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Background: The provision of data sharing statements (DSS) for clinical trials has been made mandatory by different stakeholders. DSS are a device to clarify whether there is intention to share individual participant data (IPD). What is missing is a detailed assessment of whether DSS are providing clear and understandable information about the conditions for data sharing of IPD for secondary use. Methods: A random sample of 200 COVID-19 clinical trials with explicit DSS was drawn from the ECRIN clinical research metadata repository. The DSS were assessed and classified, by two experienced experts and one assessor with less experience in data sharing (DS), into different categories (unclear, no sharing, no plans, yes but vague, yes on request, yes with specified storage location, yes but with complex conditions). Results: Between the two experts the agreement was moderate to substantial (kappa=0.62, 95% CI [0.55, 0.70]). Agreement considerably decreased when these experts were compared with a third person who was less experienced and trained in data sharing ("assessor") (kappa=0.33, 95% CI [0.25, 0.41]; 0.35, 95% CI [0.27, 0.43]). Between the two experts and under supervision of an independent moderator, a consensus was achieved for those cases, where both experts had disagreed, and the result was used as "gold standard" for further analysis. At least some degree of willingness of DS (data sharing) was expressed in 63.5% (127/200) cases. Of these cases, around one quarter (31/127) were vague statements of support for data sharing but without useful detail. In around half of the cases (60/127) it was stated that IPD could be obtained by request. Only in in slightly more than 10% of the cases (15/127) it was stated that the IPD would be transferred to a specific data repository. In the remaining cases (21/127), a more complex regime was described or referenced, which could not be allocated to one of the three previous groups. As a result of the consensus meetings, the classification system was updated. Conclusion: The study showed that the current DSS that imply possible data sharing are often not easy to interpret, even by relatively experienced staff. Machine based interpretation, which would be necessary for any practical application, is currently not possible. Machine learning and / or natural language processing techniques might improve machine actionability, but would represent a very substantial investment of research effort. The cheaper and easier option would be for data providers, data requestors, funders and platforms to adopt a clearer, more structured and more standardised approach to specifying, providing and collecting DSS. Trial registration: The protocol for the study was pre-registered on ZENODO (https://zenodo.org/record/7064624#.Y4DIAHbMJD8). [ABSTRACT FROM AUTHOR]

For life science infrastructures, sensitive data generate an additional layer of complexity. Cross-domain categorisation and discovery of digital resources related to sensitive data presents major interoperability challenges. To support this FAIRification process, a toolbox demonstrator aiming at support for discovery of digital objects related to sensitive data (e.g., regulations, guidelines, best practice, tools) has been developed. The toolbox is based upon a categorisation system developed and harmonised across a cluster of 6 life science research infrastructures. Three different versions were built, tested by subsequent pilot studies, finally leading to a system with 7 main categories (sensitive data type, resource type, research field, data type, stage in data sharing life cycle, geographical scope, specific topics). 109 resources attached with the tags in pilot study 3 were used as the initial content for the toolbox demonstrator, a software tool allowing searching of digital objects linked to sensitive data with filtering based upon the categorisation system. Important next steps are a broad evaluation of the usability and user-friendliness of the toolbox, extension to more resources, broader adoption by different life-science communities, and a long-term vision for maintenance and sustainability. [ABSTRACT FROM AUTHOR]

Public health researchers may have to decide whether to perform a meta‐analysis including only high‐quality randomized clinical trials (RCTs) or whether to include a mixture of all the available evidence, namely RCTs of varying quality and observational studies (OS). The main hurdle when combining disparate evidence in a meta‐analysis is that we are not only combining results of interest but we are also combining multiple biases. Therefore, commonly applied meta‐analysis methods may lead to misleading conclusions. In this paper, we present a new Bayesian hierarchical model, called the bias‐corrected (BC) meta‐analysis model, to combine different study types in meta‐analysis. This model is based on a mixture of two random effects distributions, where the first component corresponds to the model of interest and the second component to the hidden bias structure. In this way, the resulting model of interest is adjusted by the internal validity bias of the studies included in a systematic review. We illustrate the BC model with two meta‐analyses: The first one combines RCTs and OS to assess effectiveness of vaccination to prevent invasive pneumococcal disease. The second one investigates the effectiveness of stem cell treatment in heart disease patients. Our results show that ignoring internal validity bias in a meta‐analysis may lead to misleading conclusions. However, if a meta‐analysis model contemplates a bias adjustment, then RCTs results may increase their precision by including OS in the analysis. The BC model has been implemented in JAGS and R, which facilitate its application in practice. [ABSTRACT FROM AUTHOR]

Objective: Concordance-analysis and evaluation of existing algorithms detecting late-onset preeclampsia during first trimester screeningMethods: Retrospective cohort study investigating risk algorithms of late-onset preeclampsia during first trimester screening in a German prenatal center. Three previously developed algorithms including anamnestic factors (Apriori) and biophysical markers (BioM) were investigated by using detection rates (DR) with fixed FPR 10% and fixed cutoff >1:100. Furthermore, we set up a concordance-analysis of test results in late-onset preeclampsia cases to examine the effect of influencing factors and to detect potential weaknesses of the algorithms. Therefore, we modeled the probability of discordances as a function of the influencing factors based on a logistic regression, that was fitted using a Bayesian approach.Results: 6,113 pregnancies were considered, whereof 700 have been excluded and 5,413 pregnancies were analyzed. 98 (1.8%) patients developed preeclampsia (79 late-onsets, 19 early-onsets). The Apriori-algorithm reaches a DR of 34.2%, by adding BioM (MAP and UtA-PI) the DR improves to 57.0% (FPR of 10%). In concordance-analysis of Apriori algorithm and Apriori+BioM algorithms, influencing factor BMI<25 increases the chance of discordances sigificantly. Additional, in the subgroup of late-onset preeclampsias with BMI<25 the DR is higher in Apriori+BioM algorithms than in Apriori algorithm alone. If both compared algorithms include BioM, influencing factor MAP decreases the chance of discordances significantly. All other tested influencing factors do not have a statistically significant effect on discordancesConclusion: Normal-weight patients benefit more from the integration of MAP and UtA-PI compared to overweight/obese patients. [ABSTRACT FROM AUTHOR]

This report presents the rationale and design of a multi-center clinical trial that examines the efficacy and safety of antipsychotic combination treatment in acutely ill schizophrenia patients compared to antipsychotic monotherapy. Antipsychotic combination treatment is common in clinical practice worldwide, despite clinical guidelines generally not recommending such practice due to lacking evidence for its efficacy and safety. Olanzapine has a related chemical structure and comparable receptor-binding profile as clozapine, which demonstrated superior efficacy in combination studies, but has a more unfavorable side-effect profile compared to olanzapine. Amisulpride and olanzapine have shown promising therapeutic efficacy in meta-analyses in monotherapy for people with schizophrenia. Combining amisulpride and olanzapine, complementary receptor-binding properties may enhance efficacy and possibly reduce (or at least not augment) side effects due to the different receptor profiles and metabolization pathways. Accordingly, we hypothesize that patients treated with amisulpride plus olanzapine show greater improvement on the Positive and Negative Syndrome Scale total score after 8 weeks versus either monotherapy. A randomized, double-blind controlled trial is performed at 16 German centers comparing flexibly dosed monotherapy of oral amisulpride (400–800 mg/day), and olanzapine (10–20 mg/day) and amisulpride–olanzapine co-treatment. Sample size was calculated to be n = 101 per treatment arm, assuming an effect size of 0.500 and a two-sided alpha = 0.025 and beta = 0.90. Recruitment for this trial started in June 2012. Until December 2018, 328 patients have been randomized. Trial conduct has been extended to reach the projected sample size. Publication of the study results is expected in 2019 informing an evidence-based recommendation regarding specific antipsychotic combination treatment. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the critical shoulder angle (CSA), acromion index (AI) and further acromion parameters in patients with isolated SLAP lesions compared with patients without SLAP lesions.Methods: Between 2012 and 2016, the CSA, AI, lateral acromion angle (LAA) and acromion slope (AS) were radiologically examined in consecutive patients > 18 years having had a shoulder arthroscopy with isolated SLAP lesion types II-IV. These were compared to controls without SLAP lesions and without (control group I) or with (control group II) complete supraspinatus tendon (SSP) tears.Results: 75/103 patients with isolated SLAP lesion types II-IV with a mean age of 46.5 years (± 13.0, 18.1-76.3) were analyzed, 61% of them being male. For control, n = 211 consecutive patients (47% male) with an intact SSP and SLAP complex and a mean age of 52.3 years (± 15.0, 18.6-88.4) and n = 115 patients (60% male) with an intact SLAP complex but complete SSP tears, mean age 66.6 years (± 9.3, 44.7-87.9) were examined. The CSA in SLAP patients was 29.6° (± 3.5, 21.0-38.0), 33.8° (± 3.7, 25.1-46.9) in no SLAP and no SSP (p < 0.001) and 36.7° (± 3.6, 29.1-46.6) in no SLAP but SSP (p < 0.001). The area under the curve (AUC) for CSA was 0.83 for SLAP lesions resulting in a probability of 83% for patients with SLAP lesion to be associated with a specific CSA.Conclusions: Isolated SLAP lesion types II-IV are associated with a low CSA < 30°. The AI, the AS as well as the LAA showed no correlation with SLAP lesions.Level Of Evidence: Retrospective comparative study, Level III. [ABSTRACT FROM AUTHOR]

Introduction: To prospectively evaluate the outcome of arthroscopic resection of a symptomatic medial plica in patients under 30 years with evaluating the influence of sports, knee trauma and plica type.Methods: 35 consecutive patients (38 knees), mean age 16.2 ± 4.7 years (9-26 years), 28 females (73.7%) were prospectively included. Patients with any additional surgical procedures or cartilage lesions > ICRS grade I were excluded. The influence of trauma to the knee, level of sport and the morphologic plica type on the outcome was evaluated in addition to standard knee scores before and 20.1 ± 9.3 months (12-44 months) after surgery.Results: The Knee Injury and Osteoarthritis Outcome Score improved significantly from 50.2 ± 19.1% (12.5-94.6) to 80.7 ± 15.3% (48.2-100; p < 0.001). The Tegner Activity Scale improved significantly from 2.2 ± 1.5 (0-6) to 4.9 ± 1.7 (3-10; p < 0.001) and the Kujala Anterior Knee Pain Scale improved significantly from 52.6 ± 16.6 (16-86) to 80.7 ± 16.5 (46-100; p < 0.001). The level of pain in the knee decreased from 7.9 ± 2.0 (1-10) to 3.1 ± 2.6 (0-9; p < 0.001) at follow-up on a numeric rating scale (0-10). Neither trauma to the knee, high impact sport, cartilage lesions to the medial femoral condyle nor the plica type or associated ICRS grade I cartilage lesion to the medial femoral condyle had a significant effect on the outcome parameters.Conclusion: Arthroscopic resection of a symptomatic medial plica provides excellent clinical results in young patients. Trauma, high impact sports, ICRS grade I cartilage lesions to the medial femoral condyle or the plica type are not associated with a poorer outcome.Level Of Evidence: Level IV, prospective case series with no control group. [ABSTRACT FROM AUTHOR]

The hierarchical metaregression (HMR) approach is a multiparameter Bayesian approach for meta‐analysis, which generalizes the standard mixed effects models by explicitly modeling the data collection process in the meta‐analysis. The HMR allows to investigate the potential external validity of experimental results as well as to assess the internal validity of the studies included in a systematic review. The HMR automatically identifies studies presenting conflicting evidence and it downweights their influence in the meta‐analysis. In addition, the HMR allows to perform cross‐evidence synthesis, which combines aggregated results from randomized controlled trials to predict effectiveness in a single‐arm observational study with individual participant data (IPD). In this paper, we evaluate the HMR approach using simulated data examples. We present a new real case study in diabetes research, along with a new R package called jarbes (just a rather Bayesian evidence synthesis), which automatizes the complex computations involved in the HMR. [ABSTRACT FROM AUTHOR]

AIM: The study aims to test whether simultaneous measurement of fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) is feasible, safe and effective during regadenoson-induced hyperemia. METHODS AND RESULTS: FFR, CFR and IMR were measured simultaneously during regadenoson (Rapiscan 400 μg) -induced hyperemia in 50 patients with stable coronary artery disease with a SYNTAX score of <22. Simultaneous measurement of FFR, CFR and IMR was technically feasible in all cases (50/50). No side effects occurred and even patients fulfilling classical contraindications for the use of adenosine (10/50) could be included. Regadenoson-induced hyperemia remained stable after maximal pressure drop for more than 35 sec as measured by systemic aortic and distal coronary pressure. There was a significant drop in transit mean time from baseline to hyperemia of more than 50% (1.0 ± 0.6 s vs. 0.4 ± 0.2 s, p < 0.01). Patients' mean IMR value was 23.4, and IMR values above 75th percentile significantly correlated with metformin demanding diabetes mellitus with OR 21.76 and nicotine abuse with OR 10.28. CONCLUSION: A single intravenous regadenoson bolus via peripheral line increases coronary blood flow without harmful systemic side effects enabling interventionists to simultaneously assess FFR, CFR and IMR in patients with stable coronary artery disease. [ABSTRACT FROM AUTHOR]

Objective  This study aimed to quantify knowledge on neonatal topics among obstetricians and pediatricians participating in a perinatal teaching program aimed at reducing neonatal mortality in Laos. Study Design  Obstetricians and pediatricians from Vientiane and the surrounding areas participated in a 1-week teaching program in obstetric and neonatal topics and responded to pre- and posttests questionnaires to quantify their knowledge. Results  Although questions were predominantly related to neonatal topics, obstetricians performed significantly better than pediatricians during the pretest. Both groups increased their knowledge significantly as quantified by the results of the posttest. Conclusion  The teaching program was effective in improving knowledge on perinatal mortality related topics of the participants. These results may be related to the fact that most of the obstetricians had participated in a structured teaching program previously, whereas the pediatricians did not. We thus speculate that there is a sustained effect of even a 1-week teaching program in neonatology even several years after the initial teaching. [ABSTRACT FROM AUTHOR]

Objective: Investigating the proportions of anamnestic and biochemical variables of the previous and current pregnancies for the prediction of small for gestational age (SGA) neonates in the current pregnancy.Methods: In this observational retrospective study, 45 029 pregnancies were examined, including 3862 patients with more than one pregnancy. Odds ratios for SGA using anamnestic parameters and pregnancy-associated plasma protein A (PAPP-A) values from all pregnancies were estimated by using a logistic regression model.Results: There were 2552 (5.7%) SGA neonates. Two threshold PAPP-A values were identified at 0.15 MoM and 0.33 MoM with probabilities for SGA of 23% and 17%, respectively. A previous SGA < 10th centile and a current PAPP-A MoM value < 5th centile result in odds ratios of 4.8 (95% CI: 3.5-6.5) and 3.0 (95% CI: 1.8-5.0), respectively. The parameters' combined odds ratio is 14.1 (95% CI: 3.9-50.3) with a number needed to screen of ten for one SGA neonate at a detection rate of 37%.Conclusion: Information on previous pregnancies affected by SGA and a current pregnancy's low PAPP-A value are reliable predictors for a SGA delivery. First-trimester biochemical analysis should be maintained to detect women at risk for delivering a SGA neonate. [ABSTRACT FROM AUTHOR]

Objectives [ABSTRACT FROM AUTHOR]

Aims: We investigated the prevalence of mild cognitive impairment (MCI) and its subtypes according to the original (MCI-original) and modified (MCI-modified; neglecting cognitive complaints) Petersen criteria. Methods: 4,145 subjects (aged 50-80 years) from a German population-based study completed a cognitive screening test and were poststratified into 2 groups with sample sizes of 1,125 for impaired and 3,020 for age-appropriate performance. Random samples of 445 impaired participants and 211 age-appropriate participants received a detailed neuropsychological evaluation. The prevalence of MCI was estimated by a bias correction estimator based on stratum weights. The association between MCI and age, gender and education was analyzed in a logistic regression model. Results: The estimated MCI prevalence was 7.8% (95% CI: 5.7-9.9%) for the original, and 12.1% (95% CI: 9.8-14.4%) for the modified criteria. In the MCI-original group, amnestic MCI subtypes were slightly less common than non-amnestic MCI subtypes (3.5 vs. 4.3%). MCI-original was associated with lower education and older age. In the MCI-modified group, the amnestic subtypes were more common than the non-amnestic MCI subtypes (7.8 vs. 4.3%), and MCI was associated with age, gender and education. Conclusions: Prevalence rates of MCI are high in the general population and vary considerably according to the criteria applied. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Several studies have demonstrated positive relationships between high hospital volume and improved outcome following total knee replacement. To our knowledge, it has not been demonstrated whether improved outcomes are causally determined by selective referral to high-volume hospitals. We therefore evaluated the effect of a national regulation regarding minimum hospital volume for total knee replacement on two short-term outcome parameters. Methods: We performed a comparison of the years before (2004, 2005) and after (2006) the implementation of a national regulation on minimum hospital volume for total knee replacement through a secondary analysis of a national database on the quality of inpatient care in Germany as reflected by the number of cases per hospital and the postoperative rates of wound infection and wound hematoma or secondary hemorrhage. Results: We analyzed 110,349 cases from 2004, 118,922 cases from 2005, and 125,322 cases from 2006. Implementation of the regulation had a significant effect on the number of cases per hospital. Of the hospitals that had performed one to forty-nine cases in 2005, 35.6% moved to higher-volume categories and 21.2% dropped out in 2006. Multiple logistic regression analysis adjusting for patient characteristics demonstrated risk reductions of 22.5% (odds ratio, 0.775; 95% confidence interval, 0.700 to 0.857) for postoperative wound infection and of 44% (odds ratio, 0.562; 95% confidence interval, 0.531 to 0.596) for wound hematoma or secondary hemorrhage from 2005 to 2006. For wound infection, approximately half of the improvement was attributable to the effects of the minimum-volume regulation. For wound hematoma and secondary hemorrhage, the improvement could not be explained by the minimum-volume regulation. Conclusions: Implementation of the minimum-volume regulation for total knee replacement resulted in more patients being managed at higher-volume hospitals than expected. Following the implementation of a minimum-volume regulation, effects on two short-term outcome parameters were observed, but definite conclusions could only be made regarding wound infection, with the minimum-volume regulation resulting in a decreased rate of infection. [ABSTRACT FROM AUTHOR]

Study objective: To systematically study the separate and combined effects of organisational downsizing and work related stress on a measure of health in "survivors of layoffs". Design: Using Rothman's approach, separate and combined effects of the two exposures in estimating the risk of poor self rated health (work related symptoms) are analysed in a large sample of male and female employees. Selling: 0.1 % cross sectional sample of the German working population. Participants: 12 240 men and 10 319 women, aged 16 to 59 years, surveyed in 1998-1999. Main results: Compared with the reference group, the group of participants who were simultaneously exposed to downsizing and work related stress (effort-reward imbalance) exhibited odds ratios (OR) of three or more work related symptoms that were by far higher (OR 4.41 in men and OR 5.37 in women) than those associated with single exposures. Altogether 21 % (men) and 31 % (women) of the effect size of the combined exposure was attributable to synergistic interaction. Conclusion: Although reduced health associated with organisational downsizing is partly attributable to an increase in work related stress these findings show an additional synergy effect produced by the combined exposure to both conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: We compared the predictive and prognostic performance of different lymph node classification systems regarding overall survival in patients with colorectal cancer (CRC). Distinct lymph node ratio (LNR) and Log odds of positive lymph nodes (LODDS) classifications demonstrated prognostic superiority over the N category only in patients with Stage III CRC. Background: Lymph node ratio (LNR) and the Log odds of positive lymph nodes (LODDS) have been proposed as a new prognostic indicator in surgical oncology. Various studies have shown a superior discriminating power of LODDS over LNR and lymph node category (N) in diverse cancer entities, when examined as a continuous variable. However, for each of the classification systems various cut-off values have been defined, with the question of the most appropriate for patients with CRC still remaining open. The present study aimed to compare the predictive impact of different lymph node classification systems and to define the best cut-off values regarding accurate evaluation of overall survival in patients with resectable, non-metastatic colorectal cancer (CRC). Methods: CRC patients who underwent surgical resection from 1996 to 2018 were extracted from our medical data base. Cox proportional hazards regression models and C-statistics were performed to assess the discriminative power of 25 LNR and 26 LODDS classifications. Regression models were adjusted for age, sex, extent of the tumor, differentiation, tumor size and localization. Results: Our study group consisted of 654 consecutive patients with non-metastatic CRC. C-statistic revealed 2 LNR and 5 LODDS classifications that demonstrated superior prognostic performance in patients with UICC III CRC, compared to the N category. No clear advantage of one classification over another could be demonstrated in any other patient subgroup. Conclusions: Distinct LNR and LODDS classifications demonstrate a prognostic superiority over the N category only in patients with Stage III radically resected CRC. [ABSTRACT FROM AUTHOR]