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Summary Background COBRA-BPS (Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan, Sri Lanka), a multi-component hypertension management programme that is led by community health workers, has been shown to be efficacious at reducing systolic blood pressure in rural communities in Bangladesh, Pakistan, and Sri Lanka. In this study, we aimed to assess the budget required to scale up the programme and the incremental cost-effectiveness ratios. Methods In a cluster-randomised trial of COBRA-BPS, individuals aged 40 years or older with hypertension who lived in 30 rural communities in Bangladesh, Pakistan, and Sri Lanka were deemed eligible for inclusion. Costs were quantified prospectively at baseline and during 2 years of the trial. All costs, including labour, rental, materials and supplies, and contracted services were recorded, stratified by programme activity. Incremental costs of scaling up COBRA-BPS to all eligible adults in areas covered by community health workers were estimated from the health ministry (public payer) perspective. Findings Between April 1, 2016, and Feb 28, 2017, 11 510 individuals were screened and 2645 were enrolled and included in the study. Participants were examined between May 8, 2016, and March 31, 2019. The first-year per-participant costs for COBRA-BPS were US$10·65 for Bangladesh, $10·25 for Pakistan, and $6·42 for Sri Lanka. Per-capita costs were $0·63 for Bangladesh, $0·29 for Pakistan, and $1·03 for Sri Lanka. Incremental cost-effectiveness ratios were $3430 for Bangladesh, $2270 for Pakistan, and $4080 for Sri Lanka, per cardiovascular disability-adjusted life year averted, which showed COBRA-BPS to be cost-effective in all three countries relative to the WHO-CHOICE threshold of three times gross domestic product per capita in each country. Using this threshold, the cost-effectiveness acceptability curves predicted that the probability of COBRA-BPS being cost-effective is 79·3% in Bangladesh, 85·2% in Pakistan, and 99·8% in Sri Lanka. Interpretation The low cost of scale-up and the cost-effectiveness of COBRA-BPS suggest that this programme is a viable strategy for responding to the growing cardiovascular disease epidemic in rural communities in low-income and middle-income countries where community health workers are present, and that it should qualify as a priority intervention across rural settings in south Asia and in other countries with similar demographics and health systems to those examined in this study. Funding The UK Department of Health and Social Care, the UK Department for International Development, the Global Challenges Research Fund, the UK Medical Research Council, Wellcome Trust.

ImportanceAssessing booster effectiveness of COVID-19 mRNA vaccine and inactivated SARS-CoV-2 vaccine over longer time intervals and in response to any further SARS-CoV-2 variants is crucial in determining optimal COVID-19 vaccination strategies.ObjectiveTo determine levels of protection against severe COVID-19 and confirmed SARS-CoV-2 infection by types and combinations of vaccine boosters in Singapore during the Omicron wave.Design, Setting, and ParticipantsThis cohort study included Singapore residents aged 30 years or more vaccinated with either at least 2 doses of mRNA COVID-19 vaccines (ie, Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) or inactivated SARS-CoV-2 vaccines (Sinovac CoronaVac or Sinopharm BBIBP-CorV) as of March 10, 2022. Individuals with a known SARS-CoV-2 infection prior to December 27, 2021, an infection on or before the date of their second vaccine dose, or with reinfection cases were excluded.ExposuresTwo or 3 doses of Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, Sinovac CoronaVac, or Sinopharm BBIBP-CorV.Main Outcomes and MeasuresNotified infections from December 27, 2021, to March 10, 2022, adjusted for age, sex, race, housing status, and calendar days. Estimated booster effectiveness, defined as the relative incidence-rate reduction of severe disease (supplemental oxygen, intensive care, or death) or confirmed infection following 3-dose vaccination compared with 5 months after second mRNA dose, was determined using binomial regression.ResultsAmong 2 441 581 eligible individuals (1 279 047 [52.4%] women, 846 110 (34.7%) aged 60 years and older), there were 319 943 (13.1%) confirmed SARS-CoV-2 infections, of which 1513 (0.4%) were severe COVID-19 cases. mRNA booster effectiveness against confirmed infection 15 to 60 days after boosting was estimated to range from 31.7% to 41.3% for the 4 boosting combinations (homologous BNT162b2, homologous mRNA-1273, 2-dose BNT162b2/mRNA-1273 booster, and 2-dose mRNA-1273/BNT162b2 booster). Five months and more after boosting, estimated booster effectiveness against confirmed infection waned, ranging from –2.8% to 14.6%. Against severe COVID-19, estimated mRNA booster effectiveness was 87.4% (95% CI, 83.3%-90.5%) 15 to 60 days after boosting and 87.2% (95% CI, 84.2%-89.7%) 5 to 6 months after boosting, with no significant difference comparing vaccine combinations. Booster effectiveness against severe COVID-19 15 days to 330 days after 3-dose inactivated COVID-19 vaccination, regardless of combination, was estimated to be 69.6% (95% CI, 48.7%-81.9%).Conclusions and RelevanceBooster mRNA vaccine protection against severe COVID-19 was estimated to be durable over 6 months. Three-dose inactivated SARS-CoV-2 vaccination provided greater protection than 2-dose but weaker protection compared with 3-dose mRNA.

Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (90Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.

Background: MRSA has caused enormous burden to affected Western patients and society. However, only limited study results originated from the Asia-Pacific populations. Aim: To assess the burden of Methicillin-resistant S. aureus infections (MRSA) among patients from a large tertiary care hospital in Singapore. Methods: Retrospective study using data from the hospital discharge database to identify patients with MRSA and Methicillin-sensitive S. aureus infections (MSSA) using International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Australian Modification (ICD-9-AM) codes. Findings: Amongst 543,068 hospitalized patients between 2004 and 2010, 8,664(1.6%) were infected with S. Aureus, including 4,868(0.9%) with MRSA. Compared with uninfected controls, MRSA patients had longer hospital stay (geometric mean, GM, 12.2 vs. 3.0 days), higher hospitalization costs (GM, $6294.7 vs. $2295.7), higher in-hospital mortality rate (7.8% vs. 2.8%) and higher 30-day all-cause unscheduled readmission rate (36.3% vs. 23.7%, all p

Background Involvement of clinicians in biomedical research is imperative for the future of healthcare. Several factors influence clinicians’ inclination towards research: the medical school experience, exposure to research article reading and writing, and knowledge of research. This cohort study follows up medical students at time of graduation to explore changes in their inclination towards research and pursuing a research career compared to their inclination at time of entry into medical school. Methods Students from medical schools in six different countries were enrolled in their first year of school and followed-up upon graduation in their final year. Students answered the same self-administered questionnaire at both time points. Changes in inclination towards research and pursuing a research career were assessed. Factors correlated with these changes were analysed. Results Of the 777 medical students who responded to the study questionnaire at entry into medical school, 332 (42.7%) completed the follow-up survey. Among these 332 students, there was no significant increase in inclination towards research or pursuing a research career over the course of their medical schooling. Students from a United States based school, in contrast to those from schools other countries, were more likely to report having research role models to guide them (51.5% vs. 0%–26.4%) and to have published in a peer-reviewed journal (75.7% vs. 8.9%–45%). Absence of a role model was significantly associated with a decrease in inclination towards research, while an increased desire to learn more about statistics was significantly associated with an increase in inclination towards pursuing a research career. Conclusion Most medical students did not experience changes in their inclination towards research or pursuing a research career over the course of their medical schooling. Factors that increased their inclination to undertaking research or pursuing a research career were availability of a good role model, and a good knowledge of both the research process and the analytical tools required. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Randomised controlled trials (RCTs) with sufficiently high statistical power are not always feasible for patients when the administration of the treatment is burdensome. Nevertheless, useful information concerning the relative effectiveness of the Test and Standard therapies, may be gleaned from under powered trials, non-randomised comparative studies and/or clinician's beliefs: the latter possibly additionally providing some suggestion of the strength of evidence required in order to adopt the Test therapy into clinical practice. In such circumstances, a Bayesian synthesis may be useful in quantifying the evidence of treatment effectiveness. In this article, we aim to present a Bayesian approach for synthesizing the cumulative evidence of the use of adjuvant hepatic intra-arterial iodine-131-lipiodol (I131L) following curative resection in hepatocellular carcinoma (HCC) patients. We constructed a posterior distribution using the information from two small RCTs, three non-randomised comparative studies, three single arm studies and the views of investigators on the use of I131L. This distribution enables calculation of the probability that the Test therapy is more effective than the Standard by a pre-stipulated amount. If this is very high, then for example, one may conclude the Test may replace the Standard therapy. If it is not, then the Standard would be retained for clinical use. Despite a strong early indication of the effectiveness of I131L, the evolving evidence over a 10-year period became more sceptical of its value. Although highly recommended, difficulties of implementing a Bayesian approach in this context are highlighted.

Approximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients. This investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy. Definitive data comparing these two therapies will help to determine clinical practice in the large group of patients with locally advanced HCC and improve outcomes for such patients. ClinicalTrials.gov identifier, NCT01135056 , first received 24, May 2010.