Optimizing Antibiotic Prescribing for Acute Respiratory Tract Infections in German Primary Care: Results of the Regional Intervention Study CHANGE-3 and the Nested cRCT.

Within primary care, acute respiratory tract infections (ARTIs) are the most common reason for prescribing antibiotics. The aim of the CHANGE-3 study was to investigate how antibiotic prescribing for non-complicated ARTIs can be reduced to a reasonable level. The trial was conducted as a prospective study consisting of a regional public awareness intervention in two regions of Germany and a nested cluster randomised controlled trial (cRCT) of a complex implementation strategy. The study involved 114 primary care practices and comprised an intervention period of six winter months for the nested cRCT and two times six winter months for the regional intervention. The primary outcome was the percentage of antibiotic prescribing for ARTIs between baseline and the two following winter seasons. The regression analysis confirmed a general trend toward the restrained use of antibiotics in German primary care. This trend was found in both groups of the cRCT without significant differences between groups. At the same time, antibiotic prescribing was higher in routine care (with the public campaign only) than in both groups of the cRCT. With regard to secondary outcomes, in the nested cRCT, the prescribing of quinolones was reduced, and the proportion of guideline-recommended antibiotics increased.

Family Conferences to Facilitate Deprescribing in Older Outpatients With Frailty and With Polypharmacy: The COFRAIL Cluster Randomized Trial.

Importance: For older adults with frailty syndrome, reducing polypharmacy may have utility as a safety-promoting treatment option. Objective: To investigate the effects of family conferences on medication and clinical outcomes in community-dwelling older adults with frailty receiving polypharmacy. Design, Setting, and Participants: This cluster randomized clinical trial was conducted from April 30, 2019, to June 30, 221, at 110 primary care practices in Germany. The study included community-dwelling adults aged 70 years or older with frailty syndrome, daily use of at least 5 different medications, a life expectancy of at least 6 months, and no moderate or severe dementia. Interventions: General practitioners (GPs) in the intervention group received 3 training sessions on family conferences, a deprescribing guideline, and a toolkit with relevant nonpharmacologic interventions. Three GP-led family conferences for shared decision-making involving the participants and family caregivers and/or nursing services were subsequently held per patient at home over a period of 9 months. Patients in the control group received care as usual. Main Outcomes and Measures: The primary outcome was the number of hospitalizations within 12 months, as assessed by nurses during home visits or telephone interviews. Secondary outcomes included the number of medications, the number of European Union list of the number of potentially inappropriate medication (EU[7]-PIM) for older people, and geriatric assessment parameters. Both per-protocol and intention-to-treat analyses were conducted. Results: The baseline assessment included 521 individuals (356 women [68.3%]; mean [SD] age, 83.5 [6.17] years). The intention-to-treat analysis with 510 patients showed no significant difference in the adjusted mean (SD) number of hospitalizations between the intervention group (0.98 [1.72]) and the control group (0.99 [1.53]). In the per-protocol analysis including 385 individuals, the mean (SD) number of medications decreased from 8.98 (3.56) to 8.11 (3.21) at 6 months and to 8.49 (3.63) at 12 months in the intervention group and from 9.24 (3.44) to 9.32 (3.59) at 6 months and to 9.16 (3.42) at 12 months in the control group, with a statistically significant difference at 6 months in the mixed-effect Poisson regression model (P = .001). After 6 months, the mean (SD) number of EU(7)-PIMs was significantly lower in the intervention group (1.30 [1.05]) than in the control group (1.71 [1.25]; P = .04). There was no significant difference in the mean number of EU(7)-PIMs after 12 months. Conclusions and Relevance: In this cluster randomized clinical trial with older adults taking 5 or more medications, the intervention consisting of GP-led family conferences did not achieve sustainable effects in reducing the number of hospitalizations or the number of medications and EU(7)-PIMs after 12 months. Trial Registration: German Clinical Trials Register: DRKS00015055.

[Acute respiratory tract infections and antibiotic prescriptions: What are patients' expectations?] / Akute Atemwegsinfekte und Antibiotikaverordnungen: Welche Erwartungen haben Patient*innen?

INTRODUCTION: The use of antibiotics in human medicine is partly responsible for the global increase in antibiotic resistance. Significant reductions in antibiotic prescribing were realised through educational campaigns, communication training and prescribing feedback. Based on data from the cluster-randomised CHANGE-3 trial, the present analysis focuses on the question of patient expectations for an antibiotic in acute respiratory infections. METHODS: 106 of 114 General Practitioner (GP) practices in Baden-Württemberg and Mecklenburg-Western Pomerania took part in the study. 4736 patients who visited the practices with acute respiratory infections from October 2018 to May 2019 filled out a questionnaire after the doctor's consultation. The analysis was descriptive. RESULTS: 16.7 % of patients with acute respiratory infections reported receiving antibiotics from their GP. 13.3 % of patients had hoped for an antibiotic and 5.5 % stated that they had asked their GP for an antibiotic prescription. The lowest prescription rate for antibiotics was reported by patients who had received a diagnosis of influenza from their GP. With specific diagnoses differentiated from uncomplicated respiratory tract infection, an increase in both the number of antibiotics hoped for and the number of antibiotics prescribed was observed. DISCUSSION: Patients still receive antibiotics more often than they actually hope for. On the part of GPs, prescriptions may still be written because of perceived pressure from patients, but this is not reflected in patient expectations. In addition to dealing openly with patients' expectations, strengthening patients' health literacy, mindful doctor-patient communication and offered opportunities for re-presentation in the case of specific diagnoses could further reduce the perceived pressure on GPs.

Challenges and opportunities for general practice specific CME in Europe - a narrative review of seven countries.

BACKGROUND: Several changes have led to general practitioners (GPs) working in a more differentiated setting today and being supported by other health professions. As practice changes, primary care specific continuing medical education (CME) may also need to adapt. By comparing different primary care specific CME approaches for GPs across Europe, we aim at identifying challenges and opportunities for future development. METHODS: Narrative review assessing, analysing and comparing CME programs for general practitioners across different north-western European countries (UK, Norway, the Netherlands, Belgium (Flanders), Germany, Switzerland, and France). Templates containing detailed items across seven dimensions of country-specific CME were developed and used. These dimensions are role of primary care within the health system, legal regulations regarding CME, published aims of CME, actual content of CME, operationalisation, funding and sponsorship, and evaluation. RESULTS: General practice specific CME in the countries under consideration are presented and comparatively analysed based on the dimensions defined in advance. This shows that each of the countries examined has different strengths and weaknesses. A clear pioneer cannot be identified. Nevertheless, numerous impulses for optimising future GP training systems can be derived from the examples presented. CONCLUSIONS: Independent of country specific CME programs several fields of potential action were identified: the development of curriculum objectives for GPs, the promotion of innovative teaching and learning formats, the use of synergies in specialist GP training and CME, the creation of accessible yet comprehensive learning platforms, the establishment of clear rules for sponsorship, the development of new financing models, the promotion of fair competition between CME providers, and scientifically based evaluation.

Audiovisual teleconsultation for patients with epilepsy in primary care in rural Germany: a pilot study on feasibility and acceptance.

BACKGROUND: In rural areas, epilepsy patients have limited access to specialist secondary care. Substantial travel and waiting times of several hours are common. Communication between general practitioners (GP) and specialist epileptologists regarding diagnosis and treatment is further complicated by the high workload on both sides and the different prioritisation of treatment goals. This study aims to investigate the feasibility of an interprofessional audiovisual patient-doctor teleconsultation, and its acceptance in clinical practice in patients with epilepsy in a rural region in Germany. METHOD: Ten patients participated in telemedicine consultations in their GP practice. The practice was located in a sparsely populated region of Mecklenburg-Western Pomerania, and was equipped with technical equipment specifically procured for the project. An explorative qualitative interview was conducted with all participants. We based this paper on the consolidated criteria for reporting qualitative research (COREQ). RESULTS: Despite initial uncertainties on the patients' side regarding the consultation setting, all participants found the teleconsultation helpful. Some patients were initially intimidated and felt slightly overwhelmed by the attention provided and the technology used (multiple HD cameras, large high-resolution screens). However, during the consultation, they felt supported by their GP and were satisfied that their needs were addressed in an appropriate and timely manner. The hardware used was not felt to be a nuisance or to interfere with the conversation between doctor and patient. Patients also appreciated the time saved and the organisational convenience compared to a visit to a university outpatient clinic. Most consultations led to therapeutic consequences. Some patients seemed to benefit particularly, for example those who needed a medication change. CONCLUSION: This pilot study provides first evidence that teleconsultations between patients, specialists, and GPs are possible in rural areas. Interprofessional collaboration between GPs and epileptologists can improve the care of patients with epilepsy. Further research should investigate the effectiveness and efficiency of interprofessional telemedicine consultations for epilepsy and other conditions.

Development of a deprescribing manual for frail older people for use in the COFRAIL study and in primary care.

Introduction: Many older adults are affected by multimorbidity and subsequent polypharmacy which is associated with adverse outcomes. This is especially relevant for frail older patients. Polypharmacy may be reduced via deprescribing. As part of the complex intervention in the COFRAIL study, we developed a deprescribing manual to be used by general practitioners (GPs) in family conferences, in which GPs, patients and caregivers jointly discuss treatments. Methods: We selected indications with a high prevalence in older adults in primary care (e.g. diabetes mellitus, hypertension) and conducted a literature search to identify deprescribing criteria for these indications. We additionally reviewed clinical practice guidelines. Based on the extracted information, we created a deprescribing manual which was then piloted in an expert workshop and in family conferences with volunteer patients according to the inclusion and exclusion criteria of the study protocol. Results: Initially, 13 indications/topics were selected. The literature search identified deprescribing guides, reviews and clinical trials as well as lists of potentially inappropriate medication and systematic reviews on the risk and benefits of specific drugs and drug classes in older patients. After piloting and revisions, the deprescribing manual now covers 11 indications/topics. In each chapter, patient- and medication-related deprescribing criteria, monitoring and communication strategies, and information about concerns related to the use of specific drugs in older patients are provided. Discussion: We found varying deprescribing strategies in the literature, which we consolidated in our deprescribing manual. Whether this approach leads to successful deprescribing in family conferences is being investigated in the cluster-randomised controlled COFRAIL study. Plain Language Summary: Development of a manual to help doctors to identify which medications can be withdrawn Many older adults suffer from chronic diseases and take multiple medications concurrently. This can lead to side effects and other undesired events. We developed a manual to help doctors identify which medications can be withdrawn, so that they can discuss this with their patients. This manual was used in the COFRAIL study where doctors, patients and caregivers met in family conferences to discuss their preferences and decide together how future treatments should be handled. The manual contains information on common medications, symptoms and diseases in older patients such as diabetes and high blood pressure. Before the manual was used in the study, it was tested by volunteer patients and their doctors and caregivers to make sure that it is user-friendly.

[Acute respiratory tract infections and antibiotic prescriptions: What are patients' expectations?] / Akute Atemwegsinfekte und Antibiotika-Verordnungen: Welche Erwartungen haben Patient*innen?

INTRODUCTION: The use of antibiotics in human medicine is partly responsible for the global increase in antibiotic resistance. Significant reductions in antibiotic prescribing were realised through educational campaigns, communication training and prescribing feedback. Based on data from the cluster-randomised CHANGE-3 trial, the present analysis focuses on the question of patient expectations for an antibiotic in acute respiratory infections. METHODS: 106 of 114 General Practitioner (GP) practices in Baden-Württemberg and Mecklenburg-Western Pomerania took part in the study. 4736 patients who visited the practices with acute respiratory infections from October 2018 to May 2019 filled out a questionnaire after the doctor's consultation. The analysis was descriptive. RESULTS: 16.7 % of patients with acute respiratory infections reported receiving antibiotics from their GP. 13.3 % of patients had hoped for an antibiotic and 5.5 % stated that they had asked their GP for an antibiotic prescription. The lowest prescription rate for antibiotics was reported by patients who had received a diagnosis of influenza from their GP. With specific diagnoses differentiated from uncomplicated respiratory tract infection, an increase in both the number of antibiotics hoped for and the number of antibiotics prescribed was observed. DISCUSSION: Patients still receive antibiotics more often than they actually hope for. On the part of GPs, prescriptions may still be written because of perceived pressure from patients, but this is not reflected in patient expectations. In addition to dealing openly with patients' expectations, strengthening patients' health literacy, mindful doctor-patient communication and offered opportunities for re-presentation in the case of specific diagnoses could further reduce the perceived pressure on GPs.

Shared decision making and patient-centeredness for patients with poorly controlled type 2 diabetes mellitus in primary care-results of the cluster-randomised controlled DEBATE trial.

BACKGROUND: We investigate whether an educational intervention of GPs increases patient-centeredness and perceived shared decision making in the treatment of patients with poorly controlled type 2 diabetes mellitus? METHODS: We performed a cluster-randomized controlled trial in German primary care. Patients with type 2 diabetes mellitus defined as HbA1c levels ≥ 8.0% (64 mmol/mol) at the time of recruitment (n = 833) from general practitioners (n = 108) were included. Outcome measures included subjective shared decision making (SDM-Q-9; scale from 0 to 45 (high)) and patient-centeredness (PACIC-D; scale from 1 to 5 (high)) as secondary outcomes. Data collection was performed before intervention (baseline, T0), at 6 months (T1), at 12 months (T2), at 18 months (T3), and at 24 months (T4) after baseline. RESULTS: Subjective shared decision making decreased in both groups during the course of the study (intervention group: -3.17 between T0 and T4 (95% CI: -4.66, -1.69; p < 0.0001) control group: -2.80 (95% CI: -4.30, -1.30; p = 0.0003)). There were no significant differences between the two groups (-0.37; 95% CI: -2.20, 1.45; p = 0.6847). The intervention's impact on patient-centeredness was minor. Values increased in both groups, but the increase was not statistically significant, nor was the difference between the groups. CONCLUSIONS: The intervention did not increase patient perceived subjective shared decision making and patient-centeredness in the intervention group as compared to the control group. Effects in both groups might be partially attributed to the Hawthorne-effect. Future trials should focus on patient-based intervention elements to investigate effects on shared decision making and patient-centeredness. TRIAL REGISTRATION: The trial was registered on March 10th, 2011 at ISRCTN registry under the reference ISRCTN70713571 .

Hospitalization for Acute Respiratory Tract Infection in a Low-Antibiotic-Prescribing Setting: Cross-Sectional Data from General Practice.

BACKGROUND: Acute respiratory tract infections (ARTI) are the main cause of inappropriate antibiotic prescribing. To date, there is limited evidence concerning whether low levels of antibiotic prescribing may impact patient safety. We investigate whether antibiotic prescribing for patients seeking primary care for ARTI correlates with the odds for hospitalization. METHODS: Analysis of patient baseline data (n = 3669) within a cluster-randomized controlled trial. Adult patients suffering from ARTI in German primary care are included. The main outcome measure is acute hospitalization for respiratory infection and for any acute disease from 0 to 42 days after initial consultation. RESULTS: Neither the antibiotic status of individual patients (OR 0.91; 95% CI: 0.49 to 1.69; p-value = 0.769) nor the physician-specific antibiotic prescription rates for ARTI (OR 1.22; 95% CI: 1.00 to 1.49; p-value = 0.054) had a significant effect on hospitalization. The following factors increased the odds for hospitalization: patient's age, the ARTI being defined as lower respiratory tract infections (such as bronchitis) by the physician, the physician's perception of disease severity, and being cared for within group practices (versus treated in single-handed practices). CONCLUSIONS: In a low-antibiotic-prescribing primary care setting such as Germany, lack of treatment with antibiotics for ARTI did not result in higher odds for hospitalization in an adult population.

Optimizing Antibiotic Prescribing for Acute Respiratory Tract Infection in German Primary Care: Study Protocol for Evaluation of the RESIST Program.

BACKGROUND: The emergence and increased spread of microbial resistance is a major challenge to all health care systems worldwide. In primary care, acute respiratory tract infection (ARTI) is the health condition most strongly related to antibiotic overuse. OBJECTIVE: The RESIST program aims at optimizing antibiotic prescribing for ARTI in German primary care. By completing a problem-orientated online training course, physicians are motivated and empowered to utilize patient-centered doctor-patient communication strategies, including shared decision making, in the treatment of patients with ARTI. METHODS: RESIST will be evaluated in the form of a nonrandomized controlled trial. Approximately 3000 physicians of 8 (out of 16) German federal states can participate in the program. Patient and physician data are retrieved from routine health care data. Physicians not participating in the program serve as controls, either among the 8 participating regional Associations of Statutory Health Insurance Physicians (control group 1) or among the remaining associations not participating in RESIST (control group 2). Antibiotic prescription rates before the intervention (T0: 2016, 1st and 2nd quarters of 2017) and after the intervention (T1: 3rd quarter of 2017 until 1st quarter of 2019) will be compared. The primary outcome measure is the overall antibiotic prescription rate for all patients insured with German statutory health insurance before and after provision of the online course. The secondary outcome is the antibiotic prescription rate for coded ARTI before and after the intervention. RESULTS: RESIST is publicly funded by the Innovations funds of the Federal Joint Committee in Germany and was approved in December 2016. Recruitment of physicians is now completed, and a total of 2460 physicians participated in the intervention. Data analysis started in February 2020. CONCLUSIONS: With approximately 3000 physicians participating in the program, RESIST is among the largest real-world interventions aiming at reducing inadequate antibiotic prescribing for ARTI in primary care. Long-term follow up of up to 21 months will allow for investigating the sustainability of the intervention. TRIAL REGISTRATION: ISRCTN Registry ISRCTN13934505; http://www.isrctn.com/ISRCTN13934505. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/18648.

[Approaches of general practitioners and patients to multimorbidity. Qualitative study]. / Multimorbidität aus Hausarzt- und Patientensicht. Qualitative Studie.

BACKGROUND: For general practioners (GP) the treatment of patients suffering from multimorbidity is an everyday challenge. For these patients guidelines which each focus on a specific chronic disease cannot be applied comprehensively and equally; therefore, it is necessary to prioritize. OBJECTIVE: Given this situation the study aimed at analyzing how GPs and patients deal with this challenge and what their priorities are. MATERIAL AND METHODS: Narrative interviews were conducted with 9 GPs and 19 of their multimorbid patients. The data were analyzed by means of content analysis. RESULTS: The majority of interviewed patients felt well or very well cared for by their GPs; however, GPs and multimorbid patients often had relatively different priorities. Whereas GPs mostly focused on the management of diseases that could lead to life-threatening situations, patients put an emphasis on maintaining autonomy and a social life. CONCLUSION: The results of this study suggest that there is room for development in the way GPs and multimorbid patients communicate with each other, particularly as far as shared priority setting is concerned.

Converting habits of antibiotic prescribing for respiratory tract infections in German primary care--the cluster-randomized controlled CHANGE-2 trial.

BACKGROUND: With an average prescription rate of 50%, in German primary care antibiotics are still too frequently prescribed for respiratory tract infections. The over-prescription of antibiotics is often explained by perceived patient pressure and fears of a complicated disease progression. The CHANGE-2 trial will test the effectiveness of two interventions to reduce the rate of inappropriate antibiotic prescriptions for adults and children suffering from respiratory tract infections in German primary care. METHODS/DESIGN: The study is a three-arm cluster-randomized controlled trial that measures antibiotic prescription rates over three successive winter periods and reverts to administrative data of the German statutory health insurance company AOK. More than 30,000 patients in two regions of Germany, who visit their general practitioner or pediatrician for respiratory tract infections will be included. Interventions are: A) communication training for general practitioners and pediatricians and B) intervention A plus point-of-care testing. Both interventions are tested against usual care. Outcome measure is the physicians' antibiotic prescription rate for respiratory tract infections derived from data of the health insurance company AOK. Secondary outcomes include reconsultation rate, complications, and hospital admissions. DISCUSSION: Major aim of the study is to improve the process of decision-making and to ensure that patients who are likely to benefit from antibiotics are treated accordingly. Our approach is simple to implement and might be used rapidly among general practitioners and pediatricians. We expect the results of this trial to have major impact on antibiotic prescription strategies and practices in Germany, both among general practitioners and pediatricians. TRIAL REGISTRATION: The study is registered at the Current Controlled Trials Ltd (ISRCTN01559032).

Endothelial NOS is required for SDF-1alpha/CXCR4-mediated peripheral endothelial adhesion of c-kit+ bone marrow stem cells.

In the era of intravascular approaches for regenerative cell therapy, the underlying mechanisms of stem cell migration to non-marrow tissue have not been clarified. We hypothesized that next to a local inflammatory response implying adhesion molecule expression, endothelial nitric oxide synthase (eNOS)-dependent signaling is required for stromal- cell-derived factor-1 alpha (SDF-1alpha)-induced adhesion of c-kit+ cells to the vascular endothelium. SDF-1alpha/tumor necrosis factor-alpha (TNF-alpha)-induced c-kit+-cell shape change and migration capacity was studied in vitro using immunohistochemistry and Boyden chamber assays. In vivo interaction of c-kit+ cells from bone marrow with the endothelium in response to SDF-1alpha/TNF-alpha stimulation was visualized in the cremaster muscle microcirculation of wild-type (WT) and eNOS (-/-) mice using intravital fluorescence microscopy. In addition, NOS activity was inhibited with N-nitro-L-arginine-methylester-hydrochloride in WT mice. To reveal c-kit+-specific adhesion behavior, endogenous leukocytes (EL) and c-kit+ cells from peripheral blood served as control. Moreover, intercellular adhesion molecule-1 (ICAM-1) and CXCR4 were blocked systemically to determine their role in inflammation-related c-kit+-cell adhesion. In vitro, SDF-1alpha enhanced c-kit+-cell migration. In vivo, SDF-1alpha alone triggered endothelial rolling-not firm adherence-of c-kit+ cells in WT mice. While TNF-alpha alone had little effect on adhesion of c-kit+ cells, it induced maximum endothelial EL adherence. However, after combined treatment with SDF-1alpha+TNF-alpha, endothelial adhesion of c-kit+ cells increased independent of their origin, while EL adhesion was not further incremented. Systemic treatment with anti-ICAM-1 and anti-CXCR4-monoclonal antibody completely abolished endothelial c-kit+-cell adhesion. In N-nitro-L-arginine-methylester-hydrochloride-treated WT mice as well as in eNOS (-/-) mice, firm endothelial adhesion of c-kit+ cells was entirely abrogated, while EL adhesion was significantly increased. The chemokine SDF-1alpha mediates firm adhesion c-kit+ cells only in the presence of TNF-alpha stimulation via an ICAM-1- and CXCR4-dependent mechanism. The presence of eNOS appears to be a crucial and specific factor for firm c-kit+-cell adhesion to the vascular endothelium.