CHLOROQUINE AND HYDROXYCHLOROQUINE: A MAJOR BREAKTHROUGH FOR COVID-19

Coronavirus pandemic or COVID-19 is a global public health emergency at this period. Presently, no pharmacological treatment is known to treat this condition. Hydroxychloroquine (HCQ), a derivative of chloroquine (CQ), was first synthesized in 1946 by adding a hydroxyl group to CQ, which is much less toxic than CQ in animal studies. Other than being an anti-malarial drug, it was revealed to have various pharmacological effects and one of those is its anti-viral property. CQ, as well as HCQ, has been used in SARS (Severe Acute Respiratory Syndrome) coronavirus infection due to its antiviral properties. Even though various scientists have considered HCQ as a better therapeutic approach than CQ for the treatment of coronavirus infection, there are various adverse drug reactions associated with HCQ treatment in COVID-19 patients. In this paper, we review the anti-viral mechanism, various adverse drug reactions, and side effects of HCQ for COVID-19 treatment

Relationship between pregnancy rate and number of intrauterine insemination cycles during the study of comparative efficacy of letrozole and clomiphene citrate adjuvants to gonadotropin stimulation in controlled ovarian stimulation cycles combined with intrauterine insemination therapy

Background: Infertility is commonly defined as the failure of conception after at least twelve months of unprotected intercourse. Factors contributing are both male and female in which unexplained etiology accounts for 51%, male factor 28%, endometriosis 17% and ovulatory disorders 4%.Methods: Prospective, randomized study was conducted at DRRPG medical college, Tanda, Kangra, Himachal Pradesh. In our study, patients were randomized into two groups of 30 each. Women in group A received clomiphene citrate 100mg/day and group B received letrozole 2.5 mg/day from day 3-7 of menstrual cycle. All the patients received human menopausal gonadotropin 75 U given every alternate day from day 5 until HCG administration. Ovulation was triggered with recombinant HCG (5000 IUIM) when the dominant follicles reached 18 mm in diameter. A single IUI was performed 36 hours later. A maximum of four cycles were given.Results: In our study, total number of induction cycles given in group A and B were 120 and 114 respectively. Out of these, 112 and 111 IUI cycles were done in group A and B respectively. A pregnancy rate of 1.66% and 7.87% per IUI cycle was observed in group A and B respectively.Thus it is concluded that the pregnancy rates were significantly higher in letrozole group (30%) in comparison to clomiphene citrate group (6.66%).Conclusions: Aromatase inhibitor letrozole appears to constitute a good alternative to clomiphene citrate in patients with unexplained infertility undergoing gonadotropin-stimulated COS cycles combined with IUI therapy

A huge mesenteric teratoma in reproductive age woman: a case report

The incidence of dermoid ovarian cyst is 15-20% of all ovarian neoplasm, which is a common entity. Mesenteric cyst are one of the very rare entities with incidence of 1 in 2, 50, 000. Dermoid cysts rarely present as mesenteric cysts. Mesenteric dermoid cyst have good prognosis. Here, we report a rare abdominal tumor which was initially diagnosed clinically as an ovarian dermoid cyst but operative and histology revealed it to be mesenteric dermoid cyst. A 36 year-old, multiparous presented with abdominal mass, gradually increasing in size since 1 year with recent onset of abdominal pain. Physical examination revealed abdominal mass of 22×20 cm size, globular, non-tender, mobile, and cystic to solid in consistency. Contrast-enhanced computed tomography (CECT) showed 23×21×14.4 cm heterogeneous enhancing mass lesion with areas of fat density and calcifications within, suggestive of neoplastic mass lesion, likely teratoma. Tumor markers were within normal limit. Patient was managed surgically. Laparotomy findings revealed a huge solid mesenteric mass (22×20 cm) weighing 6.5 kgs. Histopathology showed mature cartilage, osteoid formation, fibro-adipose connective tissue, focal lymphoid aggregates, congested blood vessels and focal mature neuronal component and no immature elements seen, confirming dermoid cyst. Mesenteric cyst are rare intra-abdominal tumor found most commonly in ileum (60%) next is ascending colon (40%). However, if a mesenteric cyst locates within the pelvic cavity, as in this case, it may be misdiagnosed as an ovarian cyst

A case series of Stener’s lesion of the first metacarpophalangeal joint

Ulnar collateral ligament (UCL) injuries have a high prevalence however; these are usually being missed in the initial clinical evaluation. Depending on the chronicity of the injury there are two acronyms for UCL tear. One is the skier's thumb and the other is the gamekeeper's thumb. If the UCL of the first metacarpophalangeal joint (MCP joint) has a complete tear with entrapment of aponeurosis of adductor pollicis muscle between the MCP joint and torn ligament, is called a Stener’s lesion. This is a rare clinical entity that requires early surgical correction because of entrapment. The mechanism of injury is the coerced abduction of the thumb from the index finger, causing ligament tears or sprain with or without ensuing avulsion fracture. The incidence of Stener’s lesions associated with UCL rupture has been reported to be up to 52% per intra-operative finding. In Stener’s lesions, the UCL tears from the base of the proximal phalanx (PP) then retracts proximally and displaces superficial to the adductor pollicis. Here we are presenting four cases of Stener’s lesions, with the usefulness of magnetic resonance imaging (MRI) in diagnosing this entity, which can prevent possible long-term complications such as chronic pain, joint degeneration, and joint instability

Pervasiveness of metabolic syndrome and cardiovascular disease in tribal/rural population of India: a review

Diseases classified as non-communicable diseases (NCDs) are those that are often caused by unhealthy behaviors rather than by infection or by contact with others. One of the main NCDs causing many fatalities is cardiovascular disease (CVD). Recent research has shown that the prevalence of metabolic syndrome (Mets) associated CVDs among tribal populations is increasing in rapid pace. In this review, we have included studies investigating the components of Mets and the relationships between Mets and CVDs. From the assessment of studies, we may predict a significant association between Mets and CVDs as a whole. Our evaluation of these studies revealed that carrying at least three Mets risk components, like hyperglycemia, obesity, dyslipidemia, and high blood pressure, significantly enhances the risk of CVDs. Undernutrition, smoking, and a low intake of fruits and vegetables in the Indian tribal population are the main risk factors for managing Mets associated CVDs. Furthermore, various studies have also shown that Mets may be influenced by genetic and environmental factors. Finally, healthy habits such as a balanced diet and frequent exercise should be introduced from a young age in individuals, to prevent Mets progression. In order to combat the Mets associated CVDs, functionally upgraded primary health centers and special IECs (Information, education and communication) programs may play a beneficial role. Furthermore, strengthening public healthcare systems and focusing on prevention, early identification, and treatment using medical and social interventions can be of immense help in managing the metabolic risk factors that can lead to CVDs

IMPORTANCE OF NANOCARRIERS AND PROBIOTICS IN THE TREATMENT OF ULCERATIVE COLITIS

Ulcerative colitis (UC) is an inflammatory chronic disease primarily affecting the colonic mucosa; the extent and severity of colon involvement are variable. Ulcerative colitis is identified by mucus diarrhea, tenesmus, bowel distension, and anemia. 5-aminosalicylic acid drugs, steroids, and immune suppressants are used for the therapy of ulcerative colitis. The mainchallenges in the management of thediseaseare drug-related side-effects and local targeting. To overcome these challengesprobiotics and micro and Nanoparticulate systemauspiciousapproaches to overcome drug-related adverse side effects and local targeting.Upon ingestion, the probiotics can result in beneficial health effects. Probiotics and micro and nanoparticulate approaches for suitable targeting and overcome the drug-associated side effect. Probiotics are mainly used as gut modulators but are also nowadays explored for their use in ulcerative colitis.The current therapeutic goals are to achieve clinical remission along with mucosal healing, avoidance of complications such as side effects of the drug and to improve the quality of life. The use of probiotics to increase the health of the intestine and used to block or manage intestinal disorders. They may prevent the induction of inflammatory reactions. Probiotics must be inspected for efficacy in the prevention and management of a wide spectrum of gastrointestinal diseases, like antibiotic-associated diarrhea.Micro and Nanoparticulate drug delivery system has been achieving huge importance for targeting of the drug to colon locally at a controlled and sustained rate

Quality By Design: A Systematic Approach for the Analytical Method Validation

The scientific way to develop an easy and robust analytical technique for critical analysis is a QbD approach. QbD is a systematic approach to product or method development that begins with predefined objectives and uses science and risk management approaches to achieve product and method understanding and ultimately method control. The aim of the analytical QbD is to achieve quality in measurement. The main objective of this review to explain different steps involved in method development by the QbD approach for analytical method development and describes the implementation of QbD in analytical procedure validation. The advantages of applying QbD principles to analytical technique include discovering and minimizing the source of variability that may lead to poor method robustness and ensuring that the method meets its intended performance need throughout the product and method lifecycle. Keywords: Quality by design (QbD), Risk Analysis, Analytical method validatio

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Establishing an association between pregnancy-induced hypertension changes in the fundus and fetal outcomes

Background: Involvement of the ocular system in pregnancy is a common finding in females having PIH (pregnancy-induced hypertension). Aim: To judge the association between pregnancy-induced hypertension changes in the fundus and fetal outcomes. Methods: In 306 pregnant females with a confirmed diagnosis of pregnancy-induced hypertension, fundus changes were assessed along with fetal outcomes. The fetal outcomes included neonatal death, stillbirth, 1-minute Apgar scores, birth weight, and gestational age. Collected data were subjected to an ANOVA test and SPSS software to assess any association. Results: Among 306 subjects, 42 subjects had fundus changes and 264 subjects had no fundus changes. Mean systolic blood pressure (BP) was 182.88±33.62 in subjects with fundus changes and 150.74±12.84 mmHg in subjects without any fundus changes which was significantly higher in fundus changes. Diastolic pressure was also significantly higher, 125.26±21.34 mmHg in subjects with fundus changes compared to 100.09±9.49 mmHg in subjects without fundus changes. Fetal outcomes were comparable in subjects with or without fundus changes. A significant association was seen between optic nerve head and retinal changes with low birth weight (p<0.05). Conclusion: Low birth weight has an association with changes in the optic nerve head and retina