Patient-centred innovation for multimorbidity care : mixed-methods, randomized trial and qualitative study of the patients’ experience

Background Patient-centred interventions to help patients with multimorbidity have had mixed results. Aim To assess the effectiveness of a provider-created, patient-centred, multi-provider case conference with follow-up, and understand underwhal circumstances it worked. and did not work Design and setting Mixed-methods design with a pragmatic randomised trial and qualitative study. involving nine urban primary care sites in Ontario, Canada. Method Patients aged 18-80 years with >= 3 chronic conditions were referred to the Telemedicine IMPACT Plus intervention; a nurse and patient planned a multi provider case conference during which a care plan could be created. The patients were randomised into an intervention or control group. Two subgroup analyses and a fidelity assessment were conducted, with the primary outcomes at 4 months being self-management and self-efficacy. Secondary outcomes were mental and physical health status, quality of life, and health behaviours. A thematic analysis explored the patients' experiences of the intervention. Results A total of 86 patients in the intervention group and 77 in the control group showed no differences, except that the intervention improved mental health status in the subgroup with an annual income of >= C$50 000 [beta-coefficient 11.003, P= 0.006]. More providers and follow-up hours were associated with poorer outcomes. Five themes were identified in the qualitative study: valuing the team, patients feeling supported. receiving a follow-up plan, being offered new and helpful additions to their treatment regimen, and experiencing positive outcomes. Conclusion Overall, the intervention showed improvements only for patients who had an annual income of >= C$50 000, implying a need to address the Wsis of intervention components not covered by existing health policies. Findings suggest a need to optimise learn composition by revising the number and type of providers according to patient preferences and to enhance the hours of nurse follow-up to better support the patient in carrying out the case conference's recommendations

Long-term Psychological and Occupational Effects of Providing Hospital Healthcare during SARS Outbreak

TOC Summary Line: Healthcare workers in hospitals affected by SARS experience increased psychological stress 1–2 years after the outbreak

Optimization and Characterization of N-Acetamide Indoles as Antimalarials That Target PfATP4

To discover new antimalarials, a screen of the Janssen Jumpstarter library against Plasmodium falciparum uncovered the N-acetamide indole hit class. The structure-activity relationship of this chemotype was defined and culminated in the optimized frontrunner analog WJM664, which exhibited potent asexual stage activity and high metabolic stability. Resistant selection and whole-genome sequencing revealed mutations in PfATP4, which was validated as the target by showing that analogs exhibited reduced potency against parasites with resistance-conferring mutations in PfATP4, a metabolomic signature similar to that of the PfATP4 inhibitor KAE609, and inhibition of Na+-dependent ATPase activity consistent with on-target inhibition of PfATP4. WJM664 inhibited gamete development and blocked parasite transmission to mosquitoes but exhibited low efficacy in aPlasmodium berghei mouse model, which was attributed to ATP4 species differentiation and its moderate systemic exposure. Optimization of these attributes is required for N-acetamide indoles to be pursued for development as a curative and transmission-blocking therapy.</p

Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research

No abstract available

Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study

INTRODUCTION: Increased mortality has been demonstrated in older adults with COVID-19, but the effect of frailty has been unclear.METHODS: This multi-centre cohort study involved patients aged 18years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty, and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation, and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS), and delirium on risk of increased care requirements on discharge, adjusting for the same variables.RESULTS: Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, IQR 54-83; 55.2% male). The risk of death increased independently with increasing age (&gt;80 vs 18-49: HR 3.57, CI 2.54-5.02), frailty (CFS 8 vs 1-3: HR 3.03, CI 2.29-4.00) inflammation, renal disease, cardiovascular disease, and cancer, but not delirium. Age, frailty (CFS 7 vs 1-3: OR 7.00, CI 5.27-9.32), delirium, dementia, and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9.CONCLUSIONS: Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n1⁄42,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n1⁄43,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombinedo5108) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist

Comparison of self-rated and objective successful ageing in an international cohort

ABSTRACTUnderstanding predictors of successful ageing is essential to policy development promoting quality-of-life of an ageing population. Initial models precluded successful ageing in the presence of chronic disease/functional disability; however, this is discrepant with self-reported successful ageing. Indicators of social, psychological and physical health in 1,735 people aged 65–74, living in Canada, Columbia, Brazil or Albania, were analysed in the International Mobility in Ageing Study. Multiple logistic regression analysis was performed to estimate the change in self-rated successful ageing in relation to physical health, depression, social connectedness, resilience and site, while controlling for age, gender and income sufficiency. Sixty-five per cent of participants self-rated as ageing successfully; however, this was significantly different across sites (p &lt; 0.0005, range 17–85%) and gender (p = 0.019). Using objective measures, 6 per cent were classified as ‘successful’, with significant variability amongst sites (p &lt; 0.0005, range 0–12%). Subjective successful ageing was associated with fewer (not absence of) chronic diseases, absence of depression and less dysfunction in activities of daily living, but not with objective measures of physical dysfunction. Social connectedness and resilience also aligned with self-rated successful ageing. Traditional definitions of objective successful ageing are likely too restrictive, and thus, do not approximate self-rated successful ageing. International differences suggest that site could be a surrogate for variables other than physical/mental health and social engagement.</jats:p