Introduction: A well-trained and experienced staff in epidemiological studies is essential for the quality of the study implementation and the data and analyses collected from it. A broad understanding of Good Epidemiological Practice (GEP) can increase the motivation of staff to collect evaluable data. There are no special training opportunities for non-academic staff. This report describes the development and evaluation of an “EPI Study Nurse” (ESN) pilot course to train staff in epidemiological studies. Project description: The development of a concept for a pilot course was initiated by a project group from the study centers of the German National Cohort (NAKO) in early 2020. It was carried out in close collaboration with the Robert Koch Institute (RKI) and the professional societies “Deutsche Gesellschaft für Sozialmedizin und Prävention” (DGSMP), “Deutsche Gesellschaft für Epidemiologie” (DGEpi), and “Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V.” (GMDS). A training plan with 12 modules covering the relevant contents of the GEP was defined and a timetable was drawn up. Those responsible for the modules and teachers as well as participants in the pilot course were recruited through inquiries from the institutions mentioned above. After each module, the expectations and satisfaction of participants and teachers were surveyed. The pilot course was financed by the participating institutions from their own resources. Discussion: The pilot phase of the continuing education course was successfully implemented within one year (2022–2023) (preparation of a curriculum, registration of participants and recruitment of lecturers, organisation and execution of the course and final examination) and evaluated. A particular challenge was the definition of the module-specific timeframes for the lectures and group work as well as the targeted consideration of the different levels of experience of the participants. For future courses, it must be taken into account that administrative tasks in particular require considerable human resources (e.g., creating the curriculum, organizing and moderating the course) and financial resources (e.g., fees, travel expenses). The project was approved as part of the application for the third funding phase of the NAKO (June 2024 – April 2028) and the courses will be offered once a year.

Background:In Germany, approximately 1,100 beds are allocated to early neurological-neurosurgical rehabilitation (ENNR) for patients with severe neurological illness requiring weaning from mechanical ventilation. Specialized ENNR institutions play a major role in maintaining ICU capacity in acute care hospitals and in reducing the number of patients dependent on home intensive care. However, nationwide structural data on ENNR weaning centers-together with detailed patient characteristics-remain unavailable. This lack of information poses significant challenges for healthcare planning, resource allocation, and understanding the national weaning capacity. Methods:In June 2022, an online survey was conducted to collect structural data on institutions and wards, as well as cross-sectional clinical data from mechanically ventilated neurological patients. The survey was sent to the members of the weaning commission of the German Society for Neurological Rehabilitation (DGNR), to participants of a preceding study, and also to institutions recruited through personal communication. Findings:Data were collected from 24 institutions, including 46 wards and 182 patients. Institutions showed considerable variability in diagnostic and therapeutic resources; however, most relied on multidisciplinary teams and intensive monitoring, indicating high medical complexity of the patient population. The most frequent primary diagnoses included ischemic stroke (n = 27, 15%), intracerebral hemorrhage (n = 21, 12%), hypoxic-ischemic encephalopathy (n = 12, 7%), and subarachnoid hemorrhage (n = 12, 7%). The most frequent comorbidities were coronary heart disease (n = 40, 22%), left ventricular failure (37, 20%), and COPD (37, 20%). Mechanical ventilation was predominantly invasive (n = 180, 99%). The median number of days on mechanical ventilation during the stay in ENNR was 22 (IQR 9-41) days, and the median duration of ventilation was 18 (IQR 10-24) h during the last 24 h before data collection. Fourteen (8%) patients needed renal replacement therapy. Palliative therapy limitations were implemented in 22 (12%) patients. Interpretation:Institutions providing weaning in ENNR commonly treat older, medically complex patients who have undergone pretreatment in acute intensive care units. These patients typically present with severe neurological illness accompanied with cardiopulmonary comorbidities. In order to meet their needs, multidisciplinary teams deliver rehabilitation, intensive care, and palliative care.

Introduction:The increasing prevalence of life-threatening neurological diseases raises the need for neuropalliative care. Setting up neurological palliative outpatient clinics is one way of addressing this need. This study aims to describe the patient clientele of a neurological palliative outpatient clinic and the spectrum of necessary treatments and interventions. Methods:In this longitudinal analysis, clinical routine data from a single centre were collected retrospectively from adult patients. The patient characteristics related to disease and treatment were evaluated descriptively. Factors influencing the need for ventilation were modelled in a logistic regression. The required treatment effort was modelled with a zero-inflated Beta regression. Results were reported as odds ratios with 95% confidence intervals (CIs). Results:Two hundred and thirty-two patients were included in the study. Ninety-one patients were women, 141 were men, and the mean age was 55.42 years. Neuropalliative patients represented diagnoses such as amyotrophic lateral sclerosis (ALS) (n = 81), ischemic stroke (n = 15), intracerebral haemorrhage (n = 15), Duchenne muscular dystrophy (n = 12), or craniocerebral trauma (n = 10). Palliative care counselling was the most common intervention for patients (n = 203), their close relatives (n = 177), and their nursing services (n = 75). Respiratory therapy (n = 188), speech and language therapy (n = 145), and physiotherapy (n = 143) were also frequently applied interventions. Sixty patients received botulinum toxin A treatment for hypersalivation, and 32 for spasticity. The odds of needing invasive ventilation increased by 3.7 (CI 1.7-7.8), and the need for mechanical insufflation-exsufflation increased by 2.2 (CI 1.1-4.3) in patients previously discharged from early neurological-neurosurgical rehabilitation. Prior intensive care treatment increased the odds of invasive ventilation by 5.1 (CI 2.2-11.5) and the use of mechanical insufflation-exsufflation by 2.3 (CI 1.1-4.8). Conclusion:Neuropalliative outpatient clinics demand a wide range of diagnostic measures and interventions as well as a multidisciplinary approach. Further research is necessary to investigate the relation between diagnosis and treatment needs. Clinical trial registration:https://drks.de/search/en/trial/DRKS00030778, identifier DRKS00030778.

BACKGROUND:Crohn's disease (CD) is a chronic inflammatory bowel disease leading to symptoms such as abdominal pain, diarrhea, weight loss, fatigue, and complications such as strictures and fistulas. Ustekinumab (CNTO 1275) and briakinumab (ABT-874) are monoclonal antibodies that target the standard p40 subunit of the cytokines interleukin-12 and interleukin-23 (IL-12/23p40), which are involved in the pathogenesis of CD. Briakinumab has been withdrawn for the treatment of CD, making ustekinumab the only available antibody against the p40 subunit of interleukin-12 and interleukin-23 approved for this purpose. OBJECTIVES:To assess the benefits and harms of anti-IL-12/23p40 antibodies for induction of remission in CD, as compared to no treatment, placebo, other drug treatment, or varying dosing schedules. SEARCH METHODS:We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and MEDLINE (from inception to 2 February 2024) and Embase (from inception until 12 August 2022). We also searched ClinicalTrials.gov, WHO ICTRP, references, and conference abstracts to identify additional studies. SELECTION CRITERIA:We included randomized controlled trials (RCTs) of at least four weeks' duration in which monoclonal antibodies against IL-12/23p40 were compared to placebo, no treatment, or another active comparator in people with active CD. We also included trials examining different doses of antibodies against IL-12/23p40. DATA COLLECTION AND ANALYSIS:Two review authors independently screened studies for inclusion and extracted data. We assessed the methodological quality of the included studies using Cochrane's RoB 2 tool. The primary outcome was failure to induce clinical remission by week 8, or 6 to 12 as available. Secondary outcomes included failure to induce clinical improvement (clinical response), induction of endoscopic remission, quality of life, and adverse events, serious adverse events, and withdrawals due to adverse events. We calculated the risk ratio (RR) or risk difference (RD) and 95% confidence intervals (95% CI) for each outcome unless substantial heterogeneity was detected. We analyzed data on an intention-to-treat basis. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS:Eight RCTs involving a total of 3224 participants with CD met the inclusion criteria. All studies were double-blinded. We assessed the risk of bias for most outcomes as either low risk of bias or some concerns. Based on a pooled analysis of three trials, ustekinumab decreased the number of participants failing to achieve clinical remission at eight weeks when compared to placebo. Seventy-four per cent (693/938) of participants in the ustekinumab group and 87% (421/483) of those in the placebo group did not enter clinical remission (RR 0.85, 95% CI 0.81 to 0.89; 3 studies; 1421 participants; high-certainty evidence). Treatment with ustekinumab likely did not lead to more serious adverse events when compared to placebo, with 5% (48/966) and 6% (30/505) of participants affected in the ustekinumab and placebo groups, respectively (RD -0.01, 95% CI -0.03 to 0.01; 3 studies; 1471 participants; moderate-certainty evidence). A single small study in children compared two different induction doses of ustekinumab. The evidence for this outcome is very uncertain due to wide CIs. Eighty-one per cent (17/21) of participants receiving the higher induction dose (9 mg/kg or 390 mg) did not enter clinical remission at eight weeks, compared to 78% (18/23) of participants receiving the lower induction dose of 3 mg/kg or 130 mg (RR 1.03, 95% CI 0.77 to 1.39; 1 study; 44 participants; very low-certainty evidence). Separate safety data for the eight-week time point were not available for this comparison. Based on one trial comparing ustekinumab to adalimumab, the evidence is very uncertain about which is the more beneficial drug. Fifty per cent (95/191) of participants receiving ustekinumab did not enter remission compared to 52% (101/195) of participants receiving adalimumab (RR 0.96, 95% CI 0.79 to 1.17; 1 study; 386 participants; very low-certainty evidence). Separate results on adverse events at eight weeks were not reported for this comparison. AUTHORS' CONCLUSIONS:Ustekinumab reduces the risk of people with CD failing to enter clinical remission at eight weeks. It probably does not lead to more serious adverse events when compared to placebo. There were inadequate data to conclude the more effective induction dose of ustekinumab in children. No studies evaluated adverse events at eight weeks for this comparison. There may be little to no difference between ustekinumab and other biologics, such as adalimumab or guselkumab, in inducing clinical remission at week 8, but the evidence is very uncertain, and separate data on adverse events at eight weeks were not available.

BACKGROUND:Maintenance of remission is essential in inflammatory bowel disease (IBD) in terms of disease course and long-term prognosis. The thiopurines azathioprine and 6-mercaptopurine have longstanding merit in ulcerative colitis, but more therapeutic options have been developed. This review is an update and extension of a review last published in 2016. OBJECTIVES:To assess the effectiveness and safety of azathioprine and 6-mercaptopurine in monotherapy or combined therapy regimens compared to placebo or active controls for the maintenance of remission in ulcerative colitis. SEARCH METHODS:We searched Cochrane Central Register of Controlled Trials (until May 2023), ClinicalTrials.gov (until May 2023), Embase (until August 2022), MEDLINE (until May 2023), and WHO ICTRP (until May 2023). We checked reference lists of the included studies and, if needed, contacted the authors to request more data or information. SELECTION CRITERIA:Randomized controlled trials (RCTs) of at least 24 weeks' duration comparing azathioprine or 6-mercaptopurine with placebo or any other medication, or comparing different treatment modalities of azathioprine or 6-mercaptopurine, in persons of any age with quiescent ulcerative colitis were eligible. We only considered studies with mixed IBD populations or with a preceding induction period if separate results on participants with ulcerative colitis in remission were available or could be calculated. The primary outcome was failure to maintain clinical or endoscopic remission (relapse). Secondary outcomes included change in disease activity, quality of life, hospitalization, need for surgery, days off work, adverse events, and withdrawal due to adverse events. DATA COLLECTION AND ANALYSIS:Two authors independently extracted data using standard forms, resolved any disagreements by consensus, and assessed study quality using the Cochrane risk of bias tool (RoB 2). We conducted separate analyses by type of control, calculated pooled risk ratios (RRs) or risk differences (RDs) using the fixed-effect model unless heterogeneity was likely, and assessed the certainty of evidence using the GRADE approach. MAIN RESULTS:We included 10 studies in the review, including 468 adult participants with ulcerative colitis. The risk of bias across these was low for most outcomes, but we considered some outcomes to have some concerns or high risk of bias due to insufficient information on concealment of allocation and outcome measurement. Based on five placebo-controlled studies, azathioprine or 6-mercaptopurine may reduce the risk of failing to maintain remission. In the thiopurine group, 45% (64/143) of participants failed to maintain remission compared to 67% (96/143) of participants receiving placebo (RR 0.66, 95% confidence interval (CI) 0.54 to 0.82; 5 studies, 286 participants; low-certainty evidence). Three studies reported withdrawals due to adverse events. Among participants on azathioprine, 4% (3/80) withdrew due to adverse events compared to 0% (0/82) of placebo participants (RD 0.04, 95% CI -0.02 to 0.09; 3 studies, 162 participants; low-certainty evidence). The evidence is of low certainty when comparing 6-mercaptopurine to 5-aminosalicylate. Based on one three-armed trial, 27% (3/11) of 6-mercaptopurine participants failed to maintain remission compared to 100% (2/2) of 5-aminosalicylate participants (RR 0.35, 95% CI 0.13 to 0.97; 1 study, 13 participants; low-certainty evidence). This trial also involved an induction phase; we only included the results for participants in remission. The single trial comparing 6-mercaptopurine to 5-aminosalicylate did not report separate data on adverse events and withdrawals due to adverse events for the subgroup with successful induction of remission, so we could not analyze these outcomes for this comparison. AUTHORS' CONCLUSIONS:Low-certainty evidence suggests that azathioprine or 6-mercaptopurine therapy may be more effective than placebo for the maintenance of remission in ulcerative colitis. More research is needed to evaluate the value of therapeutic drug monitoring and the effects of various treatment modalities on long-term safety.

BACKGROUND:Persons with inflammatory bowel disease (IBD) have an increased risk of suffering from psychological problems. The association is assumed to be bi-directional. Psychological treatment is expected to improve quality of life (QoL), psychological issues and, possibly, disease activity. Many trials have tested various psychotherapy approaches, often in combination with educational modules or relaxation techniques, with inconsistent results. OBJECTIVES:To assess the effects of psychological interventions on quality of life, emotional state and disease activity in persons of any age with IBD. SEARCH METHODS:We searched Web of Science Core Collection, KCI-Korean Journal Database, Russian Science Citation Index, MEDLINE, Psyndex, PsycINFO, Embase, Cochrane Central Register of Controlled Trials, and LILACS from inception to May 2023. We also searched trial registries and major gastroenterological and selected other IBD-related conferences from 2019 until 2023. SELECTION CRITERIA:Randomized controlled trials of psychological interventions in children or adults with IBD compared to no therapy, sham (i.e. simulated intervention), or other active treatment, with a minimum follow-up time of two months, were eligible for inclusion, irrespective of publication status and language of publication. Interventions included psychotherapy and other non-pharmacological interventions addressing cognitive or emotional processing, patient education, or relaxation techniques to improve individual health status. DATA COLLECTION AND ANALYSIS:Two raters independently extracted data and assessed the study quality using the Risk of Bias 2 Tool. Pooled standardized mean differences (SMD) for continuous outcomes and relative risks (RR) for event data were calculated with 95% confidence intervals (CI), based on separate random-effects models by age group, type of therapy and type of control. An SMD of 0.2 was considered a minimally relevant difference. SMD ≥ 0.4 was considered a moderate effect. Group analyses were planned to examine differential effects by type of IBD, disease activity, psychological comorbidity, therapy subtype, and treatment intensity. Statistical heterogeneity was determined by calculating the I2 statistic. Publication bias was assessed by presenting a funnel plot and calculating the Eggers Test. GRADE Profiling was used to describe the certainty of the evidence for relevant results. MAIN RESULTS:Sixty-eight studies were eligible. Of these, 48 had results reported in sufficient detail for inclusion in the meta-analyses (6111 adults, 294 children and adolescents). Two trials were excluded from the meta-analysis following sensitivity analysis and tests for asymmetry because of implausible results. Most studies used multimodular approaches. The risk of bias was moderate for most outcomes, and high for some. The most common problems in individual trials were the inability to blind participants and investigators and outcome measures susceptible to measurement bias. The main issues leading to downgrading of the certainty of the evidence were heterogeneity of results, low precision and high or moderate risk of bias in the included trials. Publication bias could not be shown for any of the inspected analyses. In adults, psychotherapy was slightly more effective than care-as-usual (CAU) in improving short-term QoL (SMD 0.23, 95% CI 0.12 to 0.34; I2 = 13%; 20 trials, 1572 participants; moderate-certainty), depression (SMD -0.27, 95% CI -0.39 to -0.16; I2 = 0%; 16 trials, 1232 participants; moderate-certainty), and anxiety (SMD -0.29, 95% CI -0.40 to -0.17; I2 = 1%; 15 studies, 1135 participants; moderate-certainty). The results for disease activity were not pooled due to high heterogeneity (I2 = 72%). Interventions which used patient education may also have small positive short-term effects on QoL (SMD 0.19, 95% CI 0.06 to 0.32; I2 = 11%; 12 trials, 1058 participants; moderate-certainty), depression (SMD -0.22, 95% CI -0.37 to -0.07; I2 = 11%; 7 studies, 765 participants; moderate-certainty) and anxiety (SMD -0.16, 95% CI -0.32 to 0.00; I2 = 10%; 6 studies, 668 participants; moderate-certainty). We did not find an effect of education on disease activity (SMD -0.09, 95% CI -0.28 to 0.10; I2 = 38%; 7 studies, 755 participants; low-certainty). Pooled results on the effects of relaxation techniques showed small effects on QoL (SMD 0.25, 95% CI 0.08 to 0.41; I2 = 30%; 12 studies, 916 participants; moderate-certainty), depression (SMD -0.18, 95% CI -0.35 to -0.02; I2 = 0%; 7 studies, 576 participants; moderate-certainty), and anxiety (SMD -0.26, 95% CI -0.43 to -0.09; I2 = 13%; 8 studies, 627 participants; moderate-certainty). Results for disease activity were not pooled due to high heterogeneity (I2 = 72%). In children and adolescents, multimodular psychotherapy increased quality of life (SMD 0.54, 95% CI 0.06 to 1.02; I2 = 19%; 3 studies, 91 participants; moderate-certainty). The results for anxiety were inconclusive (SMD -0.09; 95% CI 0.-64 to 0.46; 2 trials, 51 patients, very low-certainty). Pooled effects were not calculated for depressive symptoms. Disease activity was not assessed in any of the trials compared to CAU. In education, based on one study, there might be a positive effect of the intervention on quality of life (MD 7.1, 95% CI 2.18 to 12.02; 40 patients; low-certainty evidence) but possibly not on depression (MD -6, 95% CI -12.01 to 0.01; 41 patients; very low-certainty). Anxiety and disease activity were not assessed for this comparison. Regarding the effects of relaxation techniques on children and adolescents, all results were inconclusive (very low-certainty). AUTHORS' CONCLUSIONS:Psychological interventions in adults are likely to improve the quality of life, depression and anxiety slightly. Psychotherapy is probably also effective for improving the quality of life in children and adolescents. The evidence suggests that psychological interventions may have little to no effect on disease activity. The interpretation of these results presents a challenge due to the clinical heterogeneity of the included trials, particularly concerning the type and various components of the common multimodular interventions. This complexity underscores the need for further research and exploration in this area.

Background: The patient perspective is essential for assessing disease severity, but it is not always adequately considered. We describe how a comprehensive clinical disease severity index (DSI) for inflammatory bowel disease (IBD) correlates with patient global self-assessment (PGSA). Methods: In an individually linked parallel online survey, physicians provided the DSI, and patients provided self-assessed severity using a global question and visual analog scale (0-100) (PGSA). Mean DSI values by PGSA were calculated with 95% confidence intervals. Pearson correlation (r) and the intraclass correlation coefficient were calculated for PGSA vs DSI. Positive predictive values for identifying severe disease with PGSA categories as a reference were based on a threshold >22 points. Results: The primary analysis included 89 pairs (46 Crohn's disease [CD], 43 ulcerative colitis [UC]) with strict criteria and 147 pairs when less stringent. Common reasons for exclusion were missing values for albumin or colonoscopy. Mean DSI values showed no clear trend with increasing PGSA in CD but good discrimination between moderate, severe, and very severe PGSA in UC. For PGSA on the visual analog scale, r was 0.54 for CD and 0.59 for UC (difference in means: CD 27.7, UC 13.8; intraclass correlation coefficient: CD 0.48, UC 0.58). A high DSI predicted severe disease in 76.2% of CD and 65.2% of UC. Conclusions: The DSI showed good discrimination for patient-reported disease severity in UC but performed unsatisfactorily in CD. Correlations were moderate. Further refinement of the DSI is suggested to better reflect the patient perspective.

INTRODUCTION:Patients with neurological or neurosurgical disease can suffer from impaired cough, which may result in life-threatening retention of tracheobronchial secretions, atelectasis, pneumonia and finally death. Due to a lack of alternatives and pathophysiological plausibility, the application of mechanical insufflation-exsufflation (MI-E) has already become international standard care in neuromuscular disease and spinal cord injury although a lack of evidence for efficacy. High-quality studies to support the use of MI-E in neurological and neurosurgical patients during weaning from mechanical ventilation are missing. The goal of this exploratory study is to display the effect size of MI-E intervention on the duration of mechanical ventilation and additional outcomes.METHODS AND ANALYSIS:One hundred adult patients with a cough deficiency or retention of secretion admitted to a neurological intensive care unit (ICU) are planned to be recruited for this randomised controlled trial. Patients are randomised 1:1 to receive either MI-E or best standard care. Observation will take place until discharge from the hospital, death or end of the study period. The primary endpoint of this trial is the duration of mechanical ventilation from randomisation until successful weaning. The outcome will be analysed with Kaplan-Meier estimation and competing risks analyses. Secondary endpoint is the proportion of patients with successful weaning. Further outcomes will include the incidence of hospital-acquired pneumonia, mortality, decannulation rate, length of stay on the ICU and the total score of the Glasgow Coma Scale.ETHICS AND DISSEMINATION:The study was approved by the Medical Ethics Committee of the University of Oldenburg. The findings of this study will be submitted for publication in a peer-reviewed journal.TRIAL REGISTRATION NUMBER:DRKS00020981.

The distribution of time-to-event outcomes is usually right-skewed. While for symmetric and moderately skewed data the mean and median are appropriate location measures, the mode is preferable for heavily skewed data as it better represents the center of the distribution. Mode regression has been introduced for uncensored data to model the relationship between covariates and the mode of the outcome. Starting from nonparametric kernel density based mode regression, we examine the use of inverse probability of censoring weights to extend mode regression to handle right-censored data. We add a semiparametric predictor to add further flexibility to the model and we construct a pseudo Akaike's information criterion to select the bandwidth and smoothing parameters. We use simulations to evaluate the performance of our proposed approach. We demonstrate the benefit of adding mode regression to one's toolbox for analyzing survival data on a pancreatic cancer data set from a prospectively maintained cancer registry.

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 Background Evaluation of disease severity (DS) in the Inflammatory Bowel Diseases (IBD) requires comprehensive consideration of disease course and health status of individual patients. It is not clear how well physician assessment covers disease impact as perceived by patients. We compared patient and physician global assessment of disease severity in relation to standardized assessment using a clinical disease severity score (DSI, Siegel 2018). Methods Patients with ulcerative colitis (UC) and Crohn’s disease (CD) were prospectively recruited from the national patient organization (DCCV) and by participating physicians. Physicians (IBD experts) were approached via the DCCV advisory board and other professional contacts. Both groups graded disease severity for a random selection of written standard short cases (1 page, maximum 5 CD, 3 UC) on a simple visual analogue scale (VAS) (online survey). For analysis, VAS were transferred to a 0 (minimal severity) to 100 (maximal severity) scale, in analogy to the range of the DSI. We present graphs of mean scores by rater group with 95% CI. Differences between mean patient and physician assessments were calculated per case. In addition, we examined the difference from the DSI. Results We included 824 ratings from 319 patients (168 CD, 151 UC), and 143 ratings from 34 physicians (20 ISS, 14 external)(recruitment ongoing). UC cases received on average 124 patient ratings (range 122–125), and 21 physician ratings (range 17–26). Means from both rater groups discriminated well between disease severity as scored by the DSI. Mean physician ratings were consistently and substantially lower than patient ratings for all three UC cases. Differences between means ranged from 8.5 (95% CI 0.5 to 16.5) for mild disease to 10.1 (95% CI 1.3 to 18.9) for moderate disease (p < 0.001) (Figure 1). In contrast, deviations from the DSI did not show a clear pattern. CD cases were rated by a mean of 91 patients (77–125) and 16 physicians (13–21). Mean physician and mean patient ratings were very close, in particular in those with medium DSI (Figure 2). Conclusion Physicians agreed, on average, very well with patient grading on disease severity grading of exemplary cases of CD. Lower scores were given for UC cases, and mild CD, but the overall trend remained intact. In contrast, correlation with DSI scores was poor and will need further analysis.

Introduction Patients with inflammatory bowel diseases (IBD) often report psychological problems, unemployment, disability, sick leave and compromised quality of life. The effect of psychological interventions on health-related outcomes in IBD is controversial as previous reviews faced the obstacle of high heterogeneity among provided multimodular interventions. The heterogeneity can be addressed with network meta-analysis (NMA) and (multi)component NMA (CNMA). We aim to investigate whether psychological interventions can improve quality of life, clinical and social outcomes in IBD using NMA and CNMA. This is the study protocol. Methods and analysis We will consider randomised, quasi-randomised and non-randomised controlled trials, including cluster randomised and cross-over trials with 2 months of minimum follow-up. The conditions to be studied comprise Crohn's disease and ulcerative colitis in children, adolescents and adults. We will include any psychological intervention aiming to change the health status of the study participant. We will search Medline, Embase, Web of Science, CENTRAL, LILACS, Psyndex, PsycINFO, Google Scholar and trial registries from inception (the search will be updated before the review completion). Two authors will independently screen all references based on titles and abstracts. For data extraction, standard forms are developed and tested before extraction. All information will be assessed independently by at least two reviewers, and disagreements solved by consensus discussion or a third rater if necessary. The data synthesis will include a pairwise meta-analysis supported by meta-regression. We will conduct NMA (all treatments will constitute single nodes of the network) and CNMA (we will define all treatments as sums of core components, eg, cognitive +behaviour, or cognitive +behaviour + relaxation, and additionally consider interactions) using the R Package netmeta. Ethics and dissemination No ethical approval is required. Reports will include the final report to the funder, conference presentation, peer-reviewed publication and a patient report. PROSPERO registration number CRD42021250446.

Knowledge of clinical-epidemiological methods is indispensable for scientifically informed clinical decisions and understanding clinical research. These skills gain particular relevance in a medical curriculum committed to science and scientific evidence, as reflected in the German national competence-based catalog of learning objectives for medicine (NKLM). It is expected that knowledge of clinical-epidemiological methods will also be part of the new licensing regulations and national subject catalogs (GK) for the state examinations (STEX) in Germany. Clinical epidemiology content is, however, not explicitly marked in these catalogs. Furthermore, teaching goals related to epidemiology and related subjects are distributed over all phases of the curriculum and several topic areas. Consequently, teaching in the new curriculum poses particular challenges even for experienced instructors.The German translation of the book “Clinical Epidemiology: The Essentials“ by Fletcher et al. follows the priorities set for the new curriculum. Besides a scientific approach to medicine, this concerns consideration of the requirements of everyday medical practice (graduate profile). The book is, however, not recommended explicitly for medical students.This review critically examines the book’s suitability for the various requirements of the medical curriculum. Epidemiology-related questions from a recent exam, the new subject catalog for STEX II valid from 2022, and relevant chapters of the NKLM are described to contrast book content with curricular requirements.

Einleitung Erkrankungsschwere bei CED lässt sich aufgrund des sehr variablen meist schubweisen Verlaufes unzureichend über die aktuelle Entzündungsaktivität und Lebensqualität beschreiben. Für eine umfassendere Beschreibung steht ein arztbasierter Schwere-Index zur Verfügung (DSI. Siegel, 2018).

Background: The revised National Competence-Based Learning Catalogue for Medicine (NKLM 2.0) is available since 2021. It will be part of the new licensing regulations for physicians (ApprOÄ), which are to come into force in 2025, and will also form the basis for the subject catalogue for state examinations (GK). Aim of the report: Information on the status, structure, relevant learning objectives, their location in the NKLM and specific challenges are presented to support lecturers of epidemiology, biometrics and medical informatics ("Q1 subjects") when revising teaching concepts to comply with the new regulations. Methods and content This is a narrative report based on the published NKLM and experiences gathered during the revision phase. Following presentation of formal elements such as general structure and levels of competency, underlying concepts such as the Z-Curriculum and profile orientation are briefly explained. Subsequently, the chapter on science skills is presented in detail to show its relevance and challenges for epidemiology, medical biometry and medical informatics. Conclusion and outlook: In summary, the developments as presented in the NKLM 2.0, GK and ApprOÄ show the increasing importance of the data sciences in medical education. All subjects are challenged by the complexity and interdisciplinary character of the catalogue.

Purpose This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments. Methods Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control. Results A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13-16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2-0.9) to 0.5 (95% CI, 0.3-1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8-1.7 per 10 000 treatments). Conclusion We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature.

Purpose Anaphylaxis (ANA) is an important adverse drug reaction. We examined positive predictive values (PPV) and other test characteristics of ICD-10-GM code algorithms for detecting ANA as used in a multinational safety study (PASS). Methods We performed a cross-sectional study on routine data from a German academic hospital (2004-2019, age >= 18). Chart review was used for case verification. Potential cases were identified from the hospital administration system. The main outcome required at least one of the following: any type of specific in-hospital code (T78.2, T88.6, and T80.5) OR specific outpatient code in combination with a symptom code OR in-hospital non-specific code (T78.4, T88.7, and Y57.9) in combination with two symptom codes. PPV were calculated with 95% confidence interval. Sensitivity analyses modified type of codes, unit of analysis, verification criteria and time period. The most specific algorithm used only primary codes for ANA (numbers added in brackets). Results Four hundred and sixteen eligible cases were evaluated, and 78 (37) potential ANA cases were identified. PPV were 62.8% (95% CI 51.1-73.5) (main) and 77.4% (58.9-90.4) (most specific). PPV from all modifications ranged from 12.9% to 80.6%. The sensitivity of the main algorithm was 66.2%, specificity 91.5%, and negative predictive value 92.6%. Corresponding figures for the most specific algorithm were 32.4%, 98.0%, and 87.0%. Conclusions The PPV of the main algorithm seems of acceptable validity for use in comparative safety research but will underestimate absolute risks by about a third. Restriction to primary discharge codes markedly improves PPV to the expense of reducing sensitivity.

Expectile regression can be used to analyze the entire conditional distribution of a response, omitting all distributional assumptions. Among its benefits are computational simplicity, efficiency, and the possibility to incorporate a semiparametric predictor. Due to its advantages in full data settings, we propose an extension to right-censored data situations, where conventional methods typically focus only on mean effects. We propose to extend expectile regression with inverse probability weights. Estimates are easy to implement and computationally simple. Expectiles can be converted to more easily interpreted tail expectations, that is, the expected residual life. It provides a meaningful effect measure, similar to the hazard rate. The results from an extensive simulation study are presented, evaluating consistency and sensitivity to violations of assumptions. We use the proposed method to analyze survival times of colorectal cancer patients from a regional certified high volume cancer center.