Inadequate medical treatment of patients with coronary artery disease by primary care physicians in Germany

Aims: The DETECT study was performed to obtain representative data about the frequency, distribution, and treatment of patients with coronary artery disease (CAD) in the primary care setting in Germany. Methods and results: The DETECT study was a cross–sectional clinical– epidemiological survey of a nationally representative sample of 3795 primary care offices and 55 518 patients. Overall, 12.4% of patients were diagnosed with CAD. Stable angina pectoris and myocardial infarction were the most frequent (4.2%) subgroups, followed by status post (s/p) percutaneous coronary interventions (PCI, 3.0%) and s/p coronary bypass surgery (2.2%). Patients with CAD were prescribed AT1 receptor antagonists (in 19.4% of cases), beta blockers (57.2%), ACE inhibitors (49.9%), antiplatelet agents (52.7%), statins (43.0%), and long–term nitrates (24.5%). When comparing all CAD patients with social health care insurance to those who had private insurance, private patients had significantly higher rates of revascularisation procedures and use of preventive medications. Conclusion: Great potential remains for improving secondary prevention in primary care in Germany to reduce the risk of further coronary or vascular events, especially in patients with social health care insurance

A systematic review on the effectiveness of implementation strategies to postpone elective caesarean sections to ≥ 39 + (0-6) weeks of gestation

BACKGROUND Caesarean sections often have no urgent indication and are electively planned. Research showed that elective caesarean section should not be performed until 39 + (0-6) weeks of gestation to ensure best neonatal and maternal health if there are no contraindications. This was recommended by various guidelines published in the last two decades. With this systematic review, we are looking for implementation strategies trying to implement these recommendations to reduce elective caesarean section before 39 + (0-6) weeks of gestation. METHODS We performed a systematic literature search in MEDLINE, EMBASE, CENTRAL, and CINAHL on 3rd of March 2021. We included studies that assessed implementation strategies aiming to postpone elective caesarean section to ≥ 39 + (0-6) weeks of gestation. There were no restrictions regarding the type of implementation strategy or reasons for elective caesarean section. Our primary outcome was the rate of elective caesarean sections before 39 + (0-6) weeks of gestation. We used the ROBINS-I Tool for the assessment of risk of bias. We did a narrative analysis of the results. RESULTS We included 10 studies, of which were 2 interrupted time series and 8 before-after studies, covering 205,954 elective caesarean births. All studies included various types of implementation strategies. All implementation strategies showed success in decreasing the rate of elective caesarean sections performed < 39 + (0-6) weeks of gestation. Risk difference differed from - 7 (95% CI - 8; - 7) to - 45 (95% CI - 51; - 31). Three studies reported the rate of neonatal intensive care unit admission and showed little reduction. CONCLUSION This systematic review shows that all presented implementation strategies to reduce elective caesarean section before 39 + (0-6) weeks of gestation are effective. Reduction rates differ widely and it remains unclear which strategy is most successful. Strategies used locally in one hospital seem a little more effective. Included studies are either before-after studies (8) or interrupted time series (2) and the overall quality of the evidence is rather low. However, most of the studies identified specific barriers in the implementation process. For planning an implementation strategy to reduce elective caesarean section before 39 + (0-6) weeks of gestation, it is necessary to consider specific barriers and facilitators and take all obstetric personal into account. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017078231

Quality and risk of bias appraisals of systematic reviews are inconsistent across reviewers and centers

© 2020 The Authors. Published by Elsevier Inc. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Objective: The objective of the study was to evaluate the inter-rater and intercenter reliability, usability, and utility of A MeaSurement Tool to Assess systematic Reviews (AMSTAR), AMSTAR 2, and Risk Of Bias In Systematic reviews (ROBIS). Study design and setting: This is a prospective evaluation using 30 systematic reviews of randomized trials, undertaken at three international centers. Results: Reviewers completed AMSTAR, AMSTAR 2, and ROBIS in median (interquartile range) 15.7 (11.3), 19.7 (12.1), and 28.7 (17.4) minutes and reached consensus in 2.6 (3.2), 4.6 (5.3), and 10.9 (10.8) minutes, respectively. Across all centers, inter-rater reliability was substantial to almost perfect for 8/11 AMSTAR, 9/16 AMSTAR 2, and 12/24 ROBIS items. Intercenter reliability was substantial to almost perfect for 6/11 AMSTAR, 12/16 AMSTAR 2, and 7/24 ROBIS items. Intercenter reliability for confidence in the results of the review or overall risk of bias was moderate (Gwet's first-order agreement coefficient (AC1) 0.58, 95% confidence intervals [CI]: 0.30 to 0.85) to substantial (AC1 0.74, 95% CI: 0.30 to 0.85) for AMSTAR 2 and poor (AC1 -0.21, 95% CI: -0.55 to 0.13) to moderate (AC1 0.56, 95% CI: 0.30 to 0.83) for ROBIS. It is not clear whether using the appraisals of any tool as an inclusion criterion would alter an overview's findings. Conclusions: Improved guidance may be needed to facilitate the consistent interpretation and application of the newer tools (especially ROBIS).info:eu-repo/semantics/publishedVersio

An Innovative Protocol for Metaproteomic Analyses of Microbial Pathogens in Cystic Fibrosis Sputum

Hallmarks of cystic fibrosis (CF) are increased viscosity of mucus and impaired mucociliary clearance within the airways due to mutations of the cystic fibrosis conductance regulator gene. This facilitates the colonization of the lung by microbial pathogens and the concomitant establishment of chronic infections leading to tissue damage, reduced lung function, and decreased life expectancy. Although the interplay between key CF pathogens plays a major role during disease progression, the pathophysiology of the microbial community in CF lungs remains poorly understood. Particular challenges in the analysis of the microbial population present in CF sputum is (I) the inhomogeneous, viscous, and slimy consistence of CF sputum, and (II) the high number of human proteins masking comparably low abundant microbial proteins. To address these challenges, we used 21 CF sputum samples to develop a reliable, reproducible and widely applicable protocol for sputum processing, microbial enrichment, cell disruption, protein extraction and subsequent metaproteomic analyses. As a proof of concept, we selected three sputum samples for detailed metaproteome analyses and complemented and validated metaproteome data by 16S sequencing, metabolomic as well as microscopic analyses. Applying our protocol, the number of bacterial proteins/protein groups increased from 199-425 to 392-868 in enriched samples compared to nonenriched controls. These early microbial metaproteome data suggest that the arginine deiminase pathway and multiple proteases and peptidases identified from various bacterial genera could so far be underappreciated in their contribution to the CF pathophysiology. By providing a standardized and effective protocol for sputum processing and microbial enrichment, our study represents an important basis for future studies investigating the physiology of microbial pathogens in CF in vivo – an important prerequisite for the development of novel antimicrobial therapies to combat chronic recurrent airway infection in CF

One frame and several new infinite families of Z-cyclic whist designs

AbstractIn 2001, Ge and Zhu published a frame construction which they utilized to construct a large class of Z-cyclic triplewhist designs. In this study the power and elegance of their methodology is illustrated in a rather dramatic fashion. Primarily due to the discovery of a single new frame it is possible to combine their techniques with the product theorems of Anderson, Finizio and Leonard along with a few new specific designs to obtain several new infinite classes of Z-cyclic whist designs. A sampling of the new results contained herein is as follows: (1) Z-cyclic Wh(33p+1), p a prime of the form 4t+1; (2) Z-cyclic Wh(32n+1s+1), for all n⩾1, s=5,13,17; (3) Z-cyclic Wh(32ns+1), for all n⩾1, s=35,55,91; (4) Z-cyclic Wh(32n+1s), for all n⩾1, and for all s for which there exist a Z-cyclic Wh(3s) and a homogeneous (s,4,1)-DM; and (5) Z-cyclic Wh(32ns) for all n⩾1, s=5,13. Many other results are also obtained. In particular, there exist Z-cyclic Wh(33v+1) where v is any number for which Ge and Zhu obtained Z-cyclic TWh(3v+1)

Relationship between volume and outcome for congenital diaphragmatic hernia: a systematic review protocol

Background: Congenital diaphragmatic hernia is a rare and life-threatening anomaly that occurs during fetal development and results in an incomplete or incorrect formation of the diaphragm. Surgical therapy of the diaphragm should be performed after clinical stabilization of the neonate. Higher hospital or surgeon volume has previously been found to be associated with better clinical outcomes for different especially high-risk, low-volume procedures. Therefore, we aim to examine the relationship between hospital or surgeon volume and outcomes for congenital diaphragmatic hernia. Methods: This systematic review protocol has been designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol. We will perform a systematic literature search in MEDLINE, Embase, CINAHL and Biosis Previews without applying any limitations. In addition, we will search for relevant conference abstracts. We will screen titles and abstracts of retrieved studies, obtain potentially relevant full texts, and assess the eligibility of those full texts against our inclusion criteria. We will include comparative studies analyzing the relationship between hospital or surgeon volume and clinical outcomes. We will systematically assess risk of bias of included studies and extract data on the study design, patient characteristics, case-mix adjustments, statistical methods, hospital and surgeon volume, and outcomes into standardized tables. Title and abstract screening, full-text screening, critical appraisal, and data extraction of results will be conducted by two reviewers independently. Other data will be extracted by one reviewer and checked for accuracy by a second one. Any disagreements will be resolved by discussion. We will not perform a meta-analysis as we expect included studies to be clinically and methodologically very diverse. We will synthesize findings from primary studies in a structured narrative way and using GRADE. Discussion: Given the lack of a comprehensive summary of findings on the relationship between hospital or surgeon volume and outcomes for congenital diaphragmatic hernia, this systematic review will put things right. Results can be used to inform decision makers or clinicians and to adapt medical care. Systematic review registration: PROSPERO (CRD42018090231

Acute kidney injury and tools for risk-stratification in 456 patients with hantavirus-induced nephropathia epidemica

BACKGROUND Puumala virus (PUUV) is the most common species of hantavirus in Central Europe. Nephropathia epidemica (NE), caused by PUUV, is characterized by acute kidney injury (AKI) and thrombocytopenia. The major goals of this study were to provide a clear clinical phenotyping of AKI in patients with NE and to develop an easy prediction rule to identify patients, who are at lower risk to develop severe AKI. METHODS A cross-sectional prospective survey of 456 adult patients with serologically confirmed NE was performed. Data were collected from medical records and prospectively at follow-up visit. Severe AKI was defined by standard criteria according to the RIFLE (Risk, Injury, Failure, Loss, End-stage kidney disease) classification. Fuller statistical models were developed and validated to estimate the probability for severe AKI. RESULTS During acute NE, 88% of the patients had AKI according to the RILFE criteria during acute NE. A risk index score for severe AKI was derived by using three independent risk factors in patients with normal kidney function at time of diagnosis: thrombocytopenia [two points; odds ratios (OR): 3.77; 95% confidence intervals (CI): 1.82, 8.03], elevated C-reactive protein levels (one point; OR: 3.02; 95% CI: 1.42, 6.58) and proteinuria (one point; OR: 3.92; 95% CI: 1.33, 13.35). On the basis of a point score of one or two, the probability of severe AKI was 0.18 and 0.28 with an area under the curve of 0.71. CONCLUSION This clinical prediction rule provides a novel and diagnostically accurate strategy for the potential prevention and improved management of kidney complications in patients with NE and, ultimately, for a possible decrease in unnecessary hospitalization in a high number of patient

Fertility, pregnancy and delivery in women after biventricular repair for double outlet right ventricle

Objectives: To investigate outcome of pregnancy and fertility in women with double outlet right ventricle (DORV). Methods: Using 2 congenital heart disease registries, 21 female patients with DORV (aged 18-39 years) were retrospectively identified. Detailed recordings of each patient and their completed (>20 weeks gestation) pregnancies were recorded. Results: Overall, 10 patients had 19 pregnancies, including 3 spontaneous miscarriages (16%). During the 16 live birth pregnancies, primarily (serious) noncardiac complications were observed, e.g. premature labor/delivery (n = 7 and n = 3, respectively), small for gestational age (n = 4), preeclampsia (n = 2) and recurrence of congenital heart disease (n = 2). Except for postpartum endocarditis and deterioration of subpulmonary obstruction, only mild cardiac complication pregnancies were recorded. Two women with children reported secondary female infertility. Several menstrual cycle disorders were reported: secondary amenorrhea (n = 4), primary amenorrhea (n = 3) and oligomenorrhea (n = 2). Conclusion: Successful pregnancy in women with DORV is possible. Primarily noncardiac complications were observed and only few (minor) cardiac complications. Infertility and menstrual cycle disorders appear to be more prevalent. Copyrigh

Pan-European study of genotypes and phenotypes in the Arabidopsis relative Cardamine hirsuta reveals how adaptation, demography, and development shape diversity patterns

We study natural DNA polymorphisms and associated phenotypes in the Arabidopsis relative Cardamine hirsuta. We observed strong genetic differentiation among several ancestry groups and broader distribution of Iberian relict strains in European C. hirsuta compared to Arabidopsis. We found synchronization between vegetative and reproductive development and a pervasive role for heterochronic pathways in shaping C. hirsuta natural variation. A single, fast-cycling ChFRIGIDA allele evolved adaptively allowing range expansion from glacial refugia, unlike Arabidopsis where multiple FRIGIDA haplotypes were involved. The Azores islands, where Arabidopsis is scarce, are a hotspot for C. hirsuta diversity. We identified a quantitative trait locus (QTL) in the heterochronic SPL9 transcription factor as a determinant of an Azorean morphotype. This QTL shows evidence for positive selection, and its distribution mirrors a climate gradient that broadly shaped the Azorean flora. Overall, we establish a framework to explore how the interplay of adaptation, demography, and development shaped diversity patterns of 2 related plant species