Isoniazid resistance among rifampicin-susceptible Mycobacterium tuberculosis isolates from tuberculosis patients

AbstractObjective/BackgroundWith the introduction of novel molecular techniques that rely on rifampicin (RIF) susceptibility, resistance to isoniazid (INH) or other first-line drugs remains undetected. Such patients are prescribed first-line antituberculosis therapy and are on RIF monodrug therapy during the continuation phase, which may lead to therapeutic failure and emergence of multidrug resistance. We aimed to study INH resistance among RIF-susceptible Mycobacterium tuberculosis (MTB) isolates from retreatment patients.MethodsThe Drug Susceptibility Testing data for four first-line drugs (streptomycin [SM], INH, RIF, and ethambutol [EMB]) using BACTEC MGIT 960 (Becton Dickinson, Franklin 124 Lakes, NJ ,USA) and for two drugs (INH and RIF) using line probe assay was analyzed retrospectively at the Department of Microbiology, National Institute of Tuberculosis and Respiratory Diseases (New Delhi, India).ResultsWe analyzed 4910 drug susceptibility results performed using the BACTEC MGIT960 liquid culture system from 2009 to 2015. We found that 969 (19.7%) isolates were sensitive to all four first-line drugs, 3941 (80.3%) isolates were resistant to one or more drugs, and 3041 (61.9%) isolates were resistant to both RIF and INH with or without resistance to any other drug (multidrug resistant). Monodrug resistance to SM and EMB was observed in 94 (1.9%) and 8 (0.16%) isolates, respectively. RIF resistance without INH resistance was observed in 22 (0.44%) isolates. There were 776 isolates sensitive to RIF, but resistant to INH. Among these, INH resistance with EMB and/or SM was observed in 367 (7.47%) isolates, whereas 409 (8.3%) isolates were resistant to INH alone. The results of line probe assay from 2012 to 2015 were also analyzed, and the resistance to INH alone among all isolates with valid results was found to be 9.32% (1462/15,676). More than 75% of these isolates harbor mutations in the kat G gene associated with high-level resistance.ConclusionINH resistance among RIF-susceptible isolates was present in 10–15% of the total cases. Among these cases, the use of RIF susceptibility alone will fail to detect INH resistance. Since higher rates of failure, relapse, or acquired resistance are linked with INH resistance, rollout of techniques focusing on RIF resistance must, therefore, be accompanied by strict monitoring for better management of patients

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

A living WHO guideline on drugs for covid-19

CITATION: Agarwal, A. et al. 2022. A living WHO guideline on drugs for covid-19. British Medical Journal, 370. doi:10.1136/bmj.m3379The original publication is available at https://jcp.bmj.com/This living guideline by Arnav Agarwal and colleagues (BMJ 2020;370:m3379, doi:10.1136/bmj.m3379) was last updated on 22 April 2022, but the infographic contained two dosing errors: the dose of ritonavir with renal failure should have read 100 mg, not 50 mg; and the suggested regimen for remdesivir should have been 3 days, not 5-10 days. The infographic has now been corrected.Publishers versio

Surveillance, Evaluation of Programmatic Management of Drug Resistant Tuberculosis (PMDT) at DR-TB Centre, NITRD, New Delhi

Background: PMDT was launched in 2007 in our country but drug resistant TB remains to be a public health problem. Effective surveillance is the backbone for success of any programme and true stands for PMDT. Aim & Objectives: To identify the strengths and constraints of the surveillance evaluation system. Material & Methods: A cross sectional study was conducted in January 2015 at DR-TB Centre of NITRD, New Delhi which caters to a population of 29 lacs. PMDT surveillance system was evaluated using attributes like simplicity, data quality, acceptability, positive predictive value, representativeness and timeliness defined by CDC, USA guidelines. Relevant information was collected using data abstraction form and interview with stakeholders. Data was analysed using EpiInfo 07 version. Results: Nodal officer and District TB officer are responsible for surveillance system activities of PMDT at DR-TB centre and district level, respectively. All the reports (100%) were submitted on time and all the districts were reporting to DR-TB centre. 75% of TB-HIV coordinators found reporting formats to be simple but all the quarterly reports were found to be complete. Data quality was not found to be optimal. Conclusion: Private sector needs to be taken on board as they have no to minimal involvement in PMDT. For data quality improvement time to time training of medical officers and health workers should be organized

Outcome of conventional transarterial chemoembolization (cTACE) in the management of spontaneously ruptured hepatocellular carcinoma

Background and Objectives: Hepatocellular carcinoma (HCC) is a highly vascular tumor and mortality after spontaneous rupture of HCC remains considerably high. There are no definitive guidelines for the management of ruptured HCC and no fixed protocol has been proposed in the literature. We evaluated the outcome of conventional transarterial chemoembolization (cTACE) in the management of spontaneously ruptured HCC and factors affecting the outcome of cTACE. Materials and Methods: This is a single center retrospective study analyzing the outcome of patients presenting with spontaneous rupture of HCC who received cTACE from January 2014 to June 2017. These patients were followed up periodically for clinical and imaging findings to ascertain the technical effectiveness along with survival. Results: Sixteen patients were identified who received cTACE for ruptured HCC. Majority of the patients (81.3%) had abdominal pain, while 25% had hypovolemic shock at initial presentation. Complete response and partial response were seen in 35.7% and 57.1% of patients, respectively. One patient (7.1%) showed progressive disease in form of peritoneal spread along the liver surface. The overall cumulative survival rates at 30 days, 180 days, and at 1 year were 87.5%, 72.2%, and 54.1%, respectively. Conclusion: cTACE is safe in patients with spontaneous HCC rupture and it leads to immediate hemostasis along with overall survival advantage. Achieving quick hemostasis may be a key to better outcome

Role of routine abdominal ultrasonography in intensified tuberculosis case finding algorithms at HIV clinics in high TB burden settings

Abstract Background High proportion of TB in people living with HIV (PLHIV) is undiagnosed. Due to this active TB case finding is recommended for HIV clinics in high TB burden countries. Presently sputum examination and chest radiography are frontline tests recommended for HIV infected TB presumptives. Abdominal TB which occurs frequently in PLHIV may be missed even by existing programmatic intensified case finding protocols. This study evaluated the routine use of ultrasonography (USG) for active case finding of abdominal TB in HIV clinics. Methods Retrospective analysis of eight years’ data from an HIV Clinic in a TB hospital in India. Patients underwent chest x-ray, sputum examination, USG abdomen and routine blood tests at entry to HIV care. Case forms were scrutinized for diagnosis of TB, USG findings and CD4 cell counts. Abdominal TB was classified as probable or possible TB. Probable TB was based on presence of two major USG (abdomen) findings suggestive of active TB, or one major USG finding with at least two minor USG findings or at least two symptoms, or any USG finding with microbiologically confirmed active TB at another site. Possible TB was based on the presence of one major USG finding, or the presence of two minor USG findings with at least two symptoms. Bacteriological confirmation was not obtained. Results Eight hundred and eighty-nine people PLHIV underwent a baseline USG abdomen. One hundred and thirteen of 340 cases already diagnosed with TB and 87 of the 91 newly diagnosed with TB at time of HIV clinic registration had abdominal TB. Non-abdominal symptoms like weight loss, fever and cough were seen in 53% and 22% cases had no symptoms at all. Enlarged abdominal lymph nodes with central caseation, ascitis, splenic microabsesses, bowel thickening and hepatosplenomegaly were the USG findings in these cases. Conclusions Abdominal TB is a frequent TB site in PLHIV presenting with non-abdominal symptoms. It can be easily detected on basis of features seen on a simple abdominal ultrasound. Abdominal USG should be essential part of intensified TB case finding algorithms for HIV infected people living in high TB burden settings