Alphienes Stanley Xavier

Delamanid: A new armor in combating drug-resistant tuberculosis

Intense search has been made in the discovery of newer anti-TB drugs to tackle the issues such as drug resistance, HIV co-infection and risk of drug-drug interactions in the management of TB. Delamanid, a newer mycobacterial cell wall synthesis inhibitor, received a conditional approval from European medicines agency (EMA) for the treatment of MDR-TB. Preclinical and clinical studies have shown that delamanid has high potency, least risk for drug-drug interactions and better tolerability.

Bedaquiline - The first ATP synthase inhibitor against multi drug resistant tuberculosis.

Increasing incidence of MDR-TB, long duration of treatment and co-infection with HIV are the significant problems in achieving the eradication of tuberculosis. Bedaquiline is an anti-tuberculosis drug with unique mechanism of action. It selectively inhibits the mycobacterial energy metabolism i.e. ATP synthesis and found to be effective against all states of Mycobacterium tuberculosis like active, dormant, replicating, non-replicating, intracellular and extracellular. Preclinical studies have shown the efficacy of bedaquiline in terms of reduction in bacterial load and treatment duration. Phase II clinical studies have established the safety, tolerability and earlier sputum conversion time in patients with MDR-TB. In 2012 FDA approved bedaquiline for treatment of MDR-TB and XDR-TB.

Systematic review on vitamin D level in apparently healthy Indian population and analysis of its associated factors

Background: Vitamin D which is involved in the maintenance of bone mineral homeostasis has been found to portray various pleiotropic effects. Although it has been widely accepted that serum 25-hydroxy Vitamin D level above 30 ng/ml is considered optimal for the biological actions of Vitamin D, there is a need to explore the levels of Vitamin D reported among Indians from various regions of the country. Hence, this systematic review aims to appraise the status of Vitamin D levels reported from apparently healthy Indians across various parts of India. Methodology: A comprehensive literature search was carried out to identify the range of Vitamin D levels among apparently healthy individuals from various parts of India, with the search term “Vitamin D and India” in the search portals of PubMed, Google Scholar, Indmed, and ScienceDirect. A total of 2998 articles were retrieved by the above search strategy, of which only forty studies fulfilled the criteria to be included in the systematic review. Studies done in various states were compiled under the respective zones based on the classification of Indian zones as specified in Zonal maps of India. Results: The level of Vitamin D from all the forty included studies ranged from 3.15 ± 1.4 to 52.9 ± 33.7 ng/ml. The effect size of Vitamin D level was higher in the South Zone compared to other zones. Conclusion: The present study shows that Vitamin D deficiency is prevalent among apparently healthy Indians living in different regions of India, irrespective of their exposure to sunlight.

Comparison of different methods for causality assessment of adverse drug reactions

Background The causality assessment of adverse drug reactions (ADRs) remains a challenge, and none of the different available method of causality assessment used for assessing adverse reactions has been universally accepted as the gold standard. Objective To examine the agreement and correlation among three broad approaches for causality assessment of ADRs viz. World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system, Naranjo algorithm, and updated Logistic method. Setting ADR monitoring centre (AMC) of a tertiary care teaching hospital in India. Method A total of 230 cases of ADR from April 2017 to August 2017 were retrospectively analyzed by each of these three methods. The agreement among the different methods was calculated by Cohen’s kappa (κ), and Spearman’s correlation was used to find the correlation among these methods. Main outcome measures Cohen’s kappa value and Spearman’s correlation coefficient for comparison among the different methods. Results The Cohen’s κ used for analyzing the agreement between WHO-UMC system and Naranjo algorithm was 0.45, between WHO-UMC system and updated Logistic method was 0.405, and between Naranjo algorithm and updated Logistic method was 0.606. The Spearman’s correlation coefficient was 0.793 for Naranjo algorithm vs. updated Logistic method, 0.735 for WHO-UMC system vs. Naranjo algorithm, and 0.696 for WHO-UMC system vs. updated Logistic method. Conclusion Causality assessment based on objective measurements (scores and probabilities) like updated Logistic method and Naranjo algorithm are less prone to subjective variations compared to the WHO-UMC system which is based on expert judgement.

Acenocoumarol as an alternative anticoagulant in a patient with warfarin‐related nephropathy

Warfarin‐related nephropathy.

Prophylactic Use of Steroids and Antibiotics in Acute Hydrocarbon Poisoning in Children

Ingestion of hydrocarbons is a common cause of childhood poisoning in low and middle-income countries. Although mild ingestions are usually devoid of complications, the morbidity and mortality associated with such poisoning are primarily related to pulmonary aspiration. Subsequent complications, most importantly, secondary bacterial infections can worsen the clinical condition. Standard treatment protocol for acute accidental hydrocarbon poisoning does not advocate routine use of steroids or antibiotics. However, some studies have demonstrated beneficial effects of prophylactic steroid and antibiotic to prevent chemical pneumonitis. In this article, we have summarized the findings of the clinical studies from literature, which have evaluated the advantages of early administration of steroids and antibiotics to prevent chemical pneumonitis in acute hydrocarbon poisoning in children. From these studies, we have found that there is no convincing evidence for initiating steroid and antibiotic to improve outcome in these children.

DRESS syndrome: a detailed insight

ABSTRACT Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a serious and potentially fatal adverse effect to therapeutic medications. The incidence of this condition varies among different ethnicities because of the difference in the genetic makeup. Though fever, rash and eosinophilia are essential features for the diagnosis of this syndrome, these vary from patient to patient along with the involvement of various organs such as liver, kidney, lungs, pancreas, etc. Some of the atypical features are dysphagia, agranulocytosis, and chylous ascites. Phenytoin, phenobarbitone, carbamazepine, and allopurinol are the most common drugs responsible for developing this syndrome, although the list is fairly long. Among the criteria used for the diagnosis of DRESS syndrome, European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples (RegiSCAR) criteria is the most commonly used one. The management of this syndrome involves early removal of the causative agent and treatment with anti-histamines and emollients in the mild form, corticosteroids in the moderate form and plasmapheresis in the severe form along with other alternatives drugs. Healthcare professionals should be more vigilant about the early manifestations of this syndrome, as early diagnosis and treatment improve outcomes considerably.

Effect of metformin on exercise capacity: A meta-analysis

AIMS To evaluate the effect of metformin on various parameters of exercise capacity [oxygen consumption (VO2), peak oxygen consumption (VO2peak), heart rate (HR), exercise test duration, respiratory exchange ratio (RER), rating of perceived exertion (RPE), lactate and ventilatory anaerobic threshold (VAT)]. METHODS Studies reporting change in VO2 or VO2peak after metformin administration were included. Subgroup analyses were performed as applicable. Mean difference with 95% CIs were pooled using random-effects model [RevMan (v5.3)]. RESULTS There were no changes in VO2 and VO2peak in the overall population [VO2: n = 388, mean difference: -0.12 ml/kg/min, 95% CI: -0.74, 0.51, p = 0.71 (i2 = 0%, p = 0.99); VO2peak: n = 345, mean difference: 0.41 ml/kg/min, 95% CI: -0.51, 1.33, p = 0.38 (i2 = 0%, p = 0.89)], healthy volunteers and patients (type 2 diabetes mellitus, insulin resistance, impaired glucose tolerance/impaired fasting glucose and metabolic syndrome). For patients with insulin resistance, there was a decrease in VO2peak, but not VO2. In the overall population, there was a significant decrease in HR and RER, a significant increase in RPE, and no changes in exercise test duration and VAT. In addition, there was an increased VAT in the healthy volunteers. CONCLUSIONS In the overall population, metformin did not affect VO2, VO2peak, exercise test duration and VAT, although it significantly decreased HR, RER and increased RPE.

Agreement Among Different Scales for Causality Assessment in Drug-Induced Liver Injury

Background and ObjectiveThe causality assessment of drug-induced liver injury (DILI) remains a challenge and eagerly awaits the development of reliable hepatotoxicity biomarkers. None of the different available algorithms used for the causality assessment of DILI has been universally accepted as the gold standard. This study was conducted to examine the agreement among different causality assessment scales in reporting DILI.MethodsThe World Health Organization–Uppsala Monitoring Center (WHO–UMC), Naranjo, Roussel Uclaf Causality Assessment Method (RUCAM), Maria & Victorino (M & V) and Digestive Disease Week–Japan (DDW–J) assessment scales were used to compare the causalities in all the reported cases of DILI in our adverse drug reaction (ADR) monitoring centre from January 2014 to June 2017. The probability of the causality assessment was classified as ‘definite’, ‘probable’, ‘possible’ and ‘unlikely’. The agreement obtained among the causality assessments was analysed using the weighted kappa (κw) test.ResultsA total of 33 cases of DILI were included in our analyses. Anti-tubercular therapy (ATT) and methotrexate were the drugs that most commonly caused DILI. The overall agreement among the different scales was poor. The best agreement was found between RUCAM and DDW–J scales (κw: 0.685).ConclusionThere were discrepancies among the different causality scales in assessing DILI. This might be due to the different definitions of causality criteria and subjective variability during assessment. A personalised assessment scale incorporating the latest information on specific risk factors and evidence-based criteria for DILI is warranted.

Effect of antituberculosis treatment on CYP2C19 enzyme activity in genetically polymorphic South Indian Tamilian population

Patients on antituberculosis therapy (ATT) are more prone to drug interactions in the presence of coexisting illnesses which require drug therapy. Rifampicin is a pleiotropic inducer of CYP enzymes, and isoniazid is an enzyme inhibitor. Genetic variations are common in the gene coding for CYP2C19 enzyme. These variations would be important in predicting the individual variations in CYP2C19 activity. The objectives of the study were to find the net effect of 1‐month ATT on CYP2C19 enzyme activity and its association with CYP2C19 genetic polymorphisms. Newly diagnosed tuberculosis patients (n = 125) were included in the study. Before commencing ATT, they were given a single dose of omeprazole 20 mg as a probe drug for CYP2C19. Blood sample was collected after 3 h to carry out phenotyping for CYP2C19 enzyme by measuring omeprazole hydroxylation index (OHI) using LC‐MS/MS. The phenotyping procedure was repeated after 1 month of ATT. CYP2C19 genotyping was carried out by PCR‐RFLP method. Significant reduction in OHI was observed after 1 month of ATT in all the metabolizer groups. The percentage reduction in OHI was maximum with poor metabolizers, 84.1 (IQR – 74.6, 86.6), and minimum with ultra‐rapid metabolizers, 39.6 (IQR – 12.7, 54.7). CYP2C19 enzyme induction is predominant in patients after 1 month of antituberculosis treatment (ATT). Genetic variations in the enzyme could not clearly explain the interindividual differences in induction. There is a potential risk of drug failure/adverse effect in poor metabolizers regardless of their genotype after ATT.