Unpacking nudge sensu lato: insights from a scoping review.

Nudges may play an important role in improving infection prevention and control (IPC) in hospitals. However, despite the novelty of the framework, their objectives, strategies and implementation approaches are not new. This review aims to provide an overview of the methods typically used by nudge interventions in IPC in hospitals targeting healthcare workers (HCWs). The initial search in PubMed yielded nine hits. Consequently, the search criteria were broadened and a second search was conducted, introducing 'nudge sensu lato' which incorporates insights from sources beyond the traditional nudge framework while maintaining the same objectives, strategies and approaches. During the second search, PubMed, Epistemonikos, Web of Science and PsycInfo were searched in accordance with the PRISMA guidelines. Abstracts were screened, and reviewers from an interdisciplinary team read the full text of selected papers. In total, 5706 unique primary studies were identified. Of these, 67 were included in the review, and only four were listed as nudge sensu stricto, focusing on changing HCWs' hand hygiene. All articles reported positive intervention outcomes. Of the 56 articles focused on improving hand hygiene compliance, 71.4% had positive outcomes. For healthcare equipment disinfection, 50% of studies showed significant results. Guideline adherence interventions had a 66.7% significant outcome rate. The concept of nudge sensu lato was introduced, encompassing interventions that employ strategies, methods and implementation approaches found in the nudge framework. The findings demonstrate that this concept can enhance the scientific development of more impactful nudges. This may help clinicians, researchers and policy makers to develop and implement effective nudging interventions.

Hospital volume-outcome relationship in total knee arthroplasty: a systematic review and dose-response meta-analysis.

PURPOSE: This systematic review and dose-response meta-analysis aimed to investigate the relationship between hospital volume and outcomes for total knee arthroplasty (TKA). METHODS: MEDLINE, Embase, CENTRAL and CINAHL were searched up to February 2020 for randomised controlled trials and cohort studies that reported TKA performed in hospitals with at least two different volumes and any associated patient-relevant outcomes. The adjusted effect estimates (odds ratios, OR) were pooled using a random-effects, linear dose-response meta-analysis. Heterogeneity was quantified using the I2-statistic. ROBINS-I and the GRADE approach were used to assess the risk of bias and the confidence in the cumulative evidence, respectively. RESULTS: A total of 68 cohort studies with data from 1985 to 2018 were included. The risk of bias for all outcomes ranged from moderate to critical. Higher hospital volume may be associated with a lower rate of early revision ≤ 12 months (narrative synthesis of k = 7 studies, n = 301,378 patients) and is likely associated with lower mortality ≤ 3 months (OR = 0.91 per additional 50 TKAs/year, 95% confidence interval [0.87-0.95], k = 9, n = 2,638,996, I2 = 51%) and readmissions ≤ 3 months (OR = 0.98 [0.97-0.99], k = 3, n = 830,381, I2 = 44%). Hospital volume may not be associated with the rates of deep infections within 1-4 years, late revision (1-10 years) or adverse events ≤ 3 months. The confidence in the cumulative evidence was moderate for mortality and readmission rates; low for early revision rates; and very low for deep infection, late revision and adverse event rates. CONCLUSION: An inverse volume-outcome relationship probably exists for some TKA outcomes, including mortality and readmissions, and may exist for early revisions. Small reductions in unfavourable outcomes may be clinically relevant at the population level, supporting centralisation of TKA to high-volume hospitals. LEVEL OF EVIDENCE: III. REGISTRATION NUMBER: The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO CRD42019131209 available at: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=131209 ).

A specific gene-microbe interaction drives the development of Crohn's disease-like colitis in mice.

Bacterial dysbiosis is associated with Crohn's disease (CD), a chronic intestinal inflammatory disorder thought to result from an abnormal immune response against intestinal bacteria in genetically susceptible individuals. However, it is unclear whether dysbiosis is a cause or consequence of intestinal inflammation and whether overall dysbiosis or specific bacteria trigger the disease. Here, we show that the combined deficiency of NOD2 and phagocyte NADPH oxidase, two CD susceptibility genes, triggers early-onset spontaneous TH1-type intestinal inflammation in mice with the pathological hallmarks of CD. Disease was induced by Mucispirillum schaedleri, a Gram-negative mucus-dwelling anaerobe. NOD2 and CYBB deficiencies led to marked accumulation of Mucispirillum, which was associated with impaired neutrophil recruitment and killing of the bacterium by luminal neutrophils. Maternal immunoglobulins against Mucispirillum protected mutant mice from disease during breastfeeding. Our results indicate that a specific intestinal microbe triggers CD-like disease in the presence of impaired clearance of the bacterium by innate immunity.

[Minimum thresholds under scrutiny]. / Mindestmengen auf dem Prüfstand.

Minimum volume thresholds for specific medical treatments have been implemented in Germany since 2004. In the last 9 years the catalogue of procedures, which is determined by the Federal Joint Committee, has changed continuously and currently consists of 8 procedures. In this article the basis of decision making for the enrolment in the catalogue of procedures and the determination of minimum volume thresholds are examined. An overview of systematic reviews was published in 2012 outlining the correlation between the volume components and medical outcome. The body of evidence identified is compared to the current regulatory conditions of the Federal Joint Committee.

Adherence-enhancing interventions for highly active antiretroviral therapy in HIV-infected patients - a systematic review.

OBJECTIVES: The objective of this systematic review was to evaluate the effectiveness of adherence-enhancing interventions for highly active antiretroviral therapy (HAART) in HIV-infected patients in developed countries. METHODS: A systematic literature search was performed (January 2001 to May 2012) in EMBASE, including MEDLINE records, CENTRAL and PsycInfo. Trials meeting the following predefined inclusion criteria were included: adult patients with an HIV infection treated with HAART, an intervention to enhance patient adherence, adherence as the outcome, clinical outcomes, randomized controlled trial (RCT), article written in English or German, patient enrolment after 2001, and trial conducted in World Health Organization (WHO) stratum A. Selection was performed by two reviewers independently. All relevant data on patient characteristics, interventions, adherence measures and results were extracted in standardized tables. The methodological trial quality was evaluated by two reviewers independently. All discrepancies were discussed until a consensus was reached. A meta-analysis could not be performed because of the heterogeneity of trials. RESULTS: In total, 21 trials fulfilled all inclusion criteria. Of 21 trials, only one that examined motivational interviewing for alcohol-dependent patients showed statistically significant results for adherence rates and viral load in favour of the intervention. One trial showed a statistically significant clinical effect of the intervention; however, inconsistent results were presented for adherence depending on the underlying adherence definition. The results of the remaining 19 trials were not statistically significant or were conflicting for adherence and/or clinical outcomes. However, the methodological trial quality was low. CONCLUSIONS: It is not possible to definitively assess the effectiveness of adherence-enhancing interventions. However, it appears that most adherence interventions have no effect.

Photophysical characterisation and photo-cycle dynamics of LOV1-His domain of phototropin from Chlamydomonas reinhardtii with roseoflavin monophosphate cofactor.

The wild-type phototropin protein phot from the green alga Chlamydomonas reinhardtii with the blue-light photoreceptor domains LOV1 and LOV2 has flavin mononucleotide (FMN) as cofactor. For the LOV1-His domain from phot of C. reinhardtii studied here, the FMN chromophore was replaced by roseoflavin monophosphate (8-dimethylamino-8-demethyl-FMN, RoFMN) during heterologous expression in a riboflavin auxotropic Escherichia coli strain. An absorption and emission spectroscopic characterisation of the cofactor exchanged-LOV1-His (RoLOV1) domain was carried out in aqueous pH 8 phosphate buffer. The fluorescence of RoLOV1 is quenched by photo-induced charge transfer at room temperature. The photo-cyclic dynamics of RoLOV1 was observed by blue-light induced hypochromic and bathochromic absorption changes which recover on a minute timescale in the dark. Photo-excited RoFMN is thought to cause reversible protein and cofactor structural changes. Prolonged intense blue-light exposure caused photo-degradation of RoFMN in RoLOV1 to fully reduced flavin and lumichrome derivatives. Photo-cycle schemes of RoLOV1 and LOV1 are presented, and the photo-degradation dynamics of RoLOV1 is discussed.

Absorption and emission spectroscopic characterization of BLUF protein Slr1694 from Synechocystis sp. PCC6803 with roseoflavin cofactor.

The wild-type BLUF protein Slr1694 from Synechocystis sp. PCC6803 (BLUF=blue-light sensor using FAD) has flavin adenosine dinucleotide (FAD) as natural cofactor. This light sensor causes positive phototaxis of the marine cyanobacterium. In this study the FAD cofactor of the wild-type Slr1694 was replaced by roseoflavin (RoF) and the roseoflavin derivatives RoFMN and RoFAD during heterologous expression in a riboflavin auxotrophic E. coli strain. An absorption and emission spectroscopic characterization of the cofactor-exchanged-Slr1694 (RoSlr) was carried out both under dark conditions and under illuminated conditions. The behaviour of RoF embedded in RoSlr in aqueous solution at pH 8 is compared with the behaviour of RoF in aqueous solution. The fluorescence of RoF and RoSlr is quenched by photo-induced twisted intra-molecular charge transfer at room temperature with stronger effect for RoF. The fluorescence quenching is diminished at liquid nitrogen temperature. Light exposure of RoSlr causes irreversible conversion of the protein embedded roseoflavins to 8-methylamino-flavins, 8-dimethylamino-lumichrome and 8-methylamino-lumichrome.

Absorption and emission spectroscopic characterization of blue-light receptor Slr1694 from Synechocystis sp. PCC6803.

The BLUF protein Slr1694 from the cyanobacterium Synechocystis sp. PCC6803 is characterized by absorption and emission spectroscopy. Slr1694 expressed from E. coli which non-covalently binds FAD, FMN, and riboflavin (called Slr1694(I)), and reconstituted Slr1694 which dominantly contains FAD (called Slr1694(II)) are investigated. The receptor conformation of Slr1694 (dark adapted form Slr1694(r)) is transformed to the putative signalling state (light adapted form Slr1694(s)) with red-shifted absorption and decreased fluorescence efficiency by blue-light excitation. In the dark at 22 degrees C, the signalling state recovers back to the initial receptor state with a time constants of about 14.2s for Slr1694(I) and 17s for Slr1694(II). Quantum yields of signalling state formation of approximately 0.63+/-0.07 for both Slr1694(I) and Slr1694(II) were determined by transient transmission measurements and intensity dependent steady-state transmission measurements. Extended blue-light excitation causes some bound flavin conversion to the hydroquinone form and some photo-degradation, both with low quantum efficiency. The flavin-hydroquinone re-oxidizes slowly back (time constant 5-9 min) to the initial flavoquinone form in the dark. A photo-cycle dynamics scheme is presented.