Does delayed measurement affect patient reports of provider performance? Implications for performance measurement of medical assistance with tobacco cessation: A Dental PBRN study

<p>Abstract</p> <p>Background:</p> <p>We compared two methods of measuring provider performance of tobacco control activities: immediate "exit cards" versus delayed telephone follow-up surveys. Current standards, e.g. HEDIS, use delayed patient measures that may over or under-estimate overall performance.</p> <p>Methods:</p> <p>Patients completed exit cards in 60 dental practices immediately after a visit to measure whether the provider "asked" about tobacco use, and "advised" the patient to quit. One to six months later patients were asked the same questions by telephone survey. Using the exit cards as the standard, we quantified performance and calculated sensitivity (agreement of those responding yes on telephone surveys compared with exit cards) and specificity (agreement of those responding no) of the delayed measurement.</p> <p>Results:</p> <p>Among 150 patients, 21% reporting being asked about tobacco use on the exit cards and 30% reporting being asked in the delayed surveys. The sensitivity and specificity were 50% and 75%, respectively. Similarly, among 182 tobacco users, 38% reported being advised to quit on the exit cards and this increased to 51% on the delayed surveys. The sensitivity and specificity were 75% and 64%, respectively. Increasing the delay from the visit to the telephone survey resulted in increasing disagreement.</p> <p>Conclusion:</p> <p>Patient reports differed considerably in immediate versus delayed measures. These results have important implications because they suggest that our delayed measures may over-estimate performance. The immediate exit cards should be included in the armamentarium of tools for measuring providers' performance of tobacco control, and perhaps other service delivery.</p

Sequence variants in oxytocin pathway genes and preterm birth: a candidate gene association study

Peer reviewe

Protocol of a randomized controlled trial of the effectiveness of physician education and activation versus two rehabilitation programs for the treatment of Whiplash-associated Disorders: The University Health Network Whiplash Intervention Trial

Background: Whiplash injuries are an important public health problem that is associated with significant disability and high health care utilization. Recent cohort studies suggest that physician care may be the most effective treatment for patients with whiplash-associated disorders. However, these findings have not been tested in a randomized controlled trial. The purpose of this study is to determine which of physician care or two rehabilitation programs of care is most effective in improving recovery of patients with recent whiplash associated disorders. Methods and Design: We designed a pragmatic randomized clinical trial. A total of 444 participants (148 in each of three arms) who reside in Southern Ontario, Canada will be recruited from a large insurer. We will include individuals who are 18 years of age or older and who are diagnosed with Grade I or II Whiplash-associated Disorders. Participants will be randomized to physician-based education and activation or one of two rehabilitation programs of care currently in use in Ontario. Our primary outcome, self-rated global recovery and all secondary outcomes (neck pain intensity, whiplash disability, health-related quality of life, depressive symptomatology and satisfaction with care) will be measured at baseline by a trial coordinator and at 6 weeks, 3, 6, 9 and 12 months follow-up by an interviewer who is blind to the participants' baseline characteristics and treatment allocation. We will also collect information on general health status, other injuries, comorbidities, expectation of recovery, work status, pain coping, legal representation, and co-interventions. The primary intention-to-treat analysis will compare time to recovery between the three interventions. This trial will have 90% power at an alpha of 0.05 to detect a 20% difference in the rate of perceived recovery at one year. Secondary analyses will compare the health outcomes, rate of recurrence and the rate of adverse events between intervention groups. Conclusion: The results of this study will provide the public, clinicians and policy makers much needed evidence on the effectiveness of common approaches used to manage whiplash-associated disorders. © 2008 Côté et al; licensee BioMed Central Ltd

Protocol for an economic evaluation alongside the University Health Network Whiplash Intervention Trial: cost-effectiveness of education and activation, a rehabilitation program, and the legislated standard of care for acute whiplash injury in Ontario

Background: Whiplash injury affects 83% of persons in a traffic collision and leads to whiplash-associated disorders (WAD). A major challenge facing health care decision makers is identifying cost-effective interventions due to lack of economic evidence. Our objective is to compare the cost-effectiveness of: 1) physician-based education and activation, 2) a rehabilitation program developed by Aviva Canada (a group of property and casualty insurance providers), and 3) the legislated standard of care in the Canadian province of Ontario: the Pre-approved Framework Guideline for Whiplash developed by the Financial Services Commission of Ontario. Methods/Design. The economic evaluation will use participant-level data from the University Health Network Whiplash Intervention Trial and will be conducted from the societal perspective over the trial's one-year follow-up. Resource use (costs) will include all health care goods and services, and benefits provided during the trial's 1-year follow-up. The primary health effect will be the quality-adjusted life year. We will identify the most cost-effective intervention using the incremental cost-effectiveness ratio and incremental net-benefit. Confidence ellipses and cost-effectiveness acceptability curves will represent uncertainty around these statistics, respectively. A budget impact analysis will assess the total annual impact of replacing the current legislated standard of care with each of the other interventions. An expected value of perfect information will determine the maximum research expenditure Canadian society should be willing to pay for, and inform priority setting in, research of WAD management. Discussion. Results will provide health care decision makers with much needed economic evidence on common interventions for acute whiplash management. © 2011 van der Velde et al; licensee BioMed Central Ltd

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication