STIMULATE-ICP: A pragmatic, multi-centre, cluster randomised trial of an integrated care pathway with a nested, Phase III, open label, adaptive platform randomised drug trial in individuals with Long COVID: A structured protocol.

INTRODUCTION: Long COVID (LC), the persistent symptoms ≥12 weeks following acute COVID-19, presents major threats to individual and public health across countries, affecting over 1.5 million people in the UK alone. Evidence-based interventions are urgently required and an integrated care pathway approach in pragmatic trials, which include investigations, treatments and rehabilitation for LC, could provide scalable and generalisable solutions at pace. METHODS AND ANALYSIS: This is a pragmatic, multi-centre, cluster-randomised clinical trial of two components of an integrated care pathway (Coverscan™, a multi-organ MRI, and Living with COVID Recovery™, a digitally enabled rehabilitation platform) with a nested, Phase III, open label, platform randomised drug trial in individuals with LC. Cluster randomisation is at level of primary care networks so that integrated care pathway interventions are delivered as "standard of care" in that area. The drug trial randomisation is at individual level and initial arms are rivaroxaban, colchicine, famotidine/loratadine, compared with no drugs, with potential to add in further drug arms. The trial is being carried out in 6-10 LC clinics in the UK and is evaluating the effectiveness of a pathway of care for adults with LC in reducing fatigue and other physical, psychological and functional outcomes at 3 months. The trial also includes an economic evaluation which will be described separately. ETHICS AND DISSEMINATION: The protocol was reviewed by South Central-Berkshire Research Ethics Committee (reference: 21/SC/0416). All participating sites obtained local approvals prior to recruitment. Coverscan™ has UK certification (UKCA 752965). All participants will provide written consent to take part in the trial. The first participant was recruited in July 2022 and interim/final results will be disseminated in 2023, in a plan co-developed with public and patient representatives. The results will be presented at national and international conferences, published in peer reviewed medical journals, and shared via media (mainstream and social) and patient support organisations. TRIAL REGISTRATION NUMBER: ISRCTN10665760.

Systematic voiding programme in adults with urinary incontinence following acute stroke: the ICONS-II RCT.

BACKGROUND: Urinary incontinence affects around half of stroke survivors in the acute phase, and it often presents as a new problem after stroke or, if pre-existing, worsens significantly, adding to the disability and helplessness caused by neurological deficits. New management programmes after stroke are needed to address urinary incontinence early and effectively. OBJECTIVE: The Identifying Continence OptioNs after Stroke (ICONS)-II trial aimed to evaluate the clinical effectiveness and cost-effectiveness of a systematic voiding programme for urinary incontinence after stroke in hospital. DESIGN: This was a pragmatic, multicentre, individual-patient-randomised (1 : 1), parallel-group trial with an internal pilot. SETTING: Eighteen NHS stroke services with stroke units took part. PARTICIPANTS: Participants were adult men and women with acute stroke and urinary incontinence, including those with cognitive impairment. INTERVENTION: Participants were randomised to the intervention, a systematic voiding programme, or to usual care. The systematic voiding programme comprised assessment, behavioural interventions (bladder training or prompted voiding) and review. The assessment included evaluation of the need for and possible removal of an indwelling urinary catheter. The intervention began within 24 hours of recruitment and continued until discharge from the stroke unit. MAIN OUTCOME MEASURES: The primary outcome measure was severity of urinary incontinence (measured using the International Consultation on Incontinence Questionnaire) at 3 months post randomisation. Secondary outcome measures were taken at 3 and 6 months after randomisation and on discharge from the stroke unit. They included severity of urinary incontinence (at discharge and at 6 months), urinary symptoms, number of urinary tract infections, number of days indwelling urinary catheter was in situ, functional independence, quality of life, falls, mortality rate and costs. The trial statistician remained blinded until clinical effectiveness analysis was complete. RESULTS: The planned sample size was 1024 participants, with 512 allocated to each of the intervention and the usual-care groups. The internal pilot did not meet the target for recruitment and was extended to March 2020, with changes made to address low recruitment. The trial was paused in March 2020 because of COVID-19, and was later stopped, at which point 157 participants had been randomised (intervention, n = 79; usual care, n = 78). There were major issues with attrition, with 45% of the primary outcome data missing: 56% of the intervention group data and 35% of the usual-care group data. In terms of the primary outcome, patients allocated to the intervention group had a lower score for severity of urinary incontinence (higher scores indicate greater severity in urinary incontinence) than those allocated to the usual-care group, with means (standard deviations) of 8.1 (7.4) and 9.1 (7.8), respectively. LIMITATIONS: The trial was unable to recruit sufficient participants and had very high attrition, which resulted in seriously underpowered results. CONCLUSIONS: The internal pilot did not meet its target for recruitment and, despite recruitment subsequently being more promising, it was concluded that the trial was not feasible owing to the combined problems of poor recruitment, poor retention and COVID-19. The intervention group had a slightly lower score for severity of urinary incontinence at 3 months post randomisation, but this result should be interpreted with caution. FUTURE WORK: Further studies to assess the effectiveness of an intervention starting in or continuing into the community are required. TRIAL REGISTRATION: This trial is registered as ISRCTN14005026. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 31. See the NIHR Journals Library website for further project information.

Urinary incontinence affects around half of stroke survivors. It causes embarrassment and distress, affecting patients' ability to take part in rehabilitation. It also has a major impact on families and may determine whether or not patients are able to return home. Finding the underlying cause and addressing it can prevent, cure or reduce problems. Doing this in a systematic way for everyone with incontinence problems as early as possible after the stroke, while they are still in hospital, may work best. We also wanted to avoid using catheters in the bladder to drain the urine away, as these are often unnecessary and can cause urinary tract infections. This study aimed to test whether or not continence problems and the use of urinary catheters could be reduced if everyone with incontinence was fully assessed and given the right management and support early after hospital admission. We also wanted to find out if the benefits outweighed the costs. We planned to involve 1024 men and women with incontinence from 18 stroke units in the study, with 512 people receiving the intervention and 512 receiving usual care. However, the trial was paused because of COVID-19, at which time only 157 participants had been recruited. When we were thinking about restarting the study and looked at its progress, we found that not enough people had agreed to take part and, of those who had agreed, many had not returned their outcome questionnaires. This indicated that the trial was not feasible and should not restart. We could not make any firm conclusions about whether or not the intervention worked, as not enough people were involved. We found that stays in hospital after stroke are shorter than they were in the past. This suggests that future studies investigating ways of treating incontinence should consider interventions with management and support for incontinence that continue after patients leave the hospital.

Post-COVID-19 assessment in a specialist clinical service: a 12-month, single-centre, prospective study in 1325 individuals.

INTRODUCTION: Post-COVID-19 complications require simultaneous characterisation and management to plan policy and health system responses. We describe the 12-month experience of the first UK dedicated post-COVID-19 clinical service to include hospitalised and non-hospitalised patients. METHODS: In a single-centre, observational analysis, we report the demographics, symptoms, comorbidities, investigations, treatments, functional recovery, specialist referral and rehabilitation of 1325 individuals assessed at the University College London Hospitals post-COVID-19 service between April 2020 and April 2021, comparing by referral route: posthospitalised (PH), non-hospitalised (NH) and post emergency department (PED). Symptoms associated with poor recovery or inability to return to work full time were assessed using multivariable logistic regression. RESULTS: 1325 individuals were assessed (PH: 547, 41.3%; PED: 212, 16%; NH: 566, 42.7%). Compared with the PH and PED groups, the NH group were younger (median 44.6 (35.6-52.8) years vs 58.3 (47.0-67.7) years and 48.5 (39.4-55.7) years), more likely to be female (68.2%, 43.0% and 59.9%), less likely to be of ethnic minority (30.9%, 52.7% and 41.0%) or seen later after symptom onset (median (IQR): 194 (118-298) days, 69 (51-111) days and 76 (55-128) days; all p<0.0001). All groups had similar rates of onward specialist referral (NH 18.7%, PH 16.1% and PED 18.9%, p=0.452) and were more likely to require support for breathlessness (23.7%, 5.5% and 15.1%, p<0.001) and fatigue (17.8%, 4.8% and 8.0%, p<0.001). Hospitalised patients had higher rates of pulmonary emboli, persistent lung interstitial abnormalities and other organ impairment. 716 (54.0%) individuals reported <75% optimal health (median 70%, IQR 55%-85%). Less than half of employed individuals could return to work full time at first assessment. CONCLUSION: Post-COVID-19 symptoms were significant in PH and NH patients, with significant ongoing healthcare needs and utilisation. Trials of interventions and patient-centred pathways for diagnostic and treatment approaches are urgently required.

Maintaining musculoskeletal health using a behavioural therapy approach: a population-based randomised controlled trial (the MAmMOTH Study).

OBJECTIVE: Cognitive-behavioural therapy (CBT) has been shown to be effective in the management of chronic widespread pain (CWP); we now test whether it can prevent onset among adults at high risk. METHODS: A population-based randomised controlled prevention trial, with recruitment through UK general practices. A mailed screening questionnaire identified adults at high risk of CWP. Participants received either usual care (UC) or a short course of telephone CBT (tCBT). The primary outcome was CWP onset at 12 months assessed by mailed questionnaire. There were seven secondary outcomes including quality of life (EuroQol Questionnaire-five dimensions-five levels/EQ-5D-5L) used as part of a health economic assessment. RESULTS: 996 participants were randomised and included in the intention-to-treat analysis of which 825 provided primary outcome data. The median age of participants was 59 years; 59% were women. At 12 months there was no difference in the onset of CWP (tCBT: 18.0% vs UC: 17.5%; OR 1.05; 95% CI 0.75 to 1.48). Participants who received tCBT were more likely to report better quality of life (EQ-5D-5L utility score mean difference 0.024 (95% CI 0.009 to 0.040)); and had 0.023 (95% CI 0.007 to 0.039) more quality-adjusted life-years at an additional cost of £42.30 (95% CI -£451.19 to £597.90), yielding an incremental cost-effectiveness ratio of £1828. Most secondary outcomes showed significant benefit for the intervention. CONCLUSIONS: A short course of tCBT did not prevent onset of CWP in adults at high risk, but improved quality of life and was cost-effective. A low-cost, short-duration intervention benefits persons at risk of CWP. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02668003).

Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women.

Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.

Prevalence of secondary care multimorbidity in mid-life and its association with premature mortality in a large longitudinal cohort study.

OBJECTIVES: Multimorbidity is the coexistence of two or more health conditions in an individual. Multimorbidity in younger adults is increasingly recognised as an important challenge. We assessed the prevalence of secondary care multimorbidity in mid-life and its association with premature mortality over 15 years of follow-up, in the Aberdeen Children of the 1950s (ACONF) cohort. METHOD: A prospective cohort study using linked electronic health and mortality records. Scottish ACONF participants were linked to their Scottish Morbidity Record hospital episode data and mortality records. Multimorbidity was defined as two or more conditions and was assessed using healthcare records in 2001 when the participants were aged between 45 and 51 years. The association between multimorbidity and mortality over 15 years of follow-up (to ages 60-66 years) was assessed using Cox proportional hazards regression. There was also adjustment for key covariates: age, gender, social class at birth, intelligence at age 7, secondary school type, educational attainment, alcohol, smoking, body mass index and adult social class. RESULTS: Of 9625 participants (51% males), 3% had multimorbidity. The death rate per 1000 person-years was 28.4 (95% CI 23.2 to 34.8) in those with multimorbidity and 5.7 (95% CI 5.3 to 6.1) in those without. In relation to the reference group of those with no multimorbidity, those with multimorbidity had a mortality HR of 4.5 (95% CI 3.4 to 6.0) over 15 years and this association remained when fully adjusted for the covariates (HR 2.5 (95% CI 1.5 to 4.0)). CONCLUSION: Multimorbidity prevalence was 3% in mid-life when measured using secondary care administrative data. Multimorbidity in mid-life was associated with premature mortality.

A Durable Minimal Intervention Strategy to Reduce Benzodiazepine Use in a Primary Care Population.

BACKGROUND: Benzodiazepines are commonly prescribed drugs with approximately 10% of adults having used them in the past year. These drugs are clearly addictive, yet many patients are prescribed these for years, with long-term side effects. The present study aimed to investigate whether patients on repeat diazepam prescription had their prescription reviewed to reduce and to stop the repeat prescription wherever appropriate, and whether these changes were sustained at 24 months. METHODS: The present study used a minimal intervention strategy to reduce diazepam use in a semi-rural general practice. Patients with a current prescription for diazepam were invited to visit their general practitioner for a review. Dose reduction grids were formulated for each individual to facilitate a downward titration by 1 mg each wk/ mo. Patients with psychiatric co-morbidity were also included. Interrupted time series methods were applied to the monthly data. The outcomes were evaluated at 12 and 24 months. RESULTS: Ninety-two patients had diazepam on repeat prescription with 87 (94.6%) attending the review appointment. Twenty-seven patients (29.3%) were under psychiatric review and were supported by the psychiatrist with a downward titration regime. At 24 months, 63 patients (81.8% of the 77 still at the practice) had stopped or were in the process of stopping regular use of diazepam. A statistically significant reduction in total monthly diazepam prescription was observed (from 2.2 to 0.7 defined daily dose/1,000 patients/d). CONCLUSION: This minimal intervention strategy, in collaboration between primary and secondary care, produced a durable reduction in overall diazepam prescription at the general practice.

Development of Risk Prediction Equations for Incident Chronic Kidney Disease.

Importance: Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions. Objective: To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR). Design, Setting, and Participants: Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540). Exposures: Demographic and clinical factors. Main Outcomes and Measures: Incident eGFR of less than 60 mL/min/1.73 m2. Results: Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. Conclusions and Relevance: Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

Are there differences between those doctors who apply for a training post in Foundation Year 2 and those who take time out of the training pathway? A UK multicohort study.

INTRODUCTION: Knowledge about the career decisions of doctors in relation to specialty (residency) training is essential in terms of UK workforce planning. However, little is known about which doctors elect to progress directly from Foundation Year 2 (F2) into core/specialty/general practice training and those who instead opt for an alternative next career step. OBJECTIVE: To identify if there were any individual differences between these two groups of doctors. DESIGN: This was a longitudinal, cohort study of 'home' students who graduated from UK medical schools between 2010 and 2015 and completed the Foundation Programme (FP) between 2012 and 2017.We used the UK Medical Education Database (UKMED) to access linked data from different sources, including medical school performance, specialty training applications and career preferences. Multivariable regression analyses were used to predict the odds of taking time out of training based on various sociodemographic factors. RESULTS: 18 380/38 905 (47.2%) of F2 doctors applied for, and accepted, a training post offer immediately after completing F2. The most common pattern for doctors taking time out of the training pathway after FP was to have a 1-year (7155: 38.8%) or a 2-year break (2605: 14.0%) from training. The odds of not proceeding directly into core or specialty training were higher for those who were male, white, entered medical school as (high) school leavers and whose parents were educated to degree level. Doctors from areas of low participation in higher education were significantly (0.001) more likely to proceed directly into core or specialty training. CONCLUSION: The results show that UK doctors from higher socioeconomic groups are less likely to choose to progress directly from the FP into specialty training. The data suggest that widening access and encouraging more socioeconomic diversity in our medical students may be helpful in terms of attracting F2s into core/specialty training posts.

Relationship between sociodemographic factors and specialty destination of UK trainee doctors: a national cohort study.

OBJECTIVES: Many countries are driving forward policies to widen the socioeconomic profile of medical students and to train more medical students for certain specialties. However, little is known about how socioeconomic origin relates to specialty choice. Nor is there a good understanding of the relationship between academic performance and specialty choice. To address these gaps, our aim was to identify the relationship between socioeconomic background, academic performance and accepted offers into specialty training. DESIGN: Longitudinal, cohort study using data from the UK Medical Education Database (https://www.ukmed.ac.uk/). PARTICIPANTS: 6065 (60% females) UK doctors who accepted offers to a specialty training (residency) post after completing the 2-year generic foundation programme (UK Foundation Programme) between 2012 and 2014. MAIN OUTCOME MEASURES: Χ2 tests were used to examine the relationships between sociodemographic characteristics, academic ability and the dependent variable, specialty choice. Multiple data imputation was used to address the issue of missing data. Multinomial regression was employed to test the independent variables in predicting the likelihood of choosing a given specialty. RESULTS: Participants pursuing careers in more competitive specialties had significantly higher academic scores than colleagues pursuing less competitive ones. After controlling for the presence of multiple factors, trainees who came from families where no parent was educated to a degree level had statistically significant lower odds of choosing careers in medical specialties relative to general practice (OR=0.78, 95% CI, 0.67 to 0.92). Students who entered medical school as school leavers, compared with mature students, had odds 1.2 times higher (95% CI, 1.04 to 1.56) of choosing surgical specialties than general practice. CONCLUSIONS: The data indicate a direct association between trainees' sociodemographic characteristics, academic ability and career choices. The findings can be used by medical school, training boards and workforce planners to inform recruitment and retention strategies.

Impact of educational attainment on the association between social class at birth and multimorbidity in middle age in the Aberdeen Children of the 1950s cohort study.

OBJECTIVE: Multimorbidity (the coexistence of two or more health conditions) is increasingly prevalent. No long-term cohort study has examined the impact of contemporaneously measured birth social class along with educational attainment on adult self-reported multimorbidity. We investigated the impact of educational attainment on the relationship between social class at birth and adult self-reported multimorbidity in the Aberdeen Children of the 1950s (ACONF) cohort. METHODS: A prospective cohort study using the ACONF cohort. ACONF included 12 150 individuals born in Aberdeen, Scotland 1950-1956. In 2001, 7184 (64%) responded to a questionnaire providing information including self-reported morbidity and educational attainment. The exposure was father's social class at birth from birth records and the outcome was self-reported multimorbidity.Logistic regression assessed the association between social class and multimorbidity with adjustment for gender, then by educational attainment and finally by childhood cognition and secondary school type. ORs and 95% CIs were presented. RESULTS: Of 7184 individuals (mean age 48, 52% female), 5.4% reported multimorbidity. Birth social class was associated with adult multimorbidity. For example, the OR of multimorbidity adjusted by gender was 0.62 (95% CI 0.39 to 1.00) in the highest social class group (I/II) in relation to the reference group (III (manual)) and was 1.85 (95% CI 1.19 to 2.88) in the lowest social class group. This was partially attenuated in all social class categories by educational attainment, for example, the OR was 0.74 (95% CI 0.45 to 1.21) in group I/II following adjustment. CONCLUSION: Lower social class at birth was associated with developing multimorbidity in middle age. This was partially mediated by educational attainment and future research should consider identifying the other explanatory variables. The results are relevant to researchers and to those aiming to reduce the impact of multimorbidity.

Defining and measuring multimorbidity: a systematic review of systematic reviews.

Background: Multimorbidity, the coexistence of multiple health conditions, is a growing public health challenge. Research and intervention development are hampered by the lack of consensus regarding defining and measuring multimorbidity. The aim of this systematic review was to pool the findings of systematic reviews examining definitions and measures of multimorbidity. Methods: Medline, Embase, PubMed and Cochrane were searched from database inception to February 2017. Two authors independently screened titles, abstracts and full texts and extracted data from the included papers. Disagreements were resolved with a third author. Reviews were quality assessed. Results: Of six reviews, two focussed on definitions and four on measures. Multimorbidity was commonly defined as the presence of multiple diseases or conditions, often with a cut-off of two or more. One review developed a holistic definition including biopsychosocial and somatic factors as well as disease. Reviews recommended using measures validated for the outcome of interest. Disease counts are an alternative if no validated measure exists. Conclusions: To enable comparison between studies and settings, researchers and practitioners should be explicit about their choice of definition and measure. Using a cut-off of two or more conditions as part of the definition is widely adopted. Measure selection should be based on tools validated for the outcome being considered. Where there is no validated measure, or where multiple outcomes or populations are being considered, disease counts are appropriate.

Geographical mobility of UK trainee doctors, from family home to first job: a national cohort study.

BACKGROUND: The UK faces geographical variation in the recruitment of doctors. Understanding where medical graduates choose to go for training is important because doctors are more likely to consider practicing in areas where they completed postgraduate training. The wider literature also suggests that there is a relationship between origin and background, and where doctors wish to train/work. Thus, the purpose of this paper is to investigate the geographical mobility of UK medical graduates from different socio-economic groups in terms of where they wish to spend their first years of postgraduate training. METHODS: This was an observational study of Foundation Programme (FP) doctors who graduated from 33 UK medical schools between 2012 and 2014. Data was accessed via the UK medical education database (UKMED: https://www.ukmed.ac.uk/ ). Chi-square tests were used to examine the relationships between doctor's sociodemographic characteristics and the dependent variable, average driving time from parental home to foundation school/region. Generalised Linear Mixed Models (GLMM) were used to estimate the effects of those factors in combination against the outcome measure. RESULTS: The majority of doctors prefer to train at foundation schools that are reasonably close to the family home. Those who attended state-funded schools, from non-white ethnic groups and/or from lower socio-economic groups were significantly more likely to choose foundation schools nearer their parental home. Doctors from disadvantaged backgrounds (as determined by entitlement to free school meals, OR = 1.29, p = 0.003 and no parental degree, OR = 1.34, p < 0.001) were associated with higher odds of selecting a foundation schools that were closer to parental home. CONCLUSION: The data suggests that recruiting medical students from lower socioeconomic groups and those who originate from under-recruiting areas may be at least part of the solution to filling training posts in these areas. This has obvious implications for the widening access agenda, and equitable distribution of health services.

Evaluating service development in critical care: The impact of establishing a medical high dependency unit on intensive care unit workload, case mix, and mortality.

BACKGROUND: Critical care services underpin the delivery of many types of secondary care, and there is increasing focus on how to best deliver such services. The aim of this study was to investigate the impact of establishing a medical high dependency unit, in a tertiary referral center, on the workload, case mix, and mortality of the intensive care unit. METHODS: Single-center, 11-year retrospective study of patients admitted to the general intensive care unit, before and after the opening of the medical high dependency unit, using interrupted time series methodology. RESULTS: Over the duration of the study period, 3209 medical patients were admitted to the intensive care unit. There was a constant rate of medical admissions to the intensive care unit until the opening of the medical high dependency unit, followed by a statistically significant decline thereafter. There was a statistically significant decrease in the average severity of illness of medical patients prior to the opening of the medical high dependency unit, but there was no evidence of a change following the opening of the unit. There was no evidence of a statistically significant change in the estimated mean standardized mortality ratio for either medical or surgical admissions after the intervention. CONCLUSIONS: The opening of a medical high dependency unit had a minimal impact on the intensive care unit. There was, in all likelihood, an unmet need-of less seriously ill patients, who were previously looked after on a normal ward, but did not require intensive care unit admission-who are now cared for in the new medical high dependency unit. Interrupted time series analysis, although not without limitations, is a useful mean of evaluating changes in service delivery.

Relationship between sociodemographic factors and selection into UK postgraduate medical training programmes: a national cohort study.

INTRODUCTION: Knowledge about allocation of doctors into postgraduate training programmes is essential in terms of workforce planning, transparency and equity issues. However, this is a rarely examined topic. To address this gap in the literature, the current study examines the relationships between applicants' sociodemographic characteristics and outcomes on the UK Foundation Training selection process. METHODS: A longitudinal, cohort study of trainees who applied for the first stage of UK postgraduate medical training in 2013-2014. We used UK Medical Education Database (UKMED) to access linked data from different sources, including medical school admissions, assessments and postgraduate training. Multivariable ordinal regression analyses were used to predict the odds of applicants being allocated to their preferred foundation schools. RESULTS: Applicants allocated to their first-choice foundation school scored on average a quarter of an SD above the average of all applicants in the sample. After adjusting for Foundation Training application score, no statistically significant effects were observed for gender, socioeconomic status (as determined by income support) or whether applicants entered medical school as graduates or not. Ethnicity and place of medical qualification were strong predictors of allocation to preferred foundation school. Applicants who graduated from medical schools in Wales, Scotland and Northern Ireland were 1.17 times, 3.33 times and 12.64 times (respectively), the odds of applicants who graduated from a medical school in England to be allocated to a foundation school of their choice. CONCLUSIONS: The data provide supportive evidence for the fairness of the allocation process but highlight some interesting findings relating to 'push-pull' factors in medical careers decision-making. These findings should be considered when designing postgraduate training policy.

Hip fracture incidence and mortality in chronic kidney disease: the GLOMMS-II record linkage cohort study.

BACKGROUND: Individuals on renal replacement therapy (RRT) have increased fracture risk, but risk in less advanced chronic kidney disease (CKD) is unclear. OBJECTIVE: To investigate CKD associations with hip fracture incidence and mortality. DESIGN: Record linkage cohort study Grampian Laboratory Outcomes Mortality and Morbidity Study II. SETTING: Single health region in Scotland. PARTICIPANTS: All individuals (≥15 years) with sustained CKD stages 3-5 and those on RRT, and a 20% random sample of those with normal renal function, in the resident population in 2003. OUTCOME MEASURES: Outcomes were (1) incident hip fracture measured with (A) admissions or (B) deaths, with at least 5.5 years follow-up and (2) post-hip fracture mortality. Unadjusted and adjusted, incident rate ratios (IRRs) and mortality rate ratios were calculated using Poisson regression. RESULTS: Of 39 630 individuals identified in 2003 (41% males, mean age 63.3 years), 19 537 had CKD stages 3-5, 345 were on RRT and 19 748 had normal estimated glomerular filtration rate (eGFR). Hip fracture incidence, measured by admissions, was increased in CKD stages 3-5 (compared with normal eGFR), both overall (adjusted IRR 1.49 (95% CI 1.24 to 1.79)) and for individual CKD stages 3a, 3b and 4. Hip fracture incidence, measured using deaths, was increased in those with CKD stages 3b and 4. Post-hip fracture mortality was only increased in CKD stage 4. There was only a small number of individuals and events for CKD stage 5, resulting in insufficient statistical power. CONCLUSION: Hip fracture incidence was higher in CKD stages 3-5 compared with normal eGFR. Post-hip fracture mortality was only increased in CKD stage 4. Reducing hip fracture incidence in CKD through regular fall and fracture risk review should reduce overall deaths after hip fracture in the population.

Are efforts to attract graduate applicants to UK medical schools effective in increasing the participation of under-represented socioeconomic groups? A national cohort study.

INTRODUCTION: Attracting graduates was recommended as a means of diversifying the UK medical student population. Graduates now make up nearly a quarter of the total medical student population. Research to date has focused on comparing the sociodemographic characteristics of applicants to and/or students on traditional and graduate entry programmes (GEMs), yet GEMs account for only 40% of the graduate medical student population. Thus, we aimed to compare the sociodemographic characteristic and outcomes of graduates and non-graduate applicants across a range of programmes. METHODS: This was an observational study of 117 214 applicants to medicine who took the UK Clinical Aptitude Test (UKCAT) from 2006 to 2014 and who applied to medical school through Universities and Colleges Admissions Service (UCAS). We included applicant demographics, UKCAT total score and offers in our analysis. Applicants were assigned as graduates or non-graduates on the basis of their highest qualification. Multiple logistic regression was used to predict the odds of receiving an offer, after adjusting for confounders. RESULTS: Irrespective of graduate or non-graduate status, most applicants were from the highest socioeconomic groups and were from a white ethnic background. Receiving an offer was related to gender and ethnicity in both graduates and non-graduates. After adjusting for UKCAT score, the OR of an offer for graduates versus non-graduates was approximately 0.5 (OR=0.48, 95% CI 0.46 to 0.49). DISCUSSION: Our findings indicate that the aim of diversifying the medical student population on socioeconomic grounds by attracting graduates has been only marginally successful. Graduate applicants from widening access backgrounds are less likely than others to be offered a place at medical school. Different approaches must be considered if medicine is to attract and select more socially diverse applicants.

Post-discharge kidney function is associated with subsequent ten-year renal progression risk among survivors of acute kidney injury.

The extent to which renal progression after acute kidney injury (AKI) arises from an initial step drop in kidney function (incomplete recovery), or from a long-term trajectory of subsequent decline, is unclear. This makes it challenging to plan or time post-discharge follow-up. This study of 14651 hospital survivors in 2003 (1966 with AKI, 12685 no AKI) separates incomplete recovery from subsequent renal decline by using the post-discharge estimated glomerular filtration rate (eGFR) rather than the pre-admission as a new reference point for determining subsequent renal outcomes. Outcomes were sustained 30% renal decline and de novo CKD stage 4, followed from 2003-2013. Death was a competing risk. Overall, death was more common than subsequent renal decline (37.5% vs 11.3%) and CKD stage 4 (4.5%). Overall, 25.7% of AKI patients had non-recovery. Subsequent renal decline was greater after AKI (vs no AKI) (14.8% vs 10.8%). Renal decline after AKI (vs no AKI) was greatest among those with higher post-discharge eGFRs with multivariable hazard ratios of 2.29 (1.88-2.78); 1.50 (1.13-2.00); 0.94 (0.68-1.32) and 0.95 (0.64-1.41) at eGFRs of 60 or more; 45-59; 30-44 and under 30, respectively. The excess risk after AKI persisted over ten years of study, irrespective of AKI severity, or post-episode proteinuria. Thus, even if post-discharge kidney function returns to normal, hospital admission with AKI is associated with increased renal progression that persists for up to ten years. Follow-up plans should avoid false reassurance when eGFR after AKI returns to normal.

Three year evaluation of Xpert MTB/RIF in a low prevalence tuberculosis setting: A Scottish perspective.

OBJECTIVES: Xpert MTB/RIF (Cepheid) is a rapid molecular assay shown to be sensitive and specific for pulmonary tuberculosis (TB) diagnosis in highly endemic countries. We evaluated its diagnostic performance in a low TB prevalence setting, examined rifampicin resistance detection and quantitative capabilities predicting graded auramine microscopy and time to positivity (TTP) of culture. METHODS: Xpert MTB/RIF was used to test respiratory samples over a 3 year period. Samples underwent graded auramine microscopy, solid/liquid culture, in-house IS6110 real-time PCR, and GenoType MTBDRplus (HAIN Lifescience) to determine rifampicin and/or isoniazid resistance. RESULTS: A total of 2103 Xpert MTB/RIF tests were performed. Compared to culture sensitivity was 95.8%, specificity 99.5%, positive predictive value (PPV) 82.1%, and negative predictive value (NPV) 99.9%. A positive correlation was found between auramine microscopy grade and Xpert MTB/RIF assay load. We found a clear reduction in the median TTP as Xpert MTB/RIF assay load increased. Rifampicin resistance was detected. CONCLUSIONS: Xpert MTB/RIF was rapid and accurate in diagnosing pulmonary TB in a low prevalence area. Rapid results will influence infection prevention and control and treatment measures. The excellent NPV obtained suggests further work should be carried out to assess its role in replacing microscopy.

Acute kidney injury as an independent risk factor for unplanned 90-day hospital readmissions.

BACKGROUND: Reducing readmissions is an international priority in healthcare. Acute kidney injury (AKI) is common, serious and also a global concern. This analysis evaluates AKI as a candidate risk factor for unplanned readmissions and determines the reasons for readmissions. METHODS: GLOMMS-II is a large population cohort from one health authority in Scotland, combining hospital episode data and complete serial biochemistry results through data-linkage. 16453 people (2623 with AKI and 13830 without AKI) from GLOMMS-II who survived an index hospital admission in 2003 were used to identify the causes of and predict readmissions. The main outcome was "unplanned readmission or death" within 90 days of discharge. In a secondary analysis, the outcome was limited to readmissions with acute pulmonary oedema. 26 candidate predictors during the index admission included AKI (defined and staged 1-3 using an automated e-alert algorithm), prior AKI episodes, baseline kidney function, index admission circumstances and comorbidities. Prediction models were developed and assessed using multivariable logistic regression (stepwise variable selection), C statistics, bootstrap validation and decision curve analysis. RESULTS: Three thousand sixty-five (18.6%) patients had the main outcome (2702 readmitted, 363 died without readmission). The outcome was strongly predicted by AKI. Multivariable odds ratios for AKI stage 3; 2 and 1 (vs no AKI) were 2.80 (2.22-3.53); 2.23 (1.85-2.68) and 1.50 (1.33-1.70). Acute pulmonary oedema was the reason for readmission in 26.6% with AKI and eGFR < 60; and 4.0% with no AKI and eGFR ≥ 60. The best stepwise model from all candidate predictors had a C statistic of 0.698 for the main outcome. In a secondary analysis, a model for readmission with acute pulmonary oedema had a C statistic of 0.853. In decision curve analysis, AKI improved clinical utility when added to any model, although the incremental benefit was small when predicting the main outcome. CONCLUSIONS: AKI is a strong, consistent and independent risk factor for unplanned readmissions - particularly readmissions with acute pulmonary oedema. Pre-emptive planning at discharge should be considered to minimise avoidable readmissions in this high risk group.