A novel, multidomain, primary care nurse-led and mHealth-assisted intervention for dementia risk reduction in middle-aged adults (HAPPI MIND): study protocol for a cluster randomised controlled trial.

INTRODUCTION: Middle-aged multidomain risk reduction interventions targeting modifiable risk factors for dementia may delay or prevent a third of dementia cases in later life. We describe the protocol of a cluster randomised controlled trial (cRCT), HAPPI MIND (Holistic Approach in Primary care for PreventIng Memory Impairment aNd Dementia). HAPPI MIND will evaluate the efficacy of a multidomain, nurse-led, mHealth supported intervention for assessing dementia risk and reducing associated risk factors in middle-aged adults in the Australian primary care setting. METHODS AND ANALYSIS: General practice clinics (n≥26) across Victoria and New South Wales, Australia, will be recruited and randomised. Practice nurses will be trained to implement the HAPPI MIND intervention or a brief intervention. Patients of participating practices aged 45-65 years with ≥2 potential dementia risk factors will be identified and recruited (approximately 15 patients/clinic). Brief intervention participants receive a personalised report outlining their risk factors for dementia based on Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) scores, education booklet and referral to their general practitioner as appropriate. HAPPI MIND participants receive the brief intervention as well as six individualised dementia risk reduction sessions with a nurse trained in motivational interviewing and principles of behaviour change, a personalised risk reduction action plan and access to the purpose-built HAPPI MIND smartphone app for risk factor self-management. Follow-up data collection will occur at 12, 24 and 36 months. Primary outcome is ANU-ADRI score change at 12 months from baseline. Secondary outcomes include change in cognition, quality of life and individual risk factors of dementia. ETHICS AND DISSEMINATION: Project approved by Monash University Human Research Ethics Committee (ID: 28273). Results will be disseminated in peer-reviewed journals and at healthcare conferences. If effective in reducing dementia risk, the HAPPI MIND intervention could be integrated into primary care, scaled up nationally and sustained over time. TRIAL REGISTRATION NUMBER: ACTRN12621001168842.

Educational interventions for health professionals managing chronic obstructive pulmonary disease in primary care.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable health condition. COPD is associated with substantial burden on morbidity, mortality and healthcare resources. OBJECTIVES: To review existing evidence for educational interventions delivered to health professionals managing COPD in the primary care setting. SEARCH METHODS: We searched the Cochrane Airways Trials Register from inception to May 2021. The Register includes records from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED) and PsycINFO. We also searched online trial registries and reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs. Eligible studies tested educational interventions aimed at any health professionals involved in the management of COPD in primary care. Educational interventions were defined as interventions aimed at upskilling, improving or refreshing existing knowledge of health professionals in the diagnosis and management of COPD. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed abstracts and full texts of eligible studies, extracted data and assessed the risk of bias of included studies. We conducted meta-analyses where possible and used random-effects models to yield summary estimates of effect (mean differences (MDs) with 95% confidence intervals (CIs)). We performed narrative synthesis when meta-analysis was not possible. We assessed the overall certainty of evidence for each outcome using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). Primary outcomes were: 1) proportion of COPD diagnoses confirmed with spirometry; 2) proportion of patients with COPD referred to, participating in or completing pulmonary rehabilitation; and 3) proportion of patients with COPD prescribed respiratory medication consistent with guideline recommendations. MAIN RESULTS: We identified 38 studies(22 cluster-RCTs and 16 RCTs) involving 4936 health professionals (reported in 19/38 studies) and 71,085 patient participants (reported in 25/38 studies). Thirty-six included studies evaluated interventions versus usual care; seven studies also reported a comparison between two or more interventions as part of a three- to five-arm RCT design. A range of simple to complex interventions were used across the studies, with common intervention features including education provided to health professionals via training sessions, workshops or online modules (31 studies), provision of practice support tools, tool kits and/or algorithms (10 studies), provision of guidelines (nine studies) and training on spirometry (five studies). Health professionals targeted by the interventions were most commonly general practitioners alone (20 studies) or in combination with nurses or allied health professionals (eight studies), and the majority of studies were conducted in general practice clinics. We identified performance bias as high risk for 33 studies. We also noted risk of selection, detection, attrition and reporting biases, although to a varying extent across studies. The evidence of efficacy was equivocal for all the three primary endpoints evaluated: 1) proportion of COPD diagnoses confirmed with spirometry (of the four studies that reported this outcome, two supported the intervention); 2) proportion of patients with COPD who are referred to, participate in or complete pulmonary rehabilitation (of the four studies that reported this outcome, two supported the intervention); and 3) proportion of patients with COPD prescribed respiratory medications consistent with guideline recommendations (12 studies reported this outcome, the majority evaluated multiple drug classes and reported a mixed effect). Additionally, the low quality of evidence and potential risk of bias make the interpretation more difficult. Moderate-quality evidence (downgraded due to risk of bias concerns) suggests that educational interventions for health professionals probably improve the proportion of patients with COPD vaccinated against influenza (three studies) and probably have little impact on the proportion of patients vaccinated against pneumococcal infection (two studies). Low-quality evidence suggests that educational interventions for health professionals may have little or no impact on the frequency of COPD exacerbations (10 studies). There was a high degree of heterogeneity in the reporting of health-related quality of life (HRQoL). Low-quality evidence suggests that educational interventions for health professionals may have little or no impact on HRQoL overall, and when using the COPD-specific HRQoL instrument, the St George's Respiratory Questionnaire (at six months MD 0.87, 95% CI -2.51 to 4.26; 2 studies, 406 participants, and at 12 months MD -0.43, 95% CI -1.52 to 0.67, 4 studies, 1646 participants; reduction in score indicates better health). Moderate-quality evidence suggests that educational interventions for health professionals may improve patient satisfaction with care (one study). We identified no studies that reported adverse outcomes. AUTHORS' CONCLUSIONS: The evidence of efficacy was equivocal for educational interventions for health professionals in primary care on the proportion of COPD diagnoses confirmed with spirometry, the proportion of patients with COPD who participate in pulmonary rehabilitation, and the proportion of patients prescribed guideline-recommended COPD respiratory medications. Educational interventions for health professionals may improve influenza vaccination rates among patients with COPD and patient satisfaction with care. The quality of evidence for most outcomes was low or very low due to heterogeneity and methodological limitations of the studies included in the review, which means that there is uncertainty about the benefits of any currently published educational interventions for healthcare professionals to improve COPD management in primary care. Further well-designed RCTs are needed to investigate the effects of educational interventions delivered to health professionals managing COPD in the primary care setting.

Proinflammatory actions of thromboxane receptors to enhance cellular immune responses.

Metabolism of arachidonic acid by the cyclo-oxygenase (COX) pathway generates a family of prostanoid mediators. Nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibiting COX, thereby reducing prostanoid synthesis. The efficacy of these agents in reducing inflammation suggests a dominant proinflammatory role for the COX pathway. However, the actions of COX metabolites are complex, and certain prostanoids, such as PGE(2), in some circumstances actually inhibit immune and inflammatory responses. In these studies, we examine the hypothesis that anti-inflammatory actions of NSAIDs may be due, in part, to inhibition of thromboxane A(2) synthesis. To study the immunoregulatory actions of thromboxane A(2), we used mice with a targeted disruption of the gene encoding the thromboxane-prostanoid (TP) receptor. Both mitogen-induced responses and cellular responses to alloantigen were substantially reduced in TP(-/-) spleen cells. Similar attenuation was observed with pharmacological inhibition of TP signaling in wild-type splenocytes, suggesting that reduced responsiveness was not due to subtle developmental abnormalities in the TP-deficient mice. The absence of TP receptors reduced immune-mediated tissue injury following cardiac transplant rejection, an in vivo model of intense inflammation. Taken together, these findings show that thromboxane augments cellular immune responses and inflammatory tissue injury. Specific inhibition of the TP receptor may provide a more precise approach to limit inflammation without some of the untoward effects associated with NSAIDs.