses presented as a cause of AD: the cholinergic, tau and amyloid hypothesis. Additional risk factors include advancing age, genetics, head trauma, vascular illnesses, infections, and the environment in general. The two types of approved medications to treat AD (NMDA antagonists and cholinesterase inhibitors) are successful in treating the symptoms of AD, but are not cures or preventatives of the disease. Current AD research targets multiple processes, such as the aberrant tau protein metabolism, β-amyloid, inflammatory response, and cholinergic and free radical damage, to find viable therapeutics capable of preventing or changing the progression of Alzheimer’s disease. This review’s purpose is to illustrate the pathway that leads to this condition and oncology treatment for it. EnglishAlzheimer’s disease, Acetyl cholinesterase inhibitors, N-methyl D-aspartate receptor antagonist, Beta amyloid, Neurofibrillary tanglesINTRODUCTION             Alzheimer’s Disease is the main cause of Dementia which contributes about 60% - 80% of total Dementia patients provided by WHO.1,10,13 Dementia is one of the prime causes in individuals around the globe for impairment and dependence. AD is a psychological condition that progresses with the age destroying memory, thinking skills, cognitive abilities and eventually the ability to carry out simple daily tasks. AD is an illness that impairs the central nervous system mainly affecting the temporal lobe, entorhinal cortex and hippocampus and in progression affecting the cerebral cortex of the brain which may be responsible for language, reasoning and social behavior leading to death with the advancement of the disease.1 The main condition in the disease is Amyloid plaques, neurofibrillary tangles and Lewy bodies appear in the brain.4 AD involves the medial temporal lobe, which houses the entorhinal cortex and hippocampus. Anterograde episodic memory loss is produced by the collapse of these mechanisms, and this shows up as forgotten daily minutiae.3,4 While the issue may seem benign, the symptoms may be seen by family members and the patient. Cognitive deficits which are severe enough to affect daily functioning are the current criteria for diagnosing AD (MCI- Mild Cognitive Impairment). An estimated 10% of MCI patients may develop AD annually.11,12 AD damages cognitive and functional ability over time, including visuospatial and executive function. The latter years of the disorder are associated with an increase dependency and neurological damage (akinetic mutism). Lack of mobility often results in 6–12-year deaths from lung or venous embolism. AD is diagnosed based on the patient&#39;s clinical findings. Neuroimaging is used to diagnose out those other maladies that could cause Alzheimer&#39;s-like symptoms. Shortly, laboratory tests, such as analysis of biomarkers, genetic testing, and molecular/functional neuroimaging, will likely be added into diagnostic criteria for AD to improve the sensitivity of diagnosis, notably in the initial and latter course of the disease. Causes of AD are poorly analyzed as no perfect treatment is available to eradicate the disease. Only the progress of the disease can be slowed by medications and treatment. The pharmacological treatment available for AD is acetylcholinesterase inhibitors, antioxidants, NMDA channel blocker and other pharmacological treatments.6,9,14 The management of the disease and how medicines engage with the brain during treatment are crucial. Different aspects are discussed regarding the neuropharmacology of AD from the available literature. HISTORY In 1906, German psychiatrist and pathologist Dr. Alois Alzheimer noticed the changes in brain tissues of a female patient who died of irrefutable mental illness and reported the first case of the disease named after him. In next five years, eleven new cases of the same illness were reported just using the terminology Alzheimer’s Disease.11 The name Senile Dementia of Alzheimer’s type(SDAT)  was initially used to describe AD in individuals aged 65 years and well above, On the contrary, Classical Alzheimer&#39;s disease is used to describe patients who were younger. As time passed, the term Alzheimer&#39;s disease was used in medical literature to describe people of every age with a consistent pattern and neuropathology of typical symptoms. Nearly 47 million individuals worldwide were impacted by dementia in 2015, with a forecasted 75 million in 2030, and 131 million in 2050.13 The annual patient count is estimated at 4.6 million cases globally, which is identified as one new case every seven seconds.  Figure 1.1 shows the progression of AD. GENETICS Alzheimer&#39;s disease is acquired in about 2% of instances in progenies (autosomal dominant). Early-onset familial Alzheimer&#39;s disease is a kind of Alzheimer&#39;s disease that starts early and progresses quickly.18Early-onset Alzheimer&#39;s disease, known as younger-onset Alzheimer&#39;s or early-onset AD, is Alzheimer&#39;s disease that develops before completing age 65. It is a rare type of Alzheimer&#39;s disease, accounting for only around 5–10% of all the cases of Alzheimer&#39;s.19 Roughly 60% have a favorable family history and 13% are autosomally dominated by AD.20 The majority of occurrences of early-onset Alzheimer&#39;s, on contrary, exhibit the same characteristics as the "late-onset" type and are not generated by genetic mutations. Early-onset familial AD can be directly linked to mutations in one of three genes which are named as an amyloid-beta precursor protein (APP) and presenilins PSEN1 and PSEN2.44 The majority of APP and presenilin gene mutations increase the formation of amyloid beta (Aβ)42, a tiny protein that is the principal component of amyloid plaques. Some mutations just change the ratio between Aβ42 and the other main forms, specifically Aβ40, without enhancing Aβ42 levels. ABCA7 and SORL-1 are two more genes linked to autosomal dominant AD.2,4,15,21 The majority of Alzheimer&#39;s cases are not inherited and are termed to as sporadic Alzheimer&#39;s disease, in which environmental and genetic conditions play an important role. In contrast to familial Alzheimer&#39;s disease, the majority of sporadic Alzheimer&#39;s disease (AD) cases develop after the age of 65.18 The start of sporadic Alzheimer&#39;s disease is delayed in fewer than 5% of instances. APOEε4 is the most powerful genetic risk factor for sporadic AD.22 APOEε4 is one of the four apolipoprotein E alleles (APOE). The ε4 allele affects the activity of APOE in lipid binding proteins in lipoprotein particles.16,22 Between 40 and 80% of persons with Alzheimer&#39;s disease have at least one APOEε4 allele.22,44 several alleles in the genome elevates the threat of AD. APOE, which codes for the lipid carrier protein apolipoprotein E (ApoE). The ApoE-4 allele increases the risk of AD thrice. Although the population is just 25%, they represent half of all Alzheimer&#39;s cases.10 HYPOTHESIS RELATED TO ALZHEIMER’S DISEASE Amyloid Hypothesis For more than 25 years, the amyloid hypothesis (also known as the amyloid cascade hypothesis, the Aβ hypothesis, and so on) has been the leading explanation for the neurophysiology of Alzheimer&#39;s disease.16 The most direct anti- Aβ therapeutic technique is to limit Aβ production by attacking β - and γ -secretase.17 The original amyloid cascade theory said that “Aβ is the causative agent in Alzheimer&#39;s Disease pathogenesis, and that neurofibrillary tangles, cell death, vascular damage, and dementia come up as a direct outcome of its deposition”.23 Despite the fact that the majority of data still supports Aβ as the key initiator of the complicated pathogenic cascade in AD, more and more evidences show that Aβ serves as a trigger in the early disease process and seems to be required but not sufficient in the late stage of AD.25 Tau Hypothesis Tau is found in neurofibrillary tangles, which are another intracellular characteristic of AD. Tau aggregation in pathological situations will damage neuron axons, resulting in neurodegeneration.40Phosphorylation, arginine monomethylation, lysine acetylation, lysine monomethylation, lysine dimethylation, lysine ubiquitylation, and serine are all forms of tau modifications.26 Tau-targeting medicines remain difficult to develop due to an insufficient information of Alzheimer&#39;s disease, a lack of reliable and specific biomarkers for diagnosis and response monitoring, and a restriction of the blood-brain barrier.27 Cholinergic Hypothesis As the Neurochemistry involves study of the brain and neurotransmitters. The primary neurotransmitter deficit in AD is acetylcholine.28Neuronal loss causes cholinergic insufficiency that give cholinergic innervation to the cerebral cortex, notably those in the basal forebrain (the nucleus basalis of Meynert). Central cholinergic antagonists, such as atropine, can induce disorientation, which resembles AD dementia. This "cholinergic hypothesis" asserts, deficiency of ACh causes AD symptoms. It is essential to mention that even if "cholinergic deficiency syndrome" is equivalent to Parkinson&#39;s disease, the situation in AD is significantly more complex.31 Cortical and hippocampal targets that receive cholinergic input are destroyed, as are other neurotransmitter systems such as glutamate, 5-HT, and neuropeptides. To treat this, the cholinergic hypothesis was initially investigated in AD therapy with cholinesterase inhibitors. The first anti-AD medication accessible in the clinic was Tacrine, a cholinesterase inhibitor.30 SIGNS AND SYMPTOMS Alzheimer&#39;s disease symptoms develop gradually over time. Anyone whose symptoms worsen fast should consult a doctor in order to treat AD. There might be causes for the worsening of symptoms that can be addressed. Generally, symptoms of AD are described in 3 stages- first stage (early symptoms), Middle stage (mild or moderate symptoms) and late stage (severe symptoms). Early Stage Memory lapses are the primary sign of AD in its early stages.For example, someone with early AD may forget recent conversations or events, misplace items, may fail to remember the names of place and objects, have difficulty thinking of the right word, ask questions repeatedly, exhibit terrible judgment or having difficulty in making decisions, and become less flexible and more hesitant to try new things.54The progressive deterioration of learning and memory in patients with AD finally leads to a confirmed diagnosis. Language, executive function, perception (agnosia), and movement execution (apraxia) impairments are more common in a small number of people than memory impairments.56Not all the memory capability is adversely impaired by AD. Episodic memories, semantic memory, and implicit memory are less altered than fresh facts or memories.55 Middle Stage Memory impairments will worsen as Alzheimer&#39;s illness progresses. Additional symptoms such as increased confusion and disorientation may develop – for example, getting lost or roaming and not knowing the time, obsessive, repetitive, or impulsive behavior, delusions or feeling paranoid and suspiciousness about caregivers or family members, problems associated with language or speech (aphasia), disturbed sleep, mood changes (hallucinations).54 Progressive deterioration finally inhibits independence, with patients unable to do the majority of everyday tasks. Speech issues emerge as a result of a difficulty to retain language, resulting in frequent erroneous word replacements (paraphasias). Reading and writing abilities are also deteriorating.55 As time passes and AD worsens, convoluted motor sequences are less synchronized, increasing the risk of falling. Long-term memory, which was initially robust, begins to deteriorate.56 Late stage This is the last and the most severe stage of AD. The symptoms of AD get progressively severe in the latter stages, which can be frustrating for the person with the disease, as well as their caregivers, friends, and family. Hallucinations and delusions may appear and disappear during the disease, but they might worsen as the condition advances. People suffering from AD might become aggressive, demanding, and distrustful of those around them at times.55 People in the latter phases of AD may require full-time care as well as aid with eating, moving, and personal care.54 Language is limited to basic sentences or even single words, eventually leading to total aphasia. Although aggression may persist, excessive apathy and tiredness are far more prevalent symptoms. People suffering from AD will eventually be unable to execute even the most rudimentary duties independently; their muscular mass and mobility will decrease to the extent that they are clothed and cannot feed themselves. The cause of mortality is frequently an external issue, such as pressure ulcer infection or pneumonia, rather than the disease itself.55,56 TREATMENT AD is currently an untreatable disease. Currently, therapy plans for AD rely on symptomatic relief, with no focus on improving the target molecules. Effects and symptoms of AD can be slowed but cannot be eradicated completely. For the cure of AD, Firstly, cholinesterase antagonists such as Donepezil, Rivastigmine and Galantamine are used. Secondly, NDMA drug-like Memantine is given in the treatment of AD. Combination therapy is usually preferred for increased efficacy and relief. Cognitive symptoms treatment AD treatment relies on the optimization of cholinergic transmission. Tacrine, the first medication approved to treat AD, is currently being used relatively rarely due to its many side effects. Reversible cholinesterase antagonists (Catalysts for cleavage of acetylcholine into choline as well as acetate in the synaptic cleft) block cholinergic neurotransmission. For mild to severe AD, cholinesterase inhibitors are the first-line treatment.32 Lewy body dementia and vascular dementia are both treatable with cholinergic inhibitors. Galantamine, a cholinesterase inhibitor, which has a dual form action mechanism. Aricept is the brand name for Galantamine, which was approved in 1996. It is acetylcholine esterase’s reversible inhibitor that enhances the intrinsic effect of acetylcholine on the nicotinic receptor, resulting in enhanced cholinergic neurotransmission into CNS.56 Galantamine is centrally and peripherally operating inhibitor which inhibit acetylcholinesterase in the muscles and the brain, boosting cholinergic tone. Galantamine operates as a positive allosteric modulator in neurons for nicotinic acetylcholine receptors. It is usually given in the forms of tablets or disintegrating tablets. In clinical tests of AD, Galantamine, on the other hand, encouraged improvements in cognition, global function, activities of daily living, and behavioral symptoms.53 NAMENDA is a drug used in combination with cholinesterase inhibitors to treat AD. Alzheimer&#39;s and Parkinson&#39;s are treated with it as well. N-methyl-D-aspartate receptor antagonists like Memantine are non-competitive drugs. It binds to the Mg2+ binding site on the channel, limiting activation without causing harm. Clinical deterioration is greatly slowed by the use of memantine.5,33 The drug&#39;s genuine disease-modifying effect, reduced excitotoxicity, or clinical effects are all uncertain. Headaches and dizziness are the only serious effects of using memantine.5Behavioral and psychological symptoms of dementia (BPSD), particularly during the late phase of the disease, are not uncommon in dementia. Pharmacological and non-pharmacological options should be used concurrently. They have a minor influence, and they leave many symptoms untreated, such as agitation.34 Alzheimer&#39;s patients are frequently taking medications, therefore additional treatment choices are necessary when behavioral indications develop.51 Use of a Selective serotonin reuptake inhibitors (SSRI) or an atypical antipsychotic is frequently used to treat behavioral disorders.35 The effects of these drugs on AD pathology are not well-documented. Studies asserts that stimulants have a short-term influence on cognitive functions and behavioral manifestations. Treatment delay may be implemented on a case-by-case manner. Most of the current clinical research focuses on the synergistic benefits of inhibiting cholinesterase with alterations to specific cholinergic receptors.39 Agonists for Muscarinic Receptors Mucosal agonists are prescribed for xerostomia, urinary bladder problems, and bronchial hyperreactivity.41 Glaucoma and miotic drugs are commonly used to treat it. The involvement of cognition in muscarinic receptors is growing. Cognitive impairment induced by AD has long been treated with M1 agonists. Many other receptor subtypes appear to be engaged in the modulation of cognitive function, at least in animal models.42 Other mechanisms for selectively activating specific muscarinic receptor subtypes, such as allosteric agonists and positive allosteric modulators (PAMs), have been researched because of the absence of efficacy and substantial peripheral side effects of currently available muscarinic agonists.43 Schizophrenic and substance abuse problems as well as pain control medications all benefit from selective muscarinic subtype activators. An example is Xanomeline, a muscarinic agonist that possesses Muscarinic-1 and Muscarinic-4 subtype selectivity and was being investigated for AD as well as schizophrenia. Anticholinesterase drugs inhibit the AchE enzyme. Cholinergic nerve terminals collect ACh and hence can elicit symptoms in the PNS and CNS that are similar to excessive cholinergic receptor stimulation.44 Many non-cholinergic toxins have also been widely used as toxicants, including agricultural pesticides, herbicides, and chemical warfare "nerve agents." Other therapeutic strategies for treatment While no medicine has been proved to preserve neurons, there are two potential conceptual approaches to the therapy of AD. Firstly, Treatment that helps prevent the onset of the disease by isolating the primary progenitors or targets and reduces secondary pathologies of the disease, retards disease progression or postpones disease onset, leads to the cessation or even repair of neuronal damage after disease onset, and ultimately prevents the development of AD is one approach; secondary approach is symptomatic treatment. Neurotrophins, antioxidants, statins, non-steroidal anti-inflammatory drugs (NSAIDs), hormone replacement treatment, excitotoxicity blocking, vaccination testings, immunotherapy, and secretase effectors, 7-Methoxytacrine have all been researched, but their usage remains disputed. As a result, greater research into preventative and disease-modifying therapy options is required for the elimination of AD in the general population. Beside cognitive symptoms treatments and use of muscarinic agonists other therapeutic strategies are being researched. Use of antioxidants Melatonin, it is a hormone derived from mammals that is primarily synthesized in the pineal gland. It collects O2 and N2-based reactants produced in mitochondria by increasing the production &activity of Glutathione peroxidase, Superoxide dismutase, and NO synthetase, and it also contributes to the diminution of oxidative damage in cells.56 In currently undergoing researches, antioxidant melatonin has been demonstrated to prevent Aβ-induced toxicity and ameliorate tau hyperphosphorylation.57 Melatonin improved the learning and memory impairments present in an APP695 transgenic mouse model through in vivo, and also inhibited Aβ-induced apoptosis in AD cell models such as mouse microglial BV-2 cells, rat astroglioma C-6 cells, and PC-12 cells through in-vitro.58 In another investigation, melatonin reduced NADPH oxidase phosphorylation via a PI3K/Akt-dependent signaling pathway in microglia vulnerable to Aβ1–42.57 According to some research, melatonin reduced Aβ burden in juvenile APP Tg2576 mice models but had zero effects on F2-IsoPs or Aβburden in older plaque-bearing mice.56 Selegiline (L-deprenyl) is a monoamine oxidase-B inhibitor with antioxidant effects that can be used to treat neurodegenerative disorders. It has the ability to rapidly produce the powerful vasodilator nitric oxide, notably in cerebral blood vessels.51 It may also protect the vascular endothelium from the harmful effects of Aβ peptide and improve the function or survival of nigral neurons by blocking oxidative deamination.52 Sano et al. demonstrated in 1997 that therapy with Selegiline (10 mg/day) decreases neuronal destruction and delays the course of AD in patients having moderately severe impairment.37 These data imply that the administration of Selegiline may postpone clinically significant functional impairment in AD patients. DISCUSSION 1)AD, the most common form of dementia, has a multifactorial etiology, and the current therapy (AChEIs and memantine) cannot interrupt its progress and fatal outcome. This is reflected in the research programs oriented toward the development of new therapeutics able to operate on multiple targets involved in the disease progression. 2) The patents from 2016 to the present regarding the use of AChEIs in AD concern the development of new AChEIs, multitarget or multifunctional ligands, or the associations of AChEIs with other compounds acting on different targets involved in the AD. 3)The development of new multitarget AChEIs promises to identify compounds with significant therapeutic potential. However, it requires more time and effort to obtain drugs with the optimal pharmacodynamic profile. Otherwise, the research on new combinations of existing drugs with known pharmacodynamic and ADME profiles could shorten the time and reduce the costs of developing a new AD treatment. From the analyzed data, it seems more likely that a response to the urgent need to develop effective treatments for AD therapy could come more quickly from studies on drug combinations than from the development of new AChEIs. CONCLUSION Studies reveal that the cause of AD as a neurodegenerative condition includes extracellular amyloid plaques, intracellular neurofibrillary tangles, synaptic degradation, and neuronal death. 70% of AD risk at any given age is due to heredity. Apo lipoprotein E is the most general genetic risk factor for AD (ApoE). Aside from the genetic and biochemical aspects, a deficiency in vitamin D seems another cause of AD. In addition, brain glucose metabolism decreases in AD, which results in diabetes. Unfortunately, the currently available medications for therapy (AChEIs and memantine) only target symptoms and not the underlying cause of the condition. As a result, the possibility of new drugs that operate at the origin of the disease process and can block the gradual buildup of Aβ has been raised. It has been noted that several non-targeted therapies, such as anti-inflammatory treatment, metal chelation, antioxidant supplements, and epigenetic alterations, are more damaging than beneficial, making it impossible to predict if their correct use would enhance clinical outcomes or not. To summarize, stem cell therapy and biomarkers could be new strategies in the early diagnosis and treatment of AD. Several potential clinical trials are now undertaken, which may give new diagnostic targets and support in the resolving of the difficult AD issue. ACKNOWLEDGMENTS 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 The authors declare that no funding was provided for this editorial. CONFLICT OF INTEREST The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. AUTHORS CONTRIBUTION Shubham S Bagade (corresponding author) Collected the data and performed the analysis of the data. Wrote the entire manuscript Contacting with the journal for manuscript publication. designed the model and the computational framework and analysed the data. Drafted the manuscript and designed the figures. Laxmikant B. Borse Contributed in data collection and analysis. Collecting key points from different journals and books Directing the project. Atul R. Bendale Convinced and designed the analysis of the data Working on task to keep a plagiarism-free manuscript designed and directed the project Anil G. Jadhav contributed to the final version of the manuscript and supervised the project. All authors provided critical feedback and helped shape the research, analysis and manuscript. Englishhttp://ijcrr.com/abstract.php?article_id=4330http://ijcrr.com/article_html.php?did=43301. Kumar K, Kumar A, Keegan RM, Deshmukh R. Recent advances in the neurobiology and neuropharmacology of Alzheimer’s disease. Biomed Pharmacother. 2018;98:297–307. 2. Gilles C, Ertlé S. Pharmacological models in Alzheimer’s disease research. Dialogues Clin Neurosci. 2000;2(3):247–55. 3. Massoud F, Gauthier S. Update on the pharmacological treatment of Alzheimer’s disease. Curr Neuropharmacol. 2010;8(1):69–80. 4. Anand R, Gill KD, Mahdi AA. Therapeutics of Alzheimer’s disease: Past, present and future. Neuropharmacology. 2014;76 Pt A:27–50. 5. Rogawski MA, Wenk GL. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241142EnglishN2022January16HealthcarePharmacovigilance in India: Do Not Take a Chill Pill English9396Sanjana AgrawalEnglish Sonal DayamaEnglish Abhiruchi GalhotraEnglishPharmacovigilance is also often understood as Drug Safety. For drug safety, Adverse Drug Reaction (ADR) must be monitored throughout the life of the drug, from its development, clinical trials, and post-approval. The discipline of Pharmacovigilance has gained its due importance in India recently in the last 10 to 15 years. The importance of pharmacovigilance increases even more in the pandemic situation. Numerous drugs are being used empirically according to experience and availability to treat Covid-19. The pandemic is an insight to regulate the highly unregulated drug distribution system. The system can be strengthened by training of human resource, public-private partnerships, legislation, communication, research and innovation Pharmacovigilance has witnessed substantial development over the years, yet there is a need for a practical revolutionary roadmap to tackle all the hindrances to fortify its symphonic functioning. The public confidence around the efficiency of Pharmacovigilance will build when people have access to good-quality and safe medicines and a suitable system for the distribution of medicines that have cleared Pharmacovigilance. EnglishPharmacovigilance, Adverse side effects, Covid 19, Challenges, Recommendations, Public health professionalINTRODUCTION: Pharmacovigilance is also often understood as Drug Security or Drug Safety. The historical roots of the word "pharmacological vigilance" are pharmacon (Greek for medicine) and viglar (Latin means to watch). The World Health Organization (WHO) outlines"pharmacovigilance" as the science and activities related to detecting, evaluating, understanding, and preventing side effects or any additional problem related to drugs and vaccines.1All the medicines, drugs, vaccines, devices, and other related products undergo rigorous testing before the concerned authorities approve them for public use, but drug toxicity is still a relatively common phenomenon. The clinical trials to test the drug include few sampled individuals for a limited period. However, specific minor adverse reactions are evident only after a certain period of exposure. Once the drug or active substance is approved for the heterogeneous population over a considerably long time, the chances of getting an adverse reaction from it are significantly high. For drug safety, Adverse Drug Reaction (ADR) must be monitored throughout the life of the drug, from its development, clinical trials, and post-approval. History of Pharmacovigilance: The history of Pharmacovigilance traces its root 173 years back when a young girl (named Hannah Greiner) died on January 29, 1848, after receiving chloroform sedation before removing an infected toe&#39;s toenails. 2Then, in 1937, 107 people died in the United States from a sulfanilamide elixir containing diethyl glycol as a solvent. The solvent was then identified to be the cause of death. As a result, the Federal Food, Drug, and Cosmetic Act was created in 1938. This law aims to renew the public health vigilance system. 2 &#39;Thalidomide Tragedy&#39;:An evident change in the scenario of Pharmacovigilance occurred in 1961, when Dr. McBride, an Australian doctor, detected that the incidence of congenital deformities of babies had amplified significantly (up to 20%) in women who had taken thalidomide through pregnancy for treatment of nausea.3This tragedy has highlighted several critical issues regarding the reliability of animal testing, industrial drug company behavior, and the importance of post-marketing drug monitoring, causing a change in pharmacovigilance regimen. Automatic reporting of adverse drug reactions has become more systematic and structured.2In 1968, the WHO Programme for International Drug Monitoring was inaugurated to ensure transparency around medicines&#39; safety to the public. Pharmacovigilance in India: The pharmacovigilance system has recently gained significant importance in India over the last 10 to 15 years. An official ADR monitoring system was established in 1986 under the direction of the Pharmaceutical Controller of India. The National Pharmacovigilance Program was launched in 2005 and was renamed the Indian Pharmacovigilance Program (PvPI) in 2010 to become a robust pharmacovigilance system in India. The mission is to protect the overall health and well-being of the Indian population; by safeguarding the benefits of drugs that offset the risks associated with their use. Under the Government of India (GoI), the Ministry of Health and Family Welfare (MoHFW) recast PvPIon April 15, 2011. It transferred the National Coordination Centre (NCC) to the Indian Pharmacopoeia Commission (IPC) Ghaziabad from the All India Institute of Medical Sciences (AIIMS), New Delhi.4 The Central Pharmaceutical Standards Control Organization (CDSCO), the General Directorate of Health Services under the MoHFW, GoI, and the Indian Pharmacopoeia Commission Ghaziabad runs a nationwide pharmacovigilance program. The Indian Pharmacopoeia Committee in Ghaziabad coordinates the program as the National Coordinating Center (NCC). The Center works under the supervision of a steering committee. All technical issues related to program establishment and implementation, including technical inputs, are handled by the working group that reports to CDSCO for organizational interventions. The Quality Review Committee is responsible for the quality, causality assessment, and completeness of the data. The PvPI Signal Review Panel (SRP) consists of scientists and clinical experts from government and non-governmental, academic institutions and hospitals. This committee analyzes the data reported by various Adverse Reaction Committees (Total 270 across India) and decides which adverse effects need attention and action. 5 The Programme is supported by the Training panel, whose primary function is to identify training needs, organize national and international training programs, design modules for training. It helps conduct the training for various healthcare professionals and other key stakeholders throughout the year. PvPI also addresses counterfeit drugs, antimicrobial resistance, surveillance during mass vaccinations, and other national programs.6 In July 2017, WHO bestowed upon India to honor being one of six countries globally as a WHO collaborating Centre for Pharmacovigilance center for Public Health Programme and Regulatory services. The general activities of PvPI are to collect and manage data related to drug safety. The data is used to discover "signals," information about new or potentially changing safety issues that any drug may cause. Then evaluate the data collected to make decisions on safety issues, proactively manage risks to mitigate associated risks, defend public health, including regulatory actions, communicate and inform stakeholders and the public, and monitor critical results and related processes. 7 Pharmacovigilance and Covid-19: At present, there is no approved treatment regimen for Covid-19 disease. Numerous drugs are being used empirically according to experience and availability. Hence the role of Pharmacovigilance increases multiple folds under pandemics. Amongst all those drugs used for the treatment of Covid-19, Glucocorticoids have the highest ADR reported.8 The robust ADR monitoring system allows putting safety checks on the medicines producing severe ADRs. The scientific community is busy inventing new vaccines to deal with the pandemic. Since more and more vaccine trials develop, inevitably, more complications associated with adverse events and rare side-effects can be seen shortly. PvPI must intervene to ensure the best possible vaccine option with a minor health hazard in such circumstances. One such proven effective measure is the use of digital technologies to optimize ADR reporting in the pandemic time. The vaccine and drugs used for treatment pose challenges, but the consumption of Over-the-Counter (OTC) drugs and self-medication has exponentially increased during the pandemic.9 The drugs flowing in the private sector channel escape scrutiny via various regulating authorities, and the pharmacists provide drugs without a medical prescription.  The pandemic is an insight to regulate the highly unregulated private sector networking of drugs distribution ADR reporting mechanism both by the pharmacist and the general public. Role of Public Health Professional in Pharmacovigilance: The country has more than 23 lakh registered health care professionals, including AYSUH and dentists, who can contribute to an extensive database by reporting even a single ADR per year. All public health programs have a significant component of medical products, procurement, and distribution, with public health professionals and managers. However, the pharmacovigilance arm of the program component is weakest. It should be inherent in every new health program/scheme and old health programs and schemes. Some health programs like the Universal Immunization Programme vaccinating children and pregnant females and the National TB Elimination Programme have a robust Adverse Effect Following Immunization (AEFI) / ADR reporting mechanism. For AEFI monitoring in UIP, a whole State level AEFI task force exists. Similar efforts are needed to improve ADR reporting other national health and state health programs. All programs managers should be promoted, trained, motivated, and incentivized to identify, report, and analyze ADRs occurring amongst the beneficiaries of various health programs. They can play an active role in creating awareness about potential ADRs and their reporting in the community through health education and promotion campaigns. Challenges: The Pharmacovigilance system undergoes many challenges on a global front. The system is well developed in the high-income countries like United States, United Kingdom, and Germany, while the middle- and low-income countries like India are still evolving.10Globally, only about 500,000 to 700,000 adverse events are recorded each year. Conversely, low- and middle-income countries, which make up more than sixty-six percent of the world&#39;s population, make up a small portion of all ADR data. 11 India is the world&#39;s second most populated country, with over one billion budding drug users. Also, the country catersto more than six thousand licensed drug producers and over 60,000 branded drug preparations.12Although the country&#39;s participation is minimal in the world&#39;s ADR database.It is estimated that around 8% of hospitalizations in India are due to ADR, and 8-19% of hospitalized patients have severe ADR.13 The main challenges faced by the system include different regulatory authorities with different forms of ADRs and different timelines for each country. As the system is still evolving, there is a vast regulatory gap due to continuously changing guidelines. Such diverse regulations make compliance a big challenge. Not only this, an enormous global gap exists in the gross reporting of ADR, too, due to a lack of awareness amongst both the health care practitioners and the public. The European-Americans have has been reporting the ADR for ages while the Asian Africans are still learning. Over the years, the quality of data reported has improved in its completeness. However, the Programme has not provided the exact incidence of ADRs among different medicines, including allopathic and AYUSH medicines.5 Both ordinary people and healthcare professionals rely on foreign data and studies. Furthermore, not much research has been conducted in this area. Self-medication via herbs (owing to the high doctor-patient ratio and accessibility) and other traditional forms of medicines often possess a significant barrier in the drug safety of the third world. Cultural, linguistic diversities, and economic determinants in the eastern countries are also a setback in adequate ADR reporting mechanisms. There is little knowledge and motivation among practicing and teaching health care professionals, pharmacists, medical and laboratory technicians, and the layman about the importance of Pharmacovigilance. The Public Health Services lack laboratory services to diagnose even severe ADRs. DISCUSSION: Few perspectives on improving the system are on following domains: Training: The Pharmacovigilance System can be included in Under and Post Graduate Medical, AYUSH, and Para-Medical Courses. A comprehensive training needs to be initiated that envelope all aspects of Pharmacovigilance both in practice and clinical research. Legislation: Pharmacovigilance reporting should be made mandatory and binding for medical colleges, Private Hospitals, and Clinics to enhance the reporting. Human Resource: Motivated leaders and well-trained team members are the pillars of the success of any program. Healthcare professionals, including physicians, nurses, and pharmacists, are the backbone of the healthcare system, contributing to patient safety. There is a mandate of assigning responsibilities of Pharmacovigilance on Nodal Officer in each medical college, but no such mandate exists for private hospitals, diagnostic centers, and clinics. The private sector health care industry caters to sixty-six percent of the total Indian population 14; still, there is no legislative compulsion on the private players to recruit any Pharmacovigilance Cell/Officer or Nodal officer. Research and Innovation: The European Union introduced an inverted black triangle on medicinal products subject to additional monitoring to improve ADR reporting. The patients and healthcare professionals can quickly identify these products visualizing the black symbol. The supplementary text inside the drug packet emboldens the consumers to report any unexpected and untoward adverse reactions through national reporting systems. 7A similar initiative can be implemented in the Indian system. Studies such as the role of drug alerts have influenced the decision of Health care providers in improving patient safety; thereby, translating evidence into actions should be commissioned. Also, lessons learned from the pandemic, paperless reporting should be expanded. Once the patients&#39; data is collected using Electronic Health/Medical Records, reporting from OPD and IPD facilities enhances spontaneously. Automated, user-friendly IT systems can incorporate the revolutionary change for ADR reporting. Communication: Although the PvPI-IPC regularly issues drug alerts to the AMCs, this knowledge is seldom disseminated to the public. An effective IEC/Media Cell should be established under the PvPI, whose functions would be to issue public advisory regarding ADR, risk communication, and fight fake news circulating in print and social media. Partnership & Collaboration: The Public-Private Partnership model must be incorporated in the ADR reporting system involving critical stakeholders of pharmaceutical companies and the public sector. In India, the medicine distribution system is mainly informal. The pharmacist largely influences the population may it be the consumption of OTC drugs or otherwise. Hence the role of the pharmacist in the Indian scenario is vital. The pharmacist can advocate people to report ADR and report the ADR on behalf of patients if trained, motivated, and incentivized. Public Participation: In pill-popping countries like India, there is a rising population of "Google doctor" patients who investigate, diagnose, and treat themselves using internet search engines. They rarely use formal tax drug interaction reporting systems but actively use online platforms to research and report potential adverse drug reactions. The consumer forums are a potential platform for collecting vital data on ADRs, currently unexplored and unutilized. Involving patient groups in dissemination meetings or public hearing helps bridge the gap between doctors and patients, improve medical knowledge, increase ADR reporting and assist decision making. Conclusion: Pharmacovigilance has improved significantly over the years, but a practical and revolutionary roadmap is needed to remove all barriers to improving its symphonic performance. As more and further clinical drug trials and other clinical research activities are being conducted in countries like India, there is a prerequisite to understanding the importance of Pharmacovigilance as soon as possible. The public confidence around the efficiency of Pharmacovigilance builds when people have access to good-quality and safe medicines and a suitable system for the distribution of medicines that have cleared Pharmacovigilance. With the augmentation of Pharmacovigilance, the pharmaceutical industry is sure to witness a paradigm shift towards safe and reliable medical care for all. ACKNOWLEDGEMENT: Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. SOURCE OF FUNDING: None CONFLICT OF INTEREST: None declared AUTHOR CONTRIBUTION: SA Conceptualised the manuscript. SA, SD and AG contributed to writing and reviewing the manuscript. Englishhttp://ijcrr.com/abstract.php?article_id=4331http://ijcrr.com/article_html.php?did=43311. Pharmacovigilance. Accessed September 15, 2021. https://www.who.int/teams/health-product-and-policy-standards/about/regulation-and-prequalification 2. Fornasier G, Francescon S, Leone R, Baldo P. An historical overview over Pharmacovigilance. Int J Clin Pharm. 2018;40(4):744-747. doi:10.1007/s11096-018-0657-1 3. McBride WG (1961). The James Lind Library. Published May 26, 2010. Accessed September 15, 2021. https://www.jameslindlibrary.org/mcbride-wg-1961/ 4. Pharmacovigilance Programme of India. Accessed September 18, 2021. http://www.ipc.gov.in/PvPI/about.html 5. Kumar DA, Reddenna L, Basha SA. Pharmacovigilance Programme of India. Innov Pharm. 2015;6(1):13. 6. Kalaiselvan V, Srivastava S, Singh A, Gupta SK. Pharmacovigilance in India: Present Scenario and Future Challenges. Drug Saf. 2019;42(3):339-346. doi:10.1007/s40264-018-0730-7 7. DAUE R. Pharmacovigilance. Public Health - European Commission. Published April 24, 2017. Accessed September 18, 2021. https://ec.europa.eu/health/human-use/pharmacovigilance_en 8. Herrera-Lasso Regás V, Dordal Culla MT, Lleonart Bellfill R. Adverse reactions of drugs specifically used for the treatment of SARS-CoV-2 infection. Med Clin Engl Ed. 2020;155(10):448-453. doi:10.1016/j.medcle.2020.06.026 9. Malik M, Tahir MJ, Jabbar R, Ahmed A, Hussain R. Self-medication during Covid-19 pandemic: challenges and opportunities. Drugs Ther Perspect. Published online October 3, 2020:1-3. doi:10.1007/s40267-020-00785-z 10. Gadhade JS, Hiray RS. Global Pharmacovigilance, challenges, and future considerations: West globe and East globe: J Pharmacovigil Drug Res. 2021;2(2):2-5. 11. PHARMACOVIGILANCE: THE PRESENT STATUS AND FUTURE PROSPECTS IN INDIA. PharmaTutor. 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