The Frailty Reduction via Implementation of Exercise, Nutrition, and Deprescribing (FRIEND) Trial: Study Protocol and Recruitment Results.

INTRODUCTION: Virtually all adults in aged care facilities are frail, a condition which contributes to falls, cognitive decline, hospitalisation, and mortality. Polypharmacy, malnutrition, sedentariness, and sarcopenia are risk factors amenable to intervention. The Asia-Pacific Frailty Management Guidelines recommend anabolic exercise and the optimisation of medications and nutrition. However, no study has evaluated this best practice intervention triad in aged care. METHODS: The Frailty Reduction via the Implementation of Exercise, Nutrition, and Deprescribing (FRIEND) Trial (ANZCTR No.ACTRN12622000926730p) is a staged 6-month translational trial evaluating resident outcomes, staff/caregiver knowledge, and institutional implementation in a Townsville aged care facility. Residents received high-intensity resistance exercise and balance training and medication and nutrition optimisation co-implemented by investigators (exercise physiologist, geriatrician, pharmacist, and nutritionist) and facility staff. Staff and caregivers completed comprehensive education modules and training. We report the trial protocol and recruitment results. RESULTS: 29 residents (21 female, age: 88.6 ± 6.3 years) were recruited. At baseline, the residents were frail (frailty scale nursing home (FRAIL-NH); 6.3 ± 2.4/14), cognitively impaired (Montreal Cognitive Assessment; 13.8 ± 6.8/30), functionally impaired (Short Physical Performance Battery; 4.9 ± 3.1/12, 6 min walk distance; 222.2 ± 104.4 m), and were prescribed numerous medications (15.5 ± 5.9). Two residents died and one withdrew before the intervention's commencement. Thirty family members and 19 staff (carers, allied health assistants, nurse managers, registered nurses, lifestyle-leisure officers, kitchen/hospitality staff, and senior leadership) were recruited to receive frailty education modules. CONCLUSIONS: The FRIEND trial is currently being implemented with results expected in mid-2024. This is the first trial to evaluate the implementation of the best practice frailty guidelines including anabolic exercise and medication/nutritional optimisation in residential aged care.

COPD in Africa: risk factors, hospitalisation, readmission and associated outcomes-a systematic review and meta-analysis.

BACKGROUND: This review aims to synthesise available evidence on the prevalence of chronic obstructive pulmonary disease (COPD), associated risk factors, hospitalisations and COPD readmissions in Africa. METHOD: Using the Met-Analyses and Systematic Reviews of Observational Studies guideline, electronic databases were searched from inception to 1 October 2021. The quality of studies was assessed using the Newcastle-Ottawa Scale. Evidence from retrieved articles was synthesised, and a random-effect model meta-analysis was conducted. The protocol was registered on PROSPERO. RESULTS: Thirty-nine studies met the inclusion criteria, with 13 included in the meta-analysis. The prevalence of COPD varied between the Global Initiative for Chronic Obstructive Lung Disease (2%-24%), American Thoracic Society/European Respiratory Society (1%-17%) and Medical Research Council chronic bronchitis (2%-11%) criteria, respectively. Increasing age, wheezing and asthma were consistent risk factors for COPD from studies included in the narrative synthesis. Our meta-analysis indicated that prior tuberculosis ((OR 5.98, 95% CI 4.18 to 8.56), smoking (OR 2.80, 95% CI: 2.19 to 3.59) and use of biomass fuel (OR 1.52, 95% CI: 1.39 to 1.67)) were significant risk factors for COPD. Long-term oxygen therapy (HR 4.97, 95% CI (1.04 to 23.74)) and frequent hospitalisation (≥3 per year) (HR 11.48, 95% CI (1.31 to 100.79)) were risk factors associated with 30-day COPD readmission. CONCLUSION: This study not only highlights specific risk factors for COPD risk in Africa but also demonstrates the paucity and absence of research in several countries in a continent with substantial COPD-related mortality. Our findings contribute towards the development of evidence-based clinical guidelines for COPD in Africa.PROSPERO registration numberCRD42020210581.

Hospital Readmission Due to Chronic Obstructive Pulmonary Disease: A Longitudinal Study.

BACKGROUND: This study aimed to investigate the prevalence of hospital readmission for chronic obstructive pulmonary disease (COPD) at 30, 90 and 365 days, and to determine demographic and socioeconomic risk factors for 30-day and 90-day readmission and time to COPD-related readmission within 365 days in Tasmania. METHODS: Patients ≥40 years admitted for COPD between 2011 and 2015 were identified using administrative data from all major public hospitals in Tasmania, Australia. Factors associated with readmission and time to readmission were identified using logistic and Cox regression, respectively. RESULTS: The rates of COPD-related readmission were 6.7% within 30 days, 12.2% within 90 days and 23.7% within 365 days. Being male (odds ratio [OR]: 1.49, CI: 1.06-2.09), Indigenous (OR: 2.47, CI: 1.31-4.66) and living in the lower socioeconomic North-West region of Tasmania (OR: 1.80, CI: 1.20-2.69) were risk factors for 30-day readmission. Increased COPD-related (OR: 1.48, CI: 1.22-1.80; OR: 1.52, CI: 1.29-1.78) and non-COPD-related (OR: 1.12, CI: 1.03- 1.23; OR: 1.11, CI: 1.03-1.21) emergency department (ED) visits in the preceding six months were risk factors for both 30-day and 90-day readmissions. Being Indigenous (hazard ratio [HR]: 1.61, CI: 1.10-2.37) and previous COPD-related ED visits (HR: 1.30, CI: 1.21-1.39) decreased, while a higher Charlson Comorbidity Index (CCI) (OR: 0.91, CI: 0.83- 0.99) increased the time to readmission within 365 days. CONCLUSION: Being male, Indigenous, living in the North-West region and previous ED visits were associated with increased risk of COPD readmission in Tasmania. Interventions to improve access to primary healthcare for these groups may reduce COPD-related readmissions.

Risk factors and associated outcomes of hospital readmission in COPD: A systematic review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of unplanned readmission. There is need to identify risk factors for, and strategies to prevent readmission in patients with COPD. AIM: To systematically review and summarise the prevalence, risk factors and outcomes associated with rehospitalisation due to COPD exacerbation. METHOD: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Five databases were searched for relevant studies. RESULTS: Fifty-seven studies from 30 countries met the inclusion criteria. The prevalence of COPD-related readmission varied from 2.6 to 82.2% at 30 days, 11.8-44.8% at 31-90 days, 17.9-63.0% at 6 months, and 25.0-87.0% at 12 months post-discharge. There were differences in the reported factors associated with readmissions, which may reflect variations in the local context, such as the availability of community-based services to care for exacerbations of COPD. Hospitalisation in the previous year prior to index admission was the key predictor of COPD-related readmission. Comorbidities (in particular asthma), living in a deprived area and living in or discharge to a nursing home were also associated with readmission. Relative to those without readmissions, readmitted patients had higher in-hospital mortality rates, shorter long-term survival, poorer quality of life, longer hospital stay, increased recurrence of subsequent readmissions, and accounted for greater healthcare costs. CONCLUSIONS: Hospitalisation in the previous year was the principal risk factor for COPD-related readmissions. Variation in the prevalence and the reported factors associated with COPD-related readmission indicate that risk factors cannot be generalised, and interventions should be tailored to the local healthcare environment.

Risk factors for all-cause hospital readmission following exacerbation of COPD: a systematic review and meta-analysis.

BACKGROUND: Readmission rates following hospitalisation for COPD exacerbations are unacceptably high, and the contributing factors are poorly understood. Our objective was to summarise and evaluate the factors associated with 30- and 90-day all-cause readmission following hospitalisation for an exacerbation of COPD. METHODS: We systematically searched electronic databases from inception to 5 November 2019. Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study quality was assessed using a modified version of the Newcastle-Ottawa Scale. We synthesised a narrative from eligible studies and conducted a meta-analysis where this was possible using a random-effects model. RESULTS: In total, 3533 abstracts were screened and 208 full-text manuscripts were reviewed. A total of 32 papers met the inclusion criteria, and 14 studies were included in the meta-analysis. The readmission rate ranged from 8.8-26.0% at 30 days and from 17.5-39.0% at 90 days. Our narrative synthesis showed that comorbidities, previous exacerbations and hospitalisations, and increased length of initial hospital stay were the major risk factors for readmission at 30 and 90 days. Pooled adjusted odds ratios (95% confidence intervals) revealed that heart failure (1.29 (1.22-1.37)), renal failure (1.26 (1.19-1.33)), depression (1.19 (1.05-1.34)) and alcohol use (1.11 (1.07-1.16)) were all associated with an increased risk of 30-day all-cause readmission, whereas being female was a protective factor (0.91 (0.88-0.94)). CONCLUSIONS: Comorbidities, previous exacerbations and hospitalisation, and increased length of stay were significant risk factors for 30- and 90-day all-cause readmission after an index hospitalisation with an exacerbation of COPD.

Integration of cell line and clinical trial genome-wide analyses supports a polygenic architecture of Paclitaxel-induced sensory peripheral neuropathy.

PURPOSE: We sought to show the relevance of a lymphoblastoid cell line (LCL) model in the discovery of clinically relevant genetic variants affecting chemotherapeutic response by comparing LCL genome-wide association study (GWAS) results to clinical GWAS results. EXPERIMENTAL DESIGN: A GWAS of paclitaxel-induced cytotoxicity was conducted in 247 LCLs from the HapMap Project and compared with a GWAS of sensory peripheral neuropathy in patients with breast cancer (n = 855) treated with paclitaxel in the Cancer and Leukemia Group B (CALGB) 40101 trial. Significant enrichment was assessed by permutation resampling analysis. RESULTS: We observed an enrichment of LCL cytotoxicity-associated single-nucleotide polymorphisms (SNP) in the sensory peripheral neuropathy-associated SNPs from the clinical trial with concordant allelic directions of effect (empirical P = 0.007). Of the 24 SNPs that overlap between the clinical trial (P < 0.05) and the preclinical cytotoxicity study (P < 0.001), 19 of them are expression quantitative trait loci (eQTL), which is a significant enrichment of this functional class (empirical P = 0.0447). One of these eQTLs is located in RFX2, which encodes a member of the DNA-binding regulatory factor X family. Decreased expression of this gene by siRNA resulted in increased sensitivity of Neuroscreen-1(NS-1; rat pheochromocytoma) cells to paclitaxel as measured by reduced neurite outgrowth and increased cytotoxicity, functionally validating the involvement of RFX2 in nerve cell response to paclitaxel. CONCLUSIONS: The enrichment results and functional example imply that cellular models of chemotherapeutic toxicity may capture components of the underlying polygenic architecture of related traits in patients.