The Duffin-Schaeffer Conjecture with extra divergence II

This paper takes a new step in the direction of proving the Duffin-Schaeffer Conjecture for measures arbitrarily close to Lebesgue. The main result is that under a mild `extra divergence' hypothesis, the conjecture is true.Comment: 7 page

Large regional variation in cardiac closure procedures to prevent ischemic stroke in Switzerland a population-based small area analysis.

BACKGROUND Percutaneous closure of a patent foramen ovale (PFO) or the left atrial appendage (LAA) are controversial procedures to prevent stroke but often used in clinical practice. We assessed the regional variation of these interventions and explored potential determinants of such a variation. METHODS We conducted a population-based analysis using patient discharge data from all Swiss hospitals from 2013-2018. We derived hospital service areas (HSAs) using patient flows for PFO and LAA closure. We calculated age-standardized mean procedure rates and variation indices (extremal quotient [EQ] and systematic component of variation [SCV]). SCV values >5.4 indicate a high and >10 a very high variation. Because the evidence on the efficacy of PFO closure may differ in patients aged <60 years and ≥60 years, age-stratified analyses were performed. We assessed the influence of potential determinants of variation using multilevel regression models with incremental adjustment for demographics, cultural/socioeconomic, health, and supply factors. RESULTS Overall, 2574 PFO and 2081 LAA closures from 10 HSAs were analyzed. The fully adjusted PFO and LAA closure rates varied from 3 to 8 and from 1 to 9 procedures per 100,000 persons per year across HSAs, respectively. The regional variation was high with respect to overall PFO closures (EQ 3.0, SCV 8.3) and very high in patients aged ≥60 years (EQ 4.0, SCV 12.3). The variation in LAA closures was very high (EQ 16.2, SCV 32.1). In multivariate analysis, women had a 28% lower PFO and a 59% lower LAA closure rate than men. French/Italian language areas had a 63% lower LAA closure rate than Swiss German speaking regions and areas with a higher proportion of privately insured patients had a 86% higher LAA closure rate. After full adjustment, 44.2% of the variance in PFO closure and 30.3% in LAA closure remained unexplained. CONCLUSIONS We found a high to very high regional variation in PFO closure and LAA closure rates within Switzerland. Several factors, including sex, language area, and insurance status, were associated with procedure rates. Overall, 30-45% of the regional procedure variation remained unexplained and most probably represents differing physician practices

Prevalence of sleep-disordered breathing after stroke and TIA: A meta-analysis.

OBJECTIVE To perform a systematic review and meta-analysis on the prevalence of sleep-disordered breathing (SDB) after stroke. METHODS We searched PubMed, Embase (Ovid), the Cochrane Library, and CINAHL (from their commencements to April 7, 2017) for clinical studies reporting prevalence and/or severity of SDB after stroke or TIA. Only sleep apnea tests performed with full polysomnography and diagnostic devices of the American Academy of Sleep Medicine categories I-IV were included. We conducted random-effects meta-analysis. PROSPERO registration number: CRD42017072339. RESULTS The initial search identified 5,211 publications. Eighty-nine studies (including 7,096 patients) met inclusion criteria. Fifty-four studies were performed in the acute phase after stroke (after less than 1 month), 23 studies in the subacute phase (after 1-3 months), and 12 studies in the chronic phase (after more than 3 months). Mean apnea-hypopnea index was 26.0/h (SD 21.7-31.2). Prevalence of SDB with apnea-hypopnea index greater than 5/h and greater than 30/h was found in 71% (95% confidence interval 66.6%-74.8%) and 30% (95% confidence interval 24.4%-35.5%) of patients, respectively. Severity and prevalence of SDB were similar in all examined phases after stroke, irrespective of the type of sleep apnea test performed. Heterogeneity between studies () was mostly high. CONCLUSION The high prevalence of SDB after stroke and TIA, which persists over time, is important in light of recent studies reporting the (1) feasibility and (2) efficacy of SDB treatment in this clinical setting

CPAP as treatment of sleep apnea after stroke: A meta-analysis of randomized trials.

OBJECTIVE To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) examining the effectiveness of continuous positive airway pressure (CPAP) in stroke patients with sleep disordered breathing (SDB). METHODS In a systematic literature search of electronic databases (MEDLINE, Embase, and the Cochrane Library) from 1980 to November 2016, we identified RCTs that assessed CPAP compared to standard care or sham CPAP in adult patients with stroke or TIA with SDB. Mean CPAP use, odds ratios (ORs), and standardized mean differences (SMDs) were calculated. The prespecified outcomes were adherence to CPAP, neurologic improvement, adverse events, new vascular events, and death. RESULTS Ten RCTs (564 participants) with CPAP as intervention were included. Two studies compared CPAP with sham CPAP; 8 compared CPAP with usual care. Mean CPAP use across the trials was 4.53 hours per night (95% confidence interval [CI] 3.97-5.08). The OR of dropping out with CPAP was 1.83 (95% CI 1.05-3.21,= 0.033). The combined analysis of the neurofunctional scales (NIH Stroke Scale and Canadian Neurological Scale) showed an overall neurofunctional improvement with CPAP (SMD 0.5406, 95% CI 0.0263-1.0548) but with a considerable heterogeneity (= 78.9%,= 0.0394) across the studies. Long-term survival was improved with CPAP in 1 trial. CONCLUSION CPAP use after stroke is acceptable once the treatment is tolerated. The data indicate that CPAP might be beneficial for neurologic recovery, which justifies larger RCTs

Vascular effects of apelin in vivo in man

ObjectivesThis study was designed to establish the direct vascular effects of apelin in vivo in man.BackgroundApelin is the endogenous ligand for the previously orphaned G-protein–coupled receptor, APJ. This novel pathway is widely expressed in the cardiovascular system and is emerging as an important mediator of cardiovascular homeostasis. In pre-clinical models, apelin causes venous and arterial vasodilation.MethodsVascular effects of apelin were assessed in 24 healthy volunteers. Dorsal hand vein diameter was measured by the Aellig technique during local intravenous infusions (0.1 to 3 nmol/min) of apelin-36, (Pyr1)apelin-13, and sodium nitroprusside (0.6 nmol/min). Forearm blood flow was measured by venous occlusion plethysmography during intrabrachial infusions of apelin-36 and (Pyr1)apelin-13 (0.1 to 30 nmol/min) and subsequently in the presence or absence of a “nitric oxide clamp” (nitric oxide synthase inhibitor, L-NG-monomethylarginine [8 μmol/min], coinfused with nitric oxide donor, sodium nitroprusside [90 to 900 ng/min]), or a single oral dose of aspirin (600 mg) or matched placebo.ResultsAlthough sodium nitroprusside caused venodilation (p < 0.0001), apelin-36 and (Pyr1)apelin-13 had no effect on dorsal hand vein diameter (p = 0.2). Both apelin isoforms caused reproducible vasodilation in forearm resistance vessels (p < 0.0001). (Pyr1)apelin-13–mediated vasodilation was attenuated by the nitric oxide clamp (p = 0.004) but unaffected by aspirin (p = 0.7).ConclusionsAlthough having no apparent effect on venous tone, apelin causes nitric oxide–dependent arterial vasodilation in vivo in man. The apelin-APJ system merits further clinical investigation to determine its role in cardiovascular homeostasis

High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men

Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5′ and 3′ half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3–6 days before symptom onset and 14–17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized

A philosophical analysis of the evidence-based medicine debate

BACKGROUND: The term "evidence-based medicine" (or EBM) was introduced about ten years ago, and there has been considerable debate about the value of EBM. However, this debate has sometimes been obscured by a lack of conceptual clarity concerning the nature and status of EBM. DISCUSSION: First, we note that EBM proponents have obscured the current debate by defining EBM in an overly broad, indeed almost vacuous, manner; we offer a clearer account of EBM and its relation to the alternative approaches to medicine. Second, while EBM proponents commonly cite the philosophical work of Thomas Kuhn and claim that EBM is a Kuhnian 'paradigm shift,' we argue that such claims are seriously mistaken and unduly polarize the EBM debate. Third, we suggest that it is much more fruitful to understand the relationship between EBM and its alternatives in light of a different philosophical metaphor: W.V. Quine's metaphor of the web of belief. Seen in this way, we argue that EBM is an approach to medical practice that is indeed importantly different from the alternatives. SUMMARY: We can have a more productive debate about the value of EBM by being clearer about the nature of EBM and its relationship to alternative approaches to medicine

Effect of a Nutrition Supplement and Physical Activity Program on Pneumonia and Walking Capacity in Chilean Older People: A Factorial Cluster Randomized Trial

Alan Dangour and colleagues report results from the CENEX (Cost-effectiveness Evaluation of a Nutritional supplement and EXercise program for older people) trial, which evaluates a nutritional and exercise program aiming to prevent pneumonia and physical decline in Chilean people