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"Plate, Andreas"
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The chemokine CXCL13 is a key regulator of B cell recruitment to the cerebrospinal fluid in acute Lyme neuroborreliosis
2009
Background
The chemokine CXCL13 is known to dictate homing and motility of B cells in lymphoid tissue and has been implicated in the formation of ectopic lymphoid tissue in chronic inflammation. Whether it influences B cell trafficking during acute infection, is largely unclear. In previous studies, we showed that (I) CXCL13 levels are markedly increased in the B cell-rich cerebrospinal fluid (CSF) of patients with acute Lyme neuroborreliosis (LNB), and (II) CXCL13 is released by monocytes upon recognition of borrelial outer surface proteins by Toll-like receptor 2. Here, we assessed the role of CXCL13 - in comparison to other chemokines - in the recruitment of B cells to the CSF of patients with acute LNB.
Methods
Measurement of chemokines was done by ELISA. B cells were isolated from whole blood using magnetic cell separation (MACS). For migration experiments, a modified Boyden chamber assay was used and the migrated B cells were further analysed by FACS. The migration was inhibited either by preincubation of the CSF samples with neutralizing antibodies, heating to 60°C, removal of proteins >3 kDa, or by pre-treatment of the B cells with pertussis toxin. The principal statistical tests used were one-way analysis of variance and Bonferroni test (chemokine measurements) as well as paired Student's t-test (migration experiments).
Results
Measurements of chemokine levels revealed an increase in three of the four known major B cell chemoattractants CXCL13, CCL19 and CXCL12 in LNB CSF. The CXCL13 CSF:serum ratio, as a measure of the chemotactic gradient, was substantially higher than that of CCL19 and CXCL12. Moreover, the chemotactic activity of LNB CSF was reduced up to 56% after preincubation with a neutralizing CXCL13 antibody, while combined preincubation with antibodies against CXCL13, CCL19, and CXCL12 did not lead to further reduction. Since treatment with pertussis toxin, heating to 60°C, and removal of proteins >3 kDa abrogated the chemotactic activity, further not yet identified chemokines seem to be involved in B cell recruitment to LNB CSF.
Conclusion
Combined, our study suggests a key role of CXCL13 in B cell migration to sites of infection as shown here for the CSF of LNB patients.
Journal Article
Shared decision making for men facing prostate cancer treatment: a systematic review of randomized controlled trials
by
Neuner-Jehle, Stefan
,
Plate, Andreas
,
Senn, Oliver
in
Bibliographies
,
Cancer
,
Cancer treatment
2019
To synthesize the empirical evidence on the effectiveness of shared decision making (SDM) compared to usual care for prostate cancer (PC) treatment.
A systematic review of academic (MEDLINE, EMBASE, Cochrane Library, CINHAL, PsychINFO, and Scopus) and grey (clinicaltrials.gov, WHO trial search, meta-Register ISRCTN, Google Scholar, opengrey, and ohri.ca) literature, also identified from contacting authors and hand-searching bibliographies. We included randomized controlled trials (RCTs): 1) comparing SDM to usual care for decisions about PC treatment, 2) conducted in primary or specialized care, 3) fulfilling the key SDM features, and 4) reporting quantitative outcome data. Four RCTs from Canada (n=3) and the USA were included and comprised 1,065 randomized men, most (89.8%) of whom were in PC stage T1-T2. The studies reported 24 outcome measures. In 62.5% study estimates, SDM was similar to usual care at improving patient satisfaction and mood, and at reducing decisional conflict and decisional regret. In 37.5% study estimates, SDM significantly improved knowledge, perception of being informed and patient-perceived quality of life (QoL) at four weeks. There was a dearth of outcome data, particularly on the adherence to treatment and on patient-important and clinically relevant health outcomes such as symptoms and mortality.
SDM may positively influence men's knowledge and may have a positive but short-term effect on patient-perceived QoL. The (long-term) effects of SDM on patient-related outcomes for decisions about PC treatment are unclear. Future research needs consensus about the interventions and outcomes needed to evaluate SDM and should address the absence of evidence on health outcomes.
Journal Article
Treatment of urinary tract infections in Swiss primary care: quality and determinants of antibiotic prescribing
by
Risch, Martin
,
Stefania Di Gangi
,
Plate, Andreas
in
Antibiotics
,
Antimicrobial agents
,
Family physicians
2020
Background Urinary tract infections are one of the most common reasons for prescribing antibiotics in primary care. Current guidelines recommend fosfomycin, nitrofurantoin, or trimethoprim - sulfamethoxazol as empiric first line antimicrobial agents in uncomplicated infections. However, there is evidence that the use of fluoroquinolones, which are no longer recommended, is still inappropriate high. We determined antibiotic prescription patterns, quality and factors affecting antibiotic prescriptions in urinary tract infections in primary care in Switzerland. Methods From June 2017 to August 2018, we conducted a cross-sectional study in patients suffering from a urinary tract infection (UTI). Patient and general practitioners characteristics as well as antibiotic prescribing patterns were analysed. Results Antibiotic prescribing patterns in 1.352 consecutively recruited patients, treated in 163 practices could be analysed. In 950 (84.7%) patients with an uncomplicated UTI the prescriptions were according to current guidelines and therefore rated as appropriate. Fluoroquinolones were prescribed in 13.8% and therefore rated as inappropriate. In multivariable analysis, the age of the general practitioner was associated with increasing odds of prescribing a not guideline recommended antibiotic therapy. Conclusions We found a high degree of guideline conform antibiotic prescriptions in patients with an uncomplicated urinary tract infection in primary care in Switzerland. However, there is still a substantial use of fluoroquinolones in empiric therapy.
Journal Article
Patient leaflets on respiratory tract infections did not improve shared decision making and antibiotic prescriptions in a low-prescriber setting
by
Neuner-Jehle, Stefan
,
Selby, Kevin
,
Pichierri, Giuseppe
in
692/699/1785
,
692/700/478
,
Antibiotics
2024
Patient information leaflets can reduce antibiotic prescription rates by improving knowledge and encouraging shared decision making (SDM) in patients with respiratory tract infections (RTI). The effect of these interventions in antibiotic low-prescriber settings is unknown. We conducted a pragmatic pre-/post interventional study between October 2022 and March 2023 in Swiss outpatient care. The intervention was the provision of patient leaflets informing about RTIs and antibiotics use. Main outcomes were the extent of SDM, antibiotic prescription rates, and patients’ awareness/knowledge about antibiotic use in RTIs. 408 patients participated in the pre-intervention period, and 315 patients in the post- intervention period. There was no difference in the extent of SDM (mean score (range 0–100): 65.86 vs. 64.65,
p
= 0.565), nor in antibiotic prescription rates (no prescription: 89.8% vs. 87.2%,
p
= 0.465) between the periods. Overall awareness/knowledge among patients with RTI was high and leaflets showed only a small effect on overall awareness/knowledge. In conclusion, in an antibiotic low-prescriber setting, patient information leaflets may improve knowledge, but may not affect treatment decisions nor antibiotic prescription rates for RTIs.
Journal Article
Point-of-Care C-Reactive Protein Testing to Reduce Antibiotic Prescribing for Respiratory Tract Infections in Primary Care: Systematic Review and Meta-Analysis of Randomised Controlled Trials
by
Coenen, Samuel
,
Neuner-Jehle, Stefan
,
Martínez-González, Nahara Anani
in
antibiotic prescribing
,
antibiotic stewardship
,
antibiotic use
2020
C-reactive protein (CRP) point-of-care testing (POCT) is increasingly being promoted to reduce diagnostic uncertainty and enhance antibiotic stewardship. In primary care, respiratory tract infections (RTIs) are the most common reason for inappropriate antibiotic prescribing, which is a major driver for antibiotic resistance. We systematically reviewed the available evidence on the impact of CRP-POCT on antibiotic prescribing for RTIs in primary care. Thirteen moderate to high-quality studies comprising 9844 participants met our inclusion criteria. Meta-analyses showed that CRP-POCT significantly reduced immediate antibiotic prescribing at the index consultation compared with usual care (RR 0.79, 95%CI 0.70 to 0.90, p = 0.0003, I2 = 76%) but not during 28-day (n = 7) follow-up. The immediate effect was sustained at 12 months (n = 1). In children, CRP-POCT reduced antibiotic prescribing when CRP (cut-off) guidance was provided (n = 2). Meta-analyses showed significantly higher rates of re-consultation within 30 days (n = 8, 1 significant). Clinical recovery, resolution of symptoms, and hospital admissions were not significantly different between CRP-POCT and usual care. CRP-POCT can reduce immediate antibiotic prescribing for RTIs in primary care (number needed to (NNT) for benefit = 8) at the expense of increased re-consultations (NNT for harm = 27). The increase in re-consultations and longer-term effects of CRP-POCT need further evaluation. Overall, the benefits of CRP-POCT outweigh the potential harms (NNTnet = 11).
Journal Article
Comprehensibility of Fact Sheets Addressing Benefits and Risks of Preventive Interventions: A Cross-Sectional Evaluation Study
2026
Preventive tests and procedures (PTPs) help to reduce disease burden. However, patient expectations often differ from current guidelines, resulting in overuse or underuse of PTPs. Shared decision making can bridge this gap but requires clear, evidence-based information. This study aimed to develop and conduct an initial evaluation of prototype fact sheets designed to support informed decisions about PTPs.
We selected 11 PTPs based on their potential for over- or underuse. For each, we developed a fact sheet following guideline recommendations. These summarised key benefits, risks and relevance using verbal, numerical and graphical formats. User experience and comprehensibility were assessed through a survey among a university population. Participants rated comprehensibility, content and design on a 5-point scale. Approval was defined as the proportion of 'very good' or 'rather good' ratings. Participants giving poor ratings were invited to provide free-text comments. Subgroup analyses were performed by age and educational level.
A total of 2,082 individuals answered all relevant questions to fact sheets. The median fact sheet approval score was 77% (interquartile range: 55%, 91%). Six of the 11 fact sheets received an approval of greater than 80% for comprehensibility in general. Lower approval was reported for risk descriptions, usefulness in doctor-patient conversations and visuals. Cancer screening sheets scored the lowest. Subgroup analyses showed lower approval in younger age groups and among individuals with higher levels of education.
Initial user testing of the fact sheets showed generally positive ratings regarding comprehensibility and user experience. However, the presentation of specific risks and the use of visuals needed to be adapted, especially for cancer-related topics. The findings highlighted the importance of tailoring informational materials to effectively support shared decision making.
Journal Article
Assessment of Human Papillomavirus Vaccination in Primary Care Among Swiss University Students
by
Senn, Oliver
,
Rosemann, Thomas
,
Plate, Andreas
in
Human papillomavirus
,
Immunization
,
Primary care
2023
Importance Human papillomavirus vaccination coverage rates lie below desired thresholds in Switzerland. Because general practitioners are the main contact for the relatively rare health issues of many Swiss young adults, primary care offers an important opportunity to provide catch-up human papillomavirus vaccination. Objective To examine the knowledge, experiences, and attitudes of Swiss university students in the context of receiving human papillomavirus vaccination during primary care visits. Design, Setting, and Participants This self-administered, cross-sectional, web-based survey study was conducted among students of 3 universities and 1 educational institution for health professions in the Swiss Canton of Zurich. Specific questions about human papillomavirus vaccination experience were directed to respondents who had received at least 1 dose administered by a general practitioner. Responses were collected during 12-week intervals between November 11, 2020, and April 7, 2021, and data were analyzed from August 3 to August 30, 2022. Main Outcomes and Measures The primary outcome was whether human papillomavirus vaccination had been administered on the patient’s or the general practitioner’s initiative. Results The responses of 5524 participants (median [IQR] age, 23 [21-25] years; 3878 women [70.2%]) were analyzed. The survey completion rate was 90.9% (5524 of 6076 students who consented to participate). A total of 2029 respondents (1792 women [46.2%] and 237 men [14.6%]) reported having received at least 1 human papillomavirus vaccination dose, of whom 740 (36.5%) had received at least 1 dose administered by a general practitioner. Among these, 190 respondents (25.7%) reported that vaccine administration had occurred on their request rather than on their general practitioner’s initiative. Among all respondents, 4778 (86.5%) wanted to obtain more information about human papillomavirus vaccination at a general practitioner’s office, and 2569 (55.3%) rated acute consultations in general practice as inappropriate for addressing human papillomavirus vaccination. Conclusions and Relevance The findings of this survey study of Swiss university students suggest that primary care shows a high potential for increasing human papillomavirus vaccination coverage rates in Switzerland. However, there was room for improvement in the proactivity of general practitioners, especially with men, and in the attitudes of students toward the appropriateness of acute consultations in general practice for addressing human papillomavirus vaccination.
Journal Article
The effects of shared decision-making compared to usual care for prostate cancer screening decisions: a systematic review and meta-analysis
by
Neuner-Jehle, Stefan
,
Plate, Andreas
,
Rosemann, Thomas
in
Biomedical and Life Sciences
,
Biomedicine
,
Cancer Research
2018
Background
Shared decision-making (SDM) is recommended for men facing prostate cancer (PC) screening decisions. We synthesize the evidence on the comparative effectiveness of SDM with usual care.
Methods
We searched academic and grey literature databases, and other sources for primary randomised controlled trials (RCTs) published in English comparing SDM to usual care and conducted in primary and specialised care. We assessed the individual study risk of bias, and calculated the study-specific and pooled relative risks (RR) or standardised mean differences (SMD) [with 95% confidence intervals (CI)] to perform random-effects meta-analyses for SDM-related and patient outcomes.
Results
Four RCTs comparing SDM to usual care, involving 1760 men, were included. SDM improved knowledge (SMD 0.23, 95%CI 0.02 to 0.43; 2 RCTs), but was not different to usual care in reducing either patient participation in prostate-specific antigen (PSA) testing (RR 1.03, 95%CI 0.90 to 1.19; 2 RCTs) or decisional conflict (SMD -0.04, 95%CI -0.23 to 0.15; SMD -0.05, 95%CI -0.24 to 0.14; 2 RCTs). Individual trial estimates (46.7%) also suggest that SDM may reduce or neutralise physicians’ tendency for PSA screening, and may improve the accuracy of patients’ perception of lifetime-risks and men’s views towards screening. There was no evidence on the effects of SDM on health outcomes. The studies represent various interventions and outcomes and are prone to risk of bias.
Conclusions
There is currently insufficient evidence to support a clear association of SDM on patient- and SDM-related outcomes for decisions about PSA testing. Further research needs to assess the clinical effectiveness of SDM using well-defined SDM interventions and outcomes. It should address the absence of evidence, particularly on health outcomes.
Journal Article
Family Medicine Practice as Learning Environment: A Medical Student Evaluation in Switzerland
2024
Improving the quality of teaching placements in family medicine practice (FMP) could help to address the shortage of primary care physicians. This study aims to investigate students' evaluations of first-exposure FMP placements, to identify clusters of FMPs that might need to improve their placement quality, and to analyze students' perceptions of the FMP as a learning environment.
The design was a cross-sectional survey study, including all fourth-year undergraduate medical students at the University of Zurich, Switzerland, who completed a mandatory placement in FMP during 2019-2022. The placements consisted of individual teaching and training in the same FMP for 8 half days within an academic year. The primary outcome was the student Likert scale rating of the 14 key questions as indicators of teaching placement quality. Based on these indicators, cluster analysis was used to identify groups of FMPs with the potential for quality improvement. A framework analysis was used to analyze the students' perceptions.
A total of 713 students (response rate 81%) and 249 FMPs (median [interquartile range]: 2 [1,4] students per FMP) were included. Overall, 86% of the students were satisfied with the placement, and 95% reported that the placement gave them realistic insight into FMP work. A cluster of 25 (10%) FMPs that may improve placement quality was identified. Students most liked the opportunity to gain FMP skills, insight into FMP work, and establishment of patient relationships.
Our study described students' experiences with FMP and a method for teaching evaluation to identify FMPs that may benefit from interventions to improve their learning environment. This could upgrade the medical education offered and increase the interest in family medicine as a response to the shortage of primary care physicians.
Journal Article
Awareness, Attitudes and Clinical Practices Regarding Human Papillomavirus Vaccination among General Practitioners and Pediatricians in Switzerland
2021
In Switzerland, the human papillomavirus vaccination (HPVv) coverage rate lies below a desirable threshold. General practitioners (GPs) and pediatricians have been recognized as important providers of the HPVv, but there is little known about their self-attributed role and its relationship with their actual HPVv behavior. Therefore, the objective of this study was to explore the awareness, attitudes, and clinical practices of Swiss GPs and pediatricians concerning HPVv by means of a web-based questionnaire. We analyzed the responses of 422 physicians (72% GPs, 28% pediatricians). A substantial proportion of respondents considered the HPVv “absolutely essential” (54.2% of pediatricians, 30.6% of GPs). GPs indicated spending more time and effort on HPVv counseling for female rather than male patients more often compared to pediatricians (44.0% versus 13.9%, p < 0.001). The weekly number of patients aged 18–26 years seen in practice (p = 0.002) and whether the HPVv was deemed “absolutely essential” (adjusted odds ratio 2.39, 95% confidence interval 1.12–5.08) were factors associated with GPs administering HPVv in their practice. Shortcomings in terms of awareness, effort in the identification of potential vaccination candidates, and the role of male patients were revealed. By addressing these gaps, Swiss primary care providers could contribute to an increase in the national HPVv coverage rate.
Journal Article