EPidemiology Of Cardiogenic sHock in Scotland (EPOCHS): A multicentre, prospective observational study of the prevalence, management and outcomes of cardiogenic shock in Scotland.

Background: Despite high rates of cardiovascular disease in Scotland, the prevalence and outcomes of patients with cardiogenic shock are unknown. Methods: We undertook a prospective observational cohort study of consecutive patients with cardiogenic shock admitted to the intensive care unit (ICU) or coronary care unit at 13 hospitals in Scotland for a 6-month period. Denominator data from the Scottish Intensive Care Society Audit Group were used to estimate ICU prevalence; data for coronary care units were unavailable. We undertook multivariable logistic regression to identify factors associated with in-hospital mortality. Results: In total, 247 patients with cardiogenic shock were included. After exclusion of coronary care unit admissions, this comprised 3.0% of all ICU admissions during the study period (95% confidence interval [CI] 2.6%-3.5%). Aetiology was acute myocardial infarction (AMI) in 48%. The commonest vasoactive treatment was noradrenaline (56%) followed by adrenaline (46%) and dobutamine (40%). Mechanical circulatory support was used in 30%. Overall in-hospital mortality was 55%. After multivariable logistic regression, age (odds ratio [OR] 1.04, 95% CI 1.02-1.06), admission lactate (OR 1.10, 95% CI 1.05-1.19), Society for Cardiovascular Angiographic Intervention stage D or E at presentation (OR 2.16, 95% CI 1.10-4.29) and use of adrenaline (OR 2.73, 95% CI 1.40-5.40) were associated with mortality. Conclusions: In Scotland the prevalence of cardiogenic shock was 3% of all ICU admissions; more than half died prior to discharge. There was significant variation in treatment approaches, particularly with respect to vasoactive support strategy.

Non-COVID-19 intensive care admissions during the pandemic: a multinational registry-based study.

BACKGROUND: The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, there is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment. METHODS: We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry. FINDINGS: Among 1 642 632 non-COVID-19 admissions, there was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95% CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95% CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes. INTERPRETATION: Increased ICU mortality occurred among non-COVID-19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles.

Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B Trial): protocol for a multicentre phase 3 pragmatic clinical and cost-effectiveness randomised trial in the UK.

INTRODUCTION: Almost all patients receiving mechanical ventilation (MV) in intensive care units (ICUs) require analgesia and sedation. The most widely used sedative drug is propofol, but there is uncertainty whether alpha2-agonists are superior. The alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B) trial aims to determine whether clonidine or dexmedetomidine (or both) are clinically and cost-effective in MV ICU patients compared with usual care. METHODS AND ANALYSIS: Adult ICU patients within 48 hours of starting MV, expected to require at least 24 hours further MV, are randomised in an open-label three arm trial to receive propofol (usual care) or clonidine or dexmedetomidine as primary sedative, plus analgesia according to local practice. Exclusions include patients with primary brain injury; postcardiac arrest; other neurological conditions; or bradycardia. Unless clinically contraindicated, sedation is titrated using weight-based dosing guidance to achieve a Richmond-Agitation-Sedation score of -2 or greater as early as considered safe by clinicians. The primary outcome is time to successful extubation. Secondary ICU outcomes include delirium and coma incidence/duration, sedation quality, predefined adverse events, mortality and ICU length of stay. Post-ICU outcomes include mortality, anxiety and depression, post-traumatic stress, cognitive function and health-related quality of life at 6-month follow-up. A process evaluation and health economic evaluation are embedded in the trial.The analytic framework uses a hierarchical approach to maximise efficiency and control type I error. Stage 1 tests whether each alpha2-agonist is superior to propofol. If either/both interventions are superior, stages 2 and 3 testing explores which alpha2-agonist is more effective. To detect a mean difference of 2 days in MV duration, we aim to recruit 1437 patients (479 per group) in 40-50 UK ICUs. ETHICS AND DISSEMINATION: The Scotland A REC approved the trial (18/SS/0085). We use a surrogate decision-maker or deferred consent model consistent with UK law. Dissemination will be via publications, presentations and updated guidelines. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03653832.

Effectiveness of holistic assessment-based interventions for adults with multiple long-term conditions and frailty: an umbrella review of systematic reviews.

Holistic assessment-based interventions (HABIs) are effective in older people admitted to hospital, but it is unclear whether similar interventions are effective in adults with multiple long-term conditions or frailty in the community. We conducted an umbrella review to comprehensively evaluate the literature on HABIs for adults (aged ≥18 years) with multiple long-term conditions, and frailty. We searched eight databases for systematic reviews reporting on experimental or quasi-experimental studies. Of 9803 titles screened, we identified 29 eligible reviews (14 with meta-analysis) reporting on 14 types of HABIs. The evidence for the effectiveness of HABIs was largely inconsistent across different types of interventions, settings, and outcomes. We found evidence of no benefit from hospital HABIs on health-related quality of life (HRQoL) and emergency department re-attendance, and evidence of no benefit from community HABIs on overall health-care utilisation rates, emergency department attendance, nursing home admissions, and mortality. The best evidence of effectiveness was for hospital comprehensive geriatric assessment (CGA) on nursing home admissions, keeping patients alive and in their own homes. There was some evidence of benefit from community CGA on hospital admissions, and from CGA spanning community and hospital settings on HRQoL. Patient-centred medical homes had beneficial effects on HRQoL, mental health, self-management, and hospital admissions.

Effectiveness of holistic assessment-based interventions in improving outcomes in adults with multiple long-term conditions and/or frailty: an umbrella review protocol.

OBJECTIVE: This umbrella review will synthesize evidence on the effectiveness of holistic assessment-based interventions in improving health outcomes in adults (aged ≥18) with multiple long-term conditions and/or frailty. INTRODUCTION: Health systems need effective, evidence-based interventions to improve health outcomes for adults with multiple long-term conditions. Holistic assessment-based interventions are effective in older people admitted to hospital (usually called "comprehensive geriatric assessments" in that context); however, the evidence is inconclusive on whether similar interventions are effective in community settings. INCLUSION CRITERIA: We will include systematic reviews examining the effectiveness of community and/or hospital holistic assessment-based interventions in improving health outcomes for community-dwelling and hospitalized adults aged ≥ 18 with multiple long-term conditions and/or frailty. METHODS: The review will follow the JBI methodology for umbrella reviews. MEDLINE, Embase, PsycINFO, CINAHL Plus, Scopus, ASSIA, Cochrane Library, and the TRIP Medical Database will be searched to identify reviews published in English from 2010 till the present. This will be followed by a manual search of reference lists of included reviews to identify additional reviews. Two reviewers will independently screen titles and abstracts against the selection criteria, followed by screening of full texts. Methodological quality will be assessed using the JBI critical appraisal checklist for systematic reviews and research syntheses and data will be extracted using an adapted and piloted JBI data extraction tool. The summary of findings will be presented in tabular format, with narrative descriptions and visual indications. The citation matrix will be generated and the corrected covered area calculated to analyze the overlap in primary studies across the reviews. REVIEW REGISTRATION: PROSPERO CRD42022363217.

Variation in general practice referral rate to acute medicine services and association with hospital admission. A retrospective observational study.

BACKGROUND: Variation in general practice (GP) referral rates to outpatient services is well described however variance in rates of referral to acute medical units is lacking. OBJECTIVE: To investigate variance in GP referral rate for acute medical assessment and subsequent need for hospital admission. METHODS: A retrospective cohort study of acute medical referrals from 88 GPs in Lothian, Scotland between 2017 and 2020 was performed using practice population size, age, deprivation, care home residence, and distance from hospital as explanatory variables. Patient-level analysis of demography, deprivation, comorbidity, and acuity markers was subsequently performed on referred and clinically assessed acute medical patients (n = 42,424) to examine how practice referral behaviour reflects clinical need for inpatient hospital care. RESULTS: Variance in GP referral rates for acute medical assessment was high (2.53-fold variation 1st vs. 4th quartile) and incompletely explained by increasing age and deprivation (adjusted R2 0.67, P < 0.001) such that significant variance remained after correction for confounders (2.15-fold). Patients from the highest referring quartile were significantly less likely to require hospital admission than those from the third, second, or lowest referring quartiles (adjusted odds ratio 1.28 [1.21-1.36, P < 0.001]; 1.30 [1.23-1.37, P < 0.001]; 1.53 [1.42-1.65, P < 0.001]). CONCLUSIONS: High variation in GP practice referral rate for acute medical assessment is incompletely explained by practice population socioeconomic factors and negatively associates with need for urgent inpatient care. Identifying modifiable factors influencing referral rate may provide opportunities to facilitate community-based care and reduce congestion on acute unscheduled care pathways.

Managing the populations need for urgent medical care is challenge in many healthcare systems and overcrowding of urgent medical services negatively affects patient experience and can affect timely treatment. In the United Kingdom, the primary sources of patients attending for acute medical care are self-attendance to the hospital or by way of referral by a primary care physician (general practitioner). These data for the first time demonstrate high variation in referral rates for acute medical assessment between general practices which is incompletely explained by factors such as the age, deprivation, distance to the hospital or care home residence status of the care home population. Analysis of over 40,000 of these referrals for urgent medical care was subsequently undertaken to further investigate this variation. After adjusting for important clinical factors, patients referred from "high referring" practices were over 50% less likely to require inpatient hospital care than patients from lower referring practices. This suggests that the threshold for referral varies greatly between individual primary care clinicians, practices, or practice populations and many of these patients may have been suitable for less urgent community-based care. Identification of modifiable factors that account for this unexplained variation may facilitate community-based care and improve patient experience by reducing unnecessary attendance and congestion in already busy emergency care services.

Studying the Long-term Impact of COVID-19 in Kids (SLICK). Healthcare use and costs in children and young people following community-acquired SARS-CoV-2 infection: protocol for an observational study using linked primary and secondary routinely collected healthcare data from England, Scotland and Wales.

INTRODUCTION: SARS-CoV-2 infection rarely causes hospitalisation in children and young people (CYP), but mild or asymptomatic infections are common. Persistent symptoms following infection have been reported in CYP but subsequent healthcare use is unclear. We aim to describe healthcare use in CYP following community-acquired SARS-CoV-2 infection and identify those at risk of ongoing healthcare needs. METHODS AND ANALYSIS: We will use anonymised individual-level, population-scale national data linking demographics, comorbidities, primary and secondary care use and mortality between 1 January 2019 and 1 May 2022. SARS-CoV-2 test data will be linked from 1 January 2020 to 1 May 2022. Analyses will use Trusted Research Environments: OpenSAFELY in England, Secure Anonymised Information Linkage (SAIL) Databank in Wales and Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 in Scotland (EAVE-II). CYP aged ≥4 and <18 years who underwent SARS-CoV-2 reverse transcription PCR (RT-PCR) testing between 1 January 2020 and 1 May 2021 and those untested CYP will be examined.The primary outcome measure is cumulative healthcare cost over 12 months following SARS-CoV-2 testing, stratified into primary or secondary care, and physical or mental healthcare. We will estimate the burden of healthcare use attributable to SARS-CoV-2 infections in the 12 months after testing using a matched cohort study of RT-PCR positive, negative or untested CYP matched on testing date, with adjustment for confounders. We will identify factors associated with higher healthcare needs in the 12 months following SARS-CoV-2 infection using an unmatched cohort of RT-PCR positive CYP. Multivariable logistic regression and machine learning approaches will identify risk factors for high healthcare use and characterise patterns of healthcare use post infection. ETHICS AND DISSEMINATION: This study was approved by the South-Central Oxford C Health Research Authority Ethics Committee (13/SC/0149). Findings will be preprinted and published in peer-reviewed journals. Analysis code and code lists will be available through public GitHub repositories and OpenCodelists with meta-data via HDR-UK Innovation Gateway.

Multimorbidity and Its Relationship With Long-Term Outcomes After Critical Care Discharge: A Prospective Cohort Study.

BACKGROUND: Survivors of critical illness have poor long-term outcomes with subsequent increases in health care utilization. Less is known about the interplay between multimorbidity and long-term outcomes. RESEARCH QUESTION: How do baseline patient demographics impact mortality and health care utilization in the year after discharge from critical care? STUDY DESIGN AND METHODS: Using data from a prospectively collected cohort, we used propensity score matching to assess differences in outcomes between patients with a critical care encounter and patients admitted to the hospital without critical care. Long-term mortality was examined via nationally linked data as was hospital resource use in the year after hospital discharge. The cause of death was also examined. RESULTS: This analysis included 3,112 participants. There was no difference in long-term mortality between the critical care and hospital cohorts (adjusted hazard ratio, 1.09; 95% CI, 0.90-1.32; P = .39). Prehospitalization emotional health issues (eg, clinical diagnosis of depression) were associated with increased long-term mortality (hazard ratio, 1.49; 95% CI, 1.14-1.96; P < .004). Health care utilization was different between the two cohorts in the year after discharge with the critical care cohort experiencing a 29% increased risk of hospital readmission (OR, 1.29; 95% CI, 1.11-1.50; P = .001). INTERPRETATION: This national cohort study has demonstrated increased resource use for critical care survivors in the year after discharge but fails to replicate past findings of increased longer-term mortality. Multimorbidity, lifestyle factors, and socioeconomic status appear to influence long-term outcomes and should be the focus of future research.

Vaccine effectiveness of live attenuated and trivalent inactivated influenza vaccination in 2010/11 to 2015/16: the SIVE II record linkage study.

BACKGROUND: There is good evidence of vaccine effectiveness in healthy individuals but less robust evidence for vaccine effectiveness in the populations targeted for influenza vaccination. The live attenuated influenza vaccine (LAIV) has recently been recommended for children in the UK. The trivalent influenza vaccine (TIV) is recommended for all people aged ≥ 65 years and for those aged < 65 years who are at an increased risk of complications from influenza infection (e.g. people with asthma). OBJECTIVE: To examine the vaccine effectiveness of LAIV and TIV. DESIGN: Cohort study and test-negative designs to estimate vaccine effectiveness. A self-case series study to ascertain adverse events associated with vaccination. SETTING: A national linkage of patient-level general practice (GP) data from 230 Scottish GPs to the Scottish Immunisation & Recall Service, Health Protection Scotland virology database, admissions to Scottish hospitals and the Scottish death register. PARTICIPANTS: A total of 1,250,000 people. INTERVENTIONS: LAIV for 2- to 11-year-olds and TIV for older people (aged ≥ 65 years) and those aged < 65 years who are at risk of diseases, from 2010/11 to 2015/16. MAIN OUTCOME MEASURES: The main outcome measures include vaccine effectiveness against laboratory-confirmed influenza using real-time reverse-transcription polymerase chain reaction (RT-PCR), influenza-related morbidity and mortality, and adverse events associated with vaccination. RESULTS: Two-fifths (40%) of preschool-aged children and three-fifths (60%) of primary school-aged children registered in study practices were vaccinated. Uptake varied among groups [e.g. most affluent vs. most deprived in 2- to 4-year-olds, odds ratio 1.76, 95% confidence interval (CI) 1.70 to 1.82]. LAIV-adjusted vaccine effectiveness among children (aged 2-11 years) for preventing RT-PCR laboratory-confirmed influenza was 21% (95% CI -19% to 47%) in 2014/15 and 58% (95% CI 39% to 71%) in 2015/16. No significant adverse events were associated with LAIV. Among at-risk 18- to 64-year-olds, significant trivalent influenza vaccine effectiveness was found for four of the six seasons, with the highest vaccine effectiveness in 2010/11 (53%, 95% CI 21% to 72%). The seasons with non-significant vaccine effectiveness had low levels of circulating influenza virus (2011/12, 5%; 2013/14, 9%). Among those people aged ≥ 65 years, TIV effectiveness was positive in all six seasons, but in only one of the six seasons (2013/14) was significance achieved (57%, 95% CI 20% to 76%). CONCLUSIONS: The study found that LAIV was safe and effective in decreasing RT-PCR-confirmed influenza in children. TIV was safe and significantly effective in most seasons for 18- to 64-year-olds, with positive vaccine effectiveness in most seasons for those people aged ≥ 65 years (although this was significant in only one season). FUTURE WORK: The UK Joint Committee on Vaccination and Immunisation has recommended the use of adjuvanted injectable vaccine for those people aged ≥ 65 years from season 2018/19 onwards. A future study will be required to evaluate this vaccine. TRIAL REGISTRATION: Current Controlled Trials ISRCTN88072400. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 67. See the NIHR Journals Library website for further project information.

In Scotland, a new type of influenza vaccine (live attenuated influenza vaccine), administered via the nose, was introduced in 2014/15 for all children aged between 2 and 11 years. It can be difficult to evaluate any changes in health as a result of new immunisation programmes, given that randomised controlled trials of vaccines are impractical and can also be seen as unethical. These changes are therefore typically not evaluated, making it difficult to inform future policy in this field. Observational studies can be used to assess the effects of health-care interventions without influencing the care that is provided or affecting the people who receive it. An evaluation (effectiveness and safety) of this change in the immunisation programme was conducted. The vaccine programme, an inactivated vaccine administered as an injection, for other groups for whom the evidence available is limited was also evaluated [i.e. for people aged ≥ 65 years and people aged < 65 years who have a medical condition (e.g. asthma) that puts them at risk of severe illness from influenza]. The findings support the view that the intranasal vaccine is effective and safe in preventing influenza in children. The injectable vaccine in people aged < 65 years who are more at risk of complications from flu was safe and effective. Lower effectiveness was found in people aged ≥ 65 years. Both the injectable vaccine and the intranasal vaccine have high levels of uptake in the population offered vaccination. When considering these results, the important limitation of bias in observational study designs should be noted [for instance, residual confounding, whereby it is not possible to measure a characteristic of those people receiving the vaccine (e.g. being healthier)], and this is accounted for in this analysis.

Correction to: Understanding gender disparities in outcomes after sepsis.

The original version of this article unfortunately contained a mistake. There was an error in figure one. The correct figure can be found below. We apologize for the mistake.

A systematic review of natural language processing for classification tasks in the field of incident reporting and adverse event analysis.

CONTEXT: Adverse events in healthcare are often collated in incident reports which contain unstructured free text. Learning from these events may improve patient safety. Natural language processing (NLP) uses computational techniques to interrogate free text, reducing the human workload associated with its analysis. There is growing interest in applying NLP to patient safety, but the evidence in the field has not been summarised and evaluated to date. OBJECTIVE: To perform a systematic literature review and narrative synthesis to describe and evaluate NLP methods for classification of incident reports and adverse events in healthcare. METHODS: Data sources included Medline, Embase, The Cochrane Library, CINAHL, MIDIRS, ISI Web of Science, SciELO, Google Scholar, PROSPERO, hand searching of key articles, and OpenGrey. Data items were manually abstracted to a standardised extraction form. RESULTS: From 428 articles screened for eligibility, 35 met the inclusion criteria of using NLP to perform a classification task on incident reports, or with the aim of detecting adverse events. The majority of studies used free text from incident reporting systems or electronic health records. Models were typically designed to classify by type of incident, type of medication error, or harm severity. A broad range of NLP techniques are demonstrated to perform these classification tasks with favourable performance outcomes. There are methodological challenges in how these results can be interpreted in a broader context. CONCLUSION: NLP can generate meaningful information from unstructured data in the specific domain of the classification of incident reports and adverse events. Understanding what or why incidents are occurring is important in adverse event analysis. If NLP enables these insights to be drawn from larger datasets it may improve the learning from adverse events in healthcare.

Feasibility and reliability of frailty assessment in the critically ill: a systematic review.

BACKGROUND: For healthcare systems, an ageing population poses challenges in the delivery of equitable and effective care. Frailty assessment has the potential to improve care in the intensive care setting, but applying assessment tools in critical illness may be problematic. The aim of this systematic review was to evaluate evidence for the feasibility and reliability of frailty assessment in critical care. METHODS: Our primary search was conducted in Medline, Medline In-process, EMBASE, CINAHL, PsycINFO, AMED, Cochrane Database of Systematic Reviews, and Web of Science (January 2001 to October 2017). We included observational studies reporting data on feasibility and reliability of frailty assessment in the critical care setting in patients 16 years and older. Feasibility was assessed in terms of timing of evaluation, the background, training and expertise required for assessors, and reliance upon proxy input. Reliability was assessed in terms of inter-rater reliability. RESULTS: Data from 11 study publications are included, representing 8 study cohorts and 7761 patients. Proxy involvement in frailty assessment ranged from 58 to 100%. Feasibility data were not well-reported overall, but the exclusion rate due to lack of proxy availability ranged from 0 to 45%, the highest rate observed where family involvement was mandatory and the assessment tool relatively complex (frailty index, FI). Conventional elements of frailty phenotype (FP) assessment required modification prior to use in two studies. Clinical staff tended to use a simple judgement-based tool, the clinical frailty scale (CFS). Inter-rater reliability was reported in one study using the CFS and although a good level of agreement was observed between clinician assessments, this was a small and single-centre study. CONCLUSION: Though of unproven reliability in the critically ill, CFS was the tool used most widely by critical care clinical staff. Conventional FP assessment required modification for general application in critical care, and an FI-based assessment may be difficult to deliver by the critical care team on a routine basis. There is a high reliance on proxies for frailty assessment, and the reliability of frailty assessment tools in critical care needs further evaluation. PROSPERO REGISTRATION NUMBER: CRD42016052073 .

Determinants of Health-Related Quality of Life After ICU: Importance of Patient Demographics, Previous Comorbidity, and Severity of Illness.

OBJECTIVES: ICU survivors frequently report reduced health-related quality of life, but the relative importance of preillness versus acute illness factors in survivor populations is not well understood. We aimed to explore health-related quality of life trajectories over 12 months following ICU discharge, patterns of improvement, or deterioration over this period, and the relative importance of demographics (age, gender, social deprivation), preexisting health (Functional Comorbidity Index), and acute illness severity (Acute Physiology and Chronic Health Evaluation II score, ventilation days) as determinants of health-related quality of life and relevant patient-reported symptoms during the year following ICU discharge. DESIGN: Nested cohort study within a previously published randomized controlled trial. SETTING: Two ICUs in Edinburgh, Scotland. PATIENTS: Adult ICU survivors (n = 240) who required more than 48 hours of mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We prospectively collected data for age, gender, social deprivation (Scottish index of multiple deprivation), preexisting comorbidity (Functional Comorbidity Index), Acute Physiology and Chronic Health Evaluation II score, and days of mechanical ventilation. Health-related quality of life (Medical Outcomes Study Short Form version 2 Physical Component Score and Mental Component Score) and patient-reported symptoms (appetite, fatigue, pain, joint stiffness, and breathlessness) were measured at 3, 6, and 12 months. Mean Physical Component Score and Mental Component Score were reduced at all time points with minimal change between 3 and 12 months. In multivariable analysis, increasing pre-ICU comorbidity count was strongly associated with lower health-related quality of life (Physical Component Score ß = -1.56 [-2.44 to -0.68]; p = 0.001; Mental Component Score ß = -1.45 [-2.37 to -0.53]; p = 0.002) and more severe self-reported symptoms. In contrast, Acute Physiology and Chronic Health Evaluation II score and mechanical ventilation days were not associated with health-related quality of life. Older age (ß = 0.33 [0.19-0.47]; p < 0.001) and lower social deprivation (ß = 1.38 [0.03-2.74]; p = 0.045) were associated with better Mental Component Score health-related quality of life. CONCLUSIONS: Preexisting comorbidity counts, but not severity of ICU illness, are strongly associated with health-related quality of life and physical symptoms in the year following critical illness.

Five-Year Mortality and Hospital Costs Associated with Surviving Intensive Care.

RATIONALE: Survivors of critical illness experience significant morbidity, but the impact of surviving the intensive care unit (ICU) has not been quantified comprehensively at a population level. OBJECTIVES: To identify factors associated with increased hospital resource use and to ascertain whether ICU admission was associated with increased mortality and resource use. METHODS: Matched cohort study and pre/post-analysis using national linked data registries with complete population coverage. The population consisted of patients admitted to all adult general ICUs during 2005 and surviving to hospital discharge, identified from the Scottish Intensive Care Society Audit Group registry, matched (1:1) with similar hospital control subjects. Five-year outcomes included mortality and hospital resource use. Confounder adjustment was based on multivariable regression and pre/post within-individual analyses. MEASUREMENTS AND MAIN RESULTS: Of 7,656 ICU patients, 5,259 survived to hospital discharge (5,215 [99.2%] matched to hospital control subjects). Factors present before ICU admission (comorbidities/pre-ICU hospitalizations) were stronger predictors of hospital resource use than acute illness factors. In the 5 years after the initial hospital discharge, compared with hospital control subjects, the ICU cohort had higher mortality (32.3% vs. 22.7%; hazard ratio, 1.33; 95% confidence interval, 1.22-1.46; P < 0.001), used more hospital resources (mean hospital admission rate, 4.8 vs. 3.3/person/5 yr), and had 51% higher mean 5-year hospital costs ($25,608 vs. $16,913/patient). Increased resource use persisted after confounder adjustment (P < 0.001) and using pre/post-analyses (P < 0.001). Excess resource use and mortality were greatest for younger patients without significant comorbidity. CONCLUSIONS: This complete, national study demonstrates that ICU survivorship is associated with higher 5-year mortality and hospital resource use than hospital control subjects, representing a substantial burden on individuals, caregivers, and society.

Equity of Access to Critical Care Among Elderly Patients in Scotland: A National Cohort Study.

OBJECTIVE: To compare elderly (≥ 80 yr), older (65-79 yr), and younger (< 65 yr) ICU admissions in Scotland in relation to trends in admission rates, regional variation in admissions, ICU treatment intensity, and ICU and 1-year mortality. DESIGN: National 5-year cohort study of ICU first admissions (January 1, 2005, to December 31, 2009). SETTING: All admissions to ICUs and combined units (level 2/3 care) in Scotland captured by the Scottish Intensive Care Society Audit Group database, linked with hospital discharge data and death records. PATIENTS: A total of 40,142 patients: 3,865 were 80 years old or older (9.6%), 13,904 (34.6%) were 65-79 years old; and 22,373 were younger than 65 years (55.7%). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between 2005 and 2009, elderly admission rates decreased from 36.6/10,000 (95% CI, 34.0-39.2) in 2005 to 28.7/10,000 (95% CI, 26.5-30.9) in 2009 (p < 0.001; relative decrease, 22.0%); older admission rates also decreased, but less steeply (31.1 [95% CI, 29.9-32.2] to 26.1 [95% CI, 25.1-27.1] per 10,000 population; p < 0.001; relative decrease, 16.1%). Rates were static for younger patients. Restricted to mechanically ventilated elderly patients, rates ranged from 13.9 to 30.1/10,000 between healthboard administrative regions (p < 0.001). Emergency surgical diagnoses were more prevalent for elderly patients (elderly, 39.8%; older, 25.1%; younger, 20.3%; p < 0.001). Subgroup analyses limited to pneumonia admissions (elderly, n = 242; older, n = 1,226; younger, n = 1,836) indicated similar acute physiology scores, but fewer preexisting comorbidities among elderly patients (p = 0.007), who received a shorter duration of organ support and ICU stay. Mortality rates were higher in elderly patients at ICU discharge (elderly, 26.5%; older, 25.0%; younger, 17.0%; p < 0.001; confounder adjusted odds ratio elderly vs younger, 2.33 [95% CI, 2.11-2.58]; p < 0.001). Differences persisted at 1 year (elderly, 52.2%; older, 43.8%; younger, 27.6%; adjusted odds ratio elderly vs younger, 3.72 [95% CI, 3.42-4.06]; p < 0.001). CONCLUSIONS: In Scotland, elderly and older ICU admission rates are decreasing, with regional geographic variation. Although limited by an absence of a measure of frailty, patient characteristics and treatment intensity suggest selection of less comorbid elderly patients, indicating possible rationing based on chronologic age.

Socioeconomic status, comorbidity and mortality in patients with type 2 diabetes mellitus in Scotland 2004-2011: a cohort study.

BACKGROUND: Mortality in people with and without diabetes often exhibits marked social patterning, risk of death being greater in deprived groups. This may reflect deprivation-related differences in comorbid disease (conditions additional to diabetes itself). This study sought to determine whether the social patterning of mortality in a population with type 2 diabetes mellitus (T2DM) is explained by differential comorbidity. METHODS: Hospital records for 70 197 men and 56 451 women diagnosed with T2DM at 25 years of age and above in Scotland during the period 2004-2011 were used to construct comorbidity histories. Sex-specific logistic models were fitted to predict mortality at 1 year after diagnosis with T2DM, predicted initially by age and socioeconomic status (SES) then extended to incorporate in turn 5 representations of comorbidity (including the Charlson Index). The capacity of comorbidity to explain social mortality gradients was assessed by observing the change in regression coefficients for SES following the addition of comorbidity. RESULTS: After adjustment for age and Charlson Index, the OR for the contrast between the least deprived and most deprived quintiles of SES for men was 0.79 (95% CI 0.67 to 0.94). For women, the OR was 0.81 (0.67 to 0.97). Similar results were obtained for the 4 other comorbidity measures used. CONCLUSIONS: The social patterning of mortality in people with T2DM is not fully explained by differing levels of comorbid disease additional to T2DM itself. Other dimensions of deprivation are implicated in the elevated death rates observed in deprived groups of people with T2DM.

Early estimation of pandemic influenza Antiviral and Vaccine Effectiveness (EAVE): use of a unique community and laboratory national data-linked cohort study.

BACKGROUND: After the introduction of any new pandemic influenza, population-level surveillance and rapid assessment of the effectiveness of a new vaccination will be required to ensure that it is targeted to those at increased risk of serious illness or death from influenza. OBJECTIVE: We aimed to build a pandemic influenza reporting platform that will determine, once a new pandemic is under way: the uptake and effectiveness of any new pandemic vaccine or any protective effect conferred by antiviral drugs once available; the clinical attack rate of pandemic influenza; and the existence of protection provided by previous exposure to, and vaccination from, A/H1N1 pandemic or seasonal influenza/identification of susceptible groups. DESIGN: An observational cohort and test-negative study design will be used (post pandemic). SETTING: A national linkage of patient-level general practice data from 41 Practice Team Information general practices, hospitalisation and death certification, virological swab and serology-linked data. PARTICIPANTS: We will study a nationally representative sample of the Scottish population comprising 300,000 patients. Confirmation of influenza using reverse transcription polymerase chain reaction and, in a subset of the population, serology. INTERVENTIONS: Future available pandemic influenza vaccination and antivirals will be evaluated. MAIN OUTCOME MEASURES: To build a reporting platform tailored towards the evaluation of pandemic influenza vaccination. This system will rapidly measure vaccine effectiveness (VE), adjusting for confounders, estimated by determining laboratory-confirmed influenza; influenza-related morbidity and mortality, including general practice influenza-like illnesses (ILIs); and hospitalisation and death from influenza and pneumonia. Once a validated haemagglutination inhibition assay has been developed (and prior to the introduction of any vaccination), cross-reactivity with previous exposure to A/H1N1 or A/H1N1 vaccination, other pandemic influenza or other seasonal influenza vaccination or exposure will be measured. CONCLUSIONS: A new sentinel system, capable of rapidly determining the estimated incidence of pandemic influenza, and pandemic influenza vaccine and antiviral uptake and effectiveness in preventing influenza and influenza-related clinical outcomes, has been created. We have all of the required regulatory approvals to allow rapid activation of the sentinel systems in the event of a pandemic. Of the 41 practices expressing an interest in participating, 40 have completed all of the necessary paperwork to take part in the reporting platform. The data extraction tool has been installed in these practices. Data extraction and deterministic linkage systems have been tested. Four biochemistry laboratories have been recruited, and systems for serology collection and linkage of samples to general practice data have been put in place. FUTURE WORK: The reporting platform has been set up and is ready to be activated in the event of any pandemic of influenza. Building on this infrastructure, there is now the opportunity to extend the network of general practices to allow important subgroup analyses of VE (e.g. for patients with comorbidities, at risk of serious ILI) and to link to other data sources, in particular to test for maternal outcomes in pregnant patients. STUDY REGISTRATION: This study is registered as ISRCTN55398410. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Comparative efficacy of inhaled corticosteroid and long-acting beta agonist combinations in preventing COPD exacerbations: a Bayesian network meta-analysis.

BACKGROUND: A combination therapy with inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations. Currently, there are five ICS/LABA combination products available on the market. The purpose of this study was to systematically review the efficacy of various ICS/LABA combinations with a network meta-analysis. METHODS: Several databases and manufacturer's websites were searched for relevant clinical trials. Randomized control trials, at least 12 weeks duration, comparing an ICS/LABA combination with active control or placebo were included. Moderate and severe exacerbations were chosen as the outcome assessment criteria. The primary analyses were conducted with a Bayesian Markov chain Monte Carlo method. RESULTS: Most of the ICS/LABA combinations reduced moderate-to-severe exacerbations as compared with placebo and LABA, but none of them reduced severe exacerbations. However, many studies excluded patients receiving long-term oxygen therapy. Moderate-dose ICS was as effective as high-dose ICS in reducing exacerbations when combined with LABA. CONCLUSION: ICS/LABA combinations had a class effect with regard to the prevention of COPD exacerbations. Moderate-dose ICS/LABA combination therapy would be sufficient for COPD patients when indicated. The efficacy of ICS/LABA combination therapy appeared modest and had no impact in reducing severe exacerbations. Further studies are needed to evaluate the efficacy of ICS/LABA combination therapy in severely affected COPD patients requiring long-term oxygen therapy.

Surviving intensive care: a systematic review of healthcare resource use after hospital discharge*.

OBJECTIVES: Intensive care survivors continue to experience significant morbidity following acute hospital discharge, but healthcare costs associated with this ongoing morbidity are poorly described. As the demand for intensive care increases, understanding the magnitude of postacute hospital healthcare costs is of increasing relevance to clinicians and healthcare planners. We undertook a systematic review of the literature reporting major healthcare resource use by intensive care survivors following discharge from the hospital and identified factors associated with increased resource use. DATA SOURCES: Seven electronic databases (1990 to August 2012), conference proceedings, and reference lists were searched. STUDY SELECTION: Studies published in English were included that reported postacute hospital discharge healthcare resource use at the individual level for survivors of intensive care. DATA EXTRACTION: Two reviewers screened abstracts and one abstracted data using standardized templates. Study quality was assessed using recognized appraisal methods specific to economic evaluation, epidemiological studies, and randomized trials. DATA SYNTHESIS: From 4,909 articles, 18 articles representing 14 cohorts fulfilled inclusion criteria. There was substantial variation in methodology, especially the resource categories included in the studies. Following standardization to a common currency and year, variation in cost of resource use was evident (range 2011 US $18,847-$148,454 for year 1 postdischarge). Studies undertaken within the United States reported the highest costs; those in the United Kingdom reported substantially lower costs. Factors associated with increased resource use included increasing age, comorbidities, organ dysfunction score, and previous resource use. CONCLUSIONS: Wide variation in methodological approaches limited study comparability and external validity of findings. We found substantial variation in the cost of resource use, especially among countries. Careful description of patient cohorts and healthcare systems is required to maximize generalizability. We give recommendations for a more standardized approach to improve design and reporting of future studies.