Influence of Vitamin D Level on Inflammatory and Prognostic Markers in COVID-19 - A Retrospective Study.

OBJECTIVE: The ongoing pandemic of severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2) has caused an immense public health crisis worldwide. Emerging evidence has suggested that inflammatory response plays a critical role in the pathogenesis and prognosis of the disease. As vitamin D can modulate the immune system, this study has been designed to correlate vitamin D with inflammatory and prognostic markers in COVID-19 patients. METHODS: The present study is a retrospective study examining the relationship between vitamin D levels and inflammatory markers in the COVID-19 disease. COVID-19 patients who were investigated for vitamin D, ferritin, D-dimer, C-reactive protein (CRP), and procalcitonin (PCT) level were only included. The patients were divided into hypovitaminosis D, and normal vitamin D. Correlation and logistic regression analyses were carried out to identify the strength and association of hypovitaminosis D with inflammatory markers in COVID-19 disease. RESULTS: The hypovitaminosis D group had significantly higher inflammatory markers compared to the normal vitamin D group. The correlation between hypovitaminosis D and procalcitonin was negative (r = -0.433), with a strong and significant association (p = 0.002). The correlation between hypovitaminosis D, CRP, and ferritin was weak and insignificant. The logistic regression between hypovitaminosis D and procalcitonin established a significant regression equation, leading to a significant linear model. CONCLUSION: This study concludes that patients with hypovitaminosis D should be treated with vitamin D therapy to reduce the severity of COVID-19 disease.

Hydroxychloroquine pre-exposure prophylaxis provides no protection against COVID-19 among health care workers: a cross-sectional study in a tertiary care hospital in North India.

OBJECTIVES: The use of Hydroxychloroquine (HCQ) prophylaxis has been recommended by the National task force constituted by the Indian Council of Medical Research (ICMR) for the prevention of corona virus disease 2019 (COVID-19) among healthcare workers (HCWs). However, this recommendation was based essentially on the preclinical data and limited clinical experience. The aim of this study was to evaluate the efficacy and safety of HCQ as a pre-exposure prophylaxis for COVID-19 infection among Indian HCWs. METHODS: A cross-sectional study was conducted among HCWs of a tertiary care hospital in north India. The HCQ prophylaxis was initiated among 996 HCWs and they were followed up to 8 weeks for conversion to COVID-19 positive status and any adverse drug reaction (ADR). RESULTS: About 10.3% of the study participants were tested positive for COVID-19 which was comparable to the positivity rate among HCWs not taking HCQ prophylaxis (9.7%). CONCLUSIONS: HCQ was well tolerated at a weekly dose of 400 mg for 8 weeks but provided no additional benefit in prevention of COVID-19 among HCWs.

Comparison of efficacy & safety of iron polymaltose complex & ferrous ascorbate with ferrous sulphate in pregnant women with iron-deficiency anaemia.

Background & objectives: Iron-deficiency anaemia (IDA) is a common nutritional deficiency among pregnant women in India. It has a significant impact on the health of the mother as well as that of the foetus. IDA generally responds well to treatment with oral iron supplementation. However, oral iron supplements are toxic to the gastrointestinal mucosa and intolerance is common, resulting in poor compliance and failure of treatment. The iron salts such as iron hydroxide polymaltose complex (IPC) and ferrous ascorbate (FeA) are claimed to have low gastrointestinal intolerance, therefore better patient compliance than the conventionally used ferrous sulphate (FS). These preparations also claim to increase haemoglobin level faster as well as improve the iron storage better than FS. This study was done to compare the efficacy and safety of FS with IPC and FeA. Methods: It was a randomized, parallel, open label, study among pregnant women of gestational age between 12 to 26 wk with moderate anaemia. Patients were randomly allocated to receive either FS, IPC or FeA. They were then followed up for 90 days to observe for improvement in the haemoglobin levels and other haematological parameters or any adverse drug reaction. Results: The haemoglobin levels were comparable in the three groups except at day 90 when FeA group had significantly higher haemoglobin level as compared to FS group (P<0.05). The overall adverse effect profiles were also comparable among the study groups except epigastric pain which was more commonly reported in the FS group. Interpretation & conclusions: The results of the study showed that FS, IPC and FeA have comparable efficacy and safety profile in the treatment of IDA of pregnancy.

Attenuation of oxidative stress and neurotoxicity involved in the antidepressant-like effect of the MK-801(dizocilpine) in Bacillus Calmette-Guerin-induced depression in mice.

Background The emerging line of research suggests that neuro-inflammation and oxidative stress are linked to the development of depression-like behavior. The tryptophan metabolizing enzyme, indolamine 2,3-dioxygenase (IDO), serves as an important interface between chronic inflammation and depression. IDO is induced by pro-inflammatory cytokines and diverts tryptophan towards the kynurenine pathway, decreasing serotonin synthesis. Further, the metabolites of kynurenine pathway increase brain oxidative stress and also cause N-methyl-D-aspartate (NMDA) receptor-mediated exitotoxicity. The resulting oxidative damage and dysfunction in glutamatergic neurotransmission alters the network connectivity of the brain, which may be the further mechanism for emergence of depression-like symptoms. Methods A depression-like illness was induced in mice by injecting Bacillus Calmette-Guerin (BCG) suspended in isotonic saline at a dose of 107 CFU I.P. The mice were then divided into different groups and were administered MK-801 or normal saline for the next 21 days, after which a battery of behavior and biochemical tests were conducted to assess them. Results The BCG group had significantly reduced sucrose preference index and an increase in immobility time in forced swim test (FST) and Tail Suspension Test (TST) as compared to the saline group. There was also a significant increase in the brain MDA levels and a decline in the brain GSH levels. The hippocampal tissue from the BCG group had significantly more comet cells than the saline group. The NMDA receptor antagonist, MK-801, was able to reverse the BCG-induced depression-like behaviour. MK-801 also showed significant decrease in brain oxidative stress but failed to show significant protection against BCG-induced neurotoxicity observed in comet assay. Conclusions The NMDA receptor antagonist, MK-801, mitigated BCG-induced, depressive-like behavior in mice by improving the sucrose preference and decreasing the duration of immobility time in TST and FST. The overall improvement in depression-like behavior was accompanied by a reduction in brain oxidative stress and comet cells, thus suggesting the antioxidant and neuroprotective action of MK-801.

Tuberculosis - Depression syndemic: A public health challenge.

INTRODUCTION: Depression is common in Tuberculosis (TB) and associated with adverse outcomes through pathogenic mechanisms and impaired self-care behaviours including reduced treatment adherence. Undiagnosed depression can threaten the robustness of DOTS model despite large public health investment. The Depression-Tuberculosis Syndemic requires collaborative partnership with mental health professionals. AIM: To study the evidence base for Depression-Tuberculosis Syndemic. METHODOLOGY: A Pubmed and Google Scholar search was conducted using the key words "Depression", "Tuberculosis" and "Syndemic" and abstracts screened for appropriateness and relevance. RESULT: Depression-TB Syndemic is common with a bidirectional relationship. Depression is associated with higher hazard ratio and increased prevalence of TB. Depression is independently associated with higher morbidity, mortality, drug resistance, risk of TB reactivation and community TB transmission. The underlying biopsychosocial mechanism of Depression- Tuberculosis Syndemic includes biological factors like inflammatory cascade, HPA axis dysregulation and psychosocial factors like perceived stigma and treatment non-adherence. DISCUSSION: Depression is a poor prognostic factor in TB. The National Mental Health Programme (NMHP) and National Strategic Plan (NSP) for Tuberculosis Elimination (2017-2025) work in independent verticals with no integration at policy or at ground level. This results in lack of identification and appropriate management of depression in patients with Tuberculosis despite repeated contact with health care personnel in DOTS centres. A collaborative approach for early diagnosis and management of depression in patients with Tuberculosis (Secondary Prevention) can help decrease the burden of disease and improve outcomes. CONCLUSION: Depression-TB Syndemic requires collaborative approaches at the program level and at the point of service delivery.

Drug-induced optic neuropathy in a case of extensively drug-resistant pulmonary tuberculosis.

We report a 26-year-old male patient diagnosed with extensively drug-resistant pulmonary tuberculosis presenting with reversible bilateral toxic optic neuropathy induced by the use of linezolid along with high-dose isoniazid. The case emphasizes the importance of recognizing toxic optic neuritis in patients on antitubercular therapy. Prompt recognition and treatment of such adverse drug reactions will reduce the associated morbidity.

Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression-like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression in mice.

BACKGROUND: The inflammatory response system has been implicated in the pathophysiology of major depression. The pro-inflammatory cytokines like interferon-γ induce the enzyme indoleamine-2,3-dioxygenase (IDO) of the kynurenine pathway of tryptophan metabolism. The induction of IDO reduces the availability of tryptophan for serotonin synthesis. Furthermore, the metabolites of kynurenine pathway have neurotoxic property, which along with decreased serotonin may account for depression-like illness. METHODS: The aim of this study was to compare the effects of treatment with fluoxetine and 1-methyl-L-tryptophan (1-MT) on Bacillus Calmette-Guerin (BCG)-induced inflammatory model of depression in mice. Behavioral tests included locomotor activity, forced swim test (FST) and tail suspension test (TST). Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in homogenized whole brain samples. Comet assays were performed to assess neurotoxicity. RESULTS: The results of this study demonstrate that BCG treatment resulted in an increase in duration of immobility in FST and TST as compared to the saline group. Further, it produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. The hippocampal tissue from BCG group had significantly more comet cells than the saline group. 1-MT and fluoxetine were able to reverse the BCG-induced depression-like behavior and the derangement in oxidative stress parameters. Fluoxetine and 1-MT also reversed the BCG-induced neurotoxicity in such mice. CONCLUSIONS: 1-Methyl-L-tryptophan exhibits antidepressant-like effect comparable to that of fluoxetine in treating BCG-induced depression-like behavior in mice.

Generic medicines: issues and relevance for global health.

Generic medicine is a pharmaceutical product which is bioequivalent to the innovator product in terms of dosage form, strength, route of administration, quality, safety, performance characteristics, and intended use. Generic medicines are a cornerstone for providing affordable medicines to patients. The major generic markets in the world include United States of America followed by European Union, Canada, Japan, and Australia. The major suppliers of generic medicines China and India are showing tremendous growth in the generic medicine sector. There are many legal and regulatory issues along with quality concerns associated with the use of the generic products. Lately, bilateral international agreements called free trade agreements, delaying tactics by originator companies like strategic patenting and litigations on generic manufacturers, have been a major setback for the generic medicine industry. These issues need to be addressed to optimize the use of generic medicines. The sustainability of generic medicine sector is crucial for improving access to essential medicines for the worldwide.