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Background: UK guidelines recommend the QFracture tool to predict the risk of major osteoporotic fracture and hip fracture, but QFracture calibration is poor, partly because it does not account for competing mortality risk. The aim of this study was to derive and validate a competing risk model to predict major osteoporotic fracture and hip fracture (CFracture) and compare its performance with that of QFracture in UK primary care. Methods: We used UK linked primary care data from the Clinical Practice Research Datalink GOLD database to identify people aged 30–99 years, split into derivation and validation cohorts. In the derivation cohort, we derived models (CFracture) using the same covariates as QFracture with Fine-Gray competing risk modelling, and included the Charlson Comorbidity Index score as an additional predictor of non-fracture death. In a separate validation cohort, we examined discrimination (using Harrell's C-statistic) and calibration of CFracture compared with QFracture. Reclassification analysis examined differences in the characteristics of patients reclassified as higher risk by CFracture but not by QFracture. Findings: The derivation cohort included 1 831 606 women and 1 789 820 men, and the validation cohort included 915 803 women and 894 910 men. Overall discrimination of CFracture was excellent (C-statistic=0·813 [95% CI 0·810–0·816] for major osteoporotic fracture and 0·914 [0·908–0·919] for hip fracture in women; 0·734 [0·729–0·740] for major osteoporotic fracture and 0·886 [0·877–0·895] for hip fracture in men) and was similar to QFracture. CFracture calibration overall and in people younger than 75 years was generally excellent. CFracture overpredicted major osteoporotic fracture and hip fracture in older people and people with comorbidity, but was better calibrated than QFracture. Patients classified as high-risk by CFracture but not by QFracture had a higher prevalence of current smoking and previous fracture, but lower prevalence of dementia, cancer, cardiovascular disease, renal disease, and diabetes. Interpretation: CFracture has similar discrimination to QFracture but is better calibrated overall and in younger people. Both models performed poorly in adults aged 85 years and older. Competing risk models should be recommended for fracture risk prediction to guide treatment recommendations. Funding: National Institute for Health and Care Research, Wellcome Trust, Health Data Research UK.

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.

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?70years with sarcopenia, defined as low gait speed (

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 (

Additional file 1: Figure S1. Flow chart for cohort identification from CPRD GOLD. Table S1. Missing data handling for variables included in the model. Table S3. Incidence rates of cardiovascular disease per 1000 person years in derivation cohort Table S4. Adjusted subdistribution hazard ratios for CVD in women in the derivation cohort for CRISK-CCI. Table S5. Adjusted subdistribution hazard ratios for CVD in men in the derivation cohort for CRISK-CCI. Table S6. Characteristics of patients reclassified by CRISK-CCI in the validation cohort.

Additional file 1: Figure S1: Survival curve stratified by AKI category. Table S1: Recovery status at 7- and 90-days post-AKI diagnosis. Table S2: Characteristics of tested versus untested patients with CA-CM AKI. Table S3: 90-day status of patients untested within the first 7 days post AKI diagnosis. Figure S2: Association between individual predictors and progression to AKD (main analysis). Table S4 and Figure S3: Association between individual predictors and non-recovery at day 7 (sensitivity analysis). Figure S4: Association between individual predictors and non-recovery at day 90 in patients who entered the AKD phase (main analysis). Table S5 and Figure S5: Association between individual predictors and non-recovery at day 90 in patients who entered the AKD phase (sensitivity analysis). Figure S6: Correlation matrix for pairs of candidate risk factors. Table S6: Association between progression to AKD and subsequent risk of death or development of de novo CKD.

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Additional file 2: Table S2. Follow-up status at 10 years by sex, age and co-morbidity in the derivation cohort.

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To evaluate effects of remote monitoring of adjuvant chemotherapy related side effects via the Advanced Symptom Management System (ASyMS) on symptom burden, quality of life, supportive care needs, anxiety, self-efficacy, and work limitations. DESIGN Multicentre, repeated measures, parallel group, evaluator masked, stratified randomised controlled trial. SETTING Twelve cancer centres in Austria, Greece, Norway, Republic of Ireland, and UK. PARTICIPANTS 829 patients with non-metastatic breast cancer, colorectal cancer, Hodgkin’s disease, or nonHodgkin’s lymphoma receiving first line adjuvant chemotherapy or chemotherapy for the first time in five years. INTERVENTION Patients were randomised to ASyMS (intervention; n=415) or standard care (control; n=414) over six cycles of chemotherapy. MAIN OUTCOME MEASURES The primary outcome was symptom burden (Memorial Symptom Assessment Scale; MSAS). Secondary outcomes were health related quality of life (Functional Assessment of Cancer Therapy-General; FACT-G), Supportive Care Needs Survey Short-Form (SCNS-SF34), State-Trait Anxiety Inventory-Revised (STAI-R), Communication and Attitudinal Self-Efficacy scale for cancer (CASE-Cancer), and work limitations questionnaire (WLQ). RESULTS For the intervention group, symptom burden remained at pre-chemotherapy treatment levels, whereas controls reported an increase from cycle 1 onwards (least squares absolute mean difference -0.15, 95% confidence interval -0.19 to -0.12; P(0.001; Cohen’s D effect size=0.5). Analysis of MSAS sub-domains indicated significant reductions in favour of ASyMS for global distress index (-0.21, -0.27 to -0.16; P(0.001), psychological symptoms (-0.16, -0.23 to - 0.10; P(0.001), and physical symptoms (-0.21, -0.26 to -0.17; P(0.001). FACT-G scores were higher in the intervention group across all cycles (mean difference 4.06, 95% confidence interval 2.65 to 5.46; P(0.001), whereas mean scores for STAI-R trait (-1.15, -1.90 to - 0.41; P=0.003) and STAI-R state anxiety (-1.13, -2.06 to -0.20; P=0.02) were lower. CASE-Cancer scores were higher in the intervention group (mean difference 0.81, 0.19 to 1.43; P=0.01), and most SCNS-SF34 domains were lower, including sexuality needs (-1.56, -3.11 to - 0.01; P(0.05), patient care and support needs (-1.74, - 3.31 to -0.16; P=0.03), and physical and daily living needs (-2.8, -5.0 to -0.6; P=0.01). Other SCNS-SF34 domains and WLQ were not significantly different. Safety of ASyMS was satisfactory. Neutropenic events were higher in the intervention group. CONCLUSIONS Significant reduction in symptom burden supports the use of ASyMS for remote symptom monitoring in cancer care. A “medium” Cohen’s effect size of 0.5 showed a sizable, positive clinical effect of ASyMS on patients’ symptom experiences. Remote monitoring systems will be vital for future services, particularly with blended models of care delivery arising from the covid-19 pandemic. TRIAL REGISTRATION Clinicaltrials.gov NCT02356081.

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Additional File 2: Appendix 2. Possible Outcomes following abnormal liver function tests (DOC 70 KB)

Additional File 1: Appendix 1. Indications for liver function tests with no obvious liver disease, and consequent investigations (DOC 54 KB)

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Supplemental material, Supplemental_Material for Dynamic Lycra® orthoses as an adjunct to arm rehabilitation after stroke: a single-blind, two-arm parallel group, randomized controlled feasibility trial by Jacqui H Morris, Alexandra John, Lucy Wedderburn, Petra Rauchhaus and Peter T Donnan in Clinical Rehabilitation

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.

Introduction Hepatitis C virus (HCV) infection affects 0.7% of the general population, and up to 40% of people prescribed opioid substitution therapy (OST) in Scotland. In conventional care, less than 10% of OST users are tested for HCV and less than 25% of these initiate treatment. Community pharmacists see this group frequently to provide OST supervision. This study examines whether a pharmacist-led ‘test & treat’ pathway increases cure rates for HCV. Methods and analysis This protocol describes a cluster-randomised trial where 60 community pharmacies provide either conventional or pharmacy-led care. All pharmacies offer dried blood spot testing (DBST) for HCV. Participants have attended the pharmacy for OST for 3 months; are positive for HCV genotype 1 or 3; are not co-infected with HIV and/or hepatitis B; have no decompensated liver disease; are not pregnant. For conventional care, pharmacists refer HCV-positive participants to a local centre for assessment. In the pharmacy-led arm, pharmacists assess participants themselves in the pharmacy. Drug prescribing is by nurse prescribers (conventional arm) or pharmacist prescribers (pharmacy-led arm). Treatment in both arms is delivered as daily modified directly observed therapy in a pharmacy. Primary trial outcome is number of sustained virological responses at 12 weeks after treatment completion. Secondary trial outcomes are number of tests taken; treatment uptake; completion; adherence; re-infection. An economic evaluation will assess potential cost-effectiveness. Qualitative research interviews with clients and health professionals assess acceptability of a pharmacist-led pathway. Ethics and dissemination This protocol has been ethically approved by the East of Scotland Research Ethics Committee 2 (15/ES/0086) and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Caldicott guardian approval was given on 16 December 2016 to allow NHS Tayside to pass information to the cluster community pharmacies about the HCV test status of patients that they are seeing to provide OST supervision. NHS R&D approvals have been obtained from each health board taking part in the study. Informed consent is obtained before study enrolment and only anonymised data are stored in a secured database, enabling an audit trail. Results will be submitted to international peer-reviewed journals and presented at international conferences. Trial registration number NCT02706223; Pre-results.

Simona Hapca,1 Bruce Guthrie,1 Vera Cvoro,2 Feifei Bu,3 Alasdair C Rutherford,3 Emma Reynish,3 Peter T Donnan1 1Population Health and Genomics, School of Medicine, University of Dundee, Dundee DD2 4BF, UK; 2NHS Fife, Kirkcaldy, Fife KY2 5AH, UK; 3Dementia and Ageing Research Group, Faculty of Social Science, University of Stirling, Stirling, FK9 4LA, UK Purpose: Cognitive impairment is common in older people admitted to hospital, but the outcomes are generally poorly understood, and previous research has shown inconsistent associations with mortality depending on the type of cognitive impairment examined and duration of follow-up. This study examines mortality in older people with any cognitive impairment during acute hospital admission.Patients and methods: Prospective cohort of 6,724 people aged ≥65 years with a structured cognitive assessment on acute admission were included in this study. Cognitive spectrum disorder (CSD) was defined as delirium alone, known dementia alone, delirium superimposed on known dementia, or unspecified cognitive impairment. Mortality associated with different types of CSD was examined using a non-proportional hazards model with 2-year follow-up.Results: On admission, 35.4% of patients had CSD, of which 52.6% died within 2 years. After adjustment for demographics and comorbidity, delirium alone was associated with increased mortality in the 6 months post-admission (HR =1.45, 95% CI 1.28–1.65) and again after 1 year (HR =1.44, 95% CI 1.17–1.77). Patients with known dementia (alone or with superimposed delirium) had increased mortality only after 3 months from admission (HR =1.85, 95% CI 1.56–2.18 and HR =1.80, 95% CI 1.52–2.14) compared with patients with unspecified cognitive impairment after 6 months (HR =1.55, 95% CI 1.21–1.99). Similar but partially attenuated associations were seen after adjustment for functional ability.Conclusion: Mortality post-admission is high in older people with CSD. Immediate risk is highest in those with delirium, while dementia or unspecified cognitive impairment is associated with medium- to long-term risk. These findings suggest that individuals without dementia who develop delirium are more seriously ill (have required a larger acute insult in order to precipitate delirium) than those with pre-existing brain pathology (dementia). Further research to explain the mortality patterns observed is required in order to translate the findings into clinical care. Keywords: acute admission, elderly, cognition, function, non-proportional hazards

Purpose: Cognitive impairment is common in older people admitted to hospital, but the outcomes are generally poorly understood, and previous research has shown inconsistent associations with mortality depending on the type of cognitive impairment examined and duration of follow-up. This study examines mortality in older people with any cognitive impairment during acute hospital admission. Patients and methods: Prospective cohort of 6,724 people aged ≥65 years with a structured cognitive assessment on acute admission were included in this study. Cognitive spectrum disorder (CSD) was defined as delirium alone, known dementia alone, delirium superimposed on known dementia, or unspecified cognitive impairment. Mortality associated with different types of CSD was examined using a non-proportional hazards model with 2-year follow-up. Results: On admission, 35.4% of patients had CSD, of which 52.6% died within 2 years. After adjustment for demographics and comorbidity, delirium alone was associated with increased mortality in the 6 months post-admission (HR =1.45, 95% CI 1.28–1.65) and again after 1 year (HR =1.44, 95% CI 1.17–1.77). Patients with known dementia (alone or with superimposed delirium) had increased mortality only after 3 months from admission (HR =1.85, 95% CI 1.56–2.18 and HR =1.80, 95% CI 1.52–2.14) compared with patients with unspecified cognitive impairment after 6 months (HR =1.55, 95% CI 1.21–1.99). Similar but partially attenuated associations were seen after adjustment for functional ability. Conclusion: Mortality post-admission is high in older people with CSD. Immediate risk is highest in those with delirium, while dementia or unspecified cognitive impairment is associated with medium- to long-term risk. These findings suggest that individuals without dementia who develop delirium are more seriously ill (have required a larger acute insult in order to precipitate delirium) than those with pre-existing brain pathology (dementia). Further research to explain the mortality patterns observed is required in order to translate the findings into clinical care.

Objective To determine whether spironolactone could benefit older people with osteoarthritis (OA), based on a previous study showing that spironolactone improved quality of life. Methods This parallel‐group, randomized, placebo‐controlled, double‐blind trial randomized community‐dwelling people ages ≥70 years with symptomatic knee OA to 12 weeks of 25 mg daily oral spironolactone or matching placebo. The primary outcome was between‐group difference in change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores. Secondary outcomes included WOMAC stiffness and physical function subscores, EuroQol 5‐domain (EQ‐5D) 3L score, and mechanistic markers. Analysis was by intent to treat, using mixed‐model regression, adjusting for baseline values of test variables. Results A total of 421 people had eligibility assessed, and 86 were randomized. Mean ± SD age was 77 ± 5 years and 53 of 86 (62%) were women. Adherence to study medication was 99%, and all participants completed the 12‐week assessment. No significant improvement was seen in the WOMAC pain score (adjusted treatment effect 0.5 points [95% confidence interval (95% CI) − 0.3, 1.3]; P = 0.19). No improvement was seen in WOMAC stiffness score (0.2 points [95% CI −0.6, 1.1]; P = 0.58), WOMAC physical function score (0.0 points [95% CI −0.7, 0.8]; P = 0.98), or EQ‐5D 3L score (0.04 points [95% CI −0.04, 0.12]; P = 0.34). Cortisol, matrix metalloproteinase 3, and urinary C‐telopeptide of type II collagen were not significantly different between groups. More minor adverse events were noted in the spironolactone group (47 versus 32), but no increase in death or hospitalization was evident. Conclusion Spironolactone did not improve symptoms, physical function, or health‐related quality of life in older people with knee OA.

Aims To test the effectiveness of a theoretically based text‐message intervention to reduce binge drinking among socially disadvantaged men. Design A multi‐centre parallel group, pragmatic, individually randomized controlled trial. Setting Community‐based study conducted in four regions of Scotland. Participants A total of 825 men aged 25–44 years recruited from socially disadvantaged areas who had two or more episodes of binge drinking (> 8 UK units on a single occasion) in the preceding 28 days: 411 men were randomized to the intervention and 414 to the control. Intervention and comparator A series of 112 interactive text messages was delivered by mobile phone during a 12‐week period. The intervention was structured around the Health Action Process Approach, a comprehensive model which allows integration of a range of evidence‐based behaviour change techniques. The control group received 89 texts on general health, with no mention of alcohol or use of behaviour change techniques. Measurements The primary outcome measure was the proportion of men consuming > 8 units on three or more occasions (in the previous 28 days) at 12 months post‐intervention. Findings The proportion of men consuming > 8 units on three or more occasions (in the previous 28 days) was 41.5% in the intervention group and 47.8% in the control group. Formal analysis showed that there was no evidence that the intervention was effective [odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.57–1.08; absolute reduction 5.7%, 95% CI = −13.3 to 1.9]. The Bayes factor for this outcome was 1.3, confirming that the results were inconclusive. The retention was high and similar in intervention (84.9%) and control (86.5%) groups. Most men in the intervention group engaged with the text messages: almost all (92%) replied to text messages and 67% replied more than 10 times. Conclusions A theoretically based text‐messaging intervention aimed at reducing binge drinking in disadvantaged men was not found to reduce prevalence of binge drinking at 12‐month follow‐up.

This study was funded by the NIHR Public Health Research programme (11/3050/30). Aims To test the effectiveness of a theoretically based text‐message intervention to reduce binge drinking among socially disadvantaged men. Design A multi‐centre parallel group, pragmatic, individually randomized controlled trial. Setting Community‐based study conducted in four regions of Scotland. Participants A total of 825 men aged 25–44 years recruited from socially disadvantaged areas who had two or more episodes of binge drinking (> 8 UK units on a single occasion) in the preceding 28 days: 411 men were randomized to the intervention and 414 to the control. Intervention and comparator A series of 112 interactive text messages was delivered by mobile phone during a 12‐week period. The intervention was structured around the Health Action Process Approach, a comprehensive model which allows integration of a range of evidence‐based behaviour change techniques. The control group received 89 texts on general health, with no mention of alcohol or use of behaviour change techniques. Measurements The primary outcome measure was the proportion of men consuming > 8 units on three or more occasions (in the previous 28 days) at 12 months post‐intervention. Findings The proportion of men consuming > 8 units on three or more occasions (in the previous 28 days) was 41.5% in the intervention group and 47.8% in the control group. Formal analysis showed that there was no evidence that the intervention was effective [odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.57–1.08; absolute reduction 5.7%, 95% CI = −13.3 to 1.9]. The Bayes factor for this outcome was 1.3, confirming that the results were inconclusive. The retention was high and similar in intervention (84.9%) and control (86.5%) groups. Most men in the intervention group engaged with the text messages: almost all (92%) replied to text messages and 67% replied more than 10 times. Conclusions A theoretically based text‐messaging intervention aimed at reducing binge drinking in disadvantaged men was not found to reduce prevalence of binge drinking at 12‐month follow‐up. Publisher PDF

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 shortand 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.

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.

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: Cardiovascular disease (CVD) is a common comorbidity in people with asthma. However, safety concerns have caused heterogeneity in clinical guideline recommendations over the use of cardioselective beta-blockers in people with asthma and CVD, partly because risk in the general population has been poorly quantified. The aim of this study was to measure the risk of asthma exacerbations with beta-blockers prescribed to a general population with asthma and CVD.Methods: Linked data from the UK Clinical Practice Research Datalink was used to perform nested case-control studies among people with asthma and CVD matched on age, gender and calendar time. Adjusted incidence rate ratios (IRR) were calculated for the association between oral beta-blocker use and moderate asthma exacerbations (rescue oral steroids) or severe asthma exacerbations (hospitalisation or death) using conditional logistic regression.Results: The cohort consisted of 35502 people identified with active asthma and CVD, of which 14.1% and 1.2% were prescribed cardioselective and non-selective beta-blockers respectively during follow-up. Cardioselective beta-blocker use was not associated with a significantly increased risk of moderate or severe asthma exacerbations. Consistent results were obtained following sensitivity analyses and a self-controlled case series approach. In contrast, non-selective beta-blockers were associated with a significantly increased risk of moderate asthma exacerbations when initiated at low to moderate doses (IRR 5.16, 95%CI 1.83-14.54, p=0.002), and both moderate and severe exacerbations when prescribed chronically at high dose (IRR 2.68, 95%CI 1.08-6.64, p=0.033 and IRR 12.11, 95%CI 1.02-144.11, p=0.048 respectively).Conclusions: Cardioselective beta-blockers prescribed to people with asthma and CVD were not associated with a significantly increased risk of moderate or severe asthma exacerbations and potentially could be used more widely when strongly indicated.

Although absolute risk of death associated with raised blood pressure increases with age, the benefits of treatment are greater in elderly patients. Despite this, the 'rule of halves' particularly applies to this group. We conducted a randomised controlled trial to evaluate different levels of feedback designed to improve identification, treatment and control of elderly hypertensives. Fifty-two general practices were randomly allocated to either: Control (n=19), Audit only feedback (n=16) or Audit plus Strategic feedback, prioritising patients by absolute risk (n=17). Feedback was based on electronic data, annually extracted from practice computer systems. Data were collected for 265,572 patients, 30,345 aged 65-79. The proportion of known hypertensives in each group with BP recorded increased over the study period and the numbers of untreated and uncontrolled patients reduced. There was a significant difference in mean systolic pressure between the Audit plus Strategic and Audit only groups and significantly greater control in the Audit plus Strategic group. Providing patient-specific practice feedback can impact on identification and management of hypertension in the elderly and produce a significant increase in control.

Introduction: Recent evaluations of IT innovations in primary care have highlighted variations between centres and practices in uptake and use. We evaluated whether structural characteristics of a general practice were associated with variations in use of a web-based clinical information system underpinning a Managed Clinical Network in diabetes, between the years 2001 and 2003. Methods: Using a computerised audit trail, we calculated the numbers of web-based operations that occurred in each practice, stratified by staff type and year, and adjusted for the numbers of registered diabetic patients. In regression analyses, we determined whether total use was associated with structural characteristics of the practice (total list size, training status, numbers of GPs (general practitioners), mean age of the GPs, numbers of female GPs, level of deprivation of the population and whether staff had received advanced training in diabetes care). Results: Initially there were a few practices which made very frequent use of the information system, with relatively high numbers of practices using the facility infrequently. However, overall use gradually became more evenly spread. This effect was particularly evident among nurse users. Frequent use by GPs was evident in only a small number of practices, with mean GP use decreasing over the three years. In linear regression analyses, none of the general practice variables were associated with online use, either overall or stratified by staff type, except for the numbers of diabetes-educated staff. This was consistently associated with increased use by nurses and GPs. Conclusions: The analyses show that structural characteristics of a practice are not associated with uptake of a new IT facility, but that its use may be influenced by post-graduate education in the relevant clinical condition. For this diabetes system at least, practice nurse use was critical in spreading uptake beyond initial GP enthusiasts and for sustained and rising use in subsequent years.