Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

New evidence supporting lung cancer screening with low dose CT & surgical implications

IntroductionLung cancer is the leading cause of cancer-death worldwide. The U.S. Preventative Services Task Force (USPTSF) approved screening for current or former smokers aged 55–80 based on the results of the National Lung Screening trial (NLST). Following the NLST, new evidence has emerged from clinical trials and updates to previous trials prior to the anticipated update to the USPSTF guideline. We review the new evidence on lung cancer screening with low dose computed tomography (LDCT) and the surgical implications.MethodsA review of new literature was performed pertaining to lung cancer screening since implementation of UPSTF guidelines. Articles for inclusion were identified by both authors’, then search of the Pubmed and Cochrane database was performed from January 1st, 2013 through February 4th, 2020 using the MeSH search terms: “lung cancer”; “screening”; “low dose CT”. The results of these studies are summarized.ResultsWe identified multiple prospective randomized control trials and meta-analysis since the NLST supporting lung cancer-specific mortality with screening. We identified new nodule classification systems and the development of risk-models which may reduce false positive rates and identify high risk patients not currently eligible for screening. Finally, we discussed the surgical implications of screening.ConclusionNew data supports NLST findings and show ongoing benefit to LDCT for lung cancer screening. Standardized LDCT screening classification has been shown to reduce harm and lower false positive rates. Further study is needed regarding use of risk-modeling. Screening will require an increase in the thoracic workforce to accommodate the amount of surgically operable cancers.     

Impact and implementation of active case finding for tuberculosis in homeless populations: a systematic review

BackgroundIdentifying tuberculosis in homeless populations through active case finding (ACF) is recommended to address health inequalities and contribute to wider control strategies for tuberculosis. We aimed to assess the effectiveness of ACF.MethodsThis systematic review assessed studies on ACF done in countries with low or medium burden of tuberculosis across Europe, the USA, and Australia. We systematically searched EMBASE, CINAHL Plus, ASSIA, Pro-Quest, Scopus, and the Cochrane Library and grey literature for English language publications up to Jan 5, 2019 (no earlier date limit). We used concepts of “ACF”, “tuberculosis”, and “homeless person”. We identified studies that analysed ACF and reported on our outcome measures, in homeless populations, in low-burden and medium-burden countries. ACF screening included testing for latent tuberculosis infection (LTBI) or active tuberculosis affecting any site. Studies into outbreak control or other populations were excluded. Primary study outcomes were the effectiveness of ACF (using population measures of tuberculosis prevalence or incidence) and interventions to improve ACF uptake and completion of the diagnostic pathway. Secondary outcomes were yield of ACF, cost-effectiveness, and characteristics of participants.Findings21 studies met the inclusion criteria. Study heterogeneity precluded meta-analysis. Three time-trend analyses produced some evidence that ACF was effective, because it was associated with reductions in tuberculosis incidence, prevalence, or clustering. A modelling study also showed that ACF was more effective than passive case finding in reducing population tuberculosis burden. Material incentives have the strongest evidence for improving uptake of ACF, with mixed evidence for peer educators. Observational evidence shows professional support and mandatory screening might also enhance uptake, and additional community-based support improves completion of the diagnostic pathway. Across all studies, the yield of screening (defined as the proportion of screened individuals who test positive) ranged from 1·5% to 57% for LTBI (total 41 684 individuals screened), and 0–3·1% for active tuberculosis (total 91 771 individuals screened). ACF can be cost-effective; population prevalence and screening modalities are determinants of cost-effectiveness. Considering ACF participants, subgroups most likely to be diagnosed with tuberculosis appeared less likely to accept screening.InterpretationACF should be considered in both tuberculosis and homelessness strategies, with evidence-based interventions to improve implementation. Outcomes varied widely, meaning programmes must be tailored to local populations. Strengths of our study include generalisable results to homeless populations from diverse settings. Limitations include restriction to the English language, the fairly low grade of the evidence identified, and the low number of studies screening for LTBI or using newer screening tests.FundingThe South West Public Health Training Programme.     

Evolution of bone mineral density,bone metabolism and fragility fractures in Spinal Muscular Atrophy (SMA) types 2 and 3

With recent advances in the treatment of Spinal Muscular Atrophy (SMA), there is a strong need to increase knowledge on the involvement of organs and systems outside the central nervous system. We investigated bone metabolism, bone mineral density (BMD) and fractures, and their possible correlation with age and motor capacities. Thirty-two children with SMA (27 type 2, 5 type 3), mean age 40 ± 32.3 months, underwent two evaluations at an 18-month interval (V1 and V2). Twelve of these children also underwent a third evaluation at month 36 (V3). Diet, bone metabolism, BMD, X-rays, and motor function (by the Hammersmith Functional Motor Scale Expanded – HFMSE – and the Upper Limb Module – ULM) were assessed. At V1, 25-OH vitamin D₃ (25OH D) therapy was started, and dietary calcium intake adjusted according to the recommended dietary allowance. Low 25OH D levels and asymptomatic vertebral fractures were mainly observed at V1. At all visits, bone resorption markers were higher than normal. At V2 and V3, decreased BMD was observed. Higher spine BMD values at follow-up were associated with HFMSE score >12 at baseline (p<0.03). This study suggests that even young children with SMA are at risk of severe bone fragility. Further investigations of the molecular mechanisms leading to altered bone metabolism in SMA could help identify novel therapeutic targets and establish better guidelines for bone fragility management.     

Marine omega-3 fatty acid supplementation in non-alcoholic fatty liver disease: Plasma proteomics in the randomized WELCOME* trial

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