Abstract Background To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen. Study design This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2–5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed. Statistical analysis plan N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0–10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients’ global assessment of treatment success are secondary outcomes. Discussion The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals. Trial registration ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered).

Introduction Antimicrobial resistance is closely linked with the health and stability of environmental systems and therefore a challenge for the health of the planet. General Practitioners, owing to their trusted positions and close patient relationships, can play a crucial role in addressing antimicrobial resistance within the framework of Planetary Health. The goal of our study was to examine General Practitioners' knowledge, attitude, and practice regarding the linkage of antimicrobial resistance with Planetary Health to understand their potential as agents of change in this domain.Materials and methods We conducted 19 guided interviews with General Practitioners from four different German federal states (August-September 2022). Participants were selected from the intervention group of the RedAres randomized controlled trial, a study designed to optimize therapy and prescribing practices for uncomplicated urinary tract infections in general practice. Data were analyzed using Mayring's structured qualitative content analysis and the typology approach by Kelle and Kluge.Results General Practitioners generally demonstrated the ability to identify the interlinkages between antimicrobial resistance and Planetary Health. However, they exhibited varying levels of knowledge, problem awareness, and accountability for the associated challenges and partially outsourced the responsibility for Planetary Health. Some General Practitioners were capable of integrating Planetary Health arguments into patient counseling. They recognized rational prescribing practice, self-reflection on antimicrobial resistance and Planetary Health, interprofessional exchange, and raising awareness among patients as potential avenues for engagement in promoting Planetary Health.Discussion As antimicrobial resistance is increasingly recognized as a Planetary Health challenge, empowering General Practitioners as change agents requires tailored measures based on their level of previous knowledge and their attitude toward Planetary Health. General Practitioners express a need for concrete advice on how to integrate antimicrobial resistance as a Planetary Health topic into their daily activities. Developing and evaluating adaptable training materials is essential. Additionally, the integration of Planetary Health outcomes into clinical guidelines could accelerate the adoption of this dimension in antibiotic prescribing practices within primary care settings.

Urinary tract infections (UTIs) are among the most common reasons patients seeking health care and antibiotics to be prescribed in primary care. However, general practitioners' (GPs) guideline adherence is low. The RedAres randomised controlled trial aims to increase guideline adherence by implementing a multimodal intervention consisting of four elements: information on current UTI guidelines (1) and regional resistance data (2); feedback regarding prescribing behaviour (3); and benchmarking compared to peers (4). The RedAres process evaluation assesses GPs' perception of the multimodal intervention and the potential for implementation into routine care. We carried out 19 semi-structured interviews with GPs (intervention arm). All interviews were carried out online and audio recorded. For transcription and analysis, Mayring's qualitative content analysis was used. Overall, GPs considered the interventions helpful for knowledge gain and confirmation when prescribing. Information material and resistance were used for patient communication and teaching purposes. Feedback was considered to enhance reflection by breaking routines of clinical workup. Implementation into routine practice could be enhanced by integrating feedback loops into patient management systems and conveying targeted information via trusted channels or institutions. The process evaluation of RedAres intervention was considered beneficial by GPs. It confirms the convenience of multimodal interventions to enhance guideline adherence.

OBJECTIVES:To evaluate whether a multimodal intervention in general practice reduces the proportion of second line antibiotic prescriptions and the overall proportion of antibiotic prescriptions for uncomplicated urinary tract infections in women. DESIGN:Parallel, cluster randomised, controlled trial. SETTING:General practices in five regions in Germany. Data were collected between 1 April 2021 and 31 March 2022. PARTICIPANTS:General practitioners from 128 randomly assigned practices. INTERVENTIONS:Multimodal intervention consisting of guideline recommendations for general practitioners and patients, provision of regional data for antibiotic resistance, and quarterly feedback, which included individual first line and second line proportions of antibiotic prescribing, benchmarking with regional or supra-regional practices, and telephone counselling. Participants in the control group received no information on the intervention. MAIN OUTCOME MEASURES:Primary outcome was the proportion of second line antibiotics prescribed by general practices, in relation to all antibiotics prescribed, for uncomplicated urinary tract infections after one year between the intervention and control group. General practices were randomly assigned in blocks (1:1), with a block size of four, into the intervention or control group using SAS version 9.4; randomisation was stratified by region. The secondary outcome was the prescription proportion of all antibiotics, relative within all cases (instances of UTI diagnosis), for the treatment of urinary tract infections after one year between the groups. Adverse events were assessed as exploratory outcomes. RESULTS:110 practices with full datasets identified 10 323 cases during five quarters (ie, 15 months). The mean proportion of second line antibiotics prescribed was 0.19 (standard deviation 0.20) in the intervention group and 0.35 (0.25) in the control group after 12 months. After adjustment for preintervention proportions, the mean difference was -0.13 (95% confidence interval -0.21 to -0.06, P<0.001). The overall proportion of all antibiotic prescriptions for urinary tract infections over 12 months was 0.74 (standard deviation 0.22) in the intervention and 0.80 (0.15) in the control group with a mean difference of -0.08 (95% confidence interval -0.15 to -0.02, P<0.029). No differences were noted in the number of complications (ie, pyelonephritis, admission to hospital, or fever) between the groups. CONCLUSIONS:The multimodal intervention in general practice significantly reduced the proportion of second line antibiotics and all antibiotic prescriptions for uncomplicated urinary tract infections in women. TRIAL REGISTRATION:German Clinical Trials Register (DRKS), DRKS00020389.

Abstract Background Gout is the most common form of rheumatic disease in which monosodium urate crystals are deposited in the joints followed by acute inflammatory reactions. There are various approved drugs that can be prescribed for pain relief during an acute gout attack. However, to date, no direct comparison of efficacy of colchicine and prednisolone for the treatment of acute gout attacks has been investigated. Furthermore, the majority of previous research studies were not only conducted in tertiary centres but also excluded patients with common comorbidities due to contraindications to naproxen. Methods This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial investigates whether prednisolone (intervention) is non-inferior to treatment with colchicine (active control) in patients with acute gout. Adult patients presenting with acute gout to their general practitioners in 60 practices across 3 university sites (Greifswald, Göttingen, and Würzburg) are eligible to participate in the study. Participants in the intervention group receive 30 mg prednisolone for 5 days. Those in the control group receive low-dose colchicine (day 1: 1.5 mg; days 2–5: 1 mg). The primary outcome is the absolute level of the most severe pain on day 3 (in the last 24 h) measured with an 11-item numerical rating scale. Day 0 is the day patients take their study medication for the first time. They are then asked to fill out a study diary the same time each day for pain quantification. Pain scores are used for comparison between the two medications. Secondary outcomes are average response to treatment, swelling, tenderness and physical function of the joint, patients’ global assessment of treatment success, use of additional pain medication and non-pharmacological pain therapies. For safety reasons, potential side effects and course of systolic blood pressure are assessed. Discussion This trial will provide evidence on the effectiveness of pain reduction and side effects of colchicine and prednisolone in acute gout in primary care. Trial registration ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered). URL of trial registry record: https://clinicaltrials.gov/study/NCT05698680

Background:Since 2019, the competence center for specialist training in family medicine Bavaria (KWAB) offers an individual mentoring program to accompany specialist training in family medicine. The mentors are confidants for matters of specialist training, private practice, career development and compatibility of work and family life. The training takes place after registration via an online portal.Methods:The evaluation was conducted 24 months after the start of KWAB mentoring (06/30/2021-08/01/2021). All active participants were interviewed via online survey. In each case, separate questionnaires were developed, which inquire on the one hand about the content-related aspects of the mentoring, such as topics discussed, and on the other hand about the individual mentoring relationship, such as the interpersonal relationship. The mentees received 39 questions (34 closed, 5 open) and the mentors received 26 questions (21 closed, 5 open), which were subsequently analyzed using descriptive statistics.Results:N = 30 mentors and N = 72 mentees were invited to participate in the evaluation (25 (83 %) mentors and 32 (44 %) mentees participated). More than half of the participants met each other at least twice. The main methods of communication were telephone, face-to-face meetings, and email contacts. The individual time commitment in each case was judged to be appropriate. According to the mentors, the mentees showed interest in the content of the program and demonstrated availability and commitment. All respondents indicated a high level of satisfaction with one-on-one mentoring and would recommend it to others.Conclusions:Mentors and mentees in family medicine residency reported a great benefit from the one-on-one mentoring offered and a will to continue their mentoring relationships even after the project period.

Das Kompetenzzentrum Weiterbildung Allgemeinmedizin Bayern (KWAB) bietet seit 2019 ein Einzel-Mentoring als Begleitung der hausärztlichen Weiterbildung an. Die hausärztlichen Mentorinnen und Mentoren sind Ansprechpersonen für Fragen u.a. zur Weiterbildung, Niederlassung, Karriereentwicklung und Vereinbarkeit von Familie und Beruf. Die Tandembildung erfolgt nach Registrierung über ein Onlineportal. Die Evaluation wurde 24 Monate nach Start des KWAB-Mentorings durchgeführt (30.06.2021–01.08.2021). Mittels Onlineumfrage wurden alle aktiv Teilnehmenden befragt. Es wurden eigene Fragebögen entwickelt, die einerseits die inhaltlichen Aspekte des Mentorings, wie besprochene Themen, und andererseits die individuelle Mentoring-Beziehung, wie zum Beispiel das zwischenmenschliche Verhältnis, erfragen. Die Mentees erhielten 39 Fragen (34 geschlossen, 5 offen) und die Mentorinnen und Mentoren erhielten 26 Fragen (21 geschlossen, 5 offen), die im Anschluss mittels deskriptiver Statistik ausgewertet werden. Es wurden N = 30 Mentorinnen und Mentoren und N = 72 Mentees zur Evaluation eingeladen (Teilnahmequote: 25 (83

INTRODUCTION:Contrary to current guideline recommendations, second-line antibiotics are still frequently used in the ambulatory treatment of uncomplicated urinary tract infections (UTI), which are associated with a high risk of antibiotic resistance development. The REDARES project (REDuction of Antibiotic RESistance in uncomplicated urinary tract infections by treatment according to national guidelines in ambulatory care), funded by the Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA)/Innovation Fund is developing a multimodal intervention for primary care physicians to support them in a guideline-based approach. The intervention consists of the following components: (1) provision of local resistance data of pathogens of uncomplicated UTI (Robert Koch Institute), (2) concise guideline content on the therapy of uncomplicated UTI for patients (paper and online), and (3) prescription feedback on practice level and benchmarking among the study participants (anonymized). In a participatory approach and as part of the process evaluation, representatives of the intended target group were interviewed in advance about the acceptance and feasibility of the intervention.METHODS:Using guided individual interviews, Thuringian GPs were interviewed before the start of the intervention phase. Following a description of the study concept and the planned components of the intervention, the interviewees were asked about their assessment regarding acceptance and feasibility. The individual interviews were recorded, transcribed verbatim and qualitatively analyzed according to Mayring.RESULTS:A total of ten interviews with an average duration of 29minutes were conducted and evaluated. 40 per cent of the interviewed GPs were female and, on average, 45 years old. The interviewees described the uncomplicated UTI as an easily manageable condition. The practical nature of the research question was described as a reason to potentially participate in the intervention phase; lack of time or human resources were cited as potential barriers. Regarding the intervention elements, the provision of local resistance data of UTI pathogens was considered beneficial to their own work. The extraction of their own antibiotic prescription data from the practice software was basically assessed as feasible. The interviewees differed in their assessment of whether they would take account of the feedback on their prescribing behavior in their daily work.DISCUSSION:The interviews generated a detailed picture of the different diagnostic and therapeutic pathways used by respondents for uncomplicated UTI. Overall, they predominantly regarded both the study concept and the intervention components as feasible. Although the study population is small and not representative, some of the results seem to be transferable to other regions in Germany.CONCLUSION:A research question relating to their daily routine can increase participation of primary care physicians in (intervention) studies. Starting the process evaluation before the intervention seems to be reasonable since the results will be integrated into the design of the intervention. The method of data extraction from practice software by practice teams seems to be promising.

Das Kompetenzzentrum Weiterbildung Allgemeinmedizin Bayern hat 2019 ein Eins-zu-eins-Mentoring für Ärztinnen und Ärzte in Weiterbildung eingeführt. Hierfür wurden Mentorinnen und Mentoren rekrutiert und geschult. Thema war neben „Feedback geben“ der „Umgang mit entscheidungskritischen Situationen im hausärztlichen Alltag“. Dieser Artikel beschreibt Aufbau, Inhalt und Evaluationsergebnisse der Schulungen. Die Schulungen wurden an vier bayerischen allgemeinmedizinischen Hochschulstandorten in Präsenz abgehalten und direkt im Anschluss schriftlich mithilfe von EvaSys® in anonymisierter Form evaluiert. Der Fragebogen wurde von der Leitung der AG Evaluation und Lehrqualifikation der LMU konzipiert und orientierte sich an Fragebögen der Lehre, ergänzt durch die besonderen Aspekte des Mentoringprogramms. Es wurden inhaltliche Aspekte und die Bewertung der gesamten Veranstaltung erfragt (6 geschlossene, 4 offene Fragen) und von zwei Autorinnen deskriptiv ausgewertet. Freitexte wurden thematisch geclustert und Haupt- und Unterkategorien gebildet. 2019 fanden vier Schulungen mit insgesamt 48 Mentorinnen und Mentoren statt, von 43 lagen Evaluationen vor. Die Mentorinnen und Mentoren sind mehrheitlich männlich, zwischen 50 und 60 Jahre alt und in ländlichen Praxen tätig. Sowohl Format als auch Inhalt der Schulungen wurden sehr gut angenommen und positiv evaluiert. Über 90

The animal and the vegetative side of 15 embryos ofXenopus laevis were studied from the 5th cleavage to gastrulation by means of time-lapse cinematography. The duration of cleavage cycles, defined for the embryo as a whole as the period between the earliest blastomere divisions of one cycle to those of the next, varies quite a lot between individual embryos, both with respect to synchronous and lengthened cycles. Cycle lengthening may start at either cycle 10, 11 or 12. Cycle 13 deviates from the individual rhythm, and moreover its duration is inversely correlated with the period elapsing from the beginning of this cycle to the onset of gastrulation which occurs in cycles 14 or 15. In each cleavage cycle, the regional sequence of first blastomere divisions is visible on films as a “cleavage wave” runming over the animal cap. The direction of the waves varies in different embryos during the synchronous period but begins to change from cycle 10 onwards, resulting in a similar direction in most embryos prior to gastrulation: from the ventral/left to the dorsal/right half. This change reflects an asymmetry in the lengthening of the cycles in the animal cap: more dorsally than ventrally, and more on the right than on the left. The possible significance of the results for the timing of gastrulation and for the pattern of the future embryo is discussed.