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

Feasibility of supervised self-testing using an oral fluid-based HIV rapid testing method:a cross-sectional, mixed method study among pregnant women in rural India

Introduction: HIV self-testing can increase coverage of essential HIV services. This study aimed to establish the acceptability, concordance and feasibility of supervised HIV self-testing among pregnant women in rural India. Methods: A cross-sectional, mixed methods study was conducted among 202 consenting pregnant women in a rural Indian hospital between August 2014 and January 2015. Participants were provided with instructions on how to self-test using OraQuick® HIV antibody test, and subsequently asked to self-test under supervision of a community health worker. Test results were confirmed at a government-run integrated counselling and testing centre. A questionnaire was used to obtain information on patient demographics and the ease, acceptability and difficulties of self-testing. In-depth interviews were conducted with a sub-sample of 35 participants to understand their experiences. Results: In total, 202 participants performed the non-invasive, oral fluid-based, rapid test under supervision for HIV screening. Acceptance rate was 100%. Motivators for self-testing included: ease of testing (43.4%), quick results (27.3%) and non-invasive procedure (23.2%). Sensitivity and specificity were 100% for 201 tests, and one test was invalid. Concordance of test result interpretation between community health workers and participants was 98.5% with a Cohen’s Kappa (k) value of k=0.566 with p<0.001 for inter-rater agreement. Although 92.6% participants reported that the instructions for the test were easy to understand, 18.7% required the assistance of a supervisor to self-test. Major themes that emerged from the qualitative interviews indicated the importance of the following factors in influencing acceptability of self-testing: clarity and accessibility of test instructions; time-efficiency and convenience of testing; non-invasiveness of the test; and fear of incorrect results. Overall, 96.5% of the participants recommended that the OraQuick® test kits should become publicly available. Conclusions: Self-testing for HIV status using an oral fluid-based rapid test under the supervision of a community health worker was acceptable and feasible among pregnant women in rural India. Participants were supportive of making self-testing publicly available. Policy guidelines and implementation research are required to advance HIV self-testing for larger populations at scale

Dalai Lama: 50 years after the fall

Documentaire die een duidelijke en intieme blik op de situatie in Tibet geeft. Op 10 maart is het vijftig jaar geleden dat Tibet viel en de Dalai Lama in ballingschap ging. Zijn grootste uitdaging is nu een oplossing te vinden voor het Tibetaanse vraagstuk. De Dalai Lama werd gevolgd tijdens een roerig jaar met o.a. de protesten in Tibet, de Olympische Spelen en de beëindiging van de dialoog tussen de Dalai Lama en de Chinese regering. Het samenspel tussen het persoonlijke en de geschiedenis en tussen spiritualiteit en politiek wordt onderzocht. Ook is er nog de spanning tussen de pogingen van de Dalai Lama om een vreedzame oplossing te vinden voor de situatie in Tibet en de jonge Tibetanen die een koers van confrontatie willen varen.

Developing Telemedicine Curriculum Competencies for Graduate Medical Education: Outcomes of a Modified Delphi Process

Purpose Telemedical applications have only recently begun to coalesce into the field of telemedicine due to varying definitions of telemedicine and issues around reimbursement. This process has been accelerated by the COVID-19 pandemic and the ensuing expansion of telemedicine delivery. This article demonstrates the development of a set of proposed competencies for a telemedicine curriculum in graduate medical education. Method A modified Delphi process was used to create a panel of competencies. This included a systematic review of the telemedicine literature through November 2019 to create an initial set of competencies, which were analyzed and edited by a focus group of experts in January 2020. Initial competencies were distributed in a series of 3 rounds of surveys to a group of 23 experts for comments and rating from April to August 2020. Competencies that obtained a score of 4.0 or greater on a 5-point Likert scale in at least 2 rounds were recommended. Results Fifty-five competencies were developed based on the systematic review. A further 32 were added by the expert group for a total of 87. After 3 rounds of surveys, 34 competencies reached the recommendation threshold. These were 10 systems-based practice competencies, 7 professionalism, 6 patient care, 4 practice-based learning and improvement, 4 interpersonal and communication skills, and 3 medical knowledge competencies. Conclusions Half (17/34) of the competencies approved by the focus group and surveyed expert panel pertained to either systems-based practice or professionalism. Both categories exhibit more variation between telemedicine and in-person practice than other categories. The authors offer a set of proposed educational competencies that can be used in the development of curricula for a wide range of providers and are based on the best evidence and expert opinion available

IL-27 attenuates IL-23 mediated inflammatory arthritis.

Interleukin 27 has both pro-inflammatory and anti-inflammatory properties in autoimmunity. The anti-inflammatory effects of IL-27 are linked with inhibition of Th17 differentiation but the IL-27 effect on myeloid cells is less studied. Herein we demonstrate that IL-27 inhibits IL-23-induced inflammation associated not only with Th17 cells but also with myeloid cell infiltration in the joints and splenic myeloid populations of CD11b+ GR1+ and CD3-CD11b+CD11c-GR1- cells. The IL-27 anti-inflammatory response was associated with reduced levels of myeloid cells in the spleen and bone marrow. Overall, our data demonstrate that IL-27 has an immunosuppressive role that affects IL-23-dependent myelopoiesis in the bone marrow and its progression to inflammatory arthritis and plays a crucial role in controlling IL-23 driven joint inflammation by negatively regulating the expansion of myeloid cell subsets

Xantogranulomatous Salpingo Oophritis, Lessons Learnt: Report of Two Cases With Unusual Presentation

Xanthogranulomatous inflammation is a rare form of chronic inflammatory response consisting of macrophages, lymphocytes, plasma cells and neutrophils too. Due to its locally destructive nature and mass forming capacity as a result of adhesions, this type of inflammation may mimic  malignancy or tuberculosis both clinically and radiologically. We present a report of two such cases, one mimicking tuberculosis and the other mimicking malignancy clinically. Awareness of this condition and a higher index of suspicion among clinicians, radiologists and pathologists can help in early diagnosis and more appropriate treatment of this potentially destructive disorder

Absence of pathogenic calcium sensing receptor mutations in sporadic idiopathic hypoparathyroidism

Background: Sporadic idiopathic hypoparathyroidism (SIH) is the most common cause of hypoparathyroidism. While calcium sensing receptor (CaSR) autoantibodies are observed in 49% of cases, aetiopathogenetic mechanisms in others are under investigation. Mutations in the PTH gene including its 3' untranslated region, autoimmune regulator gene and lead CTLA-4 gene single nucleotide polymorphism (SNPs) are not associated with the disease. There are reports of de novo activating mutations of the CaSR gene in a few patients with SIH. Objective: To assess the frequency of CaSR mutations in patients with SIH. Subjects and methods: DNA sequencing of all six translating exons and nine of 12 intron/exon boundaries of the CaSR gene was performed by Sangers dideoxy chain termination method using an automated sequencer in 39 patients with SIH. Spot urinary calcium/creatinine ratio in the fasting state and ultrasonography of the abdomen was performed to assess hypercalciuria and nephrolithiasis. The PCR-RFLP analysis was performed using Hin1II restriction endonuclease in 32 additional patients with SIH and 90 healthy controls to further assess the prevalence of a novel missense SNP observed in the DNA sequencing. Results: Nucleotide sequence analysis revealed the presence of a wild type CaSR gene in all subjects, except in one patient who showed a missense mutation (Val621Met) due to substitution of base G→A in the heterozygous state at position 79877 in exon 7 (codon 621) coding for the first transmembrane loop of the CaSR. The V621M polymorphism was confirmed by PCR-RFLP and was due to a maternal allele. However, the mother and brother of this patient with the same SNP were asymptomatic and had normal serum chemistry indicating the functionally inert nature of the polymorphism. None of the additional 32 patients with SIH and 90 controls showed V621M SNP. The urinary calcium/creatinine ratio and ultrasonography were normal in all patients with SIH. Conclusion: De novo activating mutation of the CaSR gene typical of familial hypoparathyroidism is not common among patients with SIH in India