Improving chronic disease prevention and screening in primary care: results of the BETTER pragmatic cluster randomized controlled trial.

BackgroundPrimary care provides most of the evidence-based chronic disease prevention and screening services offered by the healthcare system. However, there remains a gap between recommended preventive services and actual practice. This trial (the BETTER Trial) aimed to improve preventive care of heart disease, diabetes, colorectal, breast and cervical cancers, and relevant lifestyle factors through a practice facilitation intervention set in primary care.MethodsPragmatic two-way factorial cluster RCT with Primary Care Physicians' practices as the unit of allocation and individual patients as the unit of analysis. The setting was urban Primary Care Team practices in two Canadian provinces. Eight Primary Care Team practices were randomly assigned to receive the practice-level intervention or wait-list control; 4 physicians in each team (32 physicians) were randomly assigned to receive the patient-level intervention or wait-list control. Patients randomly selected from physicians' rosters were stratified into two groups: 1) general and 2) moderate mental illness. The interventions involved a multifaceted, evidence-based, tailored practice-level intervention with a Practice Facilitator, and a patient-level intervention involving a one-hour visit with a Prevention Practitioner where patients received a tailored 'prevention prescription'. The primary outcome was a composite Summary Quality Index of 28 evidence-based chronic disease prevention and screening actions with pre-defined targets, expressed as the ratio of eligible actions at baseline that were met at follow-up. A cost-effectiveness analysis was conducted.Results789 of 1,260 (63%) eligible patients participated. On average, patients were eligible for 8.96 (SD 3.2) actions at baseline. In the adjusted analysis, control patients met 23.1% (95% CI: 19.2% to 27.1%) of target actions, compared to 28.5% (95% CI: 20.9% to 36.0%) receiving the practice-level intervention, 55.6% (95% CI: 49.0% to 62.1%) receiving the patient-level intervention, and 58.9% (95% CI: 54.7% to 63.1%) receiving both practice- and patient-level interventions (patient-level intervention versus control, P < 0.001). The benefit of the patient-level intervention was seen in both strata. The extra cost of the intervention was $26.43CAN (95$16 to $44) per additional action met.ConclusionsA Prevention Practitioner can improve the implementation of clinically important prevention and screening for chronic diseases in a cost-effective manner

Dendritic polyglycerol nanoparticles show charge dependent bio-distribution in early human placental explants and reduce hCG secretion

A thorough understanding of nanoparticle bio-distribution at the feto-maternal interface will be a prerequisite for their diagnostic or therapeutic application in women of childbearing age and for teratologic risk assessment. Therefore, the tissue interaction of biocompatible dendritic polyglycerol nanoparticles (dPG-NPs) with first- trimester human placental explants were analyzed and compared to less sophisticated trophoblast-cell based models. First-trimester human placental explants, BeWo cells and primary trophoblast cells from human term placenta were exposed to fluorescence labeled, ∼5 nm dPG-NPs, with differently charged surfaces, at concentrations of 1 µM and 10 nM, for 6 and 24 h. Accumulation of dPGs was visualized by fluorescence microscopy. To assess the impact of dPG-NP on trophoblast integrity and endocrine function, LDH, and hCG releases were measured. A dose- and charge- dependent accumulation of dPG-NPs was observed at the early placental barrier and in cell lines, with positive dPG-NP-surface causing deposits even in the mesenchymal core of the placental villi. No signs of plasma membrane damage could be detected. After 24 h we observed a significant reduction of hCG secretion in placental explants, without significant changes in trophoblast apoptosis, at low concentrations of charged dPG-NPs. In conclusion, dPG-NP’s surface charge substantially influences their bio-distribution at the feto- maternal interface, with positive charge facilitating trans-trophoblast passage, and in contrast to more artificial models, the first-trimester placental explant culture model reveals potentially hazardous influences of charged dPG-NPs on early placental physiology

Health Professions Students\u27 Attitudes Toward Teamwork Before and After an Interprofessional Education Co-Curricular Experience

Background: Effective interprofessional collaboration may positively impact clinical outcomes, patient satisfaction, and cost effectiveness. However, educational silos and discipline-specific socialization have reinforced each health profession’s independent values, attitudes, and problem-solving approaches. Methods and Findings: Students’ (N = 376) attitudes about teamwork were measured with the Interprofessional Attitudes Scale, Teamwork, Roles, and Responsibilities subscale using a pretest-posttest design. Experiential learning strategies and a case study approach were used to introduce students to the roles and responsibilities of the students’ disciplines. There was a positive mean difference in pretest-posttest measures (p \u3c .001) with a moderate effect size (r = .27). Conclusions: Providing opportunities for pre-licensure health sciences students to understand the roles and responsibilities of other disciplines through IPE co-curricular learning can enhance positive attitudes toward teamwork

Increased cancer prevalence in peripartum cardiomyopathy

Objectives This study was designed to analyze the prevalence and potential genetic basis of cancer and heart failure in peripartum cardiomyopathy (PPCM). Background PPCM manifests as heart failure late in pregnancy or postpartum in women without previous heart disease. Methods Clinical history and cancer prevalence were evaluated in a cohort of 236 PPCM patients from Germany and Sweden. Exome sequencing assessed variants in 133 genes associated with cancer predisposition syndromes (CPS) and in 115 genes associated with dilated/hypertrophic cardiomyopathy (DCM/HCM) in 14 PPCM patients with a history of cancer, and in 6 PPCM patients without a history of cancer. Results The prevalence of cancer was 16-fold higher (8.9%, 21 of 236 patients) in PPCM patients compared to age-matched women (German cancer registry, Robert-Koch-Institute: 0.59%; p < 0.001). Cancer before PPCM occurred in 12 of 21 patients of whom 11 obtained cardiotoxic cancer therapies. Of those, 17% fully recovered cardiac function by 7 ± 2 months of follow-up compared to 55% of PPCM patients without cancer (p = 0.015). Cancer occurred after PPCM in 10 of 21 patients; 80% had left ventricular ejection fraction of ≥50% after cancer therapy. Whole-exome sequencing in 14 PPCM patients with cancer revealed that 43% (6 of 14 patients) carried likely pathogenic (Class IV) or pathogenic (Class V) gene variants associated with DCM/HCM in CPT2, DSP, MYH7, TTN, and/or with CPS in ATM, ERCC5, NBN, RECQL4, and SLX4. All CPS variants affected DNA damage response genes. Conclusions Cardiotoxic cancer therapy before PPCM is associated with delayed full recovery. The high cancer prevalence in PPCM is linked to likely pathogenic/pathogenic gene variants associated with DCM/HCM and/or CPS/DNA damage response–related cancer risk. This may warrant genetic testing and screening for heart failure in pregnant women with a cancer history and screening for cancer in PPCM patients

In peripartum cardiomyopathy plasminogen activator inhibitor-1 is a potential new biomarker with controversial roles

Aims Peripartum cardiomyopathy (PPCM) is a life-threatening heart disease occurring in previously heart-healthy women. A common pathomechanism in PPCM involves the angiostatic 16 kDa-prolactin (16 kDa-PRL) fragment, which via NF-kappa B-mediated up-regulation of microRNA-(miR)-146a induces vascular damage and heart failure. We analyse whether the plasminogen activator inhibitor-1 (PAI-1) is involved in the pathophysiology of PPCM. Methods and results In healthy age-matched postpartum women (PP-Ctrl, n = 53, left ventricular ejection fraction, LVEF > 55%), PAI-1 plasma levels were within the normal range (21 +/- 10 ng/mL), but significantly elevated (64 +/- 38 ng/mL, P <0.01) in postpartum PPCM patients at baseline (BL, n = 64, mean LVEF: 23 +/- 8%). At 6-month follow-up (n = 23), PAI-1 levels decreased (36 +/- 14 ng/mL, P <0.01 vs. BL) and LVEF (49 +/- 11%) improved. Increased N-terminal pro-brain natriuretic peptide and Troponin T did not correlate with PAI-1. C-reactive protein, interleukin (IL)-6 and IL-1 beta did not differ between PPCM patients and PP-Ctrl. MiR-146a was 3.6-fold (P <0.001) higher in BL-PPCM plasma compared with PP-Ctrl and correlated positively with PAI-1. In BL-PPCM serum, 16 kDa-PRL coprecipitated with PAI-1, which was associated with higher (P <0.05) uPAR-mediated NF-kappa B activation in endothelial cells compared with PP-Ctrl serum. Cardiac biopsies and dermal fibroblasts from PPCM patients displayed higher PAI-1 mRNA levels (P <0.05) than healthy controls. In PPCM mice (due to a cardiomyocyte-specific-knockout for STAT3, CKO), cardiac PAI-1 expression was higher than in postpartum wild-type controls, whereas a systemic PAI-1-knockout in CKO mice accelerated peripartum cardiac fibrosis, inflammation, heart failure, and mortality. Conclusion In PPCM patients, circulating and cardiac PAI-1 expression are up-regulated. While circulating PAI-1 may add 16 kDa-PRL to induce vascular impairment via the uPAR/NF-kappa B/miR-146a pathway, experimental data suggest that cardiac PAI-1 expression seems to protect the PPCM heart from fibrosis. Thus, measuring circulating PAI-1 and miR-146a, together with an uPAR/NF-kappa B-activity assay could be developed into a specific diagnostic marker assay for PPCM, but unrestricted reduction of PAI-1 for therapy may not be advised

Health-related quality of life in patients with locally recurrent or metastatic breast cancer treated with etirinotecan pegol versus treatment of physician’s choice: Results from the randomised phase III BEACON trial

Background: Health-related quality of life (HRQoL) enhances understanding of treatment effects that impact clinical decision-making. Although the primary end-point was not achieved, the BEACON (BrEAst Cancer Outcomes with NKTR-102) trial established etirinotecan pegol, a long-acting topoisomerase-1 (TOP1) inhibitor, as a promising therapeutic for patients with advanced/metastatic breast cancer (MBC) achieving clinically meaningful benefits in median overall survival (OS) for patients with stable brain metastases, with liver metastases or ≥ 2 sites of metastatic disease compared to treatment of physician’s choice (TPC). Reported herein are the findings from the preplanned secondary end-point of HRQoL. Patients and methods: HRQoL, assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) (version 3.0) supplemented by the breast cancer-specific Quality of Life Questionnaire (QLQ-BR23), was evaluated post randomisation in 733 of 852 patients with either anthracycline-, taxane- and capecitabine-pretreated locally recurrent or MBC randomised to etirinotecan pegol (n = 378; 145 mg/m2 every 3 weeks (q3wk)) or single-agent TPC (n = 355). Patients completed assessments at screening, every 8 weeks (q8wk) during treatment, and end-of-treatment. Changes from baseline were analysed, and the proportions of patients achieving differences (≥5 points) in HRQoL scores were compared. Results: Differences were seen favouring etirinotecan pegol up to 32 weeks for global health status (GHS) and physical functioning scales (P &lt; 0.02); numerical improvement was reported in other functional scales. The findings from HRQoL symptom scales were consistent with adverse event profiles; etirinotecan pegol was associated with worsening gastrointestinal symptoms whereas TPC was associated with worsened dyspnoea and other systemic side-effects. Analysis of GHS and physical functioning at disease progression showed a decline in HRQoL in both treatment arms, with a mean change from baseline of −9.4 and −10.8 points, respectively. Conclusion: There was evidence of benefit associated with etirinotecan pegol compared with current standard of care agents in multiple HRQoL measurements, including global health status and physical functioning, despite worse gastrointestinal symptoms (e.g. diarrhoea). Patients in both arms had a decline in HRQoL at disease progression. Study number: NCT01492101

Why Are Regulations Changed? A Parcel Analysis of Upzoning in Los Angeles

Planners, officials, and neighborhood groups often debate zoning changes, yet there is little empirical evidence explaining why zoning and other land use regulations are changed. I use logistic regression models to examine density-enabling rezoning (“upzoning”) in Los Angeles. I find that upzoning occurs where there are development opportunities combined with limited political resistance. Upzoning is most likely on well-located parcels zoned for low-intensity, nonresidential uses. Meanwhile, homeowners—and particularly homeowners with access to valuable amenities—are associated with regulatory stasis. I conclude by recommending strategies for addressing homeowners’ concerns about higher density housing

Examination of psychological risk factors for chronic pain following cardiac surgery: protocol for a prospective observational study

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: Approximately 400 000 Americans and 36 000 Canadians undergo cardiac surgery annually, and up to 56% will develop chronic postsurgical pain (CPSP). The primary aim of this study is to explore the association of pain-related beliefs and gender-based pain expectations on the development of CPSP. Secondary goals are to: (A) explore risk factors for poor functional status and patient-level cost of illness from a societal perspective up to 12 months following cardiac surgery; and (B) determine the impact of CPSP on quality-adjusted life years (QALYs) borne by cardiac surgery, in addition to the incremental cost for one additional QALY gained, among those who develop CPSP compared with those who do not. METHODS AND ANALYSES: In this prospective cohort study, 1250 adults undergoing cardiac surgery, including coronary artery bypass grafting and open-heart procedures, will be recruited over a 3-year period. Putative risk factors for CPSP will be captured prior to surgery, at postoperative day 3 (in hospital) and day 30 (at home). Outcome data will be collected via telephone interview at 6-month and 12-month follow-up. We will employ generalised estimating equations to model the primary (CPSP) and secondary outcomes (function and cost) while adjusting for prespecified model covariates. QALYs will be estimated by converting data from the Short Form-12 (version 2) to a utility score. ETHICS AND DISSEMINATION: This protocol has been approved by the responsible bodies at each of the hospital sites, and study enrolment began May 2015. We will disseminate our results through CardiacPain.Net, a web-based knowledge dissemination platform, presentation at international conferences and publications in scientific journals. TRIAL REGISTRATION NUMBER: NCT01842568