Estimating quality-adjusted life expectancy (QALE) for local authorities in Great Britain and its association with indicators of the inclusive economy: a cross-sectional study.

OBJECTIVES: Quantifying area-level inequalities in population health can help to inform policy responses. We describe an approach for estimating quality-adjusted life expectancy (QALE), a comprehensive health expectancy measure, for local authorities (LAs) in Great Britain (GB). To identify potential factors accounting for LA-level QALE inequalities, we examined the association between inclusive economy indicators and QALE. SETTING: 361/363 LAs in GB (lower tier/district level) within the period 2018-2020. DATA AND METHODS: We estimated life tables for LAs using official statistics and utility scores from an area-level linkage of the Understanding Society survey. Using the Sullivan method, we estimated QALE at birth in years with corresponding 80% CIs. To examine the association between inclusive economy indicators and QALE, we used an open access data set operationalising the inclusive economy, created by the System Science in Public Health and Health Economics Research consortium. RESULTS: Population-weighted QALE estimates across LAs in GB were lowest in Scotland (females/males: 65.1 years/64.9 years) and Wales (65.0 years/65.2 years), while they were highest in England (67.5 years/67.6 years). The range across LAs for females was from 56.3 years (80% CI 45.6 to 67.1) in Mansfield to 77.7 years (80% CI 65.11 to 90.2) in Runnymede. QALE for males ranged from 57.5 years (80% CI 40.2 to 74.7) in Merthyr Tydfil to 77.2 years (80% CI 65.4 to 89.1) in Runnymede. Indicators of the inclusive economy accounted for more than half of the variation in QALE at the LA level (adjusted R2 females/males: 50%/57%). Although more inclusivity was generally associated with higher levels of QALE at the LA level, this association was not consistent across all 13 inclusive economy indicators. CONCLUSIONS: QALE can be estimated for LAs in GB, enabling further research into area-level health inequalities. The associations we identified between inclusive economy indicators and QALE highlight potential policy priorities for improving population health and reducing health inequalities.

Systems science methods in public health: what can they contribute to our understanding of and response to the cost-of-living crisis?

BACKGROUND: Many complex public health evidence gaps cannot be fully resolved using only conventional public health methods. We aim to familiarise public health researchers with selected systems science methods that may contribute to a better understanding of complex phenomena and lead to more impactful interventions. As a case study, we choose the current cost-of-living crisis, which affects disposable income as a key structural determinant of health. METHODS: We first outline the potential role of systems science methods for public health research more generally, then provide an overview of the complexity of the cost-of-living crisis as a specific case study. We propose how four systems science methods (soft systems, microsimulation, agent-based and system dynamics models) could be applied to provide more in-depth understanding. For each method, we illustrate its unique knowledge contributions, and set out one or more options for studies that could help inform policy and practice responses. RESULTS: Due to its fundamental impact on the determinants of health, while limiting resources for population-level interventions, the cost-of-living crisis presents a complex public health challenge. When confronted with complexity, non-linearity, feedback loops and adaptation processes, systems methods allow a deeper understanding and forecasting of the interactions and spill-over effects common with real-world interventions and policies. CONCLUSIONS: Systems science methods provide a rich methodological toolbox that complements our traditional public health methods. This toolbox may be particularly useful in early stages of the current cost-of-living crisis: for understanding the situation, developing solutions and sandboxing potential responses to improve population health.

Large socioeconomic gap in period life expectancy and life years spent with complications of diabetes in the Scottish population with type 1 diabetes, 2013-2018.

BACKGROUND: We report the first study to estimate the socioeconomic gap in period life expectancy (LE) and life years spent with and without complications in a national cohort of individuals with type 1 diabetes. METHODS: This retrospective cohort study used linked healthcare records from SCI-Diabetes, the population-based diabetes register of Scotland. We studied all individuals aged 50 and older with a diagnosis of type 1 diabetes who were alive and residing in Scotland on 1 January 2013 (N = 8591). We used the Scottish Index of Multiple Deprivation (SIMD) 2016 as an area-based measure of socioeconomic deprivation. For each individual, we constructed a history of transitions by capturing whether individuals developed retinopathy/maculopathy, cardiovascular disease, chronic kidney disease, and diabetic foot, or died throughout the study period, which lasted until 31 December 2018. Using parametric multistate survival models, we estimated total and state-specific LE at an attained age of 50. RESULTS: At age 50, remaining LE was 22.2 years (95% confidence interval (95% CI): 21.6 - 22.8) for males and 25.1 years (95% CI: 24.4 - 25.9) for females. Remaining LE at age 50 was around 8 years lower among the most deprived SIMD quintile when compared with the least deprived SIMD quintile: 18.7 years (95% CI: 17.5 - 19.9) vs. 26.3 years (95% CI: 24.5 - 28.1) among males, and 21.2 years (95% CI: 19.7 - 22.7) vs. 29.3 years (95% CI: 27.5 - 31.1) among females. The gap in life years spent without complications was around 5 years between the most and the least deprived SIMD quintile: 4.9 years (95% CI: 3.6 - 6.1) vs. 9.3 years (95% CI: 7.5 - 11.1) among males, and 5.3 years (95% CI: 3.7 - 6.9) vs. 10.3 years (95% CI: 8.3 - 12.3) among females. SIMD differences in transition rates decreased marginally when controlling for time-updated information on risk factors such as HbA1c, blood pressure, BMI, or smoking. CONCLUSIONS: In addition to societal interventions, tailored support to reduce the impact of diabetes is needed for individuals from low socioeconomic backgrounds, including access to innovations in management of diabetes and the prevention of complications.

Effect of Intraoperative Handovers of Anesthesia Care on Mortality, Readmission, or Postoperative Complications Among Adults: The HandiCAP Randomized Clinical Trial.

Importance: Intraoperative handovers of anesthesia care are common. Handovers might improve care by reducing physician fatigue, but there is also an inherent risk of losing critical information. Large observational analyses report associations between handover of anesthesia care and adverse events, including higher mortality. Objective: To determine the effect of handovers of anesthesia care on postoperative morbidity and mortality. Design, Setting, and Participants: This was a parallel-group, randomized clinical trial conducted in 12 German centers with patients enrolled between June 2019 and June 2021 (final follow-up, July 31, 2021). Eligible participants had an American Society of Anesthesiologists physical status 3 or 4 and were scheduled for major inpatient surgery expected to last at least 2 hours. Interventions: A total of 1817 participants were randomized to receive either a complete handover to receive anesthesia care by another clinician (n = 908) or no handover of anesthesia care (n = 909). None of the participating institutions used a standardized handover protocol. Main Outcomes and Measures: The primary outcome was a 30-day composite of all-cause mortality, hospital readmission, or serious postoperative complications. There were 19 secondary outcomes, including the components of the primary composite, along with intensive care unit and hospital lengths of stay. Results: Among 1817 randomized patients, 1772 (98%; mean age, 66 [SD, 12] years; 997 men [56%]; and 1717 [97%] with an American Society of Anesthesiologists physical status of 3) completed the trial. The median total duration of anesthesia was 267 minutes (IQR, 206-351 minutes), and the median time from start of anesthesia to first handover was 144 minutes in the handover group (IQR, 105-213 minutes). The composite primary outcome occurred in 268 of 891 patients (30%) in the handover group and in 284 of 881 (33%) in the no handover group (absolute risk difference [RD], -2.5%; 95% CI, -6.8% to 1.9%; odds ratio [OR], 0.89; 95% CI, 0.72 to 1.10; P = .27). Nineteen of 889 patients (2.1%) in the handover group and 30 of 873 (3.4%) in the no handover group experienced all-cause 30-day mortality (absolute RD, -1.3%; 95% CI, -2.8% to 0.2%; OR, 0.61; 95% CI, 0.34 to 1.10; P = .11); 115 of 888 (13%) vs 136 of 872 (16%) were readmitted to the hospital (absolute RD, -2.7%; 95% CI, -5.9% to 0.6%; OR, 0.80; 95% CI, 0.61 to 1.05; P = .12); and 195 of 890 (22%) vs 189 of 874 (22%) experienced serious postoperative complications (absolute RD, 0.3%; 95% CI, -3.6% to 4.1%; odds ratio, 1.02; 95% CI, 0.81 to 1.28; P = .91). None of the 19 prespecified secondary end points differed significantly. Conclusions and Relevance: Among adults undergoing extended surgical procedures, there was no significant difference between the patients randomized to receive handover of anesthesia care from one clinician to another, compared with the no handover group, in the composite primary outcome of mortality, readmission, or serious postoperative complications within 30 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04016454.

Effect of therapeutic drug monitoring-based dose optimization of piperacillin/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial.

PURPOSE: Insufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy improves outcomes. METHODS: Randomized, multicenter, controlled trial from January 2017 to December 2019. Adult patients (n = 254) with sepsis or septic shock were randomly assigned 1:1 to receive continuous infusion of piperacillin/tazobactam with dosing guided by daily TDM of piperacillin or continuous infusion with a fixed dose (13.5 g/24 h if eGFR ≥ 20 mL/min). Target plasma concentration was four times the minimal inhibitory concentration (range ± 20%) of the underlying pathogen, respectively, of Pseudomonas aeruginosa in empiric situation. Primary outcome was the mean of daily total Sequential Organ Failure Assessment (SOFA) score up to day 10. RESULTS: Among 249 evaluable patients (66.3 ± 13.7 years; female, 30.9%), there was no significant difference in mean SOFA score between patients with TDM (7.9 points; 95% CI 7.1-8.7) and without TDM (8.2 points; 95% CI 7.5-9.0) (p = 0.39). Patients with TDM-guided therapy showed a lower 28-day mortality (21.6% vs. 25.8%, RR 0.8, 95% CI 0.5-1.3, p = 0.44) and a higher rate of clinical (OR 1.9; 95% CI 0.5-6.2, p = 0.30) and microbiological cure (OR 2.4; 95% CI 0.7-7.4, p = 0.12), but these differences did not reach statistical significance. Attainment of target concentration was more common in patients with TDM (37.3% vs. 14.6%, OR 4.5, CI 95%, 2.9-6.9, p < 0.001). CONCLUSION: TDM-guided therapy showed no beneficial effect in patients with sepsis and continuous infusion of piperacillin/tazobactam with regard to the mean SOFA score. Larger studies with strategies to ensure optimization of antimicrobial exposure are needed to definitively answer the question.

Flash monitor initiation is associated with improvements in HbA1c levels and DKA rates among people with type 1 diabetes in Scotland: a retrospective nationwide observational study.

AIMS/HYPOTHESIS: We assessed the real-world effect of flash monitor (FM) usage on HbA1c levels and diabetic ketoacidosis (DKA) and severe hospitalised hypoglycaemia (SHH) rates among people with type 1 diabetes in Scotland and across sociodemographic strata within this population. METHODS: This study was retrospective, observational and registry based. Using the national diabetes registry, 14,682 individuals using an FM at any point between 2014 and mid-2020 were identified. Within-person change from baseline in HbA1c following FM initiation was modelled using linear mixed models accounting for within-person pre-exposure trajectory. DKA and SHH events were captured through linkage to hospital admission and mortality data. The difference in DKA and SHH rates between FM-exposed and -unexposed person-time was assessed among users, using generalised linear mixed models with a Poisson likelihood. In a sensitivity analysis, we tested whether changes in these outcomes were seen in an age-, sex- and baseline HbA1c-matched sample of non-users over the same time period. RESULTS: Prevalence of ever-FM use was 45.9% by mid-2020, with large variations by age and socioeconomic status: 64.3% among children aged <13 years vs 32.7% among those aged ≥65 years; and 54.4% vs 36.2% in the least-deprived vs most-deprived quintile. Overall, the median (IQR) within-person change in HbA1c in the year following FM initiation was -2.5 (-9.0, 2.5) mmol/mol (-0.2 [-0.8, 0.2]%). The change varied widely by pre-usage HbA1c: -15.5 (-31.0, -4.0) mmol/mol (-1.4 [-2.8, -0.4]%) in those with HbA1c > 84 mmol/mol [9.8%] and 1.0 (-2.0, 5.5) mmol/mol (0.1 [-0.2, 0.5]%) in those with HbA1c < 54 mmol/mol (7.1%); the corresponding estimated fold change (95% CI) was 0.77 (0.76, 0.78) and 1.08 (1.07, 1.09). Significant reductions in HbA1c were found in all age bands, sexes and socioeconomic strata, and regardless of prior/current pump use, completion of a diabetes education programme or early FM adoption. Variation between the strata of these factors beyond that driven by differing HbA1c at baseline was slight. No change in HbA1c in matched non-users was observed in the same time period (median [IQR] within-person change = 0.5 [-5.0, 5.5] mmol/mol [0.0 (-0.5, 0.5)%]). DKA rates decreased after FM initiation overall and in all strata apart from the adolescents. Estimated overall reduction in DKA event rates (rate ratio) was 0.59 [95% credible interval (CrI) 0.53, 0.64]) after FM vs before FM initiation, accounting for pre-exposure trend. Finally, among those at higher risk for SHH, estimated reduction in event rates was rate ratio 0.25 (95%CrI 0.20, 0.32) after FM vs before FM initiation. CONCLUSIONS/INTERPRETATION: FM initiation is associated with clinically important reductions in HbA1c and striking reduction in DKA rate. Increasing uptake among the socioeconomically disadvantaged offers considerable potential for tightening the current socioeconomic disparities in glycaemia-related outcomes.

Impact of the COVID-19 pandemic on emergency medical resources : An observational multicenter study including all hospitals in a major urban center of the Rhein-Ruhr metropolitan region.

BACKGROUND: With the coronavirus disease 2019 (COVID-19) outbreak hospitals prepared for increasing numbers of patients without knowing how patient populations were evolving and what resources would be required. The present study aimed to analyze the impact of the local COVID-19 pandemic on emergency resources of all hospitals in a major urban center (Mönchengladbach) in Germany. METHODS: This observational multicenter study involved all acute care hospitals (n = 4). Systemic emergency department (ED) parameters from weeks 4-24 in 2020 were compared to the corresponding period in 2019 for each hospital and in a summative data analysis using a logistic regression model. RESULTS: The first regional COVID-19 patients were detected in week 9 of 2020. The cumulative number of ED visits dropped from 34,659 in 2019 to 28,008 in 2020. Weekly ED visits per hospital decreased from week 8 onwards between 38% and 48% per week and hospital and began to rise again after week 16. The pooled data analysis of ED patients showed significant decreases in outpatient visits (20,152 vs. 16,477, p < 0.001), hospital admissions (14,507 vs. 11,531, p < 0.001), and work-related accidents (2290 vs. 1468, p < 0.001). The decrease in ED to ICU admissions showed no significance (2093 vs. 1566, p = 0.255). The decline in ED cases was equally distributed between the medical specialties. CONCLUSION: The regional COVID-19 outbreak led to significantly reduced ED contacts in a German major urban region after the first COVID-19 cases appeared. Both hospital admissions and the number of ED to ICU admissions decreased, whereas the ratio of emergency outpatients vs. inpatients remained stable. Therefore, it can be assumed that patients with severe medical problems did not seek emergency care. These secondary effects of the pandemic on healthcare and the socioeconomic impact should be analyzed further.

Gender differences in time to first hospital admission at age 60 in Denmark, 1995-2014.

Women have consistently lower mortality rates than men at all ages and with respect to most causes. However, gender differences regarding hospital admission rates are more mixed, varying across ages and causes. A number of intuitive metrics have previously been used to explore changes in hospital admissions over time, but have not explicitly quantified the gender gap or estimated the cumulative contribution from cause-specific admission rates. Using register data for the total Danish population between 1995 and 2014, we estimated the time to first hospital admission for Danish men and women aged 60. This is an intuitive population-level metric with the same interpretive and mathematical properties as period life expectancy. Using a decomposition approach, we were able to quantify the cumulative contributions from eight causes of hospital admission to the gender gap in time to first hospital admission. Between 1995 and 2014, time to first admission increased for both, men (7.6 to 9.4 years) and women (8.3 to 10.3 years). However, the magnitude of gender differences in time to first admission remained relatively stable within this time period (0.7 years in 1995, 0.9 years in 2014). After age 60, Danish men had consistently higher rates of admission for cardiovascular conditions and neoplasms, but lower rates of admission for injuries, musculoskeletal disorders, and sex-specific causes. Although admission rates for both genders have generally declined over the last decades, the same major causes of admission accounted for the gender gap. Persistent gender differences in causes of admission are, therefore, important to consider when planning the delivery of health care in times of population ageing. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10433-021-00614-w.

Rising Rates and Widening Socioeconomic Disparities in Diabetic Ketoacidosis in Type 1 Diabetes in Scotland: A Nationwide Retrospective Cohort Observational Study.

OBJECTIVE: Whether advances in the management of type 1 diabetes are reducing rates of diabetic ketoacidosis (DKA) is unclear. We investigated time trends in DKA rates in a national cohort of individuals with type 1 diabetes monitored for 14 years, overall and by socioeconomic characteristics. RESEARCH DESIGN AND METHODS: All individuals in Scotland with type 1 diabetes who were alive and at least 1 year old between 1 January 2004 and 31 December 2018 were identified using the national register (N = 37,939). DKA deaths and hospital admissions were obtained through linkage to Scottish national death and morbidity records. Bayesian regression was used to test for DKA time trends and association with risk markers, including socioeconomic deprivation. RESULTS: There were 30,427 DKA admissions and 472 DKA deaths observed over 393,223 person-years at risk. DKA event rates increased over the study period (incidence rate ratio [IRR] per year 1.058 [95% credibility interval 1.054-1.061]). Males had lower rates than females (IRR male-to-female 0.814 [0.776-0.855]). DKA incidence rose in all age-groups other than 10- to 19-year-olds, in whom rates were the highest, but fell over the study. There was a large socioeconomic differential (IRR least-to-most deprived quintile 0.446 [0.406-0.490]), which increased during follow-up. Insulin pump use or completion of structured education were associated with lower DKA rates, and antidepressant and methadone prescription were associated with higher DKA rates. CONCLUSIONS: DKA incidence has risen since 2004, except in 10- to 19-year-olds. Of particular concern are the strong and widening socioeconomic disparities in DKA outcomes. Efforts to prevent DKA, especially in vulnerable groups, require strengthening.

Marked improvements in glycaemic outcomes following insulin pump therapy initiation in people with type 1 diabetes: a nationwide observational study in Scotland.

AIMS/HYPOTHESIS: Our aim was to assess the use of continuous subcutaneous insulin infusion (CSII) in people with type 1 diabetes in Scotland and its association with glycaemic control, as measured by HbA1c levels, frequency of diabetic ketoacidosis (DKA) and severe hospitalised hypoglycaemia (SHH), overall and stratified by baseline HbA1c. METHODS: We included 4684 individuals with type 1 diabetes from the national Scottish register, who commenced CSII between 2004 and 2019. We presented crude within-person differences from baseline HbA1c over time since initiation, crude DKA and SHH event-rates pre-/post-CSII exposure. We then used mixed models to assess the significance of CSII exposure, taking into account: (1) the diffuse nature of the intervention (i.e. structured education often precedes initiation); (2) repeated within-person measurements; and (3) background time-trends occurring pre-intervention. RESULTS: HbA1c decreased after CSII initiation, with a median within-person change of -5.5 mmol/mol (IQR -12.0, 0.0) (-0.5% [IQR -1.1, 0.0]). Within-person changes were most substantial in those with the highest baseline HbA1c, with median -21.0 mmol/mol (-30.0, -11.0) (-1.9% [-2.7, -1.0]) change in those with a baseline >84 mmol/mol (9.8%) within a year of exposure, that was sustained: -19.0 mmol/mol (-27.6, -6.5) (-1.7% [-2.5, -0.6]) at ≥5 years. Statistical significance and magnitude of change were supported by the mixed models results. The crude DKA event-rate was significantly lower in post-CSII person-time compared with pre-CSII person-time: 49.6 events (95% CI 46.3, 53.1) per 1000 person-years vs 67.9 (64.1, 71.9); rate ratio from Bayesian mixed models adjusting for pre-exposure trend: 0.61 (95% credible interval [CrI] 0.47, 0.77; posterior probability of reduction pp = 1.00). The crude overall SHH event-rate in post-CSII vs pre-CSII person-time was also lower: 17.8 events (95% CI 15.8, 19.9) per 1000 person-years post-exposure vs 25.8 (23.5, 28.3) pre-exposure; rate ratio from Bayesian mixed models adjusting for pre-exposure trend: 0.67 (95% CrI 0.45, 1.01; pp = 0.97). CONCLUSIONS/INTERPRETATION: CSII therapy was associated with marked falls in HbA1c especially in those with high baseline HbA1c. CSII was independently associated with reduced DKA and SHH rates. CSII appears to be an effective option for intensive insulin therapy in people with diabetes for improving suboptimal glycaemic control.

The association of polypharmacy and high-risk drug classes with adverse health outcomes in the Scottish population with type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this work was to map the number of prescribed drugs over age, sex and area-based socioeconomic deprivation, and to examine the association between the number of drugs and particular high-risk drug classes with adverse health outcomes among a national cohort of individuals with type 1 diabetes. METHODS: Utilising linked healthcare records from the population-based diabetes register of Scotland, we identified 28,245 individuals with a diagnosis of type 1 diabetes on 1 January 2017. For this population, we obtained information on health status, predominantly reflecting diabetes-related complications, and information on the total number of drugs and particular high-risk drug classes prescribed. We then studied the association of these baseline-level features with hospital admissions for falls, diabetic ketoacidosis (DKA), and hypoglycaemia or death within the subsequent year using multivariate Cox proportional hazards models. RESULTS: Not considering insulin and treatment for hypoglycaemia, the mean number of prescribed drugs was 4.00 (SD 4.35). The proportion of individuals being prescribed five or more drugs at baseline consistently increased with age (proportion [95% CI]: 0-19 years 2.04% [1.60, 2.49]; 40-49 years 28.50% [27.08, 29.93]; 80+ years 76.04% [67.73, 84.84]). Controlling for age, sex, area-based socioeconomic deprivation and health status, each additional drug at baseline was associated with an increase in the hazard for hospitalisation for falls, hypoglycaemia and death but not for DKA admissions (HR [95% CI]: falls 1.03 [1.01, 1.06]; DKA 1.01 [1.00, 1.03]; hypoglycaemia 1.05 [1.02, 1.07]; death 1.04 [1.02, 1.06]). We found a number of drug classes to be associated with an increased hazard of one or more of these adverse health outcomes, including antithrombotic/anticoagulant agents, corticosteroids, opioids, antiepileptics, antipsychotics, hypnotics and sedatives, and antidepressants. CONCLUSIONS: Polypharmacy is common among the Scottish population with type 1 diabetes and is strongly patterned by sociodemographic factors. The number of prescribed drugs and the prescription of particular high-risk drug classes are strong markers of an increased risk of adverse health outcomes, including acute complications of diabetes.

Hemoadsorption: effective in reducing circulating fragments of the endothelial glycocalyx during cardiopulmonary bypass in patients undergoing on-pump cardiac surgery?

BACKGROUND: The vascular endothelial glycocalyx is susceptible to ischemia and hypoxia. Released soluble components of the endothelial glycocalyx (EG) have been identified as potential damage associated molecular patterns (DAMPs) able to enhance an ongoing inflammatory response. Shedding of the EG has been associated with released atrial-natriuretic peptide (ANP) during cardiac surgery procedures. A novel hemoadsorption technique (CytoSorb®) has been shown to effectively remove molecules up to 55 kDa unspecifically from circulation. It is not known whether ANP or glycocalyx components can be removed successfully by this technique. METHODS: In 15 patients undergoing on-pump cardiac surgery, the hemoadsorption device was integrated in the cardiopulmonary bypass (CPB) circuit. Pre- and post-adsorber concentrations of ANP, heparan sulphate (HEP), syndecan-1 (SYN) and hyaluronan (HYA) were measured at 10 (T1), 30 (T2), and 60 (T3) minutes after aortic cross-clamping and complete CPB. RESULTS: Hemoadsorption significantly reduced mean HEP concentrations (-157.5 [333.4] ng/mL; P<0.001) post adsorber. For ANP and SYN no statistically significant changes were detected whereas mean [SD] HYA concentrations even increased significantly (+21.6 [43.0] ng/mL; P<0.001) post adsorber. CONCLUSIONS: In this study representing a real-life scenario, we could demonstrate that the novel hemoadsorption device (CytoSorb®) was able to effectively adsorb HEP from the circulation if integrated in a CPB circuit. However, blood concentrations of HYA, SYN, and ANP could not be reduced during CPB in our investigation.

Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland.

BACKGROUND: We aimed to ascertain the cumulative risk of fatal or critical care unit-treated COVID-19 in people with diabetes and compare it with that of people without diabetes, and to investigate risk factors for and build a cross-validated predictive model of fatal or critical care unit-treated COVID-19 among people with diabetes. METHODS: In this cohort study, we captured the data encompassing the first wave of the pandemic in Scotland, from March 1, 2020, when the first case was identified, to July 31, 2020, when infection rates had dropped sufficiently that shielding measures were officially terminated. The participants were the total population of Scotland, including all people with diabetes who were alive 3 weeks before the start of the pandemic in Scotland (estimated Feb 7, 2020). We ascertained how many people developed fatal or critical care unit-treated COVID-19 in this period from the Electronic Communication of Surveillance in Scotland database (on virology), the RAPID database of daily hospitalisations, the Scottish Morbidity Records-01 of hospital discharges, the National Records of Scotland death registrations data, and the Scottish Intensive Care Society and Audit Group database (on critical care). Among people with fatal or critical care unit-treated COVID-19, diabetes status was ascertained by linkage to the national diabetes register, Scottish Care Information Diabetes. We compared the cumulative incidence of fatal or critical care unit-treated COVID-19 in people with and without diabetes using logistic regression. For people with diabetes, we obtained data on potential risk factors for fatal or critical care unit-treated COVID-19 from the national diabetes register and other linked health administrative databases. We tested the association of these factors with fatal or critical care unit-treated COVID-19 in people with diabetes, and constructed a prediction model using stepwise regression and 20-fold cross-validation. FINDINGS: Of the total Scottish population on March 1, 2020 (n=5 463 300), the population with diabetes was 319 349 (5·8%), 1082 (0·3%) of whom developed fatal or critical care unit-treated COVID-19 by July 31, 2020, of whom 972 (89·8%) were aged 60 years or older. In the population without diabetes, 4081 (0·1%) of 5 143 951 people developed fatal or critical care unit-treated COVID-19. As of July 31, the overall odds ratio (OR) for diabetes, adjusted for age and sex, was 1·395 (95% CI 1·304-1·494; p<0·0001, compared with the risk in those without diabetes. The OR was 2·396 (1·815-3·163; p<0·0001) in type 1 diabetes and 1·369 (1·276-1·468; p<0·0001) in type 2 diabetes. Among people with diabetes, adjusted for age, sex, and diabetes duration and type, those who developed fatal or critical care unit-treated COVID-19 were more likely to be male, live in residential care or a more deprived area, have a COVID-19 risk condition, retinopathy, reduced renal function, or worse glycaemic control, have had a diabetic ketoacidosis or hypoglycaemia hospitalisation in the past 5 years, be on more anti-diabetic and other medication (all p<0·0001), and have been a smoker (p=0·0011). The cross-validated predictive model of fatal or critical care unit-treated COVID-19 in people with diabetes had a C-statistic of 0·85 (0·83-0·86). INTERPRETATION: Overall risks of fatal or critical care unit-treated COVID-19 were substantially elevated in those with type 1 and type 2 diabetes compared with the background population. The risk of fatal or critical care unit-treated COVID-19, and therefore the need for special protective measures, varies widely among those with diabetes but can be predicted reasonably well using previous clinical history. FUNDING: None.

Preparing for the future: The changing demographic composition of hospital patients in Denmark between 2013 and 2050.

BACKGROUND: Population aging will pose huge challenges for healthcare systems and will require a promotion of positive attitudes towards older people and the encouragement of careers in geriatrics to attract young professionals into the field and to meet the needs of a rapidly growing number of old-aged patients. We describe the current demographic profile of hospital care use in Denmark and make projections for changes in the patient profile up to 2050. METHODS: The Danish population in 2013 (N = 5.63 million) was followed up for inpatient and emergency admissions recorded in Danish hospitals in 2013 using population-based registers. We combined age- and sex-specific hospital care use in 2013 with official population estimates to forecast the profile of hospital days up to 2050 with respect to age and sex. RESULTS: The total number of hospital days per year is projected to increase by 42% between 2013 and 2050, from 4.66 to 6.72 million days. While small changes are projected for the population aged 0-69, the largest change is projected to occur for the population aged 70+. The 2013 levels were 0.82 and 0.93 million days for men and women aged 70+, respectively. By 2050, these levels are projected to have reached 1.94 and 1.84 million days. While the population aged 70+ accounted for 37.5% of all days in 2013, its contribution is projected to increase to 56.2% by 2050. CONCLUSION: Our study shows one possible scenario for changes in the hospital days due to population aging by 2050: Assuming no changes in hospital care use over the forecast period, the absolute contribution of individuals aged 70+ to the total hospital days will more than double, and the relative contribution of persons aged 70+ will account for nearly 60% of all hospital days by 2050, being largest among men.

Rethinking morbidity compression.

Studies of morbidity compression routinely report the average number of years spent in an unhealthy state but do not report variation in age at morbidity onset. Variation was highlighted by Fries (1980) as crucial for identifying disease postponement. Using incidence of first hospitalization after age 60, as one working example, we estimate variation in morbidity onset over a 27-year period in Denmark. Annual estimates of first hospitalization and the population at risk for 1987 to 2014 were identified using population-based registers. Sex-specific life tables were constructed, and the average age, the threshold age, and the coefficient of variation in age at first hospitalization were calculated. On average, first admissions lasting two or more days shifted towards older ages between 1987 and 2014. The average age at hospitalization increased from 67.8 years (95% CI 67.7-67.9) to 69.5 years (95% CI 69.4-69.6) in men, and 69.1 (95% CI 69.1-69.2) to 70.5 years (95% CI 70.4-70.6) in women. Variation in age at first admission increased slightly as the coefficient of variation increased from 9.1 (95% CI 9.0-9.1) to 9.9% (95% CI 9.8-10.0) among men, and from 10.3% (95% CI 10.2-10.4) to 10.6% (95% CI 10.5-10.6) among women. Our results suggest populations are ageing with better health today than in the past, but experience increasing diversity in healthy ageing. Pensions, social care, and health services will have to adapt to increasingly heterogeneous ageing populations, a phenomenon that average measures of morbidity do not capture.

Do men avoid seeking medical advice? A register-based analysis of gender-specific changes in primary healthcare use after first hospitalisation at ages 60+ in Denmark.

BACKGROUND: It remains unclear whether women's greater primary healthcare use reflects a lower treatment-seeking threshold or a health disadvantage. We address this question by studying primary healthcare use surrounding a major health shock. METHODS: This cohort study utilises routinely-collected healthcare data covering the Danish population aged 60+ years between 1996 and 2011. Using a hurdle model, we investigate levels of non-use and levels of primary healthcare use before and after first inpatient hospitalisation for stroke, myocardial infarction (MI), chronic obstructive pulmonary disease (COPD) and gastrointestinal cancers (GIC). RESULTS: Before hospitalisation, irrespective of cause, men were more likely than women to be non-users of primary healthcare (OR (95% CI): stroke 1.802 (1.731 to 1.872); MI 1.841 (1.760 to 1.922); COPD 2.160 (2.028 to 2.292); GIC 1.609 (1.525 to 1.693)). Men who were users had fewer primary healthcare contacts than women (proportional change (eß) (95% CI): stroke 0.821 (0.806 to 0.836); MI 0.796 (0.778 to 0.814); COPD 0.855 (0.832 to 0.878); GIC 0.859 (0.838 to 0.881)). Following hospitalisation, changes in the probability of being a non-user (OR (95% CI): stroke 0.965 (0.879 to 1.052); MI 0.894 (0.789 to 0.999); COPD 0.755 (0.609 to 0.900); GIC 0.895 (0.801 to 0.988)) and levels of primary healthcare use (eß (95% CI): stroke 1.113 (1.102 to 1.124); MI 1.112 (1.099 to 1.124); COPD 1.078 (1.063 to 1.093); GIC 1.097 (1.079 to 1.114)) were more pronounced among men. Gender differences widened after accounting for survival following hospitalisation. CONCLUSION: Women's consistently higher levels of primary healthcare use are likely to be explained by a combination of a lower treatment-seeking threshold and a health disadvantage resulting from better survival in bad health.

Therapeutic drug monitoring-based dose optimisation of piperacillin/tazobactam to improve outcome in patients with sepsis (TARGET): a prospective, multi-centre, randomised controlled trial.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection with a hospital mortality in excess of 40%. Along with insufficient and delayed empirical antimicrobial therapy, inappropriate antimicrobial exposure has been identified to negatively affect patient outcomes. Receipt of prolonged infusion (i.e. extended or continuous infusion) of piperacillin/tazobactam (TZP) improves antimicrobial exposure and is associated with reduced mortality in patients with sepsis. Using therapeutic drug monitoring (TDM) with dosing tailored to the altered pharmacokinetics of the individual patient to avoid under- and overdosing may be a further strategy to improve patient outcomes. This current trial will address the question whether a TDM-guided therapy with TZP administered by continuous infusion will result in a greater resolution of organ dysfunction and hence better clinical outcome compared to continuous infusion of the total daily dose of TZP without TDM. METHODS: The study is an investigator-initiated, multi-centre, parallel-group, single-blinded, randomised controlled trial. The trial will be conducted in several centres across Germany. Adult patients (aged ≥ 18 years) with severe sepsis or septic shock will be eligible for study participation. Participants will be randomly assigned to receive either TZP by continuous infusion guided by daily TDM of piperacillin (experimental group) or by continuous infusion without TDM guidance (total daily dose in normal renal function 13.5 g TZP) (control group). The pharmacokinetic (PK)/pharmacodynamic (PD) target will be 100% f T>4MIC (percentage of time during a dosing interval that the free [f] drug concentration exceeds 4 times the minimum inhibitory concentration). The primary efficacy endpoint is the change in mean total Sequential Organ Failure Assessment score from day 1 after randomisation until day 10 or discharge from the intensive care unit or death, whichever comes first. Secondary outcomes include mortality, clinical cure, microbiological cure, overall antibiotic use, individual components of the primary outcome, adverse events and analysis of PK and (PD) indices. DISCUSSION: This trial will assess for the first time whether continuous infusion of TZP guided by daily TDM in patients with sepsis will result in a greater resolution of organ dysfunction and hence better clinical outcome compared to continuous infusion without TDM. TRIAL REGISTRATION: German Clinical Trials Register (GermanCTR), DRKS00011159 . Registered on 10 October 2016.

Incidence of peri-operative paediatric cardiac arrest and the influence of a specialised paediatric anaesthesia team: Retrospective cohort study.

BACKGROUND: Peri-operative critical events are still a major problem in paediatric anaesthesia care. Access to more experienced healthcare teams might reduce the adverse event rate and improve outcomes. OBJECTIVE: The current study analysed incidences of peri-operative paediatric cardiac arrest before and after implementation of a specialised paediatric anaesthesia team and training programme. DESIGN: Retrospective cohort study with before-and-after analysis. SETTING: Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Germany. PATIENTS: A total of 36 243 paediatric anaesthetics (0 to 18 years) were administered between 2008 and 2016. INTERVENTION: Implementation of a specialised paediatric anaesthesia team and training programme occurred in 2014 This included hands-on supervised training in all fields of paediatric anaesthesia, double staffing for critical paediatric cases and a 24/7 emergency team. A logistic regression analysis with risk factors (age, ASA physical status, emergency) was used to evaluate the impact of implementation of the specialised paediatric anaesthesia team. MAIN OUTCOME MEASURES: Incidences of peri-operative paediatric cardiac arrest and anaesthesia-attributable cardiac arrest before and after the intervention. RESULTS: Twelve of 25 paediatric cardiac arrests were classified as anaesthesia-attributable. The incidence of overall peri-operative paediatric cardiac arrest was 8.1/10 000 (95% CI 5.2 to 12.7) in the period 2008 to 2013 and decreased to 4.6/10 000 (95% CI 2.1 to 10.2) in 2014 to 2016. Likewise, the incidence of anaesthesia-attributable cardiac arrest was lower after 2013 [1.6/10 000 (95% CI 0.3 to 5.7) vs. 4.3/10 000 (95% CI 2.3 to 7.9)]. Using logistic regression, children anaesthetised after 2013 had nearly a 70% lower probability of anaesthesia-attributable cardiac arrest (odds ratio 0.306, 95% CI 0.067 to 1.397; P = 0.1263). For anaesthesia-attributable cardiac arrest, young age was the most contributory risk factor, whereas in overall paediatric cardiac arrest, ASA physical statuses 3 to 5 played a more important role. CONCLUSION: In this study on incidences of peri-operative paediatric cardiac arrest from a European tertiary care university hospital, implementation of a specialised paediatric anaesthesia team and training programme was associated with lower incidences of peri-operative paediatric cardiac arrest and a reduced probability of anaesthesia-attributable cardiac arrest.

Is Who you Ask Important? Concordance Between Survey and Registry Data on Medication Use Among Self- and Proxy-Respondents in the Longitudinal Study of Aging Danish Twins and the Danish 1905-Cohort Study.

BACKGROUND: This study investigates the accuracy of the reporting of medication use by proxy- and self-respondents, and it compares the prognostic value of the number of medications from survey and registry data for predicting mortality across self- and proxy-respondents. METHODS: The study is based on the linkage of the Longitudinal Study of Aging Danish Twins and the Danish 1905-Cohort Study with the Danish National Prescription Registry. We investigated the concordance between survey and registry data, and the prognostic value of medication use when assessed using survey and registry data, to predict mortality for self- and proxy-respondents at intake surveys. RESULTS: Among self-respondents, the agreement was moderate (κ = 0.52-0.58) for most therapeutic groups, whereas among proxy-respondents, the agreement was low to moderate (κ = 0.36-0.60). The magnitude of the relative differences was, generally, greater among proxies than among self-respondents. Each additional increase in the total number of medications was associated with 7%-8% mortality increase among self- and 4%-6% mortality increase among proxy-respondents in both the survey and registry data. The predictive value of the total number of medications estimated from either data source was lower among proxies (c-statistic = 0.56-0.58) than among self-respondents (c-statistic = 0.74). CONCLUSIONS: The concordance between survey and registry data regarding medication use and the predictive value of the number of medications for mortality were lower among proxy- than among self-respondents.