Influence of Hospital Volume on Nephrectomy Mortality and Complications: A Systematic Review and Meta-analysis Stratified by Surgical Type

Objectives The provision of complex surgery is increasingly centralised to high volume specialist hospitals. Evidence to support nephrectomy centralisation however has been inconsistent. We conducted a systematic review and meta-analysis to determine the association between hospital case volumes and perioperative outcomes in radical nephrectomy, partial nephrectomy and nephrectomy with venous thrombectomy. Methods Medline, Embase and the Cochrane Library were searched for relevant studies published between 1990 and 2016. Pooled effect estimates for nephrectomy mortality and complications were calculated for each nephrectomy type using the DerSimonian and Laird random-effects model. Sensitivity analyses were performed to examine the effects of heterogeneity on the pooled effect estimates by excluding studies with the heaviest weighting, lowest methodological score, and most likely to introduce bias from misclassification of standardised hospital volume. Results Some 226,372 patients from sixteen publications were included in our review and meta-analysis. Considerable between-study heterogeneity was noted and only a few reported volume-outcome relationships specifically in partial nephrectomy or nephrectomy with venous thrombectomy. High volume hospitals were correlated with a 26% and 52% reduction in mortality for radical nephrectomy (OR 0.74, 95% CI 0.61-0.90, p<0.01) and nephrectomy with venous thrombectomy (OR 0.48, 95% CI 0.29-0.81, p<0.01) respectively. In addition, radical nephrectomy in high volume hospitals was associated with an 18% reduction in complications (OR 0.82, 95% CI 0.73-0.92, p<0.01). No significant volume-outcome relationship in mortality (OR 0.84, 95% CI 0.31-2.26, p=0.73) or complications (OR 0.85, 95% CI 0.55-1.30, p=0.44) was observed for partial nephrectomy. Conclusions Our findings suggest that patients undergoing radical nephrectomy have improved outcomes when treated by high volume hospitals. Evidence of this in partial nephrectomy and nephrectomy with venous thrombectomy is however not yet clear and could be secondary to the low number of studies included and the small patient number in our analyses. Further investigation is warranted to establish the full potential of nephrectomy centralisation particularly as existing evidence is of low quality with significant heterogeneity.This work was supported by Addenbrooke’s Charitable Trust, the Royal College of Surgeons of England and the Urology Foundation. Cancer Research UK Advanced Clinician Scientist Fellowship award (No. C18081/A18180) has supported GL and TS

Associations between diagnostic pathways and care experience in colorectal cancer: Evidence from patient-reported data

This is the final version. Available from the publisher via the DOI in this recordObjective: To examine how different pathways to diagnosis of colorectal cancer may be associated with the experience of subsequent care. Design: Patient survey linked to information on diagnostic route. English patients with colorectal cancer (analysis sample n=6837) who responded to a patient survey soon after their hospital treatment. Main outcome measures: Odds Ratios and adjusted proportions of negative evaluation of key aspects of care for colorectal cancer, including the experience of shared decision-making about treatment, specialist nursing and care coordination, by diagnostic route (ie, screening detection, emergency presentation, urgent and elective general practitioner referral). Results: For 14 of 18 questions, there was evidence (p≤0.02) for variation in patient experience by diagnostic route, with 6-31 percentage point differences between routes in adjusted proportions of negative experience. Emergency presenters were more likely to report a negative experience for most questions, including those about adequacy of information about their diagnosis and sufficient explanation before operations. Screen-detected patients were least likely to report negative experiences except for support from primary care. Patients diagnosed through elective primary care referrals were most likely to report worse experience for questions for which overall variation by route was generally small. Conclusions: Screening-detected patients tend to report the best and emergency presenters the worst experience of subsequent care. Improvement efforts can target care integration for screening-detected patients and provision of information about the diagnosis and treatment of emergency presenters.Cancer Research U

Do comorbidities influence help-seeking for cancer alarm symptoms? A population-based survey in England

Background: We examined associations between different chronic morbidities and help-seeking for possible cancer symptoms. Methods: Postal survey of individuals aged >50 years in England. Participants could report prior morbidities in respect of 12 pre-defined conditions. Among patients experiencing possible cancer symptoms we examined associations between specific morbidities and self-reported help-seeking (i.e. contacted versus not contacted a GP) for each alarm symptom using regression analyses. Results: Among 2042 respondents (42% response rate), 936 (46%) recently experienced 1 of 14 possible cancer symptoms considered in our analysis. Of them, 80% reported one or more morbidities, most frequently hypertension/hypercholesterolemia (40%), osteomuscular (36%) and heart diseases (21%). After adjustment for socio-demographic characteristics, patients with hypertension/hypercholesterolemia were more likely to report help-seeking for possible cancer symptoms, such as unexplained cough (OR = 2.0; 95% confidence interval (CI) 1.1-3.5), pain (OR = 2.2; 95% CI 1.0-4.5) and abdominal bloating (OR = 2.3; 95% CI 1.1-4.8). Urinary morbidity was associated with increased help-seeking for abdominal bloating (OR = 5.4; 95% CI 1.2-23.7) or rectal bleeding (OR = 5.8; 95% CI 1.4-23.8). In contrast, heart problems reduced help-seeking for change in bowel habits (OR = 0.4; 95% CI 0.2-1.0). Conclusions: Comorbidities are common and may facilitate help-seeking for possible cancer symptoms, but associations vary for specific symptom-comorbidity pairs. The findings can contribute to the design of future cancer symptom awareness campaigns.This work was part of the programme of the Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis. The Policy Research Unit in Cancer Awareness, Screening, and Early Diagnosis receives funding for a research programme from the Department of Health Policy Research Programme. It is a collaboration between researchers from seven institutions (Queen Mary University of London, University College London, King’s College London, London School of Hygiene and Tropical Medicine, Hull York Medical School, Durham University and Peninsula Medical School). GL and TS were supported by Cancer Research UK Advanced Clinician Scientist Fellowship (C18081/A18180)

Long-term cardiometabolic health in people born after assisted reproductive technology: a multi-cohort analysis

Aims To examine associations of assisted reproductive technology (ART) conception (vs. natural conception: NC) with offspring cardiometabolic health outcomes and whether these differ with age. Methods and results Differences in systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), lipids, and hyperglycaemic/insulin resistance markers were examined using multiple linear regression models in 14 population-based birth cohorts in Europe, Australia, and Singapore, and results were combined using meta-analysis. Change in cardiometabolic outcomes from 2 to 26 years was examined using trajectory modelling of four cohorts with repeated measures. 35 938 (654 ART) offspring were included in the meta-analysis. Mean age ranged from 13 months to 27.4 years but was <10 years in 11/14 cohorts. Meta-analysis found no statistical difference (ART minus NC) in SBP (-0.53 mmHg; 95% CI:-1.59 to 0.53), DBP (-0.24 mmHg; -0.83 to 0.35), or HR (0.02 beat/min; -0.91 to 0.94). Total cholesterol (2.59%; 0.10-5.07), HDL cholesterol (4.16%; 2.52-5.81), LDL cholesterol (4.95%; 0.47-9.43) were statistically significantly higher in ART-conceived vs. NC offspring. No statistical difference was seen for triglycerides (TG), glucose, insulin, and glycated haemoglobin. Long-term follow-up of 17 244 (244 ART) births identified statistically significant associations between ART and lower predicted SBP/DBP in childhood, and subtle trajectories to higher SBP and TG in young adulthood; however, most differences were not statistically significant. Conclusion These findings of small and statistically non-significant differences in offspring cardiometabolic outcomes should reassure people receiving ART. Longer-term follow-up is warranted to investigate changes over adulthood in the risks of hypertension, dyslipidaemia, and preclinical and clinical cardiovascular disease.Acknowledgements We thank all cohort members and researchers who participated in the study. Cohort-specific acknowledgments can be found in Supplementary material online, Text S2. Data used in this study are available to bone fide researchers upon request to each cohort. Details of how to access the data are provided in Supplementary material online, Text S2. Please contact Professor Deborah Lawlor ([email protected]) and Dr Ahmed Elhakeem ([email protected]) if you have relevant data and would like to join the ART-Health Cohort Collaboration and contribute to future collaborations

Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies

Background Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence. Methods and findings We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries. Conclusions This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.This collaborative project received funding from the European Union's Horizon 2020 research and innovation programme (Grant Agreement No. 733206 LifeCycle, Grand Recipient VWVJ; Grant Agreement No. 824989 EUCAN-Connect, Grand Recipient AMNA). Please, see S1 Appendix for list of cohort-specific funding/support. DAL is supported by the UK Medical Research Council (MC_UU_00011/6) and British Heart Foundation (CH/F/20/90003 and AA/18/7/34219). RCW is supported by UKRI Innovation Fellowship with Health Data Research UK [MR/S003959/1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The LifeCycle Project-EU Child Cohort Network : a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.Peer reviewe

The association between crowding within households and behavioural problems in children: Longitudinal data from the Southampton Women’s Survey

BACKGROUND:In England, nearly one child in ten lives in overcrowded housing. Crowding is likely to worsen with increasing population size, urbanisation, and the ongoing concerns about housing shortages. Children with behavioural difficulties are at increased risk of mental and physical health problems and poorer employment prospects. OBJECTIVE:To test the association between the level of crowding in the home and behavioural problems in children, and to explore what factors might explain the relationship. METHODS:Mothers of 2576 children from the Southampton Women's Survey population-based mother-offspring cohort were interviewed. Crowding was measured at age 2 years by people per room (PPR) and behavioural problems assessed at age 3 years with the Strengths and Difficulties Questionnaire (SDQ). Both were analysed as continuous measures, and multivariable linear regression models were fitted, adjusting for confounding factors: gender, age, single-parent family, maternal education, receipt of benefits, and social class. Potential mediators were assessed with formal mediation analysis. RESULTS:The characteristics of the sample were broadly representative of the population in England. Median (IQR) SDQ score was 9 (6-12) and PPR was 0.75 (0.6-1). In households that were more crowded, children tended to have more behavioural problems (by 0.20 SDQ points (95% CI 0.08, 0.32) per additional 0.2 PPR, adjusting for confounding factors). This relationship was partially mediated by greater maternal stress, less sleep, and strained parent-child interactions. CONCLUSIONS:Living in a more crowded home was associated with a greater risk of behavioural problems, independent of confounding factors. The findings suggest that improved housing might reduce childhood behavioural problems and that families living in crowded circumstances might benefit from greater support