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OBJECTIVES: Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CAC score can improve the diagnosis of obstructive CAD compared with CCTA alone. METHODS: A total of 2315 patients (858 women, 37%) aged 61.1 ± 10.2 from 29 original studies were included to build two CAD prediction models based on either CCTA alone or CCTA combined with the CAC score. CAD was defined as at least 50% coronary diameter stenosis on invasive coronary angiography. Models were built by using generalized linear mixed-effects models with a random intercept set for the original study. The two CAD prediction models were compared by the likelihood ratio test, while their diagnostic performance was compared using the area under the receiver-operating-characteristic curve (AUC). Net benefit (benefit of true positive versus harm of false positive) was assessed by decision curve analysis. RESULTS: CAD prevalence was 43.5% (1007/2315). Combining CCTA with CAC improved CAD diagnosis compared with CCTA alone (AUC: 87% [95% CI: 86 to 89%] vs. 80% [95% CI: 78 to 82%]; p

Abstract Background Sepsis is associated with about 20% of deaths worldwide. It often presents with non-specific initial symptoms, making its emergency treatment an interdisciplinary and cross-sectoral challenge. Three in four sepsis survivors suffers from new cognitive, psychological, or physical sequelae for which specific treatment concepts are scarce. The AVENIR project aims to improve the understanding of patient pathways, and subjective care experiences and needs along the entire healthcare pathway before, with and after sepsis. Based on this, concrete recommendations for the organization of care and patient information materials will be developed with close patient participation. Methods Mixed-methods study including (1) analysis of anonymized nationwide health claims data from Germany, (2) linkage of health claims data with patient care reports (PCR) of emergency medical services from study regions in two federal states within Germany, and (3) qualitative exploration of the patient, relative, and care provider perspective on sepsis care. In (1), we analyze inpatient and outpatient health care utilization until 30 days pre-sepsis; clinical sepsis care including intra- and inter-hospital transfers; and rehabilitation, inpatient and outpatient aftercare of sepsis survivors as well as costs for health care utilization until 24 months post-sepsis. We attempt to identify survivor classes with similar health care utilization by Latent Class Analyses. In (2), PCR are linked with health claims data to establish a comprehensive database outlining care pathways for sepsis patients from pre-hospital to follow-up. We investigate e.g., whether correct initial assessment is associated with acute (e.g., same-day lethality) and long-term (e.g., new need for care, long-term mortality) outcomes of patients. We compare the performance of sepsis-specific screening tools such as qSOFA, NEWS-2 or PRESEP in the pre-clinical setting. In (3), semi-structured interviews as well as synchronous and asynchronous online focus groups are conducted and analyzed using qualitative content analyses techniques. Discussion The results of the AVENIR study will contribute to a deeper understanding of sepsis care pathways in Germany. They may serve as a base for improvements and innovations in sepsis care, that in the long-term can contribute to reduce the personal, medical, and societal burden of sepsis and its sepsis sequelae. Trial registration Registered at German Clinical Trial Register (ID: DRKS00031302, date of registration: 5th May 2023).

Introduction Sepsis remains the major cause of death among hospitalised patients in intensive care. While targeting sepsis-causing pathogens with source control or antimicrobials has had a dramatic impact on morbidity and mortality of sepsis patients, this strategy remains insufficient for about one-third of the affected individuals who succumb. Pharmacological targeting of mechanisms that reduce sepsis-defining organ dysfunction may be beneficial. When given at low doses, the anthracycline epirubicin promotes tissue damage control and lessens the severity of sepsis independently of the host–pathogen load by conferring disease tolerance to infection. Since epirubicin at higher doses can be myelotoxic, a first dose–response trial is necessary to assess the potential harm of this drug in this new indication.Methods and analysis Epirubicin for the Treatment of Sepsis and Septic Shock-1 is a randomised, double-blind, placebo-controlled phase 2 dose-escalation phase IIa clinical trial to assess the safety of epirubicin as an adjunctive in patients with sepsis. The primary endpoint is the 14-day myelotoxicity. Secondary and explorative outcomes include 30-day and 90-day mortality, organ dysfunction, pharmacokinetic/pharmacodynamic (PK/PD) and cytokine release. Patients will be randomised in three consecutive phases. For each study phase, patients are randomised to one of the two study arms (epirubicin or placebo) in a 4:1 ratio. Approximately 45 patients will be recruited. Patients in the epirubicin group will receive a single dose of epirubicin (3.75, 7.5 or 15 mg/m2 depending on the study phase. After each study phase, a data and safety monitoring board will recommend continuation or premature stopping of the trial. The primary analyses for each dose level will report the proportion of myelotoxicity together with a 95% CI. A potential dose-toxicity association will be analysed using a logistic regression model with dose as a covariate. All further analyses will be descriptive.Ethics and dissemination The protocol is approved by the German Federal Institute for Drugs and Medical Devices. The results will be submitted for publication in peer-reviewed journals.Trial registration number NCT05033808.

ObjectivesThere is conflicting evidence about the comparative diagnostic accuracy of the Agatston score versus computed tomography angiography (CTA) in patients with suspected obstructive coronary artery disease (CAD).PurposeTo determine whether CTA is superior to the Agatston score in the diagnosis of CAD.MethodsIn total 2452 patients with stable chest pain and a clinical indication for invasive coronary angiography (ICA) for suspected CAD were included by the Collaborative Meta-analysis of Cardiac CT (COME-CCT) Consortium. An Agatston score of > 400 was considered positive, and obstructive CAD defined as at least 50% coronary diameter stenosis on ICA was used as the reference standard.ResultsObstructive CAD was diagnosed in 44.9% of patients (1100/2452). The median Agatston score was 74. Diagnostic accuracy of CTA for the detection of obstructive CAD (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) was significantly higher than that of the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). Among patients with an Agatston score of zero, 17% (101/600) had obstructive CAD. Diagnostic accuracy of CTA was not significantly different in patients with low to intermediate (1 to < 100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000).ConclusionsResults in our international cohort show CTA to have significantly higher diagnostic accuracy than the Agatston score in patients with stable chest pain, suspected CAD, and a clinical indication for ICA. Diagnostic performance of CTA is not affected by a higher Agatston score while an Agatston score of zero does not reliably exclude obstructive CAD.Key points• CTA showed significantly higher diagnostic accuracy (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) for diagnosis of coronary artery disease when compared to the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). • Diagnostic performance of CTA was not affected by increased amount of calcium and was not significantly different in patients with low to intermediate (1 to 1000). • Seventeen percent of patients with an Agatston score of zero showed obstructive coronary artery disease by invasive angiography showing absence of coronary artery calcium cannot reliably exclude coronary artery disease.

Background: Hospital-acquired infections are a common source of sepsis. Hospital onset of sepsis was found to be associated with higher acute mortality and hospital costs, yet its impact on long-term patient-relevant outcomes and costs is unknown. Objective: We aimed to assess the association between sepsis origin and acute and long-term outcomes based on a nationwide population-based cohort of sepsis patients in Germany. Methods: This retrospective cohort study used nationwide health claims data from 23 million health insurance beneficiaries. Sepsis patients with hospital-acquired infections (HAI) were identified by ICD-10-codes in a cohort of adult patients with hospital-treated sepsis between 2013 and 2014. Cases without these ICD-10-codes were considered as sepsis cases with community-acquired infection (CAI) and were matched with HAI sepsis patients by propensity score matching. Outcomes included in-hospital/12-month mortality and costs, as well as readmissions and nursing care dependency until 12 months postsepsis. Results: We matched 33,110 HAI sepsis patients with 28,614 CAI sepsis patients and 22,234 HAI sepsis hospital survivors with 19,364 CAI sepsis hospital survivors. HAI sepsis patients had a higher hospital mortality than CAI sepsis patients (32.8% vs. 25.4%, RR 1.3, p

Abstract Background Coronary computed tomography angiography has become the foremost noninvasive imaging modality of the coronary arteries and is used as an alternative to the reference standard, conventional coronary angiography, for direct visualization and detection of coronary artery stenoses in patients with suspected coronary artery disease. Nevertheless, there is considerable debate regarding the optimal target population to maximize clinical performance and patient benefit. The most obvious indication for noninvasive coronary computed tomography angiography in patients with suspected coronary artery disease would be to reliably exclude significant stenosis and, thus, avoid unnecessary invasive conventional coronary angiography. To do this, a test should have, at clinically appropriate pretest likelihoods, minimal false-negative outcomes resulting in a high negative predictive value. However, little is known about the influence of patient characteristics on the clinical predictive values of coronary computed tomography angiography. Previous regular systematic reviews and meta-analyses had to rely on limited summary patient cohort data offered by primary studies. Performing an individual patient data meta-analysis will enable a much more detailed and powerful analysis and thus increase representativeness and generalizability of the results. The individual patient data meta-analysis is registered with the PROSPERO database (CoMe-CCT, CRD42012002780). Methods/Design The analysis will include individual patient data from published and unpublished prospective diagnostic accuracy studies comparing coronary computed tomography angiography with conventional coronary angiography. These studies will be identified performing a systematic search in several electronic databases. Corresponding authors will be contacted and asked to provide obligatory and additional data. Risk factors, previous test results and symptoms of individual patients will be used to estimate the pretest likelihood of coronary artery disease. A bivariate random-effects model will be used to calculate pooled mean negative and positive predictive values as well as sensitivity and specificity. The primary outcome of interest will be positive and negative predictive values of coronary computed tomography angiography for the presence of coronary artery disease as a function of pretest likelihood of coronary artery disease, analyzed by meta-regression. As a secondary endpoint, factors that may influence the diagnostic performance and clinical value of computed tomography, such as heart rate and body mass index of patients, number of detector rows, and administration of beta blockade and nitroglycerin, will be investigated by integrating them as further covariates into the bivariate random-effects model. Discussion This collaborative individual patient data meta-analysis should provide answers to the pivotal question of which patients benefit most from noninvasive coronary computed tomography angiography and thus help to adequately select the right patients for this test.

This study aimed to investigate the impact of influencing factors (sex, eicosapentaenoic acid (EPA) status at baseline, linoleic acid (LA) intake, milk fat intake) on the conversion of α-linolenic acid (ALA) obtained from linseed oil into its long-chain metabolites. In addition, the effect of ALA on cardiovascular risk markers was investigated. This study used a parallel design approach by randomly assigning the 134 subjects to one of four diets (high in LA (HLA); low in LA (LLA); high in milk fat (MF); control (Western diet)) each enriched with linseed oil (10 en%, 22–27 mL ≙ 13–16 g ALA). Blood samples were taken at baseline and after 4, 8, and 12 weeks of dietary intervention. The study was fully completed by 105 subjects (57.4 ± 12.1 years; 65.7% female). Results showed that ALA (296–465%), C-20:4n3 (54–140%), and EPA (37–73%) concentrations in erythrocytes increased in all groups (p < 0.01). In contrast, docosahexaenoic acid (19–35%, p < 0.01) and n-3 index (10–21%, p < 0.05) dropped in the HLA, LLA, and control groups. An increase in C-22:5n3 was only observed in the MF (36%) and control groups (11%) (p < 0.05). In addition, an increase in LA (7–27%) was found in the HLA, LLA, and control groups, whereas C-20:3n6 (16–22%), arachidonic acid (10–16%), C-22:4n6 (12–30%), and C-22:5n6 (32–47%) decreased (p < 0.01). The conversion into EPA was higher in men than in women (69 vs. 39%, p = 0.043) and in subjects with low EPA status compared to participants with high EPA status (79 vs. 29%, p < 0.001). A high LA status attenuates the conversion rate. In line with the literature, no clear effects on blood lipids and parameters of glucose metabolism were found in relation to ALA supplementation.

BackgroundLong-term impairments after sepsis can impede the return to work in survivors. We aimed to describe rates of return to work 6 and 12 months postsepsis.MethodsThis retrospective, population-based cohort study was based on health claims data of the German AOK health insurance of 23.0 million beneficiaries. We included 12-months survivors after hospital-treated sepsis in 2013/2014, who were ≤60 years at the time of the admission and were working in the year presepsis. We assessed the prevalence of return to work (RTW), persistent inability to work and early retirement.ResultsAmong 7,370 working age sepsis survivors, 69.2% returned to work at 6 months postsepsis, while 22.8% were on sick leave and 8.0% retired early. At 12 months postsepsis, the RTW rate increased to 76.9%, whereas 9.8% were still on sick leave and 13.3% retired early. Survivors who returned to work had a mean of 70 (SD 93) sick leave days in the 12 months presepsis (median 28 days, IQR 108 days).ConclusionOne out of four working age sepsis survivors does not resume work in the year postsepsis. Specific rehabilitation and targeted aftercare may be opportunities to reduce barriers to RTW after sepsis.

Abstract Blood pressure (BP) shows a seasonal variation with higher levels at lower temperatures. Many hypertensives, however, report on BP disturbances rather in association with acutely changing weather conditions than with absolute temperatures. To date, the impact of changing meteorological parameters on hypertensive episodes remains elusive. We performed a retrospective time series regression analysis on 203,703 patients in three hospitals in Germany between 2010 and 2018, of whom 7362 patients were admitted for hypertensive disease. Numbers of daily admissions for hypertension were associated with metereological data obtained from three nearby weather stations. Data comprised temperature (mean, maximal, minimal and range within 24 h), athmospheric pressure, and precipitation. Changes of these parameters were calculated over a two and three day period. There was an inverse correlation between maximal daily temperature and the number of admissions for hypertensive disease, which remained significant both after adjustment for seasonality and week day in a spline model and in a constrained distributed lag model. A decrease of maximal temperature by 5 °C was associated with a 3% increase of risk for admission for hypertension and vice versa. There were no significant effects of precipitation and athmospheric pressure on the number of admissions. With regard to all observed metereological parameters, neither the change within two, nor within three days was consistently associated with the number of daily admissions. High temperatures are associated with lower numbers of hypertensive episodes requiring hospital admission. In contrast to the subjective perception of many hypertensive patients, however, acutely changing weather conditions are not associated with a higher risk of hypertensive emergency.

BackgroundMethods for assessing long-term outcome quality of acute care for sepsis are lacking. We investigated a method for measuring long-term outcome quality based on health claims data in Germany.Materials and methodsAnalyses were based on data of the largest German health insurer, covering 32% of the population. Cases (aged 15 years and older) with ICD-10-codes for severe sepsis or septic shock according to sepsis-1-definitions hospitalized in 2014 were included. Short-term outcome was assessed by 90-day mortality; long-term outcome was assessed by a composite endpoint defined by 1-year mortality or increased dependency on chronic care. Risk factors were identified by logistic regressions with backward selection. Hierarchical generalized linear models were used to correct for clustering of cases in hospitals. Predictive validity of the models was assessed by internal validation using bootstrap-sampling. Risk-standardized mortality rates (RSMR) were calculated with and without reliability adjustment and their univariate and bivariate distributions were described.ResultsAmong 35,552 included patients, 53.2% died within 90 days after admission; 39.8% of 90-day survivors died within the first year or had an increased dependency on chronic care. Both risk-models showed a sufficient predictive validity regarding discrimination [AUC = 0.748 (95% CI: 0.742; 0.752) for 90-day mortality; AUC = 0.675 (95% CI: 0.665; 0.685) for the 1-year composite outcome, respectively], calibration (Brier Score of 0.203 and 0.220; calibration slope of 1.094 and 0.978), and explained variance (R2 = 0.242 and R2 = 0.111). Because of a small case-volume per hospital, applying reliability adjustment to the RSMR led to a great decrease in variability across hospitals [from median (1st quartile, 3rd quartile) 54.2% (44.3%, 65.5%) to 53.2% (50.7%, 55.9%) for 90-day mortality; from 39.2% (27.8%, 51.1%) to 39.9% (39.5%, 40.4%) for the 1-year composite endpoint]. There was no substantial correlation between the two endpoints at hospital level (observed rates: ρ = 0, p = 0.99; RSMR: ρ = 0.017, p = 0.56; reliability-adjusted RSMR: ρ = 0.067; p = 0.026).ConclusionQuality assurance and epidemiological surveillance of sepsis care should include indicators of long-term mortality and morbidity. Claims-based risk-adjustment models for quality indicators of acute sepsis care showed satisfactory predictive validity. To increase reliability of measurement, data sources should cover the full population and hospitals need to improve ICD-10-coding of sepsis.

Medical data sciences receive attention as digitalization and artificial intelligence (AI) pose new challenges and opportunities in health care. Specific methods and skills derived from the data sciences have been driving essential developments in almost if not all areas of health care and medical research over many years. For example, evidence-based medicine is now a pillar of medical practice, combined with a stronger focus on reproducible and valid research and an improved understanding of scientific methods. The increased role of the data sciences in medical research and practice is reflected in the revised national competency-based learning objectives catalog for medicine (NKLM 2.0). Digitalization, research skills, evidence medicine and health promotion and prevention are integral parts of the curriculum from start to end. They relate to all subjects and topics in an interprofessional manner. This increase in relevance of the data sciences clearly calls for improved competencies in the clinico-theoretical disciplines previously combined as interdisciplinary domain 1 (Q1). Epidemiology, medical biometry and medical informatics will now contribute expertise throughout the whole course of studying medicine. These disciplines deal with digitalization, medical research competence, evidence-based medicine, and prevention. In addition, disease-related learning and many aspects of therapy, diagnostics, communication, and management benefit from cooperation with dedicated instruction in the medical data sciences by didactically trained experts. This article aims to support faculties and subject representatives during the implementation period of the NKLM 2.0 and beyond regarding data science skills. Tables provide an overview of essential learning objectives in epidemiology, biometry, and medical informatics across the different phases of the curriculum. In addition, we give recommendations for cooperation with other subject representatives. By this we wish to contribute to improving the medical curriculum based on graduate profile-oriented interdisciplinary-integrative teaching.

Abstract Preoperative skin preparation is an effective method to prevent surgical site infections (SSI). Alcoholic chlorhexidine (CHG) and povidone iodine (PV-I) are the most widely used antiseptic agents. This meta-analysis aims to determine their efficacy in reducing natural bacterial skin flora in clean orthopedic surgery. A systematic search was conducted through current literature up to June 2021 to identify clinical randomized trials that compared the efficacy of alcoholic chlorhexidine and povidone iodine in reducing bacterial skin colonization after preoperative skin preparation. A meta-analysis was conducted. Of 235 screened articles, 8 randomized controlled trials were included. The results of the meta-analysis demonstrate a significantly lower positive culture rate in the chlorhexidine group than in the povidone iodine group (RR = 0.53, 95% Cl: 0.32–0.88). The present data show the superiority of chlorhexidine in reducing the normal bacterial flora compared to povidone iodine in clean orthopedic surgery.

Investigations on the association between patient’s age and head and neck cancer (HNC) treatment decision are sparse. Nationwide diagnoses-related group-based data of 1,226,357 cases hospitalized with primary HNC in Germany from 2005 to 2018 were included. Negative binomial regression was performed to study the development of the treatment rates over time. For all treatment options, i.e., biopsies, surgery, radiotherapy, and chemotherapy/biologicals, increases in the treatment rates were seen in patients >80 years (surgery: oral cavity: relative risk [RR]: 1.2, CI: 1.13–1.20; oropharynx: RR: 1.2, CI: 1.15–1.34; hypopharynx: RR: 1.1, CI: 1.02–1.17; larynx: RR: 1.1, CI: 1.04–1.12; radiotherapy: oral cavity: RR: 1.1, CI: 1.07–1.23; oropharynx: RR: 1.3, CI: 1.16–1.49; hypopharynx: RR: 1.3, CI: 1.21–1.46; larynx: RR 1.2, CI: 1.03–1.29; chemotherapy: oral cavity: RR: 1.2, CI: 1.06–1.31; salivary glands: RR: 1.3, CI: 1.09–1.50; oropharynx: RR: 1.4, CI: 1.12–1.83; hypopharynx: RR: 1.3, CI: 1.06–1.48; larynx: RR: 1.3, CI: 1.08–1.52, all p < 0.05). Older age cohorts (≥80 years) need more awareness as they are mainly responsible for the increase in the rates of surgery, radiotherapy, and chemotherapy/biologics in HNC patients.

ObjectivesTo determine the decannulation rate (DR) and revision surgery rate after surgery for bilateral vocal fold paralysis (BVFP).Data SourcesFive databases (MEDLINE, PubMed, Embase, Web of Science, Scopus) were searched for the period 1908–2020.MethodsThe systematic literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were pooled using a random-mixed-effects model. Randomized controlled trials and non-randomized studies (case-control, cohort, and case series) were included to assess DR and revision surgery rate after different surgical techniques for treatment of BVFP.ResultsThe search yielded 857 publications, of which 102 with 2802 patients were included. DR after different types of surgery was: arytenoid abduction (DR 0.93, 95%-confidence interval [CI], 0.86–0.97), endolaryngeal arytenoidectomy (DR 0.92, 95%-CI, 0.86–0.96), external arytenoidectomy (DR 0.94; 95%-CI, 0.71–0.99), external arytenoidectomy and lateralisation (DR 0.87; 95%-CI, 0.73–0.94), laterofixation (DR 0.95; 95%-CI, 0.91–0.97), posterior cordectomy (DR 0.97, 95%-CI, 0.94–0.99), posterior cordectomy and arytenoidectomy (DR 0.98, 95%-CI, 0.93–0.99), posterior cordectomy and subtotal arytenoidectomy (DR 0.98, 95%-CI, 0.88–1.00), posterior cordotomy (DR 0.96, 95%-CI, 0.84–0.99), reinnervation (0.69, 95%-CI, 0.12–0.97), subtotal arytenoidectomy (DR 1.00, 95%-CI, 0.00–1.00) and transverse cordotomy (DR 1.0, 95%-CI, 0.00–1.00). No significant difference between subgroups for DR could be found (Q = 15.67, df = 11, p = 0.1540). The between-study heterogeneity was low (τ2 = 2.2627; τ = 1.5042; I2 = 0.0%). Studies were at high risk of bias.ConclusionBLVP is a rare disease and the study quality is insufficient. The existing studies suggest a publication bias and the literature review revealed that there is a lack of prospective controlled studies. There is a lack of standardized measures that takes into account both speech quality and respiratory function and allows adequate comparison of surgical methods.

Abstract Background Most spontaneous subarachnoid hemorrhages (SAH) occur unexpectedly and independently of classical risk factors. In the light of increasing climate variability and change, we investigated weather and rapid weather changes as possible short-term risk factors for SAH. Methods Seven hundred ninety one patients admitted to three major hospitals in Germany for non-traumatic SAH with a determinable onset of SAH symptoms were included in this hospital-based, case-crossover study. The effects of atmospheric pressure, relative air humidity, and ambient temperature and their 24 h changes on the onset of SAH under temperate climate conditions were estimated. Results There was no association between the risk of SAH and 24 h weather changes, mean daily temperature or mean relative air humidity in the overall population. For every 11.5 hPa higher mean daily atmospheric pressure, the risk of SAH increased by 15% (OR 1.15, 95% confidence interval (CI) 1.01–1.30) in the entire study population with a lag time of three days. Conclusion Our results suggest no relevant association between 24 h-weather changes or absolute values of ambient temperature and relative humidity and the risk of SAH. The medical significance of the statistically weak increase in SAH risk three days after exposure to high atmospheric pressure is unclear. However, as the occurrence of stable high-pressure systems will increase with global warming and potentially affect SAH risk, we call for confirming studies in different geographical regions to verify our observations.

Water is becoming an increasingly contested resource. Today, the sustainability of water use is assessed with different indicator frameworks that usually refer to the Sustainable Development Goals (SDGs) or other norms. Classifying international norms and the subsequent indicators for assessment according to their legitimacy will increase the practical relevance of assessment results. The classification will enable addressees to differentiate between mandatory obligations in water management and additional more ambitious targets for decisions on sustainable water distribution. This study presents 11 standards for sustainable water distribution which have been classified based on legitimacy and specificity. A literature review identified relevant international norms that were subsequently classified. Suggestions for the implementation of the standards and priorities in assessment methods are discussed. Through the new set of standards, assessment results can transparently be communicated to policymakers, NGOs and business and support them to identify their obligations for sustainable water use. Highlights Compiled standards can be used by decision-makers for the spatial assessment of the sustainability of water use.; Classification of norms according to legitimacy and specificity points to governmental actors where further operationalization is needed to implement and monitor sustainable water use.; In competing situations, water allocation between environment and food production remains unsolved.;

Sepsis survival is associated with adverse outcomes. Knowledge about risk factors for adverse outcomes is lacking. We performed a population-based cohort study of 116,507 survivors of hospital-treated sepsis identified in health claims data of a German health insurance provider. We determined the development and risk factors for long-term adverse events: new dependency on chronic care, chronic dialysis, long-term respiratory support, and 12-month mortality. At-risk patients were defined by absence of these conditions prior to sepsis. Risk factors were identified using simple and multivariable logistic regression analyses. In the first year post-sepsis, 48.9% (56,957) of survivors had one or more adverse outcome, including new dependency on chronic care (31.9%), dialysis (2.8%) or respiratory support (1.6%), and death (30.7%). While pre-existing comorbidities adversely affected all studied outcomes (>4 comorbidities: OR 3.2 for chronic care, OR 4.9 for dialysis, OR 2.7 for respiratory support, OR 4.7 for 12-month mortality), increased age increased the odds for chronic care dependency and 12-month mortality, but not for dialysis or respiratory support. Hospital-acquired and multi-resistant infections were associated with increased risk of chronic care dependency, dialysis, and 12-month mortality. Multi-resistant infections also increased the odds of respiratory support. Urinary or respiratory infections or organ dysfunction increased the odds of new dialysis or respiratory support, respectively. Central nervous system infection and organ dysfunction had the highest OR for chronic care dependency among all infections and organ dysfunctions. Our results imply that patient- and infection-related factors have a differential impact on adverse life changing outcomes after sepsis. There is an urgent need for targeted interventions to reduce the risk.

Abstract Aims Exposure to high levels of air pollution in industrialized urban areas is associated with an increased risk of heart failure (HF). On most days, the majority of European cities are only moderately affected by air pollution. The aim of this study was to evaluate the association between short‐term exposure to moderate levels of air pollution with the risk of HF in a city with good air quality. Methods and results We recruited 576 patients (median age 82 years; 58.2% men) admitted to a large university hospital in Central Germany for HF to participate in a hospital‐based, bidirectional, case‐crossover study. Diagnosis of HF and symptom onset were verified individually. The effect of short‐term exposure to nitrogen dioxide (NO2), particulate matter (PM10), and ozone (O3) on the risk of HF was estimated using linear and non‐linear (categorized) multivariate analyses for three different lag times (1, 2, and 3 days before HF onset). Air pollution variables were adjusted to the date of HF symptom onset. During the study period, the average daily concentration of air pollutants was only moderate and reflects the average European background air pollution. In particular, the concentration of air pollutants ranged from 2 to 63.39 μg/m3 (median = 17.46 μg/m3) for NO2, from 2 to 125.88 μg/m3 (median = 44.61 μg/m3) for O3, and from 2.21 to 166.79 μg/m3 (median = 18.67 μg/m3) for PM10. We did not find a linear or non‐linear association between short‐term exposure to NO2, O3, or PM10 and risk for HF at all lag times in the overall population and subgroups. Conclusions In an area with only moderate air pollution, short‐term exposure to major air pollutants does not increase the risk for HF. Future studies should focus on a potential threshold effect of air pollution on HF risk as a basis for evidence‐based development of statutory limits in highly polluted areas.

BACKGROUND: Metabolomics has become a valuable tool for identifying potential new biomarkers and metabolic profiles. It has the potential to improve the diagnosis and prognosis of different phenotypes of heart failure. To generate a distinctive metabolic profile, we assessed and compared the metabolic phenotypes of patients with acute decompensated heart failure (ADHF), patients with chronic heart failure (CHF), and healthy controls. METHODS: Plasma metabolites were analyzed by liquid-chromatography mass spectrometry/mass spectrometry and the MxP Quant 500 kit in 15 patients with ADHF, 50 patients with CHF (25 with dilated cardiomyopathy, 25 with ischemic cardiomyopathy), and 13 controls. RESULTS: Of all metabolites identified to be significantly altered, 3-indolepropionic acid and 1-methyl histidine showed the highest concentration differences in ADHF and CHF compared with control. Area under the curve--receiver operating characteristic analysis showed an area under the curve ≥0.8 for 3-indolepropionic acid and 1-methyl histidine, displaying good discrimination capabilities between control and patient cohorts. Additionally, symmetrical dimethylarginine (mean, 1.97±0.61 [SD]; P=0.01) was identified as a suitable biomarker candidate for ADHF and kynurenine (mean, 1.69±0.39 [SD]; P=0.009) for CHF when compared with control, both demonstrating an area under the curve ≥0.85. CONCLUSIONS: Our study provides novel insights into the metabolic differences between ADHF and CHF and healthy controls. We here identify new metabolites for potential diagnostic and prognostic purposes. [ABSTRACT FROM AUTHOR]

During adolescence both sexes experience a loss of body satisfaction, whereby the effect is greater among girls. Coming to terms with gender roles is an important step in the development of a person’s identity. Traditional gender roles tend to emphasise certain physical attributes: attractiveness in women, and strength and dominance in men. This article analyses associations between a traditional gender role orientation and body satisfaction during adolescence based on logistic regression models and using data taken from the 2017/18 Health Behaviour in School-aged Children (HBSC) study (n=1,912 girls, n=1,689 boys). The results show an overall high degree of body satisfaction, with girls scoring lower than boys. Role preconceptions were mostly not traditional, with boys being slightly more traditional than girls. In both sexes, a more traditional role orientation was accompanied by lower levels of body satisfaction; in boys, this effect was seen to decrease with age. The stereotypical features of role preconceptions are examined as a possible explanation for these differences. An alternative explanation posits that an egalitarian role orientation (i.e. one based on the principle of equality) creates a more tolerant environment with greater social support, which could foster a greater sense of self-acceptance. These results indicate that questioning traditional preconceptions of gender roles during adolescence may help prevent problems related to body image in both sexes.

The Health Behaviour in School-aged Children (HBSC) study is an international research project in collaboration with the World Health Organization (WHO) for over 35 years. HBSC is the largest study on child and adolescent health and one of the most important sources of data for the WHO’s international comparative health monitoring. Every four years, data on the health and health behaviour of students aged 11, 13 and 15, as well as the social contexts and conditions for growing up healthy, are collected. A total of 50 countries belong to the HBSC network, with 45 countries taking part in the 2017/18 survey. Germany has contributed to the HBSC surveys since 1993/94. For the most recent 2017/18 cycle, students at 146 schools in Germany were interviewed (response rate of schools: 15.6%). A net sample of n = 4,347 girls and boys was achieved for Germany (response rate: 52.7%). Participation was voluntary and the survey was conducted in German school years five, seven and nine (corresponding to ages 11, 13 and 15). A weighting procedure was applied to allow for representative findings on the health of children and adolescents in Germany. HBSC offers a valuable contribution to health monitoring and provides numerous starting points to identify needs, risk groups and fields of action to initiate targeted and actual needs-based measures of prevention and health promotion in the school setting.

Objective: The aim of this meta-analysis was to investigate the impact of intravenous iloprost therapy on pain, function, edema changes, and follow-up surgery in bone marrow edema syndrome of the proximal femur. Methods: A systematic literature search up to May 2022 was performed to find relevant papers that made a statement about the outcome of intravenous iloprost therapy alone. Factors such as the Visual Analog Scale (VAS), Harris Hip Score (HHS), edema reduction, and follow-up interventions were considered. These were compared using Forest plots. Results: In 11 studies, 190 proximal femora with bone marrow edema syndrome that received intravenous iloprost therapy without further therapeutic intravenous or surgical intervention such as core decompression were studied. There was a significant mean improvement in VAS by 3.3 cm (2.07–4.5 cm) (p < 0.001) and HHS by 24.36 points (18.23–30.49) (p < 0.001) 3–6 months after receiving iloprost therapy. Only in 9.3% of cases (1.1–24.3%) did no clinical or radiological improvement occur. Conclusions: It could be shown that the existing publications support intravenous therapy with iloprost in patients with bone marrow edema syndrome and result in good clinical outcomes.

The phase transition behavior of differently crosslinked poly(N-isopropylacrylamide)/N,N’-methylenebisacrylamide (PNiPAM/BIS) microgels with varying crosslinker content is investigated in presence of aromatic additives. The influence of meta-hydroxybenzaldehyde (m-HBA) and 2,4-dihydroxybenzaldehyde (2,4-DHBA), chosen as model drugs, on the volume phase transition temperature (VPTT) is analyzed by dynamic light scattering (DLS), differential scanning calorimetry (DSC), and 1H-NMR, monitoring and comparing the structural, calorimetric, and dynamic phase transition, respectively. Generally, the VPTT is found to increase with crosslinker content, accompanied by a drastic decrease of transition enthalpy. The presence of an additive generally decreases the VPTT, but with distinct differences concerning the crosslinker content. While the structural transition is most affected at lowest crosslinker content, the calorimetric and dynamic transitions are most affected for an intermediate crosslinker content. Additive uptake of the collapsed gel is largest for low crosslinked microgels and in case of large additive-induced temperature shifts. Furthermore, as temperature is successively raised, 1H NMR data, aided by spin relaxation rates, reveal an interesting uptake behavior, as the microgels act in a sponge-like fashion including a large initial uptake and a squeeze-out phase above VPTT.

In systematic reviews, meta-analyses are routinely applied to summarize the results of the relevant studies for a specific research question. If one can assume that in all studies the same true effect is estimated, the application of a meta-analysis with common effect (commonly referred to as fixed-effect meta-analysis) is adequate. If between-study heterogeneity is expected to be present, the method of choice is a meta-analysis with random effects. The widely used DerSimonian and Laird method for meta-analyses with random effects has been criticized due to its unfavorable statistical properties, especially in the case of very few studies. A working group of the Cochrane Collaboration recommended the use of the Knapp-Hartung method for meta-analyses with random effects. However, as heterogeneity cannot be reliably estimated if only very few studies are available, the Knapp-Hartung method, while correctly accounting for the corresponding uncertainty, has very low power. Our aim is to summarize possible methods to perform meaningful evidence syntheses in the situation with only very few (ie, 2-4) studies. Some general recommendations are provided on which method should be used when. Our recommendations are based on the existing literature on methods for meta-analysis with very few studies and consensus of the authors. The recommendations are illustrated by 2 examples coming from dossier assessments of the Institute for Quality and Efficiency in Health Care.

Abstract Background Evidence-based psychological interventions for posttraumatic stress disorder (PTSD) are available in specialized settings, but adequate care in primary care is often lacking. The aim of this systematic review was to determine the effectiveness of psychological interventions for PTSD involving primary care physicians (PCPs) and to characterize these interventions as well as their providers. Method A systematic review and meta-analyses of randomized controlled trials (RCTs). Primary outcome were symptoms of PTSD. Results Four RCTs with a total of 774 patients suffering from PTSD symptoms were included, all applying cognitive behavioural based interventions. Three studies with psychological interventions being conducted by case managers were pooled in a meta-analysis. Interventions were not effective in the short term (0–6 months; SMD, − 0.1; 95% CI, − 0.24-0.04; I2 = 0%). Only two studies contributed to the meta-analysis for long term (12–18 months) outcomes yielding a small effect (SMD, − 0.23; 95% CI, − 0.38- -0.08; I2 = 0%). Conclusions Psychological interventions for PTSD in primary care settings may be effective in the long term but number and quality of included studies was limited so the results should be interpreted with caution.

Dieser Beitrag legt am Beispiel des von Prof. Dr. Dorothee M. Meister initiierten Projektes «E-Assessment NRW» dar, welche weitreichenden Herausforderungen es bei der Einführung von E-Assessments gibt. Dabei werden drei Handlungsfelder – Technik, Didaktik und Recht – bei der Einführung, Implementierung und Umsetzung von E-Assessments betrachtet und herausgestellt, welche Chancen eine kooperative Zusammenarbeit unter Berücksichtigung hochschulinterner Prozesse bietet und welche Konsequenzen sich daraus für die Medienpraxis an Hochschulen ergeben. Der Fokus des Beitrags liegt auf der kooperativen Zusammenarbeit im Bereich von Weiterbildungs- und Vernetzungsformaten.

Purpose To investigate the global burden of sepsis in hospitalized adults by updating and expanding a systematic review and meta-analysis and to compare findings with recent Institute for Health Metrics and Evaluation (IHME) sepsis estimates. Methods Thirteen electronic databases were searched for studies on population-level sepsis incidence defined according to clinical criteria (Sepsis-1, -2: severe sepsis criteria, or sepsis-3: sepsis criteria) or relevant ICD-codes. The search of the original systematic review was updated for studies published 05/2015-02/2019 and complemented by a search targeting low- or middle-income-country (LMIC) studies published 01/1979-02/2019. We performed a random-effects meta-analysis with incidence of hospital- and ICU-treated sepsis and proportion of deaths among these sepsis cases as outcomes. Results Of 4746 results, 28 met the inclusion criteria. 21 studies contributed data for the meta-analysis and were pooled with 30 studies from the original meta-analysis. Pooled incidence was 189 [95% CI 133, 267] hospital-treated sepsis cases per 100,000 person-years. An estimated 26.7% [22.9, 30.7] of sepsis patients died. Estimated incidence of ICU-treated sepsis was 58 [42, 81] per 100,000 person-years, of which 41.9% [95% CI 36.2, 47.7] died prior to hospital discharge. There was a considerably higher incidence of hospital-treated sepsis observed after 2008 (+ 46% compared to the overall time frame). Conclusions Compared to results from the IHME study, we found an approximately 50% lower incidence of hospital-treated sepsis. The majority of studies included were based on administrative data, thus limiting our ability to assess temporal trends and regional differences. The incidence of sepsis remains unknown for the vast majority of LMICs, highlighting the urgent need for improved epidemiological sepsis surveillance., Author(s): C. Fleischmann-Struzek [sup.1], L. Mellhammar [sup.2], N. Rose [sup.1], A. Cassini [sup.3], K. E. Rudd [sup.4], P. Schlattmann [sup.5], B. Allegranzi [sup.3], K. Reinhart [sup.6] [sup.7] [sup.8] Author Affiliations: [...]

This population-based study investigated the prognostic role of intraparotid (PAR) and cervical lymph node (LN) metastasis on overall survival (OS) of primary parotid cancer. All 345 patients (median age: 66 years; 43% female, 49% N+, 31% stage IV) of the Thuringian cancer registries with parotid cancer from 1996 to 2016 were included. OS was assessed in relation to the total number of removed PAR and cervical LN, number of positive intraparotid (PAR+), positive cervical LN, LN ratio, log odds of positive LN (LODDS), as well as including the PAR as LODDS-PAR. PAR was assessed in 42% of the patients (22% of these PAR+). T and N classification were not independent predictors of OS. When combining T with LODDS instead of N, higher T (T3/T4) became a prognosticator (hazard ratio (HR) = 2.588; CI = 1.329–5.040; p = 0.005) but not LODDS (p > 0.05). When combining T classification with LODDS-PAR, both higher T classification (HR = 2.256; CI = 1.288–3.950; p = 0.004) and the alternative classification with LODDS-PAR (≥median −1.11; HR 2.078; CI = 1.155–3.739; p = 0.015) became independent predictors of worse OS. LODDS-PAR was the only independent prognosticator out of the LN assessment for primary parotid cancer.