Genetic counselling and testing in pulmonary arterial hypertension: a consensus statement on behalf of the International Consortium for Genetic Studies in PAH

Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, BMPR2 (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered

Unusual towering elevation of troponin I after ST-elevation myocardial infarction and intensive monitoring with echocardiography post-percutaneous coronary intervention: a case report

<p>Abstract</p> <p>Introduction</p> <p>The elevation of troponin levels directly corresponds to the extent of myocardial injury. Here we present a case of a robust rise in cardiac biomarkers that correspond to extensive damage to the myocardium but did not spell doom for our patient. It is important to note that, to the best of our knowledge, this is the highest level of troponin I ever reported in the literature after a myocardial injury in an acute setting.</p> <p>Case presentation</p> <p>A 53-year-old African American man with an unknown medical history presented to the emergency room of our hospital with chest pain associated with diaphoresis and altered mental status. He required emergency intubation due to acute respiratory failure and circulatory collapse within 10 minutes of his arrival. He was started on heparin and eptifibatide (Integrilin) drips but he was taken immediately for cardiac catheterization, which showed a total occlusion of his proximal left anterior descending, diffuse left circumflex disease and severe left ventricular dysfunction with segmental wall motion abnormality. He remained hypotensive throughout the procedure and an intra-aortic balloon pump was inserted for circulatory support. His urinary toxicology examination result was positive for cocaine metabolites. Serial echocardiograms showed an akinetic apex, a severely hypokinetic septum, and severe systolic dysfunction of his left ventricle. Our patient stayed at the Coronary Care Unit for a total of 15 days before he was finally discharged.</p> <p>Conclusion</p> <p>Studies demonstrate that an increase of 1 ng/ml in the cardiac troponin I level is associated with a significant increase in the risk ratio for death. The elevation of troponin I to 515 ng/ml in our patient is an unusual robust presentation which may reflect a composite of myocyte necrosis and reperfusion but without short-term mortality. Nevertheless, prolonged close monitoring is required for better outcome. We also emphasize the need for the troponin assays to be standardized and have universal cutoffs for comparisons across available data.</p

Barriers and needs in paediatric palliative home care in Germany: a qualitative interview study with professional experts

<p>Abstract</p> <p>Background</p> <p>In North-Rhine Westphalia (Germany) a pilot project for an extensive service provision of palliative care for children and adolescents has been implemented. Accompanying research was undertaken with the aim to assess the status quo of service delivery at the outset of the project and to evaluate the effects of the pilot project. As part of the research, barriers and needs with respect to paediatric palliative home care in the target region were explored.</p> <p>Methods</p> <p>Semi-structured interviews with 24 experts in the field of paediatrics, palliative and hospice care have been conducted and were analysed by qualitative content analysis.</p> <p>Results</p> <p>Four main categories emerged from the interviews: (1) specific challenges and demands in palliative care for children and adolescents, (2) lack of clear legal and financial regulations, (3) gaps in the existing care delivery, and (4) access to services. Generally the interviews reflected the observation that the whole field is currently expanding and that certain deficits are temporary barriers that will be resolvable in the medium-term perspective.</p> <p>Conclusions</p> <p>Predominant barriers were seen in the lack of clear legal and financial regulations which take into account the specific challenges of palliative care in children and adolescents, as well as in a shortcoming of specialist services for a local based care provision throughout the federal country.</p

Interventions aimed at improving the nursing work environment: a systematic review

<p>Abstract</p> <p>Background</p> <p>Nursing work environments (NWEs) in Canada and other Western countries have increasingly received attention following years of restructuring and reported high workloads, high absenteeism, and shortages of nursing staff. Despite numerous efforts to improve NWEs, little is known about the effectiveness of interventions to improve NWEs. The aim of this study was to review systematically the scientific literature on implemented interventions aimed at improving the NWE and their effectiveness.</p> <p>Methods</p> <p>An online search of the databases CINAHL, Medline, Scopus, ABI, Academic Search Complete, HEALTHstar, ERIC, Psychinfo, and Embase, and a manual search of Emerald and Longwoods was conducted. (Quasi-) experimental studies with pre/post measures of interventions aimed at improving the NWE, study populations of nurses, and quantitative outcome measures of the nursing work environment were required for inclusion. Each study was assessed for methodological strength using a quality assessment and validity tool for intervention studies. A taxonomy of NWE characteristics was developed that would allow us to identify on which part of the NWE an intervention targeted for improvement, after which the effects of the interventions were examined.</p> <p>Results</p> <p>Over 9,000 titles and abstracts were screened. Eleven controlled intervention studies met the inclusion criteria, of which eight used a quasi-experimental design and three an experimental design. In total, nine different interventions were reported in the included studies. The most effective interventions at improving the NWE were: primary nursing (two studies), the educational toolbox (one study), the individualized care and clinical supervision (one study), and the violence prevention intervention (one study).</p> <p>Conclusions</p> <p>Little is known about the effectiveness of interventions aimed at improving the NWE, and published studies on this topic show weaknesses in their design. To advance the field, we recommend that investigators use controlled studies with pre/post measures to evaluate interventions that are aimed at improving the NWE. Thereby, more evidence-based knowledge about the implementation of interventions will become available for healthcare leaders to use in rebuilding nursing work environments.</p

The association of polymorphisms in hormone metabolism pathway genes, menopausal hormone therapy, and breast cancer risk: a nested case-control study in the California Teachers Study cohort

Abstract Introduction The female sex steroids estrogen and progesterone are important in breast cancer etiology. It therefore seems plausible that variation in genes involved in metabolism of these hormones may affect breast cancer risk, and that these associations may vary depending on menopausal status and use of hormone therapy. Methods We conducted a nested case-control study of breast cancer in the California Teachers Study cohort. We analyzed 317 tagging single nucleotide polymorphisms (SNPs) in 24 hormone pathway genes in 2746 non-Hispanic white women: 1351 cases and 1395 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by fitting conditional logistic regression models using all women or subgroups of women defined by menopausal status and hormone therapy use. P values were adjusted for multiple correlated tests (P ACT). Results The strongest associations were observed for SNPs in SLCO1B1, a solute carrier organic anion transporter gene, which transports estradiol-17β-glucuronide and estrone-3-sulfate from the blood into hepatocytes. Ten of 38 tagging SNPs of SLCO1B1 showed significant associations with postmenopausal breast cancer risk; 5 SNPs (rs11045777, rs11045773, rs16923519, rs4149057, rs11045884) remained statistically significant after adjusting for multiple testing within this gene (P ACT = 0.019-0.046). In postmenopausal women who were using combined estrogen-progestin therapy (EPT) at cohort enrollment, the OR of breast cancer was 2.31 (95% CI = 1.47-3.62) per minor allele of rs4149013 in SLCO1B1 (P = 0.0003; within-gene P ACT = 0.002; overall P ACT = 0.023). SNPs in other hormone pathway genes evaluated in this study were not associated with breast cancer risk in premenopausal or postmenopausal women. Conclusions We found evidence that genetic variation in SLCO1B1 is associated with breast cancer risk in postmenopausal women, particularly among those using EPT

The impact of statins on health services utilization and mortality in older adults discharged from hospital with ischemic heart disease: a cohort study

<p>Abstract</p> <p>Background</p> <p>Cardiovascular disease (CVD) carries a high burden of morbidity and mortality and is associated with significant utilization of health care resources, especially in the elderly. Numerous randomized trials have established the efficacy of cholesterol reduction with statin medications in decreasing mortality in high-risk populations. However, it is not known what the effect of the utilization of these medications in complex older adults has had on mortality and on the utilization of health services, such as physician visits, hospitalizations or cardiovascular procedures.</p> <p>Methods</p> <p>This project linked clinical and hospital data from the Improving Cardiovascular Outcomes in Nova Scotia (ICONS) database with administrative data from the Population Health Research Unit to identify all older adults hospitalized with ischemic heart disease between October 15, 1997 and March 31, 2001. All patients were followed for at least one year or until death. Multiple regression techniques, including Cox proportional hazards models and generalized linear models were employed to compare health services utilization and mortality for statin users and non-statin users.</p> <p>Results</p> <p>Of 4232 older adults discharged alive from the hospital, 1629 (38%) received a statin after discharge. In multivariate models after adjustment for demographic and clinical characteristics, and propensity score, statins were associated with a 26% reduction in all- cause mortality (hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.63-0.88). However, statin use was not associated with subsequent reductions in health service utilization, including re-hospitalizations (HR, 0.98, 95% CI 0.91-1.06), physician visits (relative risk (RR) 0.97, 95% CI 0.92-1.02) or coronary revascularization procedures (HR 1.15, 95% CI 0.97-1.36).</p> <p>Conclusion</p> <p>As the utilization of statins continues to grow, their impact on the health care system will continue to be important. Future studies are needed to continue to ensure that those who would realize significant benefit from the medication receive it.</p

A randomized trial to assess the impact of opinion leader endorsed evidence summaries on the use of secondary prevention strategies in patients with coronary artery disease: the ESP-CAD trial protocol [NCT00175240]

BACKGROUND: Although numerous therapies have been shown to be beneficial in the prevention of myocardial infarction and/or death in patients with coronary disease, these therapies are under-used and this gap contributes to sub-optimal patient outcomes. To increase the uptake of proven efficacious therapies in patients with coronary disease, we designed a multifaceted quality improvement intervention employing patient-specific reminders delivered at the point-of-care, with one-page treatment guidelines endorsed by local opinion leaders ("Local Opinion Leader Statement"). This trial is designed to evaluate the impact of these Local Opinion Leader Statements on the practices of primary care physicians caring for patients with coronary disease. In order to isolate the effects of the messenger (the local opinion leader) from the message, we will also test an identical quality improvement intervention that is not signed by a local opinion leader ("Unsigned Evidence Statement") in this trial. METHODS: Randomized trial testing three different interventions in patients with coronary disease: (1) usual care versus (2) Local Opinion Leader Statement versus (3) Unsigned Evidence Statement. Patients diagnosed with coronary artery disease after cardiac catheterization (but without acute coronary syndromes) will be randomly allocated to one of the three interventions by cluster randomization (at the level of their primary care physician), if they are not on optimal statin therapy at baseline. The primary outcome is the proportion of patients demonstrating improvement in their statin management in the first six months post-catheterization. Secondary outcomes include examinations of the use of ACE inhibitors, anti-platelet agents, beta-blockers, non-statin lipid lowering drugs, and provision of smoking cessation advice in the first six months post-catheterization in the three treatment arms. Although randomization will be clustered at the level of the primary care physician, the design effect is anticipated to be negligible and the unit of analysis will be the patient. DISCUSSION: If either the Local Opinion Leader Statement or the Unsigned Evidence Statement improves secondary prevention in patients with coronary disease, they can be easily modified and applied in other communities and for other target conditions