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Background: The association between covid-19 vaccine and menstrual disturbance is unclear., Methods: An in-person cross-sectional survey among female members ≥ 18 years enrolled in an ongoing Zero TB prospective cohort in Northern India who had received one or two doses of covid-19 vaccine was conducted to study the characteristics and association of menstrual disturbance within six months of receiving Covishield., Results: Between June 29 and September 5, 2021, 339 females ≥ 18 years of age were administered the survey. Median age was 30 (IQR: 22-39) years; 84 % were between 18 and 49 and 16 % were ≥ 50 years old. There were 152 college students, 27 healthcare workers, and 160 nuns. Forty-two women (12 %) had received one dose and 297 (88 %) had received two doses of Covishield. Overall, 66 (20 %) women reported experiencing menstrual disturbance after receiving Covishield vaccine. The problems included early menstruation: 6 % (n = 19/339); late menstruation: 4 % (n = 14/339); and heavier bleeding: 5 % (n = 17/339). Disturbances lasted for less than seven days and cycles normalized in 1-3 months. There was no post-menopausal bleeding. There was no significant difference in menstrual disturbance based on receiving one vs. two doses of Covishield (OR: 1.58; 95 % CI: 0.55-4.57; p = 0.381). History of SARS-CoV-2 infection was not associated with the development of menstrual disturbance among the vaccinees (OR: 0.63; 95 % CI: 0.24-1.73; p = 0.379). Presence of emotional disturbance at baseline (OR: 31; 95 % CI: 3.52-267; p = 0.002) or previous history of dysmenorrhea (OR: 41; 95 % CI: 8.7-196; p < 0.001) was associated with menstrual disturbance in the vaccinees, indicating their potential to confound or bias study results., Conclusion: Menstrual problems were reported by Covishield vaccinees, but they were minor and reversible within three months and do not constitute a ground for vaccine hesitancy. Studies designed to assess causal link taking care to avoid selection bias or confounding are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The emergence of highly infectious pathogens with their potential for triggering global pandemics necessitate the development of effective treatment strategies, including broad-spectrum antiviral therapies to safeguard human health. This study investigates the antiviral activity of emetine, dehydroemetine (DHE), and congeneric compounds against SARS-CoV-2 and HCoV-OC43, and evaluates their impact on the host cell. Concurrently, we assess the potential cardiotoxicity of these ipecac alkaloids. Significantly, our data reveal that emetine and the (-)-R,S isomer of 2,3-dehydroemetine (designated in this paper as DHE4) reduce viral growth at nanomolar concentrations (i.e., IC 50 ∼ 50-100 nM), paralleling those required for inhibition of protein synthesis, while calcium channel blocking activity occurs at elevated concentrations (i.e., IC 50 ∼ 40-60 µM). Our findings suggest that the antiviral mechanisms primarily involve disruption of host cell protein synthesis and is demonstrably stereoisomer specific. The prospect of a therapeutic window in which emetine or DHE4 inhibit viral propagation without cardiotoxicity renders these alkaloids viable candidates in strategies worthy of clinical investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

More than half of Bhutan's under-five mortality is attributed to neonatal deaths. Despite this, there is a lack of local evidence on determinants of neonatal mortality. It is critical to generate new evidence to accelerate interventions to achieve sufficient reduction of neonatal mortality rate in line to sustainable development goal target 3.2. Thus, this study was aimed at exploring determinants of neonatal mortality in Bhutan. A case-control study was performed with reported neonatal deaths from hospitals and primary health centers between 2018 and 2019. A total of 181 neonatal deaths were included as cases along with three corresponding controls. Epidata and STATA were used for data management and analysis, respectively. A multivariable model was fitted to identify determinants of neonatal mortality. History of obstetric complications (odds ratio [OR] = 3.53; 95% confidence interval [CI] = 1.48-8.42), intrapartum complications (OR = 3.86; 95% CI = 1.71-8.74) gestational age (OR = 8.07; 95% CI = 2.89-22.52), and Apgar 1 minute (OR = 4.40; 95% CI =1.83-10.59) were associated with neonatal death. Therefore, quality of care during pregnancy and childbirth besides promoting supportive family environment is essential to reduce neonatal mortality., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: This study aimed to determine the effectiveness of Covishield vaccine among residents of congregate residential facilities., Design: A prospective cohort study in congregate residential facilities., Setting: Dharamshala, Himachal Pradesh, India, from December 2020 to July 2021., Participants: Residents of all ages in seven facilities-three monasteries, two old age homes and two learning centres-were enrolled., Exposures: First and second doses of Covishield vaccine against SARS-CoV-2 infection., Main Outcomes Measures: Primary outcome was development of COVID-19. Secondary outcome was unfavourable outcomes, defined as a composite of shortness of breath, hospitalisation or death. Vaccine effectiveness (%) was calculated as (1-HR)×100., Results: There were 1114 residents (median age 31 years) participating in the study, 82% males. Twenty-eight per cent (n=308/1114) were unvaccinated, 50% (n=554/1114) had received one dose and 23% (n=252/1114) had received two doses of Covishield. The point prevalence of COVID-19 for the facilities ranged from 11% to 57%. Incidence rates (95% CI) of COVID-19 were 76 (63 to 90)/1000 person-months in the unvaccinated, 25 (18 to 35)/1000 person-months in recipients of one dose and 9 (4 to 19)/1000 person-months in recipients of two doses. The effectiveness of first and second doses of Covishield were 71% (adjusted HR (aHR) 0.29; 95% CI 0.18 to 0.46; p<0.001) and 80% (aHR 0.20; 95% CI 0.09 to 0.44; p<0.001), respectively, against SARS-CoV-2 infection and 86% (aHR 0.24; 95% CI 0.07 to 0.82; p=0.023) and 99% (aHR 0.01; 95% CI 0.002 to 0.10; p<0.001), respectively, against unfavourable outcome. The effectiveness was higher after 14 days of receiving the first and second doses, 93% and 98%, respectively. Risk of infection was higher in persons with chronic hepatitis B (aHR 1.78; p=0.034) and previous history of tuberculosis (aHR 1.62; p=0.047)., Conclusion: Covishield was effective in preventing SARS-CoV-2 infection and reducing disease severity in highly transmissible settings during the second wave of the pandemic driven by the Delta variant., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We analyzed the Population and Health Census of Bhutan (PHCB) 2017 to assess the prevalence and pattern of self-reported disability among people aged ≥15 years and the associated factors. The PHCB 2017 used the Washington Group Short Set on Functioning questionnaire to assess the disability ("lot of difficulty" or "cannot do at all") in seeing, hearing, mobility, cognition, self-care, and communication. Of the 536 443 persons included in the analysis, 384 101(71.6%) were aged <45 years, 283 453(52.8%) were men, and 206 103(38.4%) were from the rural area. The prevalence of any self-reported disability was 2.8%, among whom 34.2% reported multiple disabilities. The disability prevalence (any) was significantly higher among people aged ≥65 years, illiterate, economically inactive, permanent residents, residing in a rural area, and from central and eastern regions of the country compared with their respective counterparts. Further research on access to rehabilitation and linking with social protection schemes for the disabled is required in this country.

Objectives: Bhutan is experiencing a dual burden of undernutrition and overnutrition among adolescents. Understanding dietary behavior is vital to designing evidence-based interventions to improve adolescent nutrition and prevent non-communicable diseases in adults. The aim of this study was to assess the pattern of dietary behavior and associated sociodemographic, behavioral, and metabolic risk factors among school-going adolescents in Bhutan., Methods: The Bhutan Global School-based Student Health Survey 2016 studied students in grades 7 to 11 (N = 7576), sampled from 50 schools, randomly selected based on probability proportional to enrollment size, using a standardized self-administered questionnaire. Consumption of adequate fruits and vegetables (each at least twice daily, or a combination of at least five times daily), high-protein food at least twice weekly) in the past 30 d, no fast food in the past week, and no carbonated/sweetened drinks in the past 30 d were studied. Weighted prevalence of dietary behaviors and adjusted prevalence ratio (95% confidence interval) for factors associated with them were calculated., Results: Of 5809 students from 13 to 17 y of age comprising 3255 (56%) girls and 3184 (54.8%) day students, 1166 (20.1%) were underweight, 1655 (28.5%) were tobacco users, and 1349 (23.2%) were alcohol users. Adequate fruit and vegetable intake, high protein consumption, not consuming fast foods and carbonated beverages were reported by 29.6%, 31.8%, 9.6%, and 14.9%, respectively. Being a day student, sex, and not reporting health risk behaviors were significantly associated with any healthy dietary behavior., Conclusion: Healthy eating behavior was low among Bhutanese adolescents. Policies influencing availability, affordability, and acceptability of healthy diets through peer-led, school- and community-based interventions are required to promote adolescent health and prevent non-communicable diseases., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Although individual antiretroviral drugs have been shown to be associated with elevated cardiovascular disease (CVD) risk, data are limited on the role of antiretroviral drug combinations. Therefore, we sought to investigate CVD risk associated with antiretroviral drug combinations., Methods: Using an administrative health-plan dataset, risk of acute myocardial infarction (AMI) associated with current exposure to antiretroviral drug combinations was assessed among persons living with HIV receiving antiretroviral therapy (ART) across the U.S. from October 2009 through December 2014. To account for confounding-by-indication and for factors simultaneously acting as causal mediators and confounders, we applied inverse probability of treatment weighted marginal structural models to longitudinal data of patients., Results: Over 114,417 person-years (n = 73,071 persons) of ART exposure, 602 cases of AMI occurred at an event rate of 5.26 (95% CI: 4.86, 5.70)/1000 person-years. Of the 14 antiretroviral drug combinations studied, persons taking abacavir-lamivudine-darunavir had the highest incidence rate (IR: 11/1000; 95% CI: 7.4-16.0) of AMI. Risk (HR; 95% CI) of AMI was elevated for current exposure to abacavir-lamivudine-darunavir (1.91; 1.27-2.88), abacavir-lamivudine-atazanavir (1.58; 1.08-2.31), and tenofovir-emtricitabine-raltegravir (1.35; 1.07-1.71). Tenofovir-emtricitabine-efavirenz was associated with reduced risk (0.65; 0.54-0.78). Abacavir-lamivudine-darunavir was associated with increased risk of AMI beyond that expected of abacavir alone, likely attributable to darunavir co-administration. We did not find an elevated risk of AMI when abacavir-lamivudine was combined with efavirenz or raltegravir., Conclusion: The antiretroviral drug combinations abacavir-lamivudine-darunavir, abacavir-lamivudine-atazanavir and tenofovir-emtricitabine-raltegravir were found to be associated with elevated risk of AMI, while tenofovir-emtricitabine-efavirenz was associated with a lower risk. The AMI risk associated with abacavir-lamivudine-darunavir was greater than what was previously described for abacavir, which could suggest an added risk from darunavir. The results should be confirmed in additional studies., (© 2021. The Author(s).)

Recent EEG studies on the early postmortem interval that suggest the persistence of electrophysiological coherence and connectivity in the brain of animals and humans reinforce the need for further investigation of the relationship between the brain's activity and the dying process. Neuroscience is now in a position to empirically evaluate the extended process of dying and, more specifically, to investigate the possibility of brain activity following the cessation of cardiac and respiratory function. Under the direction of the Center for Healthy Minds at the University of Wisconsin-Madison, research was conducted in India on a postmortem meditative state cultivated by some Tibetan Buddhist practitioners in which decomposition is putatively delayed. For all healthy baseline (HB) and postmortem (PM) subjects presented here, we collected resting state electroencephalographic data, mismatch negativity (MMN), and auditory brainstem response (ABR). In this study, we present HB data to demonstrate the feasibility of a sparse electrode EEG configuration to capture well-defined ERP waveforms from living subjects under very challenging field conditions. While living subjects displayed well-defined MMN and ABR responses, no recognizable EEG waveforms were discernable in any of the tukdam cases., Competing Interests: RD is the founder and president, and he serves on the board of directors for the non-profit organization, Healthy Minds Innovations, Inc. In addition, RD served on the board of directors for the Mind & Life Institute from 1992 to 2017. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lott, Yeshi, Norchung, Dolma, Tsering, Jinpa, Woser, Dorjee, Desel, Fitch, Finley, Goldman, Bernal, Ragazzi, Aroor, Koger, Francis, Perlman, Wielgosz, Bachhuber, Tamdin, Sadutshang, Dunne, Lutz and Davidson.)

Background: Tuberculosis (TB) rates among Tibetan refugee children and adolescents attending boarding schools in India are extremely high. We undertook a comprehensive case finding and TB preventive treatment (TPT) program in 7 schools in the Zero TB Kids project. We aimed to measure the TB infection and disease burden and investigate the risk of TB disease in children and adults who did and did not receive TPT in the schools., Methods and Findings: A mobile team annually screened children and staff for TB at the 7 boarding schools in Himachal Pradesh, India, using symptom criteria, radiography, molecular diagnostics, and tuberculin skin tests. TB infection (TBI) was treated with short-course regimens of isoniazid and rifampin or rifampin. TB disease was treated according to Tibetan and Indian guidelines. Between April 2017 and December 2019, 6,582 schoolchildren (median age 14 [IQR 11-16] years) and 807 staff (median age 40 [IQR 33-48] years) were enrolled. Fifty-one percent of the students and 58% of the staff were females. Over 13,161 person-years of follow-up in schoolchildren (median follow-up 2.3 years) and 1,800 person-years of follow-up in staff (median follow-up 2.5 years), 69 TB episodes occurred in schoolchildren and 4 TB episodes occurred in staff, yielding annual incidence rates of 524/100,000 (95% CI 414-663/100,000) person-years and 256/100,000 (95% CI 96-683/100,000) person-years, respectively. Of 1,412 schoolchildren diagnosed with TBI, 1,192 received TPT. Schoolchildren who received TPT had 79% lower risk of TB disease (adjusted hazard ratio [aHR] 0.21; 95% CI 0.07-0.69; p = 0.010) compared to non-recipients, the primary study outcome. Protection was greater in recent contacts (aHR 0.07; 95% CI 0.01-0.42; p = 0.004), the secondary study outcome. The prevalence of recent contacts was 28% (1,843/6,582). Two different TPT regimens were used (3HR and 4R), and both were apparently effective. No staff receiving TPT developed TB. Overall, between 2017 and 2019, TB disease incidence decreased by 87%, from 837/100,000 (95% CI 604-1,129/100,000) person-years to 110/100,000 (95% CI 36-255/100,000) person-years (p < 0.001), and TBI prevalence decreased by 42% from 19% (95% CI 18%-20%) to 11% (95% CI 10%-12%) (p < 0.001). A limitation of our study is that TB incidence could be influenced by secular trends during the study period., Conclusions: In this study, following implementation of a school-wide TB screening and preventive treatment program, we observed a significant reduction in the burden of TB disease and TBI in children and adolescents. The benefit of TPT was particularly marked for recent TB contacts. This initiative may serve as a model for TB detection and prevention in children and adolescents in other communities affected by TB., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Spouse of RC owns stock in Merck. RC has received consulting fees from Sanofi. Other authors have declared that no competing interests exist.

Village health workers (VHWs) serve as an integral health resource for many resource limited nations, including the Kingdom of Bhutan. As such, we aimed to identify community perceptions as well as utilization rates and types with relation to VHWs based on the urban-rural divide. Our team conducted a randomized survey of 429 community members in 14 villages within the Western region of Bhutan. Our findings indicate VHWs in rural communities are requested for their services twice as much as their urban counterparts. More specifically, urban VHWs are utilized 2.5 times more for general community services, while rural VHWs are utilized more for accessing medications. Additionally, our research indicates a need to increase training of VHWs as well as overall program promotion relating to the specific services that VHWs can provide. These investigations indicate the importance of differentially allocating resources, programming, and training based on the urban-rural divide.

As the COVID-19 pandemic continues, there is growing concordance and persisting conflicts on the virus and the disease process. We discuss limited transmissibility of the virus by asymptomatic and mild cases of COVID-19 patients in Bhutan. We followed up the secondary transmission of SARS-CoV-2 in the contacts of asymptomatic and mild COVID-19 patients in Bhutan. Bhutan had 33 confirmed COVID-19 cases in the country as of May 29, 2020. Of these, 22 (67%) were females. Except the first two cases (American tourists), the rest were Bhutanese living outside the country. The mean age of the Bhutanese patients was 26.3 (range 16-33) years. Close contacts of 27 of the 33 cases were followed up for signs and symptoms and COVID-19 positivity. The first two cases had 73 and 97 primary contacts, respectively, and equal number of secondary contacts (224). From the third case, a mandatory 21-day facility quarantine was instituted, all primary contacts were facility quarantined, and there were no secondary contacts. In total, the 27 cases had 1,095 primary contacts and 448 secondary contacts. Of these, 75 individuals were categorized as definite high-risk contacts. Secondary transmission occurred in seven high-risk contacts. Therefore, the overall secondary transmission was 9.0% (7/75) and 0.6% (7/1,095) among the high-risk and primary contacts, respectively. No transmission occurred in the secondary contacts. In contrast to several reports indicating high transmissibility of SARS-CoV-2 in contacts of confirmed cases, the mostly young, asymptomatic, and mild cases of COVID-19 in Bhutan showed limited secondary transmission.

Introduction: Progression of COVID-19 to severe disease and death is insufficiently understood., Objective: Summarize the prevalence of risk factors and adverse outcomes and determine their associations in COVID-19 patients who were hospitalized., Methods: We searched Medline, Embase and Web of Science for case-series and observational studies of hospitalized COVID-19 patients through August 31, 2020. Data were analyzed by fixed-effects meta-analysis using Shore's adjusted confidence intervals to address heterogeneity., Results: Seventy-seven studies comprising 38906 hospitalized patients met inclusion criteria; 21468 from the US-Europe and 9740 from China. Overall prevalence of death [% (95% CI)] from COVID-19 was 20% (18-23%); 23% (19-27%) in the US and Europe and 11% (7-16%) for China. Of those that died, 85% were aged≥60 years, 66% were males, and 66%, 44%, 39%, 37%, and 27% had hypertension, smoking history, diabetes, heart disease, and chronic kidney disease (CKD), respectively. The case fatality risk [%(95% CI)] were 52% (46-60) for heart disease, 51% (43-59) for COPD, 48% (37-63) for chronic kidney disease (CKD), 39% for chronic liver disease (CLD), 28% (23-36%) for hypertension, and 24% (17-33%) for diabetes. Summary relative risk (sRR) of death were higher for age≥60 years [sRR = 3.6; 95% CI: 3.0-4.4], males [1.3; 1.2-1.4], smoking history [1.3; 1.1-1.6], COPD [1.7; 1.4-2.0], hypertension [1.8; 1.6-2.0], diabetes [1.5; 1.4-1.7], heart disease [2.1; 1.8-2.4], CKD [2.5; 2.1-3.0]. The prevalence of hypertension (55%), diabetes (33%), smoking history (23%) and heart disease (17%) among the COVID-19 hospitalized patients in the US were substantially higher than that of the general US population, suggesting increased susceptibility to infection or disease progression for the individuals with comorbidities., Conclusions: Public health screening for COVID-19 can be prioritized based on risk-groups. Appropriately addressing the modifiable risk factors such as smoking, hypertension, and diabetes could reduce morbidity and mortality due to COVID-19; public messaging can be accordingly adapted., Competing Interests: The authors have declared that no competing interests exist.

Background: Village health workers (VHWs) in Bhutan play an all-encompassing role in supporting the health of their communities. Recent reports from the Bhutan Ministry of Health have indicated a sharp reduction in the number of working VHWs. As such, our work attempts to estimate the cost saved and the number of averted hospital admissions onto the Bhutanese healthcare system and the individuals who are served by these health workers., Methods: We utilized a dataset from the Bhutan Ministry of Health which encompassed over 95% of all reported disease cases within the nation. We examined the impact that VHWs have on hospital admission rates for eight diseases of interest by using multiple multivariate logistic regression models. Our model allowed us to estimate the potential disease cases averted when the average number of VHWs per health center is increased by one unit. Lastly, we utilized the 2011 "A Costing of Healthcare Services in Bhutan" to estimate the cost saved attributed to VHWs., Results: An average one unit increase of VHWs per health center is associated with a decrease in hospital and clinic admission for diarrhea, dysentery, wound care, depression/anxiety, dental caries, and skin infection, while a non-significant increase was observed for scabies and conjunctivitis. These findings translate to 4604 outpatient visits averted, with $28,637 saved, and 78 inpatient visits averted, with $10,711 saved. These values sum to a total of 4682 yearly averted admissions at health centers, with a total cost savings of $39,348 yearly. Additionally, we estimated a yearly savings of $13,348 in transportation costs and a total of $20,960 saved in wages to the community members that VHWs serve., Conclusions: VHWs serve as a source of cost-savings for the Kingdom of Bhutan and also act as an economic buffer for more vulnerable communities. The cost-savings associated with these health workers is likely to become more pertinent as the nation begins to develop and healthcare costs increase. It is imperative that proper action be taken to retain these health workers as every VHW who leaves the program increases healthcare costs onto the Bhutanese government.

Background: India accounts for quarter of global rifampin-resistant/multi-drug resistant-tuberculosis (RR/MDR-TB). Knowledge on risk-factors and distribution of MDR-TB at district level is limited., Objective: Study prevalence and risk factors of MDR-TB in tuberculosis patients in hilly districts of Himachal Pradesh, India., Methods: Between July 2012-June 2013, TB patients registered under the Revised National Tuberculosis Control Program in Kangra and Una districts suspected of MDR-TB were referred for Xpert® MTB/RIF testing at the Delek Hospital, Dharamsala by the district TB Office., Results: Of 378 patients enrolled (median age: 45 years; 85% males), 18% (n = 68) were rifampin-resistant. Among Xpert positives (n = 305), distributions of RR-TB were: 10% (n = 9/89) for recurrent cases who had received TB treatment for <2-months, 15% each for new (n = 9/59) or recurrent cases (n = 5/34) remaining smear positive between 2 and 4 months of treatment, 36% (n = 41/113) for treatment failures, and 40% (n = 2/5) for loss to follow-ups. Of the sputum-smear positives, 15% (n = 51/338) were Xpert negative. Seeking care in the private sector was associated with higher risk of RR-TB (OR:1.85; 95% CI:0.87-3.9)., Conclusion: Prevalence of RR-TB is generally high in patients suspected of MDR-TB in the hilly districts of Himachal Pradesh. High prevalence during early phase of treatment can suggest primary transmission of DR-TB. Universal drug susceptibility testing and innovative case finding strategies will benefit patients living in mountain districts with inadequate access to healthcare. The high proportion of sputum-smear positive but Xpert negative cases may be due to non-tubercular mycobacterial disease., (Copyright © 2019 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: Tuberculosis (TB) prevalence is high among Tibetan refugees in India, with almost half of cases occurring in congregate facilities, including schools. A comprehensive program of TB case finding and treatment of TB infection (TBI) was undertaken in schools for Tibetan refugee children., Methods: Schoolchildren and staff in Tibetan schools in Himachal Pradesh, India, were screened for TB with an algorithm using symptoms, chest radiography, molecular diagnostics, and tuberculin skin testing. Individuals with active TB were treated and those with TBI were offered isoniazid-rifampicin preventive therapy for 3 months., Results: From April 2017 to March 2018, we screened 5391 schoolchildren (median age, 13 years) and 786 staff in 11 Tibetan schools. Forty-six TB cases, including 1 with multidrug resistance, were found in schoolchildren, for a prevalence of 853 per 100 000. Extensively drug-resistant TB was diagnosed in 1 staff member. The majority of cases (66%) were subclinical. TBI was detected in 930 of 5234 (18%) schoolchildren and 334 of 634 (53%) staff who completed testing. Children in boarding schools had a higher prevalence of TBI than children in day schools (915/5020 [18%] vs 15/371 [4%]; P < .01). Preventive therapy was provided to 799 of 888 (90%) schoolchildren and 101 of 332 (30%) staff with TBI; 857 (95%) people successfully completed therapy., Conclusions: TB prevalence is extremely high among Tibetan schoolchildren. Effective active case finding and a high uptake and completion of preventive therapy for children were achieved. With leadership and community mobilization, TB control is implementable on a population level., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: Abacavir's potential to cause cardiovascular disease (CVD) among people living with HIV (PLWH) is debated. We conduct a systematic review and meta-analyses to assess CVD risk from recent and cumulative abacavir exposure., Methods: We searched Medline, Embase, Web of Science, abstracts from Conference on Retroviruses and Opportunistic Infections, and International AIDS Society/AIDS Conferences and bibliographies of review articles to identify research studies published through 2018 on CVD risk associated with abacavir exposure among PLWH. Studies assessing risk of CVD associated with recent (exposure within last 6 months) or cumulative abacavir exposure across all age-groups were eligible. Risks were quantified using fixed- and random-effects models., Results: Of 378 unique citations, 68 full-text research articles and abstracts were reviewed. Seventeen studies assessed risk of CVD from recent or cumulative abacavir exposure. Summary relative risk (sRR) is increased for recent exposure (n=16 studies, sRR=1.61; 95% confidence interval: 1.48-1.75), higher in antiretroviral-therapy-naive population (n=5, 1.91; 1.48-2.46) and all studies reported RR>1. The sRR for recent exposure was similarly increased for the outcome of acute myocardial infarction, and for studies that adjusted for substance abuse, smoking, prior CVD, traditional CVD risk factors, and CD4 cell-count/HIV viral load. The sRR was increased for cumulative abacavir exposure (per year) (n=4, 1.12; 1.05-1.20) but no increase was seen after adjusting for recent exposure (n=5, 1.00; 0.93-1.08)., Conclusions: Our findings suggest an increased risk of CVD from recent abacavir exposure. The risk remained elevated after adjusting for potential confounders. Further investigations are needed to understand CVD risk from cumulative exposure., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: There is ongoing controversy regarding abacavir use in the treatment of HIV infection and the risk of subsequent development of cardiovascular disease. It is unclear how the risk varies as exposure accumulates., Methods: Using an administrative health-plan dataset, risk of cardiovascular disease events (CVDe), defined as the first episode of an acute myocardial infarction or a coronary intervention procedure, associated with abacavir exposure was assessed among HIV-infected individuals receiving antiretroviral therapy across the U.S. from October 2009 through December 2014. The data were longitudinal, and analyzed using marginal structural models., Results: Over 114,470 person-years (n = 72,733) of ART exposure, 714 CVDe occurred at an incidence rate (IR) (95% CI) of 6·23 (5·80, 6·71)/1000 person-years. Individuals exposed to abacavir had a higher IR of CVDe of 9·74 (8·24, 11·52)/1000 person-years as compared to 5·75 (5·30, 6·24)/1000 person-years for those exposed to other antiretroviral agents. The hazard (HR; 95% CI) of CVDe was increased for current (1·43; 1·18, 1·73), recent (1·41; 1·16, 1·70), and cumulative [(1·18; 1·06, 1·31) per year] exposure to abacavir. The risk for cumulative exposure followed a bell-shaped dose-response curve peaking at 24-months of exposure. Risk was similarly elevated among participants free of pre-existing heart disease or history of illicit substance use at baseline., Conclusion: Current, recent, and cumulative use of abacavir was associated with an increased risk of CVDe. The findings were consistent irrespective of underlying cardiovascular risk factors.

The incidence of tuberculosis (TB) among Tibetan refugees in India is 431 cases/100,000 persons, compared with 181 cases/100,000 persons overall in India in 2010. More than half of TB cases in these refugees occur among students, monks, and nuns in congregate settings. We sought to increase TB case detection rates for this population through active case finding and rapid molecular diagnostics. We screened 27,714 persons for symptoms of TB and tested 3,830 symptomatic persons by using an algorithm incorporating chest radiography, sputum smear microscopy, culture, and a rapid diagnostic test; 96 (2.5%) cases of TB were detected (prevalence 346 cases/100,000 persons). Of these cases, 5% were multidrug-resistant TB. Use of the rapid diagnostic test and active case finding enabled rapid detection of undiagnosed TB cases in congregate living settings, which would not have otherwise been identified. The burden of TB in the Tibetan exile population in India is extremely high and requires urgent attention.

Background: Treatment of a multi-drug resistant tuberculosis (MDR-TB) patient is clinically challenging, requiring a minimum of 18 months of therapy. Its occurrence in a systemic lupus erythromatosus (SLE) patient may complicate management of both MDR-TB and SLE. This is the first descriptive report of MDR-TB in an SLE patient., Case Presentation: A 19-year old female receiving long-term prednisolone for SLE was diagnosed with MDR-TB. She was started on MDR-TB treatment regimen and prednisolone was replaced with azathioprine. After an initial response to therapy, patient experienced a flare of lupus symptoms. Imaging studies revealed avascular necrosis of right femoral head. She was then treated with intravenous methyl-prednisolone, followed by maintenance corticosteroid. Azathioprine was discontinued due to hematological toxicity and failure to control SLE. Her symptoms of lupus regressed and did not re-occur for the duration of her MDR-TB treatment. Patient was declared cured of MDR-TB after 18 months of ATT. She is currently scheduled for a total hip replacement surgery., Conclusions: This case highlights the challenges of simultaneously managing MDR-TB and SLE in a patient due to their over-lapping signs and symptoms, drug-drug interactions, and the need for use of immunomodulatory agents in the absence of standard guidelines and documented previous experiences. Our experience underscores the importance of appropriate selection of treatment regimens for both MDR-TB and SLE.

Background: The prevalence and consequences of financial barriers to health care among patients with multiple chronic diseases are poorly understood., Objective: We sought to assess the prevalence of self-reported financial barriers to health care among individuals with diabetes and coronary heart disease (CHD) and to determine their association with access to care, quality of care and clinical outcomes., Design: The 2007 Centers for Disease Control Behavioral Risk Factor Surveillance Survey., Participants: Diabetic patients with CHD., Main Measures: Financial barriers to health care were defined by a self-reported time in the past 12 months when the respondent needed to see a doctor but could not because of cost. The primary clinical outcome was vascular morbidity—a composite of stroke, retinopathy, nonhealing foot sores or bilateral foot amputations., Key Results: Among the 11,274 diabetics with CHD, 1,541 (13.7 %) reported financial barriers to health care. Compared to individuals without financial barriers, those with financial barriers had significantly reduced rates of medical assessments within the past 2 years, hemoglobin (Hgb) A1C measurements in the past year, cholesterol measurements at any time, eye and foot examinations within the past year, diabetic education, antihypertensive treatment, aspirin use and a higher prevalence of vascular morbidity. In multivariable analyses, financial barriers to health care were independently associated with reduced odds of medical checkups (Odds Ratio [OR], 0.61; 95 % Confidence Intervals [CI], 0.55–0.67), Hgb A1C measurement (OR, 0.85; 95 % CI, 0.77–0.94), cholesterol measurement (OR, 0.76; 95 % CI, 0.67–0.86), eye (OR, 0.85; 95 % CI, 0.79–0.92) and foot (OR, 0.92; 95 % CI, 0.84–1.00) examinations, diabetic education (OR, 0.93; 95 % CI, 0.87–0.99), aspirin use (OR, 0.88; 95 % CI, 0.81–0.96) and increased odds of vascular morbidity (OR, 1.23; 95 % CI, 1.14–1.33)., Conclusions: In diabetic adults with CHD, financial barriers to health care were associated with impaired access to medical care, inferior quality of care and greater vascular morbidity. Eliminating financial barriers and adherence to guideline-based recommendations may improve the health of individuals with multiple chronic diseases.

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.