REDuction of Antibiotic RESistance (REDARES) in urinary tract infections using treatments according to national clinical guidelines: study protocol for a pragmatic randomized controlled trial with a multimodal intervention in primary care.

BACKGROUND: Urinary tract infections (UTIs) are a common cause of prescribing antibiotics in family medicine. In Germany, about 40% of UTI-related prescriptions are second-line antibiotics, which contributes to emerging resistance rates. To achieve a change in the prescribing behaviour among family physicians (FPs), this trial aims to implement the guideline recommendations in German family medicine. METHODS/DESIGN: In a randomized controlled trial, a multimodal intervention will be developed and tested in family practices in four regions across Germany. The intervention will consist of three elements: information on guideline recommendations, information on regional resistance and feedback of prescribing behaviour for FPs on a quarterly basis. The effect of the intervention will be compared to usual practice. The primary endpoint is the absolute difference in the mean of prescribing rates of second-line antibiotics among the intervention and the control group after 12 months. To detect a 10% absolute difference in the prescribing rate after one year, with a significance level of 5% and a power of 86%, a sample size of 57 practices per group will be needed. Assuming a dropout rate of 10%, an overall number of 128 practices will be required. The accompanying process evaluation will provide information on feasibility and acceptance of the intervention. DISCUSSION: If proven effective and feasible, the components of the intervention can improve adherence to antibiotic prescribing guidelines and contribute to antimicrobial stewardship in ambulatory care.  Trial registration DRKS, DRKS00020389, Registered 30 January 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020389 .

Prednisolone Versus Colchicine for Acute Gout in Primary Care: statistical analysis plan for the pragmatic, multicenter, randomized, and double-blinded COPAGO non-inferiority trial.

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).

Prednisolone Versus Colchicine for Acute Gout in Primary Care (COPAGO): protocol for a two-arm multicentre, pragmatic, prospective, randomized, double-blind, controlled clinical trial of prednisolone and colchicine for non-inferiority with a parallel group design.

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.

Effects of a multimodal intervention in primary care to reduce second line antibiotic prescriptions for urinary tract infections in women: parallel, cluster randomised, controlled trial.

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.

GPs' Perspective on a Multimodal Intervention to Enhance Guideline-Adherence in Uncomplicated Urinary Tract Infections: A Qualitative Process Evaluation of the Multicentric RedAres Cluster-Randomised Controlled Trial.

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.

[The general practitioner perspective of a multimodal intervention for the adequate use of antibiotics in urinary tract infection - a qualitative interview study]. / Hausärztliche Perspektiven auf eine multimodale Intervention zum adäquaten Einsatz von Antibiotika beim Harnwegsinfekt ­ eine qualitative Interviewstudie.

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.

[Structured Individual Mentoring as Part of Continuing Education in Family Medicine in Bavaria - a Multicenter Evaluation]. / Strukturiertes Einzelmentoring im Rahmen der Weiterbildung Allgemeinmedizin in Bayern ­ eine multizentrische Evaluation.

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.

Efficacy and safety of preemptive anti-CMV therapy with valganciclovir after kidney transplantation.

BACKGROUND: CMV infections still pose a potentially serious threat to kidney transplant recipients and have a significant impact on graft as well as patient survival. The antiviral agent valganciclovir (VGCV) has a greater bioavailability after oral administration than oral ganciclovir (GCV) and can be considered a substitute for GCV. The substance is approved in North America and Europe for anti-CMV prophylaxis after organ transplantation. In this pilot study, we examined if VGCV could also be administered in preemptive treatment of CMV infections. METHODS: Twenty-eight renal transplant recipients suffering from 32 asymptomatic episodes of CMV infection were treated with VGCV and followed up. CMV infection was diagnosed by routine controls of pp65-antigenemia in pre-defined intervals. All patients received sequential quadruple immunosuppression. VGCV was given for up to 12 wk in a dosage adapted to renal graft function. Efficacy and safety parameters were monitored for 16 wk. RESULTS: Twenty-seven episodes of CMV antigenemia, two patients progressing to CMV syndrome and three patients progressing to CMV disease were treated. Primary efficiency was 79%, Four patients relapsed and were treated with a second course resulting in serological recovery. Two patients did not respond to oral VCGV and were switched to another antiviral agent. Graft function remained stable during and after treatment. Serious side effects were seen in seven patients, four patients complained of diarrhea and gastrointestinal pain, three patients suffered from leucopenia, in one of these treatment had to be temporary paused. Fifty-nine percent of all episodes were treated in a completely ambulatory setting. CONCLUSIONS: VGCV can be considered as an option also for preemptive treatment of CMV infections after renal transplantation. The antiviral potency seems to be adequate, potential side effects are comparable with IV GCV. Because of the improved pharmacokinetics of VGCV the substance can be used to abbreviate or even completely avoid in-hospital care of CMV infections.