Effect of a multimodal prevention strategy on dialysis-associated infection events in outpatients receiving haemodialysis: The DIPS stepped wedge, cluster-randomized trial.

OBJECTIVES: Patients with haemodialysis catheters are susceptible to dialysis-associated infections, particularly bloodstream infections. There have been few systematic attempts to reduce this burden. Our study aimed to investigate the effect of a multimodal prevention strategy on dialysis-associated infection events (DAIE) among haemodialysis outpatients. METHODS: A multicentre, stepped wedge, cluster-randomized controlled trial was done from October 2019 to September 2021. Outpatient dialysis facilities entered into the intervention phase in three randomly assigned clusters, at three predefined time points. The multimodal prevention strategy consisted of infection surveillance and hand hygiene (HH) compliance observation with active feedback and teaching aseptic procedures, and a patient flyer. The primary outcome was incidence rates of different DAIE, such as bloodstream infections, intravenous antimicrobial starts, and local access-site infections per 1000 dialysis. As secondary outcome, we analysed the HH compliance change. RESULTS: A total of 43 haemodialysis outpatient facilities with 11 251 patients and 1 413 457 proceeded haemodialysis were included in the DIPS-trial. Incidence rates were 0.71 DAIE per 1000 dialysis (95% CI, 0.65-0.78) in the control and 0.31 (95% CI, 0.27-0.36) in the intervention group. The univariable analysis yielded an incidence rate ratio (IRR) of 0.44 (95% CI, 0.33-0.59) for DAIE. Especially in patients with a central venous catheter, we saw a significant decrease in DAIE in the intervention group (IRR 0.4; 95% CI, 0.28-0.58). The HH observation combined with feedback and intensified training, resulted in an increase of HH compliance from 58-65%. DISCUSSION: A multimodal prevention strategy showed a significant preventive effect on DAIE among haemodialysis outpatients. This reduction also applied to bloodstream infections, especially in patients with a central venous catheter.

Risk factors for transmission of carbapenem-resistant Acinetobacter baumannii in outbreak situations: results of a case-control study.

BACKGROUND: An increase in patients with multidrug-resistant organisms and associated outbreaks during the COVID-19 pandemic have been reported in various settings, including low-endemic settings. Here, we report three distinct carbapenem-resistant Acinetobacter baumannii (CRAB) outbreaks in five intensive care units of a university hospital in Berlin, Germany during the COVID-19 pandemic. METHODS: A case-control study was conducted with the objective of identifying risk factors for CRAB acquisition in outbreak situations. Data utilized for the case-control study came from the investigation of three separate CRAB outbreaks during the COVID-19 pandemic (August 2020- March 2021). Cases were defined as outbreak patients with hospital-acquired CRAB. Controls did not have any CRAB positive microbiological findings and were hospitalized at the same ward and for a similar duration as the respective case. Control patients were matched retrospectively in a 2:1 ratio. Parameters routinely collected in the context of outbreak management and data obtained retrospectively specifically for the case-control study were included in the analysis. To analyze risk factors for CRAB acquisition, univariable and multivariable analyses to calculate odds ratios (OR) and 95% confidence intervals (CI) were performed using a conditional logistic regression model. RESULTS: The outbreaks contained 26 cases with hospital-acquired CRAB in five different intensive care units. Two exposures were identified to be independent risk factors for nosocomial CRAB acquisition by the multivariable regression analysis: Sharing a patient room with a CRAB patient before availability of the microbiological result was associated with a more than tenfold increase in the risk of nosocomial CRAB acquisition (OR: 10.7, CI: 2.3-50.9), while undergoing bronchoscopy increased the risk more than six times (OR: 6.9, CI: 1.3-38.1). CONCLUSIONS: The risk factors identified, sharing a patient room with a CRAB patient and undergoing bronchoscopy, could point to an underperformance of basic infection control measure, particularly hand hygiene compliance and handling of medical devices. Both findings reinforce the need for continued promotion of infection control measures. Given that the outbreaks occurred in the first year of the COVID-19 pandemic, our study serves as a reminder that a heightened focus on airborne precautions should not lead to a neglect of other transmission-based precautions.

Impact of public health interventions to curb SARS-CoV-2 spread assessed by an evidence-educated Delphi panel and tailored SEIR model.

Aim: To use a Delphi-panel-based assessment of the effectiveness of different non-pharmaceutical interventions (NPI) in order to retrospectively approximate and to prospectively predict the SARS-CoV-2 pandemic progression via a SEIR model (susceptible, exposed, infectious, removed). Methods: We applied an evidence-educated Delphi-panel approach to elicit the impact of NPIs on the SARS-CoV-2 transmission rate R0 in Germany. Effectiveness was defined as the product of efficacy and compliance. A discrete, deterministic SEIR model with time step of 1 day, a latency period of 1.8 days, duration of infectiousness of 5 days, and a share of the total population of 15% assumed to be protected by immunity was developed in order to estimate the impact of selected NPI measures on the course of the pandemic. The model was populated with the Delphi-panel results and varied in sensitivity analyses. Results: Efficacy and compliance estimates for the three most effective NPIs were as follows: test and isolate 49% (efficacy)/78% (compliance), keeping distance 42%/74%, personal protection masks (cloth masks or other face masks) 33%/79%. Applying all NPI effectiveness estimates to the SEIR model resulted in a valid replication of reported occurrence of the German SARS-CoV-2 pandemic. A combination of four NPIs at consented compliance rates might curb the CoViD-19 pandemic. Conclusion: Employing an evidence-educated Delphi-panel approach can support SARS-CoV-2 modelling. Future curbing scenarios require a combination of NPIs. A Delphi-panel-based NPI assessment and modelling might support public health policy decision making by informing sequence and number of needed public health measures. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-021-01566-2.

Successful control of Candida auris transmission in a German COVID-19 intensive care unit.

BACKGROUND: Candida auris a frequently multidrug-resistant yeast species that poses a global health threat due to its high potential for hospital outbreaks. While C. auris has become endemic in parts of Asia and Africa, transmissions have so far rarely been reported in Western Europe except for Great Britain and Spain. We describe the first documented patient-to-patient transmission of C. auris in Germany in a COVID-19 intensive care unit (ICU) and infection control measures implemented to prevent further spread of the pathogen. METHODS: Identification of C. auris was performed by MALDI-TOF and confirmed by internal transcribed spacer (ITS) sequencing. Antifungal susceptibility testing was carried out. We conducted repeated cross-sectional examinations for the presence of C. auris in the patients of the affected ICU and investigated possible routes of transmission. RESULTS: The index patient had been transferred to Germany from a hospital in Northern Africa and was found to be colonised with C. auris. The contact patient developed C. auris sepsis. Infection prevention and control (IPC) measures included strict isolation of the two C. auris patients and regular screening of non-affected patients. No further case occurred during the subsequent weeks. Reusable blades used in video laryngoscope-guided intubation were considered as the most likely vehicle of transmission. CONCLUSIONS: In view of its high risk of transmission, vigilance regarding C. auris colonisation in patients referred from endemic countries is crucial. Strict and immediate IPC measures may have the potential to prevent C. auris outbreaks.

Risk factors for nosocomial SARS-CoV-2 infections in patients: results from a retrospective matched case-control study in a tertiary care university center.

BACKGROUND: Factors contributing to the spread of SARS-CoV-2 outside the acute care hospital setting have been described in detail. However, data concerning risk factors for nosocomial SARS-CoV-2 infections in hospitalized patients remain scarce. To close this research gap and inform targeted measures for the prevention of nosocomial SARS-CoV-2 infections, we analyzed nosocomial SARS-CoV-2 cases in our hospital during a defined time period. METHODS: Data on nosocomial SARS-CoV-2 infections in hospitalized patients that occurred between May 2020 and January 2021 at Charité university hospital in Berlin, Germany, were retrospectively gathered. A SARS-CoV-2 infection was considered nosocomial if the patient was admitted with a negative SARS-CoV-2 reverse transcription polymerase chain reaction test and subsequently tested positive on day five or later. As the incubation period of SARS-CoV-2 can be longer than five days, we defined a subgroup of "definite" nosocomial SARS-CoV-2 cases, with a negative test on admission and a positive test after day 10, for which we conducted a matched case-control study with a one to one ratio of cases and controls. We employed a multivariable logistic regression model to identify factors significantly increasing the likelihood of nosocomial SARS-CoV-2 infections. RESULTS: A total of 170 patients with a nosocomial SARS-CoV-2 infection were identified. The majority of nosocomial SARS-CoV-2 patients (n = 157, 92%) had been treated at wards that reported an outbreak of nosocomial SARS-CoV-2 cases during their stay or up to 14 days later. For 76 patients with definite nosocomial SARS-CoV-2 infections, controls for the case-control study were matched. For this subgroup, the multivariable logistic regression analysis revealed documented contact to SARS-CoV-2 cases (odds ratio: 23.4 (95% confidence interval: 4.6-117.7)) and presence at a ward that experienced a SARS-CoV-2 outbreak (odds ratio: 15.9 (95% confidence interval: 2.5-100.8)) to be the principal risk factors for nosocomial SARS-CoV-2 infection. CONCLUSIONS: With known contact to SARS-CoV-2 cases and outbreak association revealed as the primary risk factors, our findings confirm known causes of SARS-CoV-2 infections and demonstrate that these also apply to the acute care hospital setting. This underscores the importance of rapidly identifying exposed patients and taking adequate preventive measures.

Determinants of Sickness Absence and Return to Work Among Employees with Common Mental Disorders: A Scoping Review.

Purpose To present an overview of the existing evidence on prognostic factors of (recurrent) sickness absence (SA) and return to work (RTW) among workers with a common mental disorder (CMD). This scoping review provides information about determinants for SA and RTW, which could be used to develop better interventions aimed at the prevention of SA and promotion of RTW among workers with a CMD. Methods Relevant articles were identified in PubMed, Embase, PsycINFO, PSYNDEX, and SINGLE up to October 2016. In order to be included, studies should provide insight into prognostic factors of SA or RTW of workers with a CMD. We classified all factors according to the domains of the International Classification of Functioning, Disability and Health. Results Our searches identified 2447 possible relevant articles, of which 71 were included for data extraction. There is consistent evidence in ≥3 studies that previous episodes of CMD, higher symptom severity, previous absenteeism, co-morbidity, high job demands, low job control, high job strain, female gender, lower educational level, smoking behavior, and low perceived general health are predictors of SA in people with CMDs. Earlier RTW is consistently predicted by lower symptom severity, having no previous absenteeism, younger age, and positive expectations concerning sick-leave duration or RTW. Conclusions The amount of research on determinants for SA and RTW in workers with CMD has increased dramatically in recent years, although most studies are from the Netherlands and Scandinavia. There are some research gaps identified in this scoping review that need further attention in primary and secondary studies. Based on the summary of the evidence, we provide guidance for policy, practice and research.

Inter-rater reliability of AMSTAR is dependent on the pair of reviewers.

BACKGROUND: Inter-rater reliability (IRR) is mainly assessed based on only two reviewers of unknown expertise. The aim of this paper is to examine differences in the IRR of the Assessment of Multiple Systematic Reviews (AMSTAR) and R(evised)-AMSTAR depending on the pair of reviewers. METHODS: Five reviewers independently applied AMSTAR and R-AMSTAR to 16 systematic reviews (eight Cochrane reviews and eight non-Cochrane reviews) from the field of occupational health. Responses were dichotomized and reliability measures were calculated by applying Holsti's method (r) and Cohen's kappa (κ) to all potential pairs of reviewers. Given that five reviewers participated in the study, there were ten possible pairs of reviewers. RESULTS: Inter-rater reliability varied for AMSTAR between r = 0.82 and r = 0.98 (median r = 0.88) using Holsti's method and κ = 0.41 and κ = 0.69 (median κ = 0.52) using Cohen's kappa and for R-AMSTAR between r = 0.77 and r = 0.89 (median r = 0.82) and κ = 0.32 and κ = 0.67 (median κ = 0.45) depending on the pair of reviewers. The same pair of reviewers yielded the highest IRR for both instruments. Pairwise Cohen's kappa reliability measures showed a moderate correlation between AMSTAR and R-AMSTAR (Spearman's ρ =0.50). The mean inter-rater reliability for AMSTAR was highest for item 1 (κ = 1.00) and item 5 (κ = 0.78), while lowest values were found for items 3, 8, 9 and 11, which showed only fair agreement. CONCLUSIONS: Inter-rater reliability varies widely depending on the pair of reviewers. There may be some shortcomings associated with conducting reliability studies with only two reviewers. Further studies should include additional reviewers and should probably also take account of their level of expertise.

Resuming the discussion of AMSTAR: What can (should) be made better?

BACKGROUND: Evidence syntheses, and in particular systematic reviews (SRs), have become one of the cornerstones of evidence-based health care. The Assessment of Multiple Systematic Reviews (AMSTAR) tool has become the most widely used tool for investigating the methodological quality of SRs and is currently undergoing revision. The objective of this paper is to present insights, challenges and potential solutions from the point of view of a group of assessors, while referring to earlier methodological discussions and debates with respect to AMSTAR. DISCUSSION: One major drawback of AMSTAR is that it relies heavily on reporting quality rather than on methodological quality. This can be found in several items. Furthermore, it should be acknowledged that there are now new methods and procedures that did not exist when AMSTAR was developed. For example, the note to item 1 should now refer to the International Prospective Register of Ongoing Systematic Reviews (PROSPERO). Furthermore, item 3 should consider the definition of hand-searching, as the process of reviewing conference proceedings using the search function (e.g. in Microsoft Word or in a PDF file) does not meet the definition set out by the Cochrane Collaboration. Moreover, methods for assessing the quality of the body of evidence have evolved since AMSTAR was developed and should be incorporated into a revised AMSTAR tool. Potential solutions are presented for each AMSTAR item with the aim of allowing a more thorough assessment of SRs. As the AMSTAR tool is currently undergoing further development, our paper hopes to add to preceding discussions and papers regarding this tool and stimulate further discussion.

[Comorbidity of diabetes mellitus and depression in the general population in Germany]. / Komorbidität von Diabetes mellitus und Depression in Deutschland.

OBJECTIVE: To assess the comorbidity of diabetes and depression in the adult general population of Germany. METHODS: Data (n = 43 312) derived from the representative cross-sectional telephone survey "German Health Update (GEDA)". Information about diagnosed chronic somatic diseases including diabetes and diagnosed depression was available for residents in private households. Age- and sex-specific adjusted logistic regressions were used to examine the association between diabetes and depression. RESULTS: 12-month prevalences: diagnosed diabetes 7.4 %, diagnosed depression 6.7 %, comorbidity of both 0.8 %. An association of diabetes and depression was found in people < 50 years and in women aged 50 - 64 years. This association was dependent on the number of additional chronic diseases. CONCLUSION: Comorbidity of diabetes and depression was quite rare. Yet according to our results every 10(th) adult with diagnosed diabetes gets a depression diagnosis and every 9(th) adult with diagnosed depression has known diabetes. Underestimation for men and older adults due to diagnostic bias is possible. The combination of diabetes and depression is relevant for medical care because of its health burden.

Microsomal triglyceride transfer protein -164 T > C gene polymorphism and risk of cardiovascular disease: results from the EPIC-Potsdam case-cohort study.

BACKGROUND: The microsomal triglyceride transfer protein (MTTP) is encoded by the MTTP gene that is regulated by cholesterol in humans. Previous studies investigating the effect of MTTP on ischemic heart disease have produced inconsistent results. Therefore, we have tested the hypothesis that the rare allele of the -164T > C polymorphism in MTTP alters the risk of cardiovascular disease (CVD), depending on the cholesterol levels. METHODS: The -164T > C polymorphism was genotyped in a case-cohort study (193 incident myocardial infarction (MI) and 131 incident ischemic stroke (IS) cases and 1 978 non-cases) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, comprising 27 548 middle-aged subjects. The Heinz Nixdorf Recall study (30 CVD cases and 1 188 controls) was used to replicate our findings. RESULTS: Genotype frequencies were not different between CVD and CVD free subjects (P = 0.79). We observed an interaction between the -164T > C polymorphism and total cholesterol levels in relation to future CVD. Corresponding stratified analyses showed a significant increased risk of CVD (HR(additve) = 1.38, 95% CI: 1.07 to 1.78) for individuals with cholesterol levels <200 mg/dL in the EPIC-Potsdam study. HR(additive) was 1.06, 95% CI: 0.33 to 3.40 for individuals in the Heinz Nixdorf Recall study. A borderline significant decrease in CVD risk was observed in subjects with cholesterol levels ≥ 200 mg/dL (HR(additve) = 0.77, 95% CI: 0.58 to 1.03) in the EPIC-Potsdam study. A similar trend was observed in the independent cohort (HR(additve) = 0.60, 95% CI: 0.29 to 1.25). CONCLUSIONS: Our study suggests an interaction between MTTP -164T > C functional polymorphism with total cholesterol levels. Thereby risk allele carriers with low cholesterol levels may be predisposed to an increased risk of developing CVD, which seems to be abolished among risk allele carriers with high cholesterol levels.

Conflicts of interest among authors of medical guidelines: an analysis of guidelines produced by German specialist societies.

BACKGROUND: Conflicts of interest can bias the recommendations of clinical guidelines. In 2010, the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) revised its rules about how conflicts of interest in guidelines should be managed. METHODS: All S2 and S3 guidelines in the AWMF database that were created in the years 2009-2011 were independently examined by two reviewers each (TL, MG, SC, BW, LF, SS). Information on conflicts of interest was extracted and descriptively analyzed. The effects of the new AWMF rules were studied with a before-and-after comparison. RESULTS: 60 (20%) of the 297 guidelines studied contained explicit declarations of conflict of interest by their authors. 680 authors (49%) stated that they had financial relationships that constituted a conflict of interest; 86% declared conflicts arising from membership in specialty societies or professional associations. From 2009 to 2011, there was a substantial rise in the frequency of conflict-of-interest declarations in guidelines (8% of 256 guidelines that were created before the AWMF revised its rules in 2010 and 95% of 41 guidelines created afterward). The percentage of persons declaring financial conflicts of interest rose after the new rules were introduced, while the mode of documentation of conflict-of-interest evaluation and of any measures that might have been taken as a result remained unchanged. CONCLUSION: From 2011 onward, all conflict-of-interest declarations by guideline authors have been published in the AWMF database. There is no current standard for the evaluation and management of conflicts of interest in guideline-creating groups, and this situation urgently needs to be remedied.

Quality of reporting of randomized controlled trials of pharmacologic treatment of bipolar disorders: a systematic review.

OBJECTIVE: This study aimed to assess (1) the quality of reporting of randomized controlled trials of pharmacologic treatment of bipolar disorder, (2) the potential improvement in quality of reporting over time, and (3) differences in quality of reporting between journals that endorse or do not endorse the Uniform Requirements for Manuscripts Submitted to Biomedical Journals developed by the International Committee of Medical Journal Editors. DATA SOURCES: A systematic literature search was done to identify all randomized controlled trials published between 2000 and 2008 relevant to the pharmacologic treatment of bipolar disorder. The search strategy of the published National Institute for Health and Clinical Excellence guideline for management of bipolar disorders was used and adapted. All included and excluded clinical trials mentioned in the guideline and published from 2000 onward were reviewed for eligibility. For an update search from July 2004 through December 2008, an adapted search strategy was used in MEDLINE, EMBASE, PsycINFO, CINAHL, Ovid, and Cochrane Central Register of Controlled Trials. Titles and abstracts were scanned for relevance, and full texts were ordered in case of uncertainty to maximize sensitivity. Reference lists of retrieved systematic reviews were checked. STUDY SELECTION: All full texts were checked for eligibility. Only relevant randomized controlled trials published between 2000 and 2008 were included. Abstracts, randomized controlled trials published before 2000, nonrandomized clinical studies, pooled analyses, editorials, reviews, case reports, observational studies, and unpublished reports were excluded. DATA EXTRACTION: A checklist based on the Consolidated Standards of Reporting Trials (CONSORT) statement was used to assess quality of reporting of all included studies. RESULTS: A total of 105 randomized controlled trials were included in the analysis. Of the 72 applicable checklist items, 42% were generally reported adequately and 25% inadequately. Reporting was especially poor for randomization procedures, with, for example, 16% of studies defining generation of random allocation sequence and 15% defining method of allocation concealment. Inadequate randomization increases the potential for bias to influence the final results. Authors of clinical guidelines or health technology assessments are forced to exclude or downgrade trials with inadequate reporting on randomization. Also, information with essential clinical relevance was generally reported inadequately, such as the effect size (in 18% of studies) and the number needed to treat (in 8% of studies). Both effect measures are more important for clinicians than individual point estimates that have been reported adequately. No consistent trend could be shown for improvement in quality of reporting over time or for reporting of essential methodological items differently in journals that endorse the Uniform Requirements for Manuscripts (URM). The reporting of information on clinical relevance and generalizability of results, however, showed a consistent trend toward better reporting in journals endorsing the URM, with significant differences for the reporting of secondary outcomes (100% vs 89.9%; P = .03) and adverse events (93.2% vs 73.8%; P = .011) and interpretation of results with regard to totality of data (30.2% vs 11.5%; P = .029). CONCLUSIONS: Our findings suggest that, while some trial-related information is well reported, a good part of the reporting quality of randomized controlled trials in bipolar disorder falls well below the required and also practically feasible level for many aspects essential for adequate interpretation of methodological quality and clinical relevance. Authors should be further encouraged to follow the CONSORT criteria.

[After seven years of National Disease Management Guidelines: quo vadis?]. / 7 Jahre Nationale VersorgungsLeitlinien (NVL)--Quo vadis?

After seven years the National Disease Management Guidelines Programme (German DM-CPG Programme) that was established under the auspices of the German Medical Association, the National Association of Statutory Health Insurance Physicians and the Association of the Scientific Medical Societies in Germany has been widely accepted by both health care professionals and patients. DM-CPGs are available as tools for knowledge and quality management for widespread chronic diseases showing need for improvement in treatment pathways and coordination between health care providers. The main objective of the German DM-CPG Programme is to establish consensus among the medical professions on evidence-based key recommendations covering all sectors of health care provision and facilitating the coordination of care for the individual patient over time and across interfaces. German DM-CPGs provide a conceptual basis for disease management and integrative care aiming at the implementation of best practice recommendations for prevention, acute care, rehabilitation, chronic care and management aspects for high priority health care topics. Thus, representatives of all disciplines, professions and patients concerned with the topic of an individual German DM-CPG are involved in the development process. The methodology of guideline development is in accordance with international standards. However, the improvement of strategies for effective implementation and continuous update remain challenging. Future work will also focus on content-related aspects such as co-morbidity, gender and migration background.

[Diversity in spite of standards: the special features of NDGMs]. / Trotz Standards--Vielfalt im Programm: Die Besonderheiten der NVL.

For seven years the German National Disease Management Guidelines Programme (NDMG Programme) has been supported by its funding bodies: the German Medical Association, the National Association of Statutory Health Insurance Physicians, and the Association of Scientific Medical Societies. The objectives of the NDMG Programme are to develop and to implement comprehensive national clinical guidelines for the management of selected illnesses. Key points of NDMG methodology are the strict adherence to the principles of evidence-based medicine as well as the avoidance of contradictory recommendations by means of neutrally facilitated consensus rounds. Despite the standardised NDMG methodology each guideline has individual structural and content features that make it unique. For example, the complex illness type 2 diabetes is presented in topic- and problem-oriented NDMG modules. For unipolar depression, the NDMG was simultaneously developed as a S3 guideline. Furthermore each NDMG group was faced with its own content-based challenges. For instance, in the case of the NDMG Low-back Pain the guideline group intensely and controversially discussed the definition of unspecific low-back pain. The NDMG Asthma does not solely address adults, but also children and adolescents, and the NDMG Heart Failure for the first time covers other health care relevant aspects such as multimorbidity and psychosocial factors in detail. The following article aims to deliver insight into the diversity of the development of National Disease Management Guidelines and to demonstrate the complexity of guideline development.