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BackgroundInterest in the application of predictive risk models (PRMs) in health care to identify people most likely to experience disease and treatment-related complications is increasing. In cancer care, these techniques are focused primarily on the prediction of survival or life-threatening toxicities (eg, febrile neutropenia). Fewer studies focus on the use of PRMs for symptoms or supportive care needs. The application of PRMs to chemotherapy-related symptoms (CRS) would enable earlier identification and initiation of prompt, personalized, and tailored interventions. While some PRMs exist for CRS, few were translated into clinical practice, and human factors associated with their use were not reported. ObjectiveWe aim to explore patients’ and clinicians’ perspectives of the utility and real-world application of PRMs to improve the management of CRS. MethodsFocus groups (N=10) and interviews (N=5) were conducted with patients (N=28) and clinicians (N=26) across 5 European countries. Interactions were audio-recorded, transcribed verbatim, and analyzed thematically. ResultsBoth clinicians and patients recognized the value of having individualized risk predictions for CRS and appreciated how this type of information would facilitate the provision of tailored preventative treatments or supportive care interactions. However, cautious and skeptical attitudes toward the use of PRMs in clinical care were noted by both groups, particularly in relationship to the uncertainty regarding how the information would be generated. Visualization and presentation of PRM information in a usable and useful format for both patients and clinicians was identified as a challenge to their successful implementation in clinical care. ConclusionsFindings from this study provide information on clinicians’ and patients’ perspectives on the clinical use of PRMs for the management of CRS. These international perspectives are important because they provide insight into the risks and benefits of using PRMs to evaluate CRS. In addition, they highlight the need to find ways to more effectively present and use this information in clinical practice. Further research that explores the best ways to incorporate this type of information while maintaining the human side of care is warranted. Trial RegistrationClinicalTrials.gov NCT02356081; https://clinicaltrials.gov/study/NCT02356081

Key message Swyer‐James‐MacLeod Syndrome is a rare obliterative lung disease typically caused by childhood infection resulting in arrested pulmonary development. Imaging findings include unilateral hyperlucency on chest x‐ray, and hyperlucency, hypovascularity and expiratory gas trapping on computed tomography. Recognition of abnormal imaging can lead to earlier diagnosis and institution of appropriate management.

Objectives This study aims to examine community antibiotic prescribing across a complete geographical area for people with a positive COVID-19 test across three pandemic waves, and to examine health and demographic factors associated with antibiotic prescribing.Design A population-based study using administrative data.Setting A complete geographical region within Scotland, UK.Participants Residents of two National Health Service Scotland health boards with SARS-CoV-2 virus test results from 1 February 2020 to 31 March 2022 (n=184 954). Individuals with a positive test result (n=16 025) had data linked to prescription and hospital admission data ±28 days of the test, general practice data for high-risk comorbidities and demographic data.Outcome measures The associations between patient factors and the odds of antibiotic prescription in COVID-19 episodes across three pandemic waves from multivariate binary logistic regression.Results Data included 768 206 tests for 184 954 individuals, identifying 16 240 COVID-19 episodes involving 16 025 individuals. There were 3263 antibiotic prescriptions ±28 days for 2395 episodes. 35.6% of episodes had a prescription only before the test date, 52.3% of episodes after and 12.1% before and after. Antibiotic prescribing reduced over time: 20.4% of episodes in wave 1, 17.7% in wave 2 and 12.0% in wave 3. In multivariate logistic regression, being female (OR 1.31, 95% CI 1.19 to 1.45), older (OR 3.02, 95% CI 2.50 to 3.68 75+ vs

IntroductionUnderstanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia.MethodsWe performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures.ResultsData from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, pConclusionIn men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass.

Abstract Background Prediction of lifetime cardiovascular disease (CVD) risk is recommended in many clinical guidelines, but lifetime risk models are rarely externally validated. The aim of this study was to externally validate the QRiskLifetime incident CVD risk prediction tool. Methods Independent external validation of QRiskLifetime using Clinical Practice Research Datalink data, examining discrimination and calibration in the whole population and stratified by age, and reclassification compared to QRISK3. Since lifetime CVD risk is unobservable, performance was evaluated at 10-years’ follow-up, and lifetime performance inferred in terms of performance for in the different age-groups from which lifetime predictions are derived. Results One million, two hundreds sixty thousand and three hundreds twenty nine women and 1,223,265 men were included in the analysis. Discrimination was excellent in the whole population (Harrell’s-C = 0.844 in women, 0.808 in men), but moderate to poor stratified by age-group (Harrell’s C in people aged 30–44 0.714 for both men and women, in people aged 75–84 0.578 in women and 0.556 in men). Ten-year CVD risk was under-predicted in the whole population, and in all age-groups except women aged 45–64, with worse under-prediction in older age-groups. Compared to those at highest QRISK3 estimated 10-year risk, those with highest lifetime risk were younger (mean age: women 50.5 vs. 71.3 years; men 46.3 vs. 63.8 years) and had lower systolic blood pressure and prevalence of treated hypertension, but had more family history of premature CVD, and were more commonly minority ethnic. Over 10-years, the estimated number needed to treat (NNT) with a statin to prevent one CVD event in people with QRISK3 ≥ 10% was 34 in women and 37 in men, compared to 99 and 100 for those at highest lifetime risk. Conclusions QRiskLifetime underpredicts 10-year CVD risk in nearly all age-groups, so is likely to also underpredict lifetime risk. Treatment based on lifetime risk has considerably lower medium-term benefit than treatment based on 10-year risk.

Abstract Background Acute kidney injury (AKI) is common and associated with adverse outcomes as well as important healthcare costs. However, evidence examining the epidemiology of acute kidney disease (AKD)—recently defined as AKI persisting between 7 and 90 days—remains limited. The aims of this study were to establish the rates of early AKI recovery, progression to AKD and non-recovery; examine risk factors associated with non-recovery and investigate the association between recovery timing and adverse outcomes, in a population-based cohort. Methods All adult residents of Tayside & Fife, Scotland, UK, with at least one episode of community or hospital-managed AKI using KDIGO creatinine-based definition during the period 1 January 2010 to 31 December 2018 were identified. Logistic regression was used to examine factors associated with non-recovery, and Cox modelling was used to establish associations between AKI recovery timing and risks of mortality and development of de novo CKD. Results Over 9 years, 56,906 patients with at least one AKI episode were identified with 18,773 (33%) of these progressing to AKD. Of those progressing to AKD, 5059 (27%) had still not recovered at day 90 post AKI diagnosis. Risk factors for AKD included: increasing AKI severity, pre-existing cancer or chronic heart failure and recent use of loop diuretics. Compared with early AKI recovery, progression to AKD was associated with increased hazard of 1-year mortality and de novo CKD (HR = 1.20, 95% CI 1.13 to 1.26 and HR = 2.21, 95% CI 1.91 to 2.57 respectively). Conclusions These findings highlight the importance of early AKI recognition and management to avoid progression to AKD and long-term adverse outcomes.

Abstract Background People who die from cancer (‘cancer decedents’) may latterly experience unpleasant and distressing symptoms. Prescribing medication for pain and symptom control is essential for good-quality palliative care; however, such provision is variable, difficult to quantify and poorly characterised in current literature. This study aims to characterise trends in prescribing analgesia, non-analgesic palliative care medication and non-palliative medications, to cancer decedents, in their last year of life, and to assess any associations with demographic or clinical factors. Methods This descriptive study, analysed all 181,247 prescriptions issued to a study population of 2443 cancer decedents in Tayside, Scotland (2013–2015), in the last year of life, linking prescribing data to demographic, and cancer registry datasets using the unique patient-identifying Community Health Index (CHI) number. Anonymised linked data were analysed in Safe Haven using chi-squared test for trend, binary logistic regression and Poisson regression in SPSSv25. Results In their last year of life, three in four cancer decedents were prescribed strong opioids. Two-thirds of those prescribed opioids were also prescribed laxatives and/or anti-emetics. Only four in ten cancer decedents were prescribed all medications in the ‘Just in Case’ medication categories and only one in ten was prescribed breakthrough analgesia in the last year of life. The number of prescriptions for analgesia and palliative care drugs increased in the last 12 weeks of life. The number of prescriptions for non-palliative care medications, including anti-hypertensives, statins and bone protection, decreased over the last year, but was still substantial. Cancer decedents who were female, younger, or had lung cancer were more likely to be prescribed strong opioids; however, male cancer decedents had higher odds of being prescribed breakthrough analgesia. Cancer decedents who had late diagnoses had lower odds of being prescribed strong opioids. Conclusions A substantial proportion of cancer decedents were not prescribed strong opioids, breakthrough medication, or medication to alleviate common palliative care symptoms (including ‘Just in Case’ medication). Many patients continued to be prescribed non-palliative care medications in their last days and weeks of life. Age, gender, cancer type and timing of diagnosis affected patients’ odds of being prescribed analgesic and non-analgesic palliative care medication.

Abstract Background Recommended cardiovascular disease (CVD) prediction tools do not account for competing mortality risk and over-predict incident CVD in older and multimorbid people. The aim of this study was to derive and validate a competing risk model (CRISK) to predict incident CVD and compare its performance to that of QRISK3 in UK primary care. Methods We used UK linked primary care data from the Clinical Practice Research Datalink (CPRD) GOLD to identify people aged 25–84 years with no previous CVD or statin treatment split into derivation and validation cohorts. In the derivation cohort, we derived models using the same covariates as QRISK3 with Fine-Gray competing risk modelling alone (CRISK) and with Charlson Comorbidity score (CRISK-CCI) as an additional predictor of non-CVD death. In a separate validation cohort, we examined discrimination and calibration compared to QRISK3. Reclassification analysis examined the number of patients recommended for treatment and the estimated number needed to treat (NNT) to prevent a new CVD event. Results The derivation and validation cohorts included 989,732 and 494,865 women and 946,784 and 473,392 men respectively. Overall discrimination of CRISK and CRISK-CCI were excellent and similar to QRISK3 (for women, C-statistic = 0.863/0.864/0.863 respectively; for men 0.833/0.819/0.832 respectively). CRISK and CRISK-CCI calibration overall and in younger people was excellent. CRISK over-predicted in older and multimorbid people although performed better than QRISK3, whilst CRISK-CCI performed the best. The proportion of people reclassified by CRISK-CCI varied by QRISK3 risk score category, with 0.7–9.7% of women and 2.8–25.2% of men reclassified as higher risk and 21.0–69.1% of women and 27.1–57.4% of men reclassified as lower risk. Overall, CRISK-CCI recommended fewer people for treatment and had a lower estimated NNT at 10% risk threshold. Patients reclassified as higher risk were younger, had lower SBP and higher BMI, and were more likely to smoke. Conclusions CRISK and CRISK-CCI performed better than QRISK3. CRISK-CCI recommends fewer people for treatment and has a lower NNT to prevent a new CVD event compared to QRISK3. Competing risk models should be recommended for CVD primary prevention treatment recommendations.

Abstract Background This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. Methods Placebo‐controlled, parallel group, double‐blind, randomized two‐by‐two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (

BackgroundAgeing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia.MethodsWe compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial.ResultsNeither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone.ConclusionThese data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.

BackgroundAngiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result. Polymorphic variation in the ACE promoter (I/D alleles) has been associated with differences in ACE activity and muscle physiology in a range of clinical conditions. This aim of this analysis was to determine whether I/D polymorphic variation is associated with muscle mass, strength, in sarcopenia or contributed to the lack of response to treatment in the LACE study.MethodsSarcopenic individuals were recruited into a 2x2 factorial multicentre double-blind study of the effects of perindopril and/or leucine versus placebo on physical performance and muscle mass. DNA extracted from blood samples (n = 130 72 women and 58 men) was genotyped by PCR for the ACE I/D polymorphism. Genotypes were then compared with body composition measured by DXA, hand grip and quadriceps strength before and after 12 months' treatment with leucine and/or perindopril in a cross-sectional analysis of the influence of genotype on these variables.ResultsAllele frequencies for the normal UK population were extracted from 13 previous studies (I = 0.473, D = 0.527). In the LACE cohort the D allele was over-represented (I = 0.412, D = 0.588, p = 0.046). This over-representation was present in men (I = 0.353, D = 0.647, p = 0.010) but not women (I = 0.458, D = 0.532, p = 0.708). In men but not women, individuals with the I allele had greater leg strength (II/ID = 18.00 kg (14.50, 21.60) vs DD = 13.20 kg (10.50, 15.90), p = 0.028). Over the 12 months individuals with the DD genotype increased in quadriceps strength but those with the II or ID genotype did not. Perindopril did not increase muscle strength or mass in any polymorphism group relative to placebo.ConclusionOur results suggest that although ACE genotype was not associated with response to ACE inhibitor therapy in the LACE trial population, sarcopenic men with the ACE DD genotype may be weaker than those with the ACE I/D or II genotype.

Background: Angiotensin-converting enzyme inhibitors and leucine are promising potential treatments for sarcopenia. Neither has yet been tested in adequately powered randomised trials in patients with sarcopenia. Objectives: To determine the efficacy of leucine and perindopril in improving physical function in older people with sarcopenia, to evaluate the effect of leucine and perindopril on muscle mass and to evaluate the predictive biomarkers of sarcopenia. Design: A placebo-controlled, parallel group, double-blind, randomised 2 × 2 factorial trial. Setting: Primary care and geriatric medicine secondary care departments in 14 UK centres. Participants: Adults aged ≥ 70 years with low muscle strength and mass, without contraindications to angiotensin-converting enzyme inhibitors and without known diagnosis-specific skeletal myopathy. Interventions: Eligible participants were randomised 1 : 1 to receive 4 mg of oral perindopril or a matching placebo and, separately, were randomised 1 : 1 to receive 2.5 g of oral leucine powder or a matching placebo powder taken thrice daily with meals. Randomisation was performed using an interactive web-based randomisation system run independently of the research team to preserve allocation concealment. Main outcome measures: The primary outcome was the between-group difference in the Short Physical Performance Battery (SPPB) score over the 12-month follow-up period. Other outcome measures included appendicular muscle mass, EQ-5D (EuroQol-5 Dimensions) quality-of-life score, grip strength, quadriceps strength, 6-minute walk distance, activities of daily living, hip bone mineral density and insulin resistance. All adverse events and falls were recorded. Protein-, DNA (deoxyribonucleic acid)- and RNA (ribonucleic acid)-based biomarkers were collected at baseline and at 3 and 12 months. Results: We screened 320 people and randomised 145 participants. Participants had a mean age of 79 (standard deviation 6) years, 78 (54%) were women and the mean SPPB was 7.0 (standard deviation 2.4). The median adherence was lower for perindopril than for placebo (76% vs. 96%; p

Abstract Background Sarcopenia is rarely diagnosed and is not recorded electronically in routine clinical care, posing challenges to trial recruitment. We describe the performance of four components of a strategy to efficiently recruit participants with sarcopenia to a trial of perindopril and/or leucine for sarcopenia: primary care vs. hospital recruitment, a comparison of central vs. local telephone pre‐screening, performance of a questionnaire on physical function conducted as part of the pre‐screening telephone call, and performance of bioimpedance measurement to identify low muscle mass. Methods Hospital‐based recruitment took place through inpatient and outpatient geriatric medicine services. Local research nurses reviewed medical notes and approached potentially eligible patients. Primary care recruitment reviewed primary care lists from collaborating practices, sending mailshots to patients aged 70 and over who were not taking angiotensin‐converting enzyme inhibitors. Telephone pre‐screening was conducted either by research nurses at each site or centrally by Tayside Clinical Trials Unit. The 10‐point SARC‐F questionnaire was used for pre‐screening. De‐identified recruitment information was held on a central electronic tracking system and analysed using SPSS. Bioimpedance was measured using the Akern BIA 101 system, with the Sergi equation used to estimate lean mass. Results Fourteen UK sites recruited to the trial. The 1202 sets of notes in hospital‐based care were reviewed at these sites; 7 participants (0.6% of total notes screened) were randomized. From primary care, 13 808 invitations were sent; 138 (1.0% of total invited) were randomized. 633/2987 primary care respondents were pre‐screened centrally; the mean number of calls per respondent was 2.3. For 10 sites where central and local pre‐screening could be compared, the conversion rate from pre‐screening to randomization was 18/588 (3.1%) for centralized calls, compared with 73/1814 (4.0%) for local pre‐screening calls (P = 0.29). A weak relationship was seen between higher (worse) SARC‐F score at screening and lower likelihood of progression to randomization (r = −0.08, P = 0.03). Muscle mass estimates generated using the Sergi equation were systematically biased, and a recalibrated equation for bioimpedance‐estimated muscle mass was derived. Conclusions Primary care recruitment led to higher response rates and overall numbers randomized than hospital‐based recruitment. Centralized pre‐screening saved local research nurses' time but did not improve conversion to randomization. SARC‐F did not help to target screening activity in this sarcopenia trial, and a recalibration of the equation for estimating muscle mass from bioimpedance measures may improve accuracy of the screening process.

Abstract Background It is estimated that around 30% of breast cancers in post-menopausal women are related to lifestyle. The breast cancer-pooling project demonstrated that sustained weight loss of 2 to 4.5 kg is associated with an 18% lower risk of breast cancer, highlighting the importance of small changes in body weight. Our study aimed to assess the effectiveness a volunteer-delivered, community based, weight management programme (ActWELL) for women with a BMI > 25 kg/m2 attending NHS Scotland Breast Screening clinics. Methods A multicentre, 1:1 parallel group, randomised controlled trial was undertaken in 560 women aged 50 to 70 years with BMI > 25 kg/m2. On completion of baseline measures, all participants received a breast cancer prevention leaflet. Intervention group participants received the ActWELL intervention which focussed on personalised diet advice and pedometer walking plans. The programme was delivered in leisure centres by (the charity) Breast Cancer Now volunteer coaches. Primary outcomes were changes between groups at 12 months in body weight (kg) and physical activity (accelerometer measured step count). Results Two hundred seventy-nine women were allocated to the intervention group and 281 to the comparison group. Twelve-month data were available from 240 (81%) intervention and 227 (85%) comparison group participants. Coaches delivered 523 coaching sessions and 1915 support calls to 279 intervention participants. Mean weight change was − 2.5 kg (95% CI − 3.1 to − 1.9) in the intervention group and − 1.2 kg (− 1.8 to 0.6) in the comparison group. The adjusted mean difference was − 1.3 kg (95% CI − 2.2 to − 0.4, P = 0.003). The odds ratio for losing 5% weight was 2.20 (95% CI 1.4 to 3.4, p = 0.0005) in favour of the intervention. The adjusted mean difference in step counts between groups was 483 steps/day (95% CI − 635 to 1602) (NS). Conclusions A community weight management intervention initiated at breast screening clinics and delivered by volunteer coaches doubled the likelihood of clinically significant weight loss at 12 months (compared with usual care) offering significant potential to decrease breast cancer risk. Trial registration Database of registration: ISCRTN. Registration number: 11057518 . Date trial registered:21.07.2017. Date of enrolment of first participant: 01.09.2017.

Summary: Background: Primary prevention of cardiovascular disease (CVD) is guided by risk-prediction tools, but these rarely account for the risk of dying from other conditions (ie, competing mortality risk). In England and Wales, the recommended risk-prediction tool is QRISK2, and a new version (QRISK3) has been derived and internally validated. We aimed to externally validate QRISK3 and to assess the effects of competing mortality risk on its predictive performance. Methods: For this retrospective population cohort study, we used data from the Clinical Practice Research Datalink. We included patients aged 25–84 years with no previous history of CVD or statin treatment who were permanently registered with a primary care practice, had up-to-standard data for at least 1 year, and had linkage to Hospital Episode Statistics discharge and Office of National Statistics mortality data. We compared the QRISK3-predicted 10-year CVD risk with the observed 10-year risk in the whole population and in important subgroups of age and multimorbidity. QRISK3 discrimination and calibration were examined with and without accounting for competing risks. Findings: Our study population included 1 484 597 women with 42 451 incident CVD events (4·9 cases per 1000 person-years of follow-up, 95% CI 4·89–4·99), and 1 420 176 men with 53 066 incident CVD events (6·7 cases per 1000 person-years, 6·66–6·78), with median follow-up of 5·0 years (IQR 1·9–9·2). Non-CVD death rose markedly with age (0·4% of women and 0·5% of men aged 25–44 years had a non-CVD death vs 20·1% of women and 19·6% of men aged 75–84 years). QRISK3 discrimination in the whole population was excellent (Harrell's C-statistic 0·865 in women and 0·834 in men) but was poor in older age groups (

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background Cognitive spectrum disorders (CSDs) are common in hospitalised older adults and associated with adverse outcomes. Their association with the maintenance of independent living has not been established. The aim was to establish the role of CSDs on the likelihood of living at home 30 days after discharge or being newly admitted to a care home. Methods A prospective cohort study with routine data linkage was conducted based on admissions data from the acute medical unit of a district general hospital in Scotland. 5570 people aged ≥ 65 years admitted from a private residence who survived to discharge and received the Older Persons Routine Acute Assessment (OPRAA) during an incident emergency medical admission were included. The outcome measures were living at home, defined as a private residential address, 30 days after discharge and new care home admission at hospital discharge. Outcomes were ascertained through linkage to routine data sources. Results Of the 5570 individuals admitted from a private residence who survived to discharge, those without a CSD were more likely to be living at home at 30 days than those with a CSD (93.4% versus 81.7%; difference 11.7%, 95%CI 9.7–13.8%). New discharge to a care home affected 236 (4.2%) of the cohort, 181 (76.7%) of whom had a CSD. Logistic regression modelling identified that all four CSD categories were associated with a reduced likelihood of living at home and an increased likelihood of discharge to a care home. Those with delirium superimposed on dementia were the least likely to be living at home (OR 0.25), followed by those with dementia (OR 0.43), then unspecified cognitive impairment (OR 0.55) and finally delirium (OR 0.57). Conclusions Individuals with a CSD are at significantly increased risk of not returning home after hospitalisation, and those with CSDs account for the majority of new admissions to care homes on discharge. Individuals with delirium superimposed on dementia are the most affected. We need to understand how to configure and deliver healthcare services to enable older people to remain as independent as possible for as long as possible and to ensure transitions of care are managed supportively.

Background: Advanced chronic kidney disease is common in older people and is frequently accompanied by metabolic acidosis. Oral sodium bicarbonate is used to treat this acidosis, but evidence is lacking on whether or not this provides a net gain in health or quality of life for older people. Objectives: The objectives were to determine whether or not oral bicarbonate therapy improves physical function, quality of life, markers of renal function, bone turnover and vascular health compared with placebo in older people with chronic kidney disease and mild acidosis; to assess the safety of oral bicarbonate; and to establish whether or not oral bicarbonate therapy is cost-effective in this setting. Design: A parallel-group, double-blind, placebo-controlled randomised trial. Setting: The setting was nephrology and geriatric medicine outpatient departments in 27 UK hospitals. Participants: Participants were adults aged ≥ 60 years with advanced chronic kidney disease (glomerular filtration rate category 4 or 5, not on dialysis) with a serum bicarbonate concentration of

Abstract Background Sarcopenia (the age-related loss of muscle mass and function) is a major contributor to loss of mobility, falls, loss of independence, morbidity and mortality in older people. Although resistance training is effective in preventing and reversing sarcopenia, many older people are sedentary and either cannot or do not want to exercise. This trial examines the efficacy of supplementation with the amino acid leucine and/or angiotensin converting enzyme inhibition to potentially improve muscle mass and function in people with sarcopenia. Promising preliminary data exist from small studies for both interventions, but neither has yet been tested in adequately powered randomised trials in patients with sarcopenia. Methods Leucine and ACE inhibitors in sarcopenia (LACE) is a multicentre, masked, placebo-controlled, 2 × 2 factorial randomised trial evaluating the efficacy of leucine and perindopril (angiotensin converting enzyme inhibitor (ACEi)) in patients with sarcopenia. The trial will recruit 440 patients from primary and secondary care services across the UK. Male and female patients aged 70 years and over with sarcopenia as defined by the European Working Group on Sarcopenia (based on low total skeletal muscle mass on bioimpedance analysis and either low gait speed or low handgrip strength) will be eligible for participation. Participants will be excluded if they have a contraindication to, or are already taking, an ACEi, angiotensin receptor blocker or leucine. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at all points between baseline and 12 months. Secondary outcomes include appendicular muscle mass measured using dual-energy X-ray absorptiometry, muscle strength, activities of daily living, quality of life, activity using pedometer step counts and falls. Participants, clinical teams, outcomes assessors and trial analysts are masked to treatment allocation. A panel of biomarkers including microRNAs, neurohormones, genetic polymorphisms and markers of inflammation relevant to muscle pathophysiology will be measured to explore predictors of response and further elucidate mechanisms underlying sarcopenia. Participants will receive a total of 12 months of either perindopril or placebo and either leucine or placebo. Discussion The results will provide the first robust test of the overall clinical and cost-effectiveness of these novel therapies for older patients with sarcopenia. Trial registration ISRCTN, ISRCTN90094835 . Registered on 18 February 2015.

Abstract Background Almost 20 years ago, the frequencies of severe hypoglycemia requiring emergency medical treatment were reported in people with types 1 and 2 diabetes in the Tayside region of Scotland. With subsequent improvements in the treatment of diabetes, concurrent with changes in the provision of emergency medical care, a decline in the frequency of severe hypoglycemia could be anticipated. The present population-based data-linkage cohort study aimed to ascertain whether a temporal change has occurred in the incidence rates of hypoglycemia requiring emergency medical services in people with types 1 and 2 diabetes. Methods The study population comprised all people with diabetes in Tayside, Scotland over the period 1 January 2011 to 31 December 2012. Patients’ data from different healthcare sources were linked anonymously to measure the incidence rates of hypoglycemia requiring emergency medical services that include treatment by ambulance staff and in hospital emergency departments, and necessitated hospital admission. These were compared with data recorded in 1997–1998 in the same region. Results In January 2011 to December 2012, 2029 people in Tayside had type 1 diabetes and 21,734 had type 2 diabetes, compared to 977 and 7678, respectively, in June 1997 to May 1998. In people with type 2 diabetes, the proportion treated with sulfonylureas had declined from 36.8 to 22.4% (p

Abstract Background Cross-sectional relationships between physical activity and health have been explored extensively, but less is known about how physical activity changes with time in older people. The aim of this study was to assess baseline predictors of how objectively measured physical activity changes with time in older people. Methods Longitudinal cohort study using data from the Physical Activity Cohort Scotland. A sample of community-dwelling older people aged 65 and over were recruited in 2009–2011, then followed up 2–3 years later. Physical activity was measured using Stayhealthy RT3 accelerometers over 7 days. Other data collected included baseline comorbidity, health-related quality of life (SF-36), extended Theory of Planned Behaviour Questionnaire and Social Capital Module of the General Household Survey. Associations between follow-up accelerometer counts and baseline predictors were analysed using a series of linear regression models, adjusting for baseline activity levels and follow-up time. Results Follow up data were available for 339 of the original 584 participants. The mean age was 77 years, 185 (55%) were female and mean follow up time was 26 months. Mean activity counts fell by between 2% per year (age 80, deprivation decile 5–10) from baseline values. In univariate analysis age, sex, deprivation decile, most SF-36 domains, most measures of social connectedness, most measures from the extended Theory of Planned Behaviour, hypertension, diabetes mellitus, chronic pain and depression score were significantly associated with adjusted activity counts at follow-up. In multivariate regression age, satisfactory friend network, SF-36 physical function score, and the presence of diabetes mellitus were independent predictors of activity counts at follow up after adjustment for baseline count and duration of follow up. Conclusions Health status and social connectedness, but not extended Theory of Planned Behaviour measures, independently predicted changes in physical activity in community dwelling older people.

Abstract Background Non-steroidal anti-inflammatory drugs (NSAIDs) are a common cause of adverse drug events (ADEs), but renal risks of NSAIDs are less well quantified than gastrointestinal and cardiac risks. This paper reports a systematic review of published population-based observational studies examining the risk of acute kidney injury (AKI) associated with NSAIDs in community-dwelling adults and those with pre-existing chronic kidney disease (CKD). Methods MEDLINE and EMBASE databases were searched until June 2016, and 3789 papers screened. Ten studies reporting NSAID risk of AKI in the general population were included in random effects meta-analysis, of which five additionally reported NSAID risk in people with CKD. Results In the general population, the pooled odds ratio (OR) of AKI for current NSAID exposure was 1.73 (95%CI 1.44 to 2.07), with somewhat higher risk observed in older people (OR 2.51, 95%CI 1.52 to 2.68). In people with CKD, individual study OR of AKI due to current NSAID exposure ranged from 1.12 to 5.25, with pooled estimate OR 1.63 (95% CI 1.22 to 2.19). Conclusions No study reported baseline risk of AKI in different populations meaning absolute risks could not be estimated, but baseline risk and therefore the absolute risk of NSAID exposure is likely to be higher in people with CKD and older people. Large population based studies measuring AKI using current definitions and estimating the absolute risk of harm are needed in order to better inform clinical decision making.

Abstract Background Cognitive impairment of various kinds is common in older people admitted to hospital, but previous research has usually focused on single conditions in highly-selected groups and has rarely examined associations with outcomes. This study examined prevalence and outcomes of cognitive impairment in a large unselected cohort of people aged 65+ with an emergency medical admission. Methods Between January 1, 2012, and June 30, 2013, admissions to a single general hospital acute medical unit aged 65+ underwent a structured specialist nurse assessment (n = 10,014). We defined ‘cognitive spectrum disorder’ (CSD) as any combination of delirium, known dementia, or Abbreviated Mental Test (AMT) score

Background: Socially disadvantaged men are more likely to binge drink frequently and to experience high levels of alcohol-related harm. Objectives: To test the effectiveness and cost-effectiveness of a text message intervention in reducing the frequency of binge drinking among disadvantaged men. Study design: A four-centre, parallel-group, pragmatic, individually randomised controlled trial was conducted. Randomisation was carried out using a secure remote web-based system. It was stratified by participating centre and recruitment method and restricted using block sizes of randomly varying lengths. Setting: The study was conducted in the community. Members of the public helped to develop the study methods. Participants: Participants were men aged 25–44 years who had ≥ 2 episodes of binge drinking (> 8 units of alcohol in a single session) in the preceding 28 days. Men were recruited from areas of high deprivation. Interventions: An empirically and theoretically based text message intervention was delivered by 112 interactive text messages over a 12-week period. The control group received an attentional control comprising 89 text messages on general health. Primary outcome measure: The primary outcome measure was the proportion of men consuming > 8 units of alcohol on ≥ 3 occasions (in the previous 28 days) at 12 months post intervention. Results: The recruitment target of 798 was exceeded and 825 men were randomised. Retention was high and similar in the intervention (84.9%) and control (86.5%) groups. Most men in the intervention group engaged enthusiastically with the text messages: almost all (92%) replied to text messages and over two-thirds (67%) replied more than 10 times. The intervention was estimated to have had a modest, statistically non-significant effect on the primary outcome at the 12-month follow-up [odds ratio 0.79, 95% confidence interval (CI) 0.57 to 1.08]. This corresponds to a net reduction of 5.7% in regular binge drinking. Five secondary outcomes showed small non-significant and inconsistent effects on alcohol consumption, with one suggesting a positive effect and four suggesting an adverse effect. Both the short- and the long-term cost per quality-adjusted life-year (QALY) analysis suggested that the brief intervention was dominated by a ‘do-nothing’ option. The intervention’s impacts on patterns of alcohol consumption, QALYs and downstream costs were inconsistent and uncertain. Limitations: The study used an active control that, combined with the recruitment procedures and baseline assessments, could have biased the treatment effect towards the null. The measurement of alcohol consumption relied on self-reported drinking. Conclusions: The trial has demonstrated that it is possible to recruit and retain large numbers of socially disadvantaged men in a research study. The text messages delivered a complex theoretically and empirically based intervention that fostered enthusiastic engagement with the key components of the behaviour change sequence. The intervention produced a modest, statistically non-significant effect on the primary outcome, with wide CIs. Further research is needed to reduce uncertainty about the treatment effect. The methods developed for this study provide a platform for the design and testing of interventions to reduce inequalities in health. Future work: A future trial could reduce the uncertainty around the treatment effect of the intervention. Trial registration: Current Controlled Trials ISRCTN07695192. Funding: This study was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 6, No. 6. See NIHR Journals Library website for further information.

Enhancing biological resilience may offer a novel way to prevent and ameliorate disease in older patients. We investigated whether changes in C-reactive protein (CRP), as a dynamic marker of the acute inflammatory response to diverse stressors, may provide a way to operationalize the concept of resilience in older adults. We tested this hypothesis by examining whether such changes could predict prognosis by identifying which individuals are at greater risk of 6-month mortality.Analysis of prospective, routinely collected datasets containing data on hospitalization, clinical chemistry and rehabilitation outcomes for rehabilitation inpatients between 1999 and 2011. Maximum CRP response during acute illness and CRP recovery indices (time and slope of CRP decay to half maximum, and to

Background: High-risk primary care prescribing is common and is known to vary considerably between practices, but the extent to which high-risk prescribing varies among individual general practitioners (GPs) is not known. Objectives: To create prescribing safety indicators usable in existing electronic clinical data and to examine (1) variation in high-risk prescribing between patients, GPs and practices including reliability of measurement and (2) changes over time in high-risk prescribing prevalence and variation between practices. Design: Descriptive analysis and multilevel logistic regression modelling of routine data. Setting: UK general practice using routine electronic medical record data. Participants: (1) For analysis of variation and reliability, 398 GPs and 26,539 patients in 38 Scottish practices. (2) For analysis of change in high-risk prescribing, ≈ 300,000 patients particularly vulnerable to adverse drug effects registered with 190 Scottish practices. Main outcome measures: For the analysis of variation between practices and between GPs, five indicators of high-risk non-steroidal anti-inflammatory drug (NSAID) prescribing. For the analysis of change in high-risk prescribing, 19 previously validated indicators. Results: Measurement of high-risk prescribing at GP level was feasible only for newly initiated drugs and for drugs similar to NSAIDs which are usually initiated by GPs. There was moderate variation between practices in total high-risk NSAID prescribing [intraclass correlation coefficient (ICC) 0.034], but this indicator was highly reliable (> 0.8 for all practices) at distinguishing between practices because of the large number of patients being measured. There was moderate variation in initiation of high-risk NSAID prescribing between practices (ICC 0.055) and larger variation between GPs (ICC 0.166), but measurement did not reliably distinguish between practices and had reliability > 0.7 for only half of the GPs in the study. Between quarter (Q)2 2004 and Q1 2009, the percentage of patients exposed to high-risk prescribing measured by 17 indicators that could be examined over the whole period fell from 8.5% to 5.2%, which was largely driven by reductions in high-risk NSAID and antiplatelet use. Variation between practices increased for five indicators and decreased for five, with no relationship between change in the rate of high-risk prescribing and change in variation between practices. Conclusions: High-risk prescribing is common and varies moderately between practices. High-risk prescribing at GP level cannot be easily measured routinely because of the difficulties in accurately identifying which GP actually prescribed the drug and because drug initiation is often a shared responsibility with specialists. For NSAID initiation, there was approximately three times greater variation between GPs than between practices. Most GPs with above average high-risk prescribing worked in practices which were not themselves above average. The observed reductions in high-risk prescribing between 2004 and 2009 were largely driven by falls in NSAID and antiplatelet prescribing, and there was no relationship between change in rate and change in variation between practices. These results are consistent with improvement interventions in all practices being more appropriate than interventions targeted on practices or GPs with higher than average high-risk prescribing. There is a need for research to understand why high-risk prescribing varies and to design and evaluate interventions to reduce it. Funding: Funding for this study was provided by the Health Services and Delivery Research programme of the National Institute for Health Research.

Background: The prevalence of male obesity is increasing alongside low uptake of existing weight management programmes by men. Football Fans in Training (FFIT) is a group-based, weight management and healthy living programme delivered by community coaches. Objectives: To assess (1) the effectiveness and cost-effectiveness of FFIT, (2) fidelity of delivery and (3) coach and participant experiences of FFIT. Design: A two-arm, pragmatic, randomised controlled trial; associated cost-effectiveness [in terms of incremental cost per quality-adjusted life-year (QALY) within trial and over individuals’ lifetimes]; and process evaluation. Participants were block randomised in a 1 : 1 ratio, stratified by club; the intervention group started FFIT within 3 weeks and the comparison group were put on a 12-month waiting list. Setting: Thirteen professional football clubs in Scotland, UK. Participants: A total of 747 men aged 35–65 years with an objectively measured body mass index (BMI) of ≥ 28 kg/m2. Interventions: FFIT was gender sensitised in context, content and style of delivery. A total of 12 weekly sessions delivered at club stadia combined effective behaviour change techniques with dietary information and physical activity sessions. Men carried out a pedometer-based walking programme. A light-touch maintenance programme included six e-mails and a reunion session at 9 months. At baseline, both groups received a weight management booklet, feedback on their BMI and advice to consult their general practitioner if blood pressure was high. Primary outcome: Mean difference in weight loss between groups at 12 months expressed as absolute weight and a percentage. Intention-to-treat analyses used all available data. Data sources: Objective measurements, questionnaires, observations, focus groups and coach interviews. Results: A total of 374 men were allocated to the intervention and 333 (89%) completed 12-month assessments; a total of 374 were allocated to the comparator and 355 (95%) completed 12-month assessments. At 12 months, the mean difference in weight loss between groups, adjusted for baseline weight and club, was 4.94 kg [95% confidence interval (CI) 3.95 kg to 5.94 kg]; percentage weight loss, similarly adjusted, was 4.36% (95% CI 3.64% to 5.08%), in favour of the intervention (p

Weather is a potentially important determinant of physical activity. Little work has been done examining the relationship between weather and physical activity, and potential modifiers of any relationship in older people. We therefore examined the relationship between weather and physical activity in a cohort of older community-dwelling people.We analysed prospectively collected cross-sectional activity data from community-dwelling people aged 65 and over in the Physical Activity Cohort Scotland. We correlated seven day triaxial accelerometry data with daily weather data (temperature, day length, sunshine, snow, rain), and a series of potential effect modifiers were tested in mixed models: environmental variables (urban vs rural dwelling, percentage of green space), psychological variables (anxiety, depression, perceived behavioural control), social variables (number of close contacts) and health status measured using the SF-36 questionnaire.547 participants, mean age 78.5 years, were included in this analysis. Higher minimum daily temperature and longer day length were associated with higher activity levels; these associations remained robust to adjustment for other significant associates of activity: age, perceived behavioural control, number of social contacts and physical function. Of the potential effect modifier variables, only urban vs rural dwelling and the SF-36 measure of social functioning enhanced the association between day length and activity; no variable modified the association between minimum temperature and activity.In older community dwelling people, minimum temperature and day length were associated with objectively measured activity. There was little evidence for moderation of these associations through potentially modifiable health, environmental, social or psychological variables.

BACKGROUND: Although liver function tests (LFTs) are routinely measured in primary care, raised levels in patients with no obvious liver disease may trigger a range of subsequent expensive and unnecessary management plans. The aim of this study was to develop and validate a prediction model to guide decision-making by general practitioners, which estimates risk of one year all-cause mortality in patients with no obvious liver disease. METHODS: In this population-based historical cohort study, biochemistry data from patients in Tayside, Scotland, with LFTs performed in primary care were record-linked to secondary care and prescription databases to ascertain baseline characteristics, and to mortality data. Using this derivation cohort a survival model was developed to predict mortality. The model was assessed for calibration, discrimination (using the C-statistic) and performance, and validated using a separate cohort of Scottish primary care practices. RESULTS: From the derivation cohort (n = 95 977), 2.7% died within one year. Predictors of mortality included: age; male gender; social deprivation; history of cancer, renal disease, stroke, ischaemic heart disease or respiratory disease; statin use; and LFTs (albumin, transaminase, alkaline phosphatase, bilirubin, and gamma-glutamyltransferase). The C-statistic for the final model was 0.82 (95% CI 0.80-0.84), and was similar in the validation cohort (n = 11 653) 0.86 (0.79-0.90). As an example of performance, for a 10% predicted probability cut-off, sensitivity = 52.8%, specificity = 94.0%, PPV = 21.0%, NPV = 98.5%. For the model without LFTs the respective values were 43.8%, 92.8%, 15.6%, 98.1%. CONCLUSIONS: The Algorithm for Liver Function Investigations (ALFI) is the first model to successfully estimate the probability of all-cause mortality in patients with no apparent liver disease having LFTs in primary care. While LFTs added to the model's discrimination and sensitivity, the clinical utility of ALFI remains to be established since LFTs did not improve an already high NPV for short term mortality and only modestly improved a very low PPV.

To assess physical activity levels objectively using accelerometers in community dwelling over 65 s and to examine associations with health, social, environmental and psychological factors.Cross sectional survey.17 general practices in Scotland, United Kingdom.Random sampling of over 65 s registered with the practices in four strata young-old (65-80 years), old-old (over 80 years), more affluent and less affluent groups.Accelerometry counts of activity per day. Associations between activity and Theory of Planned Behaviour variables, the physical environment, health, wellbeing and demographic variables were examined with multiple regression analysis and multilevel modelling.547 older people (mean (SD) age 79(8) years, 54% female) were analysed representing 94% of those surveyed. Accelerometry counts were highest in the affluent younger group, followed by the deprived younger group, with lowest levels in the deprived over 80 s group. Multiple regression analysis showed that lower age, higher perceived behavioural control, the physical function subscale of SF-36, and having someone nearby to turn to were all independently associated with higher physical activity levels (R(2) = 0.32). In addition, hours of sunshine were independently significantly associated with greater physical activity in a multilevel model.Other than age and hours of sunlight, the variables identified are modifiable, and provide a strong basis for the future development of novel multidimensional interventions aimed at increasing activity participation in later life.

Purpose: To investigate the set up and operation of a Managed Clinical Network for cardiac services and assess its impact on patient care. Methods: This single case study used process evaluation with observational before and after comparison of indicators of quality of care and costs. The study was conducted in Dumfries and Galloway, Scotland and used a three-level framework. Process evaluation of the network set-up and operation through a documentary review of minutes; guidelines and protocols; transcripts of fourteen semi-structured interviews with health service personnel including senior managers, general practitioners, nurses, cardiologists and members of the public. Outcome evaluation of the impact of the network through interrupted time series analysis of clinical data of 202 patients aged less than 76 years admitted to hospital with a confirmed myocardial infarction one-year pre and one-year post, the establishment of the network. The main outcome measures were differences between indicators of quality of care targeted by network protocols. Economic evaluation of the transaction costs of the set-up and operation of the network and the resource costs of the clinical care of the 202 myocardial infarction patients from the time of hospital admission to 6 months post discharge through interrupted time series analysis. The outcome measure was different in National Health Service resource use. Results: Despite early difficulties, the network was successful in bringing together clinicians, patients and managers to redesign services, exhibiting most features of good network management. The role of the energetic lead clinician was crucial, but the network took time to develop and ‘bed down’. Its primary “modus operand” was the development of a myocardial infarction pathway and associated protocols. Of sixteen clinical care indicators, two improved significantly following the launch of the network and nine showed improvements, which were not statistically significant. There was no difference in resource use. Discussion and conclusions: The Managed Clinical Network made a difference to ways of working, particularly in breaching traditional boundaries and involving the public, and made modest changes in patient care. However, it required a two-year “set-up” period. Managed clinical networks are complex initiatives with an increasing profile in health care policy. This study suggests that they require energetic leadership and improvements are likely to be slow and incremental.