Predictors and Significance of Readmission after Esophagogastric Surgery:A Nationwide Analysis

Objective: The aim of this study is to identify risk factors for readmission after elective esophagogastric cancer surgery and characterize the impact of readmission on long-term survival. The study will also identify whether the location of readmission to either the hospital that performed the primary surgery (index hospital) or another institution (nonindex hospital) has an impact on postoperative mortality.Background: Over the past decade, the center-volume relationship has driven the centralization of major cancer surgery, which has led to improvements in perioperative mortality. However, the impact of readmission, especially to nonindex centers, on long-term mortality remains unclear.Methods: This was a national population-based cohort study using Hospital Episode Statistics of adult patients undergoing esophagectomy and gastrectomy in England between January 2008 and December 2019.Results: This study included 27,592 patients, of which overall readmission rates were 25.1% (index 15.3% and nonindex 9.8%). The primary cause of readmission to an index hospital was surgical in 45.2% and 23.7% in nonindex readmissions. Patients with no readmissions had significantly longer survival than those with readmissions (median: 4.5 vs 3.8 years; P &lt; 0.001). Patients readmitted to their index hospital had significantly improved survival as compared to nonindex readmissions (median: 3.3 vs 4.7 years; P &lt; 0.001). Minimally invasive surgery and surgery performed in high-volume centers had improved 90-day mortality (odds ratio, 0.75; P &lt; 0.001; odds ratio, 0.60; P &lt; 0.001).Conclusion: Patients requiring readmission to the hospital after surgery have an increased risk of mortality, which is worsened by readmission to a nonindex institution. Patients requiring readmission to the hospital should be assessed and admitted, if required, to their index institution.<br/

Incidence, morbidity and mortality of patients with achalasia in England:findings from a study of nationwide hospital and primary care data

BackgroundAchalasia is an uncommon condition characterised by failed lower oesophageal sphincter relaxation. Data regarding its incidence, prevalence, disease associations and long-term outcomes are very limited.MethodsHospital Episode Statistics (HES) include demographic and diagnostic data for all English hospital attendances. The Health Improvement Network (THIN) includes the primary care records of 4.5 million UK subjects, representative of national demographics. Both were searched for incident cases between 2006 and 2016 and THIN for prevalent cases. Subjects with achalasia in THIN were compared with age, sex, deprivation tand smoking status matched controls for important comorbidities and mortality.ResultsThere were 10 509 and 711 new achalasia diagnoses identified in HES and THIN, respectively. The mean incidence per 100 000 people in HES was 1.99 (95% CI 1.87 to 2.11) and 1.53 (1.42 to 1.64) per 100 000 person-years in THIN. The prevalence in THIN was 27.1 (25.4 to 28.9) per 100 000 population. Incidence rate ratios (IRRs) were significantly higher in subjects with achalasia (n=2369) compared with controls (n=3865) for: oesophageal cancer (IRR 5.22 (95% CI: 1.88 to 14.45), p&lt;0.001), aspiration pneumonia (13.38 (1.66 to 107.79), p=0.015), lower respiratory tract infection (1.33 (1.05 to 1.70), p=0.02) and mortality (1.33 (1.17 to 1.51), p&lt;0.001). The median time from achalasia diagnosis to oesophageal cancer diagnosis was 15.5 (IQR 20.4) years.ConclusionThe incidence of achalasia is 1.99 per 100 000 population in secondary care data and 1.53 per 100 000 person-years in primary care data. Subjects with achalasia have an increased incidence of oesophageal cancer, aspiration pneumonia, lower respiratory tract infections and higher mortality. Clinicians treating patients with achalasia should be made aware of these associated morbidities and its increased mortality.</jats:sec

Common protocol for validation of the QCOVID algorithm across the four UK nations

Introduction: The QCOVID algorithm is a risk prediction tool for infection and subsequent hospitalisation/death due to SARS-CoV-2. At the time of writing, it is being used in important policy-making decisions by the UK and devolved governments for combatting the COVID-19 pandemic, including deliberations on shielding and vaccine prioritisation. There are four statistical validations exercises currently planned for the QCOVID algorithm, using data pertaining to England, Northern Ireland, Scotland and Wales, respectively. This paper presents a common procedure for conducting and reporting on validation exercises for the QCOVID algorithm. Methods and analysis: We will use open, retrospective cohort studies to assess the performance of the QCOVID risk prediction tool in each of the four UK nations. Linked datasets comprising of primary and secondary care records, virological testing data and death registrations will be assembled in trusted research environments in England, Scotland, Northern Ireland and Wales. We will seek to have population level coverage as far as possible within each nation. The following performance metrics will be calculated by strata: Harrell’s C, Brier Score, R2 and Royston's D. Ethics and dissemination: Approvals have been obtained from relevant ethics bodies in each UK nation. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journal

An external validation of the QCovid risk prediction algorithm for risk of mortality from COVID-19 in adults: a national validation cohort study in England.

BACKGROUND: Public policy measures and clinical risk assessments relevant to COVID-19 need to be aided by risk prediction models that are rigorously developed and validated. We aimed to externally validate a risk prediction algorithm (QCovid) to estimate mortality outcomes from COVID-19 in adults in England. METHODS: We did a population-based cohort study using the UK Office for National Statistics Public Health Linked Data Asset, a cohort of individuals aged 19-100 years, based on the 2011 census and linked to Hospital Episode Statistics, the General Practice Extraction Service data for pandemic planning and research, and radiotherapy and systemic chemotherapy records. The primary outcome was time to COVID-19 death, defined as confirmed or suspected COVID-19 death as per death certification. Two periods were used: (1) Jan 24 to April 30, 2020, and (2) May 1 to July 28, 2020. We assessed the performance of the QCovid algorithms using measures of discrimination and calibration. Using predicted 90-day risk of COVID-19 death, we calculated r2 values, Brier scores, and measures of discrimination and calibration with corresponding 95% CIs over the two time periods. FINDINGS: We included 34 897 648 adults aged 19-100 years resident in England. 26 985 (0·08%) COVID-19 deaths occurred during the first period and 13 177 (0·04%) during the second. The algorithms had good discrimination and calibration in both periods. In the first period, they explained 77·1% (95% CI 76·9-77·4) of the variation in time to death in men and 76·3% (76·0-76·6) in women. The D statistic was 3·761 (3·732-3·789) for men and 3·671 (3·640-3·702) for women and Harrell's C was 0·935 (0·933-0·937) for men and 0·945 (0·943-0·947) for women. Similar results were obtained for the second time period. In the top 5% of patients with the highest predicted risks of death, the sensitivity for identifying deaths in the first period was 65·94% for men and 71·67% for women. INTERPRETATION: The QCovid population-based risk algorithm performed well, showing high levels of discrimination for COVID-19 deaths in men and women for both time periods. QCovid has the potential to be dynamically updated as the pandemic evolves and, therefore, has potential use in guiding national policy. FUNDING: UK National Institute for Health Research

Multilingual Repertoire Management and Illocutionary Functions in Yiddish Signage in Manchester

Drawing on a corpus of annotated images that capture the linguistic landscape of a residential neighbourhood in Greater Manchester (UK) with a large Hasidic-Haredi (so-called ‘ultra-Orthodox’) Jewish population, we show how choices within a multilingual repertoire are both indicative and constitutive of different communicative acts and illocutions. Written Yiddish is embedded into an established tradition of literacy where creativity is accompanied by authoritative citations from Hebrew scripture. We discuss the use of Yiddish in affective, appellative, mobilising, regulatory and prohibitive actions. Semi-public use of written Yiddish is directed at participants who share a repertoire of closely intertwined social, religious and linguistic practices. Unlike many other lesser-used languages, the use of Yiddish in Haredi communities is not restricted to indexical identity flagging or commodification purposes. We show how in this multilingual setting, the indexical ordering of languages on written artefacts does not represent a hierarchy of absolute valorisation but rather a complementarity of functions that draws on simultaneous activation of several repertoire components

Keeping children safe: a multicentre programme of research to increase the evidence base for preventing unintentional injuries in the home in the under-fives

Background: Unintentional injuries among 0- to 4-year-olds are a major public health problem incurring substantial NHS, individual and societal costs. However, evidence on the effectiveness and cost-effectiveness of preventative interventions is lacking. Aim: To increase the evidence base for thermal injury, falls and poisoning prevention for the under-fives. Methods: Six work streams comprising five multicentre case–control studies assessing risk and protective factors, a study measuring quality of life and injury costs, national surveys of children’s centres, interviews with children’s centre staff and parents, a systematic review of barriers to, and facilitators of, prevention and systematic overviews, meta-analyses and decision analyses of home safety interventions. Evidence from these studies informed the design of an injury prevention briefing (IPB) for children’s centres for preventing fire-related injuries and implementation support (training and facilitation). This was evaluated by a three-arm cluster randomised controlled trial comparing IPB and support (IPB+), IPB only (no support) and usual care. The primary outcome was parent-reported possession of a fire escape plan. Evidence from all work streams subsequently informed the design of an IPB for preventing thermal injuries, falls and poisoning. Results: Modifiable risk factors for falls, poisoning and scalds were found. Most injured children and their families incurred small to moderate health-care and non-health-care costs, with a few incurring more substantial costs. Meta-analyses and decision analyses found that home safety interventions increased the use of smoke alarms and stair gates, promoted safe hot tap water temperatures, fire escape planning and storage of medicines and household products, and reduced baby walker use. Generally, more intensive interventions were the most effective, but these were not always the most cost-effective interventions. Children’s centre and parental barriers to, and facilitators of, injury prevention were identified. Children’s centres were interested in preventing injuries, and believed that they could prevent them, but few had an evidence-based strategic approach and they needed support to develop this. The IPB was implemented by children’s centres in both intervention arms, with greater implementation in the IPB+ arm. Compared with usual care, more IPB+ arm families received advice on key safety messages, and more families in each intervention arm attended fire safety sessions. The intervention did not increase the prevalence of fire escape plans [adjusted odds ratio (AOR) IPB only vs. usual care 0.93, 95% confidence interval (CI) 0.58 to 1.49; AOR IPB+ vs. usual care 1.41, 95% CI 0.91 to 2.20] but did increase the proportion of families reporting more fire escape behaviours (AOR IPB only vs. usual care 2.56, 95% CI 1.38 to 4.76; AOR IPB+ vs. usual care 1.78, 95% CI 1.01 to 3.15). IPB-only families were less likely to report match play by children (AOR 0.27, 95% CI 0.08 to 0.94) and reported more bedtime fire safety routines (AOR for a 1-unit increase in the number of routines 1.59, 95% CI 1.09 to 2.31) than usual-care families. The IPB-only intervention was less costly and marginally more effective than usual care. The IPB+ intervention was more costly and marginally more effective than usual care. Limitations: Our case–control studies demonstrate associations between modifiable risk factors and injuries but not causality. Some injury cost estimates are imprecise because of small numbers. Systematic reviews and meta-analyses were limited by the quality of the included studies, the small numbers of studies reporting outcomes and significant heterogeneity, partly explained by differences in interventions. Network meta-analysis (NMA) categorised interventions more finely, but some variation remained. Decision analyses are likely to underestimate cost-effectiveness for a number of reasons. IPB implementation varied between children’s centres. Greater implementation may have resulted in changes in more fire safety behaviours. Conclusions: Our studies provide new evidence about the effectiveness of, as well as economic evaluation of, home safety interventions. Evidence-based resources for preventing thermal injuries, falls and scalds were developed. Providing such resources to children’s centres increases their injury prevention activity and some parental safety behaviours. Future work: Further randomised controlled trials, meta-analyses and NMAs are needed to evaluate the effectiveness and cost-effectiveness of home safety interventions. Further work is required to measure NHS, family and societal costs and utility decrements for childhood home injuries and to evaluate complex multicomponent interventions such as home safety schemes using a single analytical model. Trial registration: Current Controlled Trials ISRCTN65067450 and ClinicalTrials.gov NCT01452191. Funding: The National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 5, No. 14. See the NIHR Journals Library website for further project information

Sex steroids, growth factors and mammographic density: a cross-sectional study of UK postmenopausal Caucasian and Afro-Caribbean women

INTRODUCTION: Sex steroids, insulin-like growth factors (IGFs) and prolactin are breast cancer risk factors but whether their effects are mediated through mammographic density, one of the strongest risk factors for breast cancer, is unknown. If such a hormonal basis of mammographic density exists, hormones may underlie ethnic differences in both mammographic density and breast cancer incidence rates. METHODS: In a cross-sectional study of 270 postmenopausal Caucasian and Afro-Caribbean women attending a population-based breast screening service in London, UK, we investigated whether plasma biomarkers (oestradiol, oestrone, sex hormone binding globulin (SHBG), testosterone, prolactin, leptin, IGF-I, IGF-II and IGF binding protein 3 (IGFBP3)) were related to and explained ethnic differences in mammographic percent density, dense area and nondense area, measured in Cumulus using the threshold method. RESULTS: Mean levels of oestrogens, leptin and IGF-I:IGFBP3 were higher whereas SHBG and IGF-II:IGFBP3 were lower in Afro-Caribbean women compared with Caucasian women after adjustment for higher mean body mass index (BMI) in the former group (by 3.2 kg/m(2) (95% confidence interval (CI): 1.8, 4.5)). Age-adjusted percent density was lower in Afro-Caribbean compared with Caucasian women by 5.4% (absolute difference), but was attenuated to 2.5% (95% CI: -0.2, 5.1) upon BMI adjustment. Despite ethnic differences in biomarkers and in percent density, strong ethnic-age-adjusted inverse associations of oestradiol, leptin and testosterone with percent density were completely attenuated upon adjustment for BMI. There were no associations of IGF-I, IGF-II or IGFBP3 with percent density or dense area. We found weak evidence that a twofold increase in prolactin and oestrone levels were associated, respectively, with an increase (by 1.7% (95% CI: -0.3, 3.7)) and a decrease (by 2.0% (95% CI: 0, 4.1)) in density after adjustment for BMI. CONCLUSIONS: These findings suggest that sex hormone and IGF levels are not associated with BMI-adjusted percent mammographic density in cross-sectional analyses of postmenopausal women and thus do not explain ethnic differences in density. Mammographic density may still, however, be influenced by much higher premenopausal hormone levels

Neuroanatomical Pattern of Mitochondrial Complex I Pathology Varies between Schizophrenia, Bipolar Disorder and Major Depression

BACKGROUND:Mitochondrial dysfunction was reported in schizophrenia, bipolar disorderand major depression. The present study investigated whether mitochondrial complex I abnormalities show disease-specific characteristics. METHODOLOGY/PRINCIPAL FINDINGS:mRNA and protein levels of complex I subunits NDUFV1, NDUFV2 and NADUFS1, were assessed in striatal and lateral cerebellar hemisphere postmortem specimens and analyzed together with our previous data from prefrontal and parieto-occipital cortices specimens of patients with schizophrenia, bipolar disorder, major depression and healthy subjects. A disease-specific anatomical pattern in complex I subunits alterations was found. Schizophrenia-specific reductions were observed in the prefrontal cortex and in the striatum. The depressed group showed consistent reductions in all three subunits in the cerebellum. The bipolar group, however, showed increased expression in the parieto-occipital cortex, similar to those observed in schizophrenia, and reductions in the cerebellum, yet less consistent than the depressed group. CONCLUSIONS/SIGNIFICANCE:These results suggest that the neuroanatomical pattern of complex I pathology parallels the diversity and similarities in clinical symptoms of these mental disorders