Profiles of Serial Changes in Cardiac Troponin T Concentrations and Outcome in Ambulatory Patients With Chronic Heart Failure

ObjectivesThe purpose of this study was to determine whether different profiles of cardiac troponin T (cTnT) values assessed over time would yield incremental prognostic information on clinically stable outpatients with heart failure (HF).BackgroundcTnT levels were used to estimate prognosis in HF; however, most studies evaluated hospitalized patients using single measurements.MethodsA cohort of 172 New York Heart Association functional class III to IV outpatients was prospectively studied with serial cTnT measurements collected every 3 months over a 2-year period. The primary end point was death or cardiac transplantation, and secondary end points included HF hospitalization.ResultsOf the 172 patients, 22 (13%) died or underwent transplantation during the first year. Therefore, 150 patients were included in the second-year analysis of 3 pre-determined groups: 1) no serial cTnT elevations (defined as <0.01 ng/ml); 2) 1 or more, but not all cTnT values elevated ≥0.01 ng/ml; and 3) all cTnT values elevated during the first year. During the second year, 30 events occurred: 53 patients had persistently normal cTnT levels (<0.01 ng/ml) with 6 primary events (11%); 57 patients had 1 or more but not all cTnT levels elevated with 11 events (19%); 40 patients demonstrated persistently elevated cTnT levels with 13 (33%) primary events (odds ratio: 3.77; 95% confidence interval: 1.28 to 11.07, p = 0.02).ConclusionsElevations in cTnT, even using a low threshold of 0.01 ng/ml, detected during routine clinical follow-up of ambulatory patients with HF, are highly associated with an increased risk of events, particularly with frequent or persistent cTnT elevations of ≥0.01 ng/ml. Therefore, the ability to monitor clinical change through serial cTnT measurements may add to risk assessment in the ambulatory HF population

A national surveillance project on chronic kidney disease management in Canadian primary care: a study protocol.

INTRODUCTION: Effective chronic disease care is dependent on well-organised quality improvement (QI) strategies that monitor processes of care and outcomes for optimal care delivery. Although healthcare is provincially/territorially structured in Canada, there are national networks such as the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) as important facilitators for national QI-based studies to improve chronic disease care. The goal of our study is to improve the understanding of how patients with chronic kidney disease (CKD) are managed in primary care and the variation across practices and provinces and territories to drive improvements in care delivery. METHODS AND ANALYSIS: The CPCSSN database contains anonymised health information from the electronic medical records for patients of participating primary care practices (PCPs) across Canada (n=1200). The dataset includes information on patient sociodemographics, medications, laboratory results and comorbidities. Leveraging validated algorithms, case definitions and guidelines will help define CKD and the related processes of care, and these enable us to: (1) determine prevalent CKD burden; (2) ascertain the current practice pattern on risk identification and management of CKD and (3) study variation in care indicators (eg, achievement of blood pressure and proteinuria targets) and referral pattern for specialist kidney care. The process of care outcomes will be stratified across patients' demographics as well as provider and regional (provincial/territorial) characteristics. The prevalence of CKD stages 3-5 will be presented as age-sex standardised prevalence estimates stratified by province and as weighted averages for population rates with 95% CIs using census data. For each PCP, age-sex standardised prevalence will be calculated and compared with expected standardised prevalence estimates. The process-based outcomes will be defined using established methods. ETHICS AND DISSEMINATION: The CPCSSN is committed to high ethical standards when dealing with individual data collected, and this work is reviewed and approved by the Network Scientific Committee. The results will be published in peer-reviewed journals and presented at relevant national and international scientific meetings

Dlg1 binds GKAP to control dynein association with microtubules, centrosome positioning, and cell polarity

The small GTPase Cdc42 regulates interactions of dynein with microtubules through the polarity protein Dlg1 and the scaffolding protein GKAP

Quality of Chronic Kidney Disease Management in Canadian Primary Care.

Importance: Although patients with chronic kidney disease (CKD) are routinely managed in primary care settings, no nationally representative study has assessed the quality of care received by these patients in Canada. Objective: To evaluate the current state of CKD management in Canadian primary care practices to identify care gaps to guide development and implementation of national quality improvement initiatives. Design, Setting, and Participants: This cross-sectional study leveraged Canadian Primary Care Sentinel Surveillance Network data from January 1, 2010, to December 31, 2015, to develop a cohort of 46 162 patients with CKD managed in primary care practices. Data analysis was performed from August 8, 2018, to July 31, 2019. Main Outcomes and Measures: The study examined the proportion of patients with CKD who met a set of 12 quality indicators in 6 domains: (1) detection and recognition of CKD, (2) testing and monitoring of kidney function, (3) use of recommended medications, (4) monitoring after initiation of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), (5) management of blood pressure, and (6) monitoring for glycemic control in those with diabetes and CKD. The study also analyzed associations of divergence from these quality indicators. Results: The cohort comprised 46 162 patients (mean [SD] age, 69.2 [14.0] years; 25 855 [56.0%] female) with stage 3 to 5 CKD. Only 4 of 12 quality indicators were met by 75% or more of the study cohort. These indicators were receipt of an outpatient serum creatinine test within 18 months after confirmation of CKD, receipt of blood pressure measurement at any time during follow-up, achieving a target blood pressure of 140/90 mm Hg or lower, and receiving a hemoglobin A1c test for monitoring diabetes during follow-up. Indicators in the domains of detection and recognition of CKD, testing and monitoring of kidney function (specifically, urine albumin to creatinine ratio testing), use of recommended medications, and appropriate monitoring after initiation of treatment with ACEIs or ARBs were not met. Only 6529 patients (18.4%) with CKD received a urine albumin test within 6 months of CKD diagnosis, and 3954 (39.4%) had a second measurement within 6 months of an abnormal baseline urine albumin level. Older age (≥85 years) and CKD stage 5 were significantly associated with not satisfying the criteria for the quality indicators across all domains. Across age categories, younger patients (aged 18-49 years) and older patients (≥75 years) were less likely to be tested for albuminuria (314 of 1689 patients aged 18-49 years [18.5%], 1983 of 11 919 patients aged 75-84 years [61.6%], and 614 of 5237 patients aged ≥85 years [11.7%] received the urine albumin to creatinine ratio test within 6 months of initial estimated glomerular filtration rate <60 mL/min per 1.73 m2; P < .001). Patients aged 18 to 49 years were less commonly prescribed recommended medications (222 of 2881 [7.7%]), whereas patients aged 75 to 84 years were prescribed ACEIs or ARBs most frequently (2328 of 5262 [44.2%]; P < .001). Conclusions and Relevance: The findings suggest that management of CKD across primary care practices in Canada varies according to quality indicator. This study revealed potential priority areas for quality improvement initiatives in Canadian primary care practices

Prevalence and Demographics of CKD in Canadian Primary Care Practices: A Cross-sectional Study.

INTRODUCTION: Surveillance systems enable optimal care delivery and appropriate resource allocation, yet Canada lacks a dedicated surveillance system for chronic kidney disease (CKD). Using data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), a national chronic disease surveillance system, this study describes the geographic, sociodemographic, and clinical variations in CKD prevalence in the Canadian primary care context. METHODS: This cross-sectional study included 559,745 adults in primary care in 5 provinces across Canada from 2010 through 2015. Data were analyzed by geographic (urban or rural residence), sociodemographic (age, sex, deprivation index), and clinical (medications prescribed, comorbid conditions) factors, using data from CPCSSN and the Canadian Deprivation Index. CKD stage 3 or higher was defined as 2 estimated glomerular filtration rate (eGFR) values of <60 ml/min per 1.73 m2 more than 90 days apart as of January 1, 2015. RESULTS: Prevalence of CKD was 71.9 per 1000 individuals and varied by geography, with the highest prevalence in rural settings compared with urban settings (86.2 vs. 68.4 per 1000). CKD was highly prevalent among individuals with 3 or more other chronic diseases (281.7 per 1000). Period prevalence of CKD indicated a slight decline over the study duration, from 53.4 per 1000 in 2010 to 46.5 per 1000 in 2014. CONCLUSION: This is the first study to estimate the prevalence of CKD in primary care in Canada at a national level. Results may facilitate further research, prioritization of care, and quality improvement activities to identify gaps and improvement in CKD care

Multisensory Perceptual Learning of Temporal Order: Audiovisual Learning Transfers to Vision but Not Audition

Background: An outstanding question in sensory neuroscience is whether the perceived timing of events is mediated by a central supra-modal timing mechanism, or multiple modality-specific systems. We use a perceptual learning paradigm to address this question. Methodology/Principal Findings: Three groups were trained daily for 10 sessions on an auditory, a visual or a combined audiovisual temporal order judgment (TOJ). Groups were pre-tested on a range TOJ tasks within and between their group modality prior to learning so that transfer of any learning from the trained task could be measured by post-testing other tasks. Robust TOJ learning (reduced temporal order discrimination thresholds) occurred for all groups, although auditory learning (dichotic 500/2000 Hz tones) was slightly weaker than visual learning (lateralised grating patches). Crossmodal TOJs also displayed robust learning. Post-testing revealed that improvements in temporal resolution acquired during visual learning transferred within modality to other retinotopic locations and orientations, but not to auditory or crossmodal tasks. Auditory learning did not transfer to visual or crossmodal tasks, and neither did it transfer within audition to another frequency pair. In an interesting asymmetry, crossmodal learning transferred to all visual tasks but not to auditory tasks. Finally, in all conditions, learning to make TOJs for stimulus onsets did not transfer at all to discriminating temporal offsets. These data present a complex picture of timing processes

Prevalence of polypharmacy and associated adverse health outcomes in adult patients with chronic kidney disease: protocol for a systematic review and meta-analysis

Background Polypharmacy, often defined as the concomitant use of ≥ 5 medications, has been identified as a significant global public health threat. Aging and multimorbidity are key drivers of polypharmacy and have been linked to a broad range of adverse health outcomes and mortality. Patients with chronic kidney disease (CKD) are particularly at high risk of polypharmacy and use of potentially inappropriate medications given the numerous risk factors and complications associated with CKD. The aim of this systematic review will be to assess the prevalence of polypharmacy among adult patients with CKD, and the potential association between polypharmacy and adverse health outcomes within this population. Methods/design We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and PsycINFO and grey literature from inception onwards (with no language restrictions) for observational studies (e.g., cross-sectional or cohort studies) reporting the prevalence of polypharmacy in adult patients with CKD (all stages including dialysis). Two reviewers will independently screen all citations, full-text articles, and extract data. Potential conflicts will be resolved through discussion. The study methodological quality will be appraised using an appropriate tool. The primary outcome will be the prevalence of polypharmacy. Secondary outcomes will include any adverse health outcomes (e.g., worsening kidney function) in association with polypharmacy. If appropriate, we will conduct random effects meta-analysis of observational data to summarize the pooled prevalence of polypharmacy and the associations between polypharmacy and adverse outcomes. Statistical heterogeneity will be estimated using Cochran’s Q and I2 index. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., sex, kidney replacement therapy, multimorbidity). Discussion Given that polypharmacy is a major and a growing public health issue, our findings will highlight the prevalence of polypharmacy, hazards associated with it, and medication thresholds associated with adverse outcomes in patients with CKD. Our study will also draw attention to the prognostic importance of improving medication practices as a key priority area to help minimize the use of inappropriate medications in patients with CKD. Systematic review registration PROSPERO registration number: [ CRD42020206514 ]