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Background: We studied whether an individualized digital decision aid can improve decision-making quality for or against knee arthroplasty. Methods: An app-based decision aid (EKIT tool) was developed and studied in a stepped-wedge, cluster-randomized trial. Consecutive patients with knee osteoarthritis who were candidates for knee replacement were included in 10 centers in Germany. All subjects were asked via app on a tablet about their symptoms, prior treatments, and preferences and goals for treatment. For the subjects in the intervention group, the EKIT tool was used in the doctor-patient discussion to visualize the individual disease burden and degree of fulfillment of the indication criteria, and structured information on knee arthroplasty was provided. In the control group, the discussion was conducted without the EKIT tool in accordance with the local standard in each participating center. The primary endpoint was the quality of the patient's decision on the basis of the discussion of indications, as measured with the Hip and Knee Quality Decision Instrument (HK-DQI). (Registration number: ClinicalTrials.gov:NCT04837053). Results: 1092 patients were included, and data from 1055 patients were analyzed (616 in the intervention group and 439 in the control group). Good decision quality, as rated by the HK-DQI, was achieved by 86.0% of patients in the intervention group and 67.4% of patients in the control group (relative risk, 1.24; 95 % confidence interval, [1.15; 1.33]). Conclusion: A digital decision aid significantly improved the quality of decision-making for or against knee replacement surgery. The widespread use of this instrument may have an even larger effect, as this trial was conducted mainly in hospitals with high case numbers. [ABSTRACT FROM AUTHOR]

The worldwide prevalence of obesity has nearly tripled since 1975. Between 1999 and 2017 it rose from 30.5 to 42.4% in the USA and from 11.5 to 16.3% in Germany (1). Obesity is a risk factor for osteoarthritis of the hip and even more so of the knee, which is why obese patients often present for joint replacement. However, they have a greater risk of complications in comparison with the non-obese. So far, studies dealing with this issue have only examined smaller cohorts, while data from Germany are lacking altogether. The aim of our study was to examine the association between obesity and complication rates, revision rates, and mortality after primary and revision replacement surgery of the hip and knee (HRS, R-HRS, KRS, R- KRS), respectively. [ABSTRACT FROM AUTHOR]

Abstract Background The gastrointestinal tissue plays an important role in the pathogenesis of HIV/SIV infection and serves as a viral reservoir in infected individuals under antiretroviral therapy (ART). However, the effect of ART administration in the very early stage of infection on HIV/SIV replication and pathogenesis in gastrointestinal tissue has not been fully studied. In this current study, rhesus monkeys infected with SIV were treated with ART starting at day 7 post-infection. The effect of early ART on SIV replication and infection-related pathogenic changes in mucosal tissues of the infected monkeys was examined. Methods Nuclear acids were extracted from snap frozen ileum and colon tissues and mesentery lymph nodes from SIV infected monkeys with or without ART. SIV RNA and DNA loads as well as levels of CD3, CD4 and cytokine mRNA were measured by PCR and RT PCR from the isolated nuclear acids. Tissue sections were stained by immuno-fluorescence labeled antibodies for CD3 and CD4. Results Without ART treatment, these monkeys underwent a mild SIV infection with low viral loads and slightly decreased CD4+ T cell counts in peripheral blood. In ART treated monkeys, SIV RNA loads were undetectable in blood with normal CD4+ T cell counts, however, SIV RNA and DNA were detected in the intestinal tissues and mesentery lymph nodes although the levels were lower than those in untreated monkeys. The levels of CD3 and CD4 positive cells in the tissues were similar between the infected untreated monkeys and infected ART treated monkeys based on RT-PCR and immune-fluorescence staining of the tissue sections. Furthermore, compatible levels of IL-6, TNF-a, IL-1b and MyD88 mRNAs were detected in most of intestinal tissues and mesentery lymph nodes of infected ART treated and infected untreated monkeys. Conclusions These results suggest that early ART administration could not effectively inhibit SIV replication in intestinal tissues and mesentery lymph nodes and could not reduce the immune activation induced by SIV infection in the intestinal tissues.

With the new ICD-11 developed by the WHO and translated into German for use in Germany by the Federal Institute for Drugs and Medical Devices, the German healthcare system is facing a change that is more than a simple change of a medical coding system. The ICD-11 modernises the coding system, for example, by including new, separate health conditions such as sleep-wake disorders and conditions related to sexual health, thus making the corresponding diseases more visible. The ICD-11 is more precise than the ICD-10: it allows cross-referencing between diagnoses, symptoms, functionality and locations and partially abandons the strict hierarchy of the ICD-10. In addition, a greater number of rare diseases are represented with their own specific code than was previously possible with ICD-10. Finally, the ICD-11 is also significantly more "modern" than the ICD-10 (which dates back to pre-digital times) in that it enables new, digitally-supported processes, such as keywords flexibility and sustainability when updating the system as well as actual coding at the point of care. The switch to ICD-11 can be a great opportunity for the German healthcare system that should not be missed. It will benefit health service research, which at best will be able to work with much more detailed and correct data sets. But medical care will also benefit because the ICD-11 reflects current medical knowledge. In addition, certain illnesses will be removed from the psychiatric category, meaning that those affected will no longer be stigmatised by their classification in the ICD. The improved coding of diagnoses will ultimately also support guideline-based treatments. However, the changeover is only the first step. The challenges - also for health service research - include in particular the latency of introduction and uniform use as well as the necessary change in coding habits. For ICD-11 to be a success in Germany, authorities, the medical profession, payers and patients must work together on strategies to ensure not only a rapid but also a comprehensive implementation that maximises the potential of ICD-11., Competing Interests: KB: none. The role of BfArM in the context of ICD-11 introduction in Germany includes translation and provision of the ICD-11 as well as support for the changeover process. BfArM has been a WHO Collaborating Centre since 2003. JC: Institutional grants from AbbVie, AstraZeneca, BMS, GALAPAGOS, GSK, Medac, MSD, Pfizer, UCB, Sanofi-Aventis, Lilly and grants from Pfizer, Janssen-Cilag, Idorsia Pharmaceuticals outside the submitted work. PK is an employee of Idorsia Pharmaceuticals Germany GmbH. CK is an employee of the German Cancer Society. JM is an employee of the AOK Bundesverband. CM provides institutional grants (project funding) from the Federal Ministry of Health, Federal Ministry of Education and Research and G-BA (Innovationsfonds). CS declares that he has received institutional grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Idorsia Pharmaceuticals Ltd, Inspire Medical, JAZZ, Löwenstein Medical, Mementor, Nox medical, ResMed, Respicardia, Sleepiz outside the submitted work., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: In symptomatic end-stage osteoarthritis of the ankle joint, total ankle replacement and ankle arthrodesis are the two primary surgical options for patients for whom conservative treatment fails. Published revision rates are often biased and difficult to compare. In this study, unplanned reoperation rates and revision rates were determined for both surgical interventions based on a large dataset, and risk factors for unplanned reoperations were identified., Methods: German-wide health data of the largest German health-care insurance carrier between 2001 and 2012 were retrospectively analyzed, and unplanned reoperation rates within 10 years were determined for index surgeries conducted in 2001 and 2002. Unplanned reoperation rates within 5 years for index surgeries conducted in 2001/2002 were compared to index surgeries conducted in 2006/2007. Multivariate logistic regression was used to identify risk factors for unplanned reoperations., Results: After ankle arthrodesis, 19% (95% confidence interval [CI], 16-22%) of 741 patients needed to undergo an unplanned reoperation within ten years. After total ankle replacement, the unplanned reoperation rate was 38% [95% CI, 29-48%] among 172 patients. For initial surgeries conducted at a later date, unplanned reoperation rates within five years were 21% [95% CI, 19-24%] for 1,168 ankle arthrodesis patients and 23% [95% CI, 19-28%] for 561 total ankle replacement patients. Significant risk factors for unplanned reoperations after ankle arthrodesis in the initial cohort were age < 50 years (odds ratio [OR] = 4.65 [95% CI 1.10;19.56]) and osteoporosis (OR = 3.72 [95% CI, 1.06;13.11]); after total ankle replacement, they were osteoporosis (OR = 2.96 [95% CI, 1.65;5.31]), Patient Clinical Complexity Level (PCCL) grade 3 (OR = 2.19 [95% CI, 1.19;4.03]), PCCL grade 4 (OR = 2.51 [95% CI, 1.22;5.17]) and diabetes mellitus (OR = 2.48 [95% CI, 1.33;4.66]). Kaplan-Meier analyses including 1,525 ankle arthrodesis patients and 644 total ankle replacement patients revealed an average unplanned reoperation-free time of approximately 17 years for both procedures., Conclusions: Similar revision rates and unplanned reoperation rates for both procedures in the later-date cohort can likely be attributed to a learning curve for surgeons as well as advances in implant design. This analysis of billing health insurance data supports an increase in total ankle replacement surgeries., (© 2024. The Author(s).)

Background: This nationwide routine data analysis evaluates if oral anticoagulant (OAC) use in patients with heart failure (HF) and atrial fibrillation (AF) leads to a lower mortality and reduced readmission rate. Superiority of new oral anticoagulants (NOACs), compared to vitamin K antagonists (VKA), was analyzed for these endpoints., Methods: Anonymous data of patients with a health insurance at the Allgemeine Ortskrankenkasse and a claims record for hospitalization with the main diagnosis of HF and secondary diagnosis of AF (2017-2019) were included. A hospital stay in the previous year was an exclusion criterion. Mortality and readmission for all-cause and stroke/intracranial bleeding (ICB) were analyzed 91-365 days after the index hospitalization. Kaplan-Meier survival curves and multivariable Cox regression models were used to evaluate the impact of medication on outcome., Results: 180,316 cases were included [81 years (IQR 76-86), 55.6% female, CHA 2 DS 2 -VASc score ≥ 2 (96.81%)]. In 80.6%, OACs were prescribed (VKA: 21.7%; direct factor Xa inhibitors (FXaI): 60.0%; direct thrombin inhibitors (DTI): 3.4%; with multiple prescriptions per patient included). Mortality rate was 19.1%, readmission rate was 29.9% and stroke/ICB occurred in 1.9%. Risk of death was lower with any OAC (HR 0.77, 95% CI [0.75-0.79]) but without significant differences in OAC type (VKA: HR 0.73, [0.71-0.76]; FXaI: HR 0.77, [0.75-0.78]; DTI: HR 0.71, [0.66-0.77]). The total readmission rate (HR 0.97, [0.94 to 0.99]) and readmission for stroke/ICB (HR 0.71, [0.65-0.77]) was lower with OAC., Conclusions: Nationwide data confirm a reduction in mortality and readmission rate in HF-AF patients taking OACs, without NOAC superiority., Competing Interests: Declaration of Competing Interest M.M. received speakers and consulting fees from Bayer Healthcare, BMS, Boehringer Ingelheim, Daiichi Sankyo, Astra Zeneca, Sanofi, BRAHMS GmbH and Roche Diagnostics as well as research funding from German public funding authorities for Health Care Research and Roche Diagnostics; G.M. received speaker fees from Getinge, Orion Pharma and AOP Orphan Pharmaceuticals Germany GmbH; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pancreatic cancer (PC), one of the most aggressive and life-threatening human malignancies, is known for its resistance to cytotoxic therapies. This is increasingly ascribed to the subpopulation of undifferentiated cells, known as pancreatic cancer stem cells (PCSCs), which display greater evolutionary fitness than other tumor cells to evade the cytotoxic effects of chemotherapy. PCSCs are crucial for tumor relapse as they possess 'stem cell-like' features that are characterized by self-renewal and differentiation. However, the molecular mechanisms that maintain the unique characteristics of PCSCs are poorly understood. Here, we identify the histone methyltransferase KMT2A as a physical binding partner of an RNA polymerase-associated PHF5A-PHF14-HMG20A-RAI1 protein subcomplex and an epigenetic regulator of PCSC properties and functions. Targeting the protein subcomplex in PCSCs with a KMT2A-WDR5 inhibitor attenuates their self-renewal capacity, cell viability, and in vivo tumorigenicity., (© 2023. Springer Nature Limited.)

Background: The EndoCert initiative does not yet allow a long-term assessment of outcome quality. The assessment cannot be achieved without cooperation with the German arthroplasty registry (EPRD) and other quality assurance infrastructure, such as the quality assurance system of the nationwide healthcare insurance data for inpatient hospital treatment (QSR) by the German local healthcare fund (AOK). Therefore, the quality of care of all certified centres for joint replacement (EPZ) after primary hip and knee arthroplasty was to be examined for the first time. These data were subsequently compared to the data of the EPRD., Materials and Methods: In EPZ that provided care to at least one AOK-insured patient in 2016, the risk-adjusted 3‑year revision rate and the SMR-value (standardised mortality or morbidity ratio), which is the quotient of the observed and expected revision rate, were analysed as markers for the quality of care. Annual hospital volume, type of centre and audit results were examined as possible influencing factors., Results: In the group comparison, significant differences (p = 0.042) for the SMR value of the 3‑year revision rate were demonstrated for hip arthroplasty with regard to the EPZ type. The annual number of primary hip arthroplasties, however, did not influence the 3‑year revision rate. For knee arthroplasties, no effect of the defined categories on the 3‑year revision rate and its SMR value was observed. The comparison of our 3‑year revision rates with those of the EPRD showed similar results for the hip but indicated significant differences for the knee., Conclusion: We did not observe a correlation between quality of care and annual hospital volume in certified EPZ. However, different quality assurance procedures can lead to different results with respect to the outcome quality. Therefore, a considerably improved interaction of the German quality systems must be achieved. Participation in the EPRD is not sufficient for this. Rather, a complete report of all arthroplasties must be required, at least with the achievement of a minimum reporting rate per participating hospital. Uniform inclusion and exclusion criteria should be defined., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: We aimed to define and assess risk-specific adverse outcomes after transcatheter aortic valve implantation (TAVI) in an all-comers patient population based on German administrative claims data., Methods: Administrative claims data of patients undergoing transvascular TAVI between 2017 and 2019 derived from the largest provider of statutory health-care insurance in Germany were used. Patients' risk profile was assessed using the established Hospital Frailty Risk (HFR) score and 30-day adverse events were evaluated. Multivariable logistic regression models were applied to investigate the relation of patients' risk factors to clinical outcomes and, subsequently, of clinical outcomes to mortality., Results: A total of 21,430 patients were included in the analysis. Of those, 51% were categorized as low-, 37% as intermediate-, and 12% as high-risk TAVI patients according to HFR score. Whereas low-risk TAVI patients showed low rates of periprocedural adverse events, TAVI patients at intermediate or high risk suffered from worse outcomes. An increase in HFR score was associated with an increased risk for all adverse outcome measures. The strongest association of patients' risk profile and outcome was present for cerebrovascular events and acute renal failure after TAVI. Independent of patients' risk, the latter showed the strongest relation with early mortality after TAVI., Conclusions: Differentiated outcomes after TAVI can be assessed using claims-based data and are highly dependent on patients' risk profile. The present study might be of use to define risk-adjusted outcome margins for TAVI patients in Germany on the basis of health-insurance data., (© 2022. The Author(s).)

Background: Over the last years, new transfusion guidelines and pharmaceuticals have been introduced in primary and revision total hip and knee arthroplasty (P-THA, P-TKA, R-THA, R-TKA). In the US, a substantial decrease in transfusions has been observed in recent years. Little data exists on the subject in Europe. In this context we aimed to analyze: (1) Is there also a significant decrease in blood transfusion for these procedures in Germany? (2) Which patient and hospital related factors are associated with the risk of blood transfusion? (3) Is there a trend in complications, especially venous thromboembolism and stroke events that can be linked to tranexamic acid use?, Hypothesis: There is a significant trend in decreasing blood transfusions in hip and knee arthroplasty., Methods: Using nationwide healthcare insurance data for inpatient hospital treatment, 736,061 cases treated between January 2011 and December 2017 were included (318,997 P-THAs, 43,780 R-THAs, 338,641 P-TKAs, 34,643 R-TKAs). Multivariable logistic regression was used to model the odds of transfusion as a function of the year of surgery. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated., Results: In each cohort the odds of transfusion decreased over time (2017 vs. 2011 (reference): P-THA: OR 0.42 (95%CI: 0.39-0.45), P-TKA: OR 0.41 (95%CI: 0.37-0.46), R-THA: OR 0.52 (95%CI: 0.47-0.58), R-TKA: OR 0.53 (95%CI: 0.46-0.61). Patient-related risk factors for blood transfusion included older age, female gender, lower Body Mass Index, comorbidities such as renal failure, cardiac arrhythmia, congestive heart failure, valvular disease, coagulopathy, depression, and antithrombotic medication prior to surgery. Venous thromboembolism or stroke events did not increase over the study period., Discussion: The incidence of blood transfusions in primary and revision TKA and THA decreased over the study period. This may be due to new transfusion guidelines and the introduction of novel pharmaceuticals such as tranexamic acid. A further improved patient blood management and a focus on vulnerable patient groups might lead to a further future reduction of transfusions, especially in R-THA., Level of Evidence: III; comparative observational study., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Low birthweight and major congenital malformations (MCMs) are key causes of infant mortality., Objectives: The aim of this study was to explore the prevalence of MCMs in infants with low and very low birthweight and analyze the impact of MCMs and birthweight on infant mortality., Methods: We determined prevalence and infant mortality of 28 life-threatening MCMs in very-low-birthweight (<1,500 g, VLBW), low-birthweight (1,500-2,499 g, LBW), or normal-birthweight (≥2,500 g, NBW) infants in a cohort of 2,727,002 infants born in Germany in 2006-2017, using de-identified administrative data of the largest statutory public health insurance system in Germany., Results: The rates of VLBW, LBW, and NBW infants studied were 1.3% (34,401), 4.0% (109,558), and 94.7% (2,583,043). MCMs affected 0.5% (13,563) infants, of whom >75% (10,316) had severe congenital heart disease. The prevalence (per 10,000) of any/cardiac MCM was increased in VLBW (286/176) and LBW (244/143), as compared to NBW infants (38/32). Infant mortality rates were significantly higher in infants with an MCM, as opposed to infants without an MCM, in each birthweight group (VLBW 28.5% vs. 11.5%, LBW 16.7% vs. 0.9%, and NBW 8.6% vs. 0.1%). For most MCMs, observed survival rates in VLBW and LBW infants were lower than expected, as calculated from survival rates of VLBW or LBW infants without an MCM, and NBW infants with an MCM., Conclusions: Infants with an MCM are more often born with LBW or VLBW, as opposed to infants without an MCM. Many MCMs carry significant excess mortality when occurring in VLBW or LBW infants., (© 2021 S. Karger AG, Basel.)

Endometriosis is a common chronic inflammatory condition causing pelvic pain and infertility in women, with limited treatment options and 50% heritability. We leveraged genetic analyses in two species with spontaneous endometriosis, humans and the rhesus macaque, to uncover treatment targets. We sequenced DNA from 32 human families contributing to a genetic linkage signal on chromosome 7p13-15 and observed significant overrepresentation of predicted deleterious low-frequency coding variants in NPSR1 , the gene encoding neuropeptide S receptor 1, in cases (predominantly stage III/IV) versus controls ( P = 7.8 × 10 -4 ). Significant linkage to the region orthologous to human 7p13-15 was replicated in a pedigree of 849 rhesus macaques ( P = 0.0095). Targeted association analyses in 3194 surgically confirmed, unrelated cases and 7060 controls revealed that a common insertion/deletion variant, rs142885915, was significantly associated with stage III/IV endometriosis ( P = 5.2 × 10 -5 ; odds ratio, 1.23; 95% CI, 1.09 to 1.39). Immunohistochemistry, qRT-PCR, and flow cytometry experiments demonstrated that NPSR1 was expressed in glandular epithelium from eutopic and ectopic endometrium, and on monocytes in peritoneal fluid. The NPSR1 inhibitor SHA 68R blocked NPSR1-mediated signaling, proinflammatory TNF-α release, and monocyte chemotaxis in vitro ( P < 0.01), and led to a significant reduction of inflammatory cell infiltrate and abdominal pain ( P < 0.05) in a mouse model of peritoneal inflammation as well as in a mouse model of endometriosis. We conclude that the NPSR1/NPS system is a genetically validated, nonhormonal target for the treatment of endometriosis with likely increased relevance to stage III/IV disease., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: There is convincing evidence that birth in hospitals with high birth volumes increases the chance of healthy survival in high-risk infants. However, it is unclear whether this is true also for low risk infants. The aim of this systematic review was to analyze effects of hospital's birth volume on mortality, mode of delivery, readmissions, complications and subsequent developmental delays in all births or predefined low risk birth cohorts. The search strategy included EMBASE and Medline supplemented by citing and cited literature of included studies and expert panel highlighting additional literature, published between January/2000 and February/2020. We included studies which were published in English or German language reporting effects of birth volumes on mortality in term or all births in countries with neonatal mortality < 5/1000. We undertook a double-independent title-abstract- and full-text screening and extraction of study characteristics, critical appraisal and outcomes in a qualitative evidence synthesis., Results: 13 retrospective studies with mostly acceptable quality were included. Heterogeneous volume-thresholds, risk adjustments, outcomes and populations hindered a meta-analysis. Qualitatively, four of six studies reported significantly higher perinatal mortality in lower birth volume hospitals. Volume-outcome effects on neonatal mortality (n = 7), stillbirths (n = 3), maternal mortality (n = 1), caesarean sections (n = 2), maternal (n = 1) and neonatal complications (n = 1) were inconclusive., Conclusion: Analyzed studies indicate higher rates of perinatal mortality for low risk birth in hospitals with low birth volumes. Due to heterogeneity of studies, data synthesis was complicated and a meta-analysis was not possible. Therefore international core outcome sets should be defined and implemented in perinatal registries., Systematic Review Registration: PROSPERO: CRD42018095289., (© 2021. The Author(s).)

Background: It has not been conclusively established whether, or to what extent, the time to surgery affects mortality and the risk of complications after the surgical treatment of proximal femoral fractures., Methods: Data on 106 187 hospitalizations over the period 2015-2017 involving insurees of the German AOK health insurance company aged 20 and above were drawn from pseudonymized billing data and stratified in three subgroups: osteosynthesis for pertrochanteric fracture (PTF-OS: N = 52 358), osteosynthesis for femoral neck fracture (FNF-OS: N = 7970), and endoprosthesis for femoral neck fracture (FNF-EP: N = 45 859). Multivariate regression models were used to analyze the relation between preoperative in-hospital stay (time to surgery, TTS: 0 days [reference category], 1, 2, 3, 4-7 days) and mortality and general complications within 90 days, with risk adjustment for fracture site, operative method, age, sex, accompanying illnesses, and antithrombotic medication in the preceding year., Results: Mortality was significantly elevated only with PTF-OS, and only with a TTS of 2 days (odds ratio: 1.12 [95% confidence interval: (1.02; 1.23)]). General complications in relation to TTS were significantly elevated in the following situations: PTF-OS: 2 days: OR 1.24 [1.13; 1.37], 3 days: OR 1.33 [1.11; 1.60], 4-7 days: OR 1.47 [1.21; 1.78]; FNF-EP: 3 days: OR 1.21 [1.06; 1.37], 4-7 days: OR 1.42 [1.25; 1.62]; FNF-OS: 4-7 days: OR 1.86 [1.26; 2.73]., Conclusion: A prolonged time to surgery is associated with an elevated general complication risk depending on the site of the fracture and the type of surgical procedure used.

Objective: This umbrella review summarises and critically appraises the evidence on the effects of regulated or high-volume perinatal care on outcome among very low birth weight/very preterm infants born in countries with neonatal mortality <5/1000 births., Intervention/exposition: Perinatal regionalisation, centralisation, case-volume., Primary Outcomes: Death., Secondary Outcomes: Disability, discomfort, disease, dissatisfaction., Methods: On 29 November 2019 a systematic search in MEDLINE and Embase was performed and supplemented by hand search. Relevant systematic reviews (SRs) were critically appraised with A MeaSurement Tool to Assess systematic Reviews 2., Results: The literature search revealed 508 hits and three SRs were included. Effects of perinatal regionalisation were assessed in three (34 studies) and case-volume in one SR (6 studies). Centralisation has not been evaluated. The included SRs reported effects on 'death' (eg, neonatal), 'disability' (eg, mental status), 'discomfort' (eg, maternal sensitivity) and 'disease' (eg, intraventricular haemorrhages). 'Dissatisfactions' were not reported. The critical appraisal showed a heterogeneous quality ranging from moderate to critically low. A pooled effect estimate was reported once and showed a significant favour of perinatal regionalisation in terms of neonatal mortality (OR 1.60, 95% CI 1.33-1.92). The qualitative evidence synthesis of the two SRs without pooled estimate suggests superiority of perinatal regionalisation in terms of different mortality and non-mortality outcomes. In one SR, contradictory results of lower neonatal mortality rates were reported in hospitals with higher birth volumes., Conclusions: Regionalised perinatal care seems to be a crucial care strategy to improve the survival of very low birth weight and preterm births. To overcome the low and critically low methodological quality and to consider additional clinical and patient-reported results that were not addressed by the SRs included, we recommend an updated SR. In the long term, an international, uniformly conceived and defined perinatal database could help to provide evidence-based recommendations on optimal strategies to regionalise perinatal care., Prospero Registration Number: CRD42018094835., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Nationwide, unbiased, and unselected data of hospitalised patients with COVID-19 are scarce. Our aim was to provide a detailed account of case characteristics, resource use, and outcomes of hospitalised patients with COVID-19 in Germany, where the health-care system has not been overwhelmed by the pandemic., Methods: In this observational study, adult patients with a confirmed COVID-19 diagnosis, who were admitted to hospital in Germany between Feb 26 and April 19, 2020, and for whom a complete hospital course was available (ie, the patient was discharged or died in hospital) were included in the study cohort. Claims data from the German Local Health Care Funds were analysed. The data set included detailed information on patient characteristics, duration of hospital stay, type and duration of ventilation, and survival status. Patients with adjacent completed hospital stays were grouped into one case. Patients were grouped according to whether or not they had received any form of mechanical ventilation. To account for comorbidities, we used the Charlson comorbidity index., Findings: Of 10 021 hospitalised patients being treated in 920 different hospitals, 1727 (17%) received mechanical ventilation (of whom 422 [24%] were aged 18-59 years, 382 [22%] were aged 60-69 years, 535 [31%] were aged 70-79 years, and 388 [23%] were aged ≥80 years). The median age was 72 years (IQR 57-82). Men and women were equally represented in the non-ventilated group, whereas twice as many men than women were in the ventilated group. The likelihood of being ventilated was 12% for women (580 of 4822) and 22% for men (1147 of 5199). The most common comorbidities were hypertension (5575 [56%] of 10 021), diabetes (2791 [28%]), cardiac arrhythmia (2699 [27%]), renal failure (2287 [23%]), heart failure (1963 [20%]), and chronic pulmonary disease (1358 [14%]). Dialysis was required in 599 (6%) of all patients and in 469 (27%) of 1727 ventilated patients. The Charlson comorbidity index was 0 for 3237 (39%) of 8294 patients without ventilation, but only 374 (22%) of 1727 ventilated patients. The mean duration of ventilation was 13·5 days (SD 12·1). In-hospital mortality was 22% overall (2229 of 10 021), with wide variation between patients without ventilation (1323 [16%] of 8294) and with ventilation (906 [53%] of 1727; 65 [45%] of 145 for non-invasive ventilation only, 70 [50%] of 141 for non-invasive ventilation failure, and 696 [53%] of 1318 for invasive mechanical ventilation). In-hospital mortality in ventilated patients requiring dialysis was 73% (342 of 469). In-hospital mortality for patients with ventilation by age ranged from 28% (117 of 422) in patients aged 18-59 years to 72% (280 of 388) in patients aged 80 years or older., Interpretation: In the German health-care system, in which hospital capacities have not been overwhelmed by the COVID-19 pandemic, mortality has been high for patients receiving mechanical ventilation, particularly for patients aged 80 years or older and those requiring dialysis, and has been considerably lower for patients younger than 60 years., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)