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This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To conduct a component network meta‐analysis (CNMA) comparing different SEP combinations to identify the most clinically effective exercise prescription for people with IC. To conduct an economic evaluation comparing different SEP combinations for people with IC to identify which are cost‐effective.

Contains fulltext : 299974.pdf (Publisher’s version ) (Closed access), Primary care (PC) is a unique clinical specialty and research discipline with its own perspectives and methods. Research in this field uses varied research methods and study designs to investigate myriad topics. The diversity of PC presents challenges for reporting, and despite the proliferation of reporting guidelines, none focuses specifically on the needs of PC. The Consensus Reporting Items for Studies in Primary Care (CRISP) Checklist guides reporting of PC research to include the information needed by the diverse PC community, including practitioners, patients, and communities. CRISP complements current guidelines to enhance the reporting, dissemination, and application of PC research findings and results. Prior CRISP studies documented opportunities to improve research reporting in this field. Our surveys of the international, interdisciplinary, and interprofessional PC community identified essential items to include in PC research reports. A 2-round Delphi study identified a consensus list of items considered necessary. The CRISP Checklist contains 24 items that describe the research team, patients, study participants, health conditions, clinical encounters, care teams, interventions, study measures, settings of care, and implementation of findings/results in PC. Not every item applies to every study design or topic. The CRISP guidelines inform the design and reporting of (1) studies done by PC researchers, (2) studies done by other investigators in PC populations and settings, and (3) studies intended for application in PC practice. Improved reporting of the context of the clinical services and the process of research is critical to interpreting study findings/results and applying them to diverse populations and varied settings in PC.Annals "Online First" article.

BACKGROUND: We explored the changes in gene expression correlating with dysfunction and graft failure in endomyocardial biopsies. METHODS: Genome-wide microarrays (19,462 genes) were used to define mRNA changes correlating with dysfunction (left ventricular ejection fraction [LVEF] ≤ 55) and risk of graft loss within 3 years postbiopsy. LVEF data was available for 1,013 biopsies and survival data for 779 patients (74 losses). Molecular classifiers were built for predicting dysfunction (LVEF ≤ 55) and postbiopsy 3-year survival. RESULTS: Dysfunction is correlated with dedifferentiation-decreased expression of normal heart transcripts, for example, solute carriers, along with increased expression of inflammation genes. Many genes with reduced expression in dysfunction were matrix genes such as fibulin 1 and decorin. Gene ontology (GO) categories suggested matrix remodeling and inflammation, not rejection. Genes associated with the risk of failure postbiopsy overlapped dysfunction genes but also included genes affecting microcirculation, for example, arginase 2, which reduces NO production, and endothelin 1. GO terms also reflected increased glycolysis and response to hypoxia, but decreased VEGF and angiogenesis pathways. T cell-mediated rejection was associated with reduced survival and antibody-mediated rejection with relatively good survival, but the main determinants of survival were features of parenchymal injury. Both dysfunction and graft loss were correlated with increased biopsy expression of BNP (gene NPPB). Survival probability classifiers divided hearts into risk quintiles, with actuarial 3-year postbiopsy survival >95% for the highest versus 50% for the lowest. CONCLUSIONS: Dysfunction in transplanted hearts reflects dedifferentiation, decreased matrix genes, injury, and inflammation. The risk of short-term loss includes these changes but is also associated with microcirculation abnormalities, glycolysis, and response to hypoxia.

Item does not contain fulltext, OBJECTIVE: Reporting guidelines can improve dissemination and application of findings and help avoid research waste. Recent studies reveal opportunities to improve primary care (PC) reporting. Despite increasing numbers of guidelines, none exists for PC research. This study aims to prioritise candidate reporting items to inform a reporting guideline for PC research. DESIGN: Delphi study conducted by the Consensus Reporting Items for Studies in Primary Care (CRISP) Working Group. SETTING: International online survey. PARTICIPANTS: Interdisciplinary PC researchers and research users. MAIN OUTCOME MEASURES: We drew potential reporting items from literature review and a series of international, interdisciplinary surveys. Using an anonymous, online survey, we asked participants to vote on and whether each candidate item should be included, required or recommended in a PC research reporting guideline. Items advanced to the next Delphi round if they received>50% votes to include. Analysis used descriptive statistics plus synthesis of free-text responses. RESULTS: 98/116 respondents completed round 1 (84% response rate) and 89/98 completed round 2 (91%). Respondents included a variety of healthcare professions, research roles, levels of experience and all five world regions. Round 1 presented 29 potential items, and 25 moved into round 2 after rewording and combining items and adding 2 new items. A majority of round 2 respondents voted to include 23 items (90%-100% for 11 items, 80%-89% for 3 items, 70%-79% for 3 items, 60%-69% for 3 items and 50%-59% for 3 items). CONCLUSION: Our Delphi study identified items to guide the reporting of PC research that has broad endorsement from the community of producers and users of PC research. We will now use these results to inform the final development of the CRISP guidance for reporting PC research.

Familial hypercholesterolaemia (FH) is the most common inherited metabolic disorder characterized by high cholesterol and if left untreated leads to premature cardiovascular disease, such as heart attacks. Treatment that begins early in life, particularly in childhood, is highly efficacious in preventing cardiovascular disease and cost-effective, thus early detection of FH is crucial. However, in Europe, less than 10% of people living with FH are diagnosed and even less receive life-saving treatment. The Prague Declaration is a call to action for national and European Union policymakers and decision-makers and a result of the Czech EU Presidency meeting on FH Paediatric Screening (early detection of inherited high cholesterol) at the Czech Senate in Prague on 6th September 2022. It builds on a considerable body of evidence which was discussed at the Technical Meeting under the auspices of the Slovenian EU Presidency in October 2021. The Prague meeting addressed the outstanding barriers to the systematic implementation of FH paediatric screening across Europe. In this article, we present the key points from the Prague meeting and concrete actions needed to move forward.

BackgroundOne-fifth of conveyances to the emergency department (ED) are due to acute-on-chronic breathlessness. Paramedic breathlessness management may ease distress quicker and/or reduce ED conveyances. We evaluated the feasibility of a full trial of a paramedic delivered intervention to reduce avoidable conveyances (recruitment, randomisation, consent, training and intervention acceptability, adherence, data quality, best primary outcome, sample size estimation). The intervention comprised evidence-based non-drug techniques and a self-management booklet.MethodsThis mixed-methods feasibility cluster randomised controlled trial (ISRCTN80330546) with embedded qualitative study about trial processes, training and intervention delivery, randomised paramedics to usual care or to intervention+usual care. Retrospective patient consent to use call-out data and prospective patient/carer consent for follow-up was sought. Potential primary outcomes were breathlessness intensity (numerical rating scale) and ED conveyance. Follow-up included an interview for patients/carers and questionnaires at 14 days, 1 and 6 months and paramedic focus groups and survey.ResultsRecruitment was during the COVID-19 pandemic, leading to high demands on paramedics and fewer call-outs by eligible patients. We enrolled 29 paramedics; 9 withdrew. Randomisation/trial procedures were acceptable. Paramedics recruited 13 patients; 8 were followed up. Data quality was good. The intervention did not extend call-out time, was delivered with fidelity and no contamination and was acceptable to patients, carers, and paramedics. There were no repeat call-outs < 48 hours. Recruitment stop-go criteria were not met. We had insu

INTRODUCTION: One-fifth of emergency department presentations by ambulance are due to acute-on-chronic breathlessness. We explored the feasibility of an evaluation-phase, cluster randomised controlled trial (cRCT) of the effectiveness and cost-effectiveness of a paramedic-administered, non-pharmacological breathlessness intervention for people with acute-on-chronic breathlessness at ambulance call-out (BREATHE) regarding breathlessness intensity and conveyance to hospital. METHODS: This mixed-methods, feasibility cRCT (ISRCTN80330546) randomised paramedics to usual care or intervention plus usual care. Retrospective patient consent to use call-out data (primary end-point) and prospective patient/carer consent for follow-up was sought. Potential primary outcomes included breathlessness intensity (numerical rating scale) and conveyance. Follow-up included: interviews with patients/carers and questionnaires at 14 days, 1 and 6 months; paramedic focus groups and surveys. RESULTS: Recruitment was during COVID-19, with high demands on paramedics and fewer call-outs by eligible patients. We enrolled 29 paramedics; nine withdrew. Randomisation/trial procedures were acceptable. Paramedics recruited 13 patients, not meeting recruitment target (n=36); eight patients and three carers were followed-up. Data quality was good but insufficient for future sample size estimation. The intervention did not extend call-out time, was delivered with fidelity and was acceptable to patients, carers and paramedics. There were no repeat call-outs within 48 h. All trained paramedics strongly recommended BREATHE as a highly relevant, simple intervention. CONCLUSION: Patient recruitment to target was not feasible during the pandemic. Training and intervention were acceptable and delivered with fidelity. Results include valuable information on recruitment, consent, attrition and data collection that will inform the design and delivery of a definitive trial.