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Background Oseltamivir is usually not often prescribed (or reimbursed) for non-high-risk patients consulting for influenza-like-illness (ILI) in primary care in Europe. We aimed to evaluate the cost-effectiveness of adding oseltamivir to usual primary care in adults/adolescents (13 years +) and children with ILI during seasonal influenza epidemics, using data collected in an open-label, multi-season, randomised controlled trial of oseltamivir in 15 European countries. Methods Direct and indirect cost estimates were based on patient reported resource use and official country-specific unit costs. Health-Related Quality of Life was assessed by EQ-5D questionnaires. Costs and quality adjusted life-years (QALY) were bootstrapped (N = 10,000) to estimate incremental cost-effectiveness ratios (ICER), from both the healthcare payers’ and the societal perspectives, with uncertainty expressed through probabilistic sensitivity analysis and expected value for perfect information (EVPI) analysis. Additionally, scenario (self-reported spending), comorbidities subgroup and country-specific analyses were performed. Results The healthcare payers’ expected ICERs of oseltamivir were €22,459 per QALY gained in adults/adolescents and €13,001 in children. From the societal perspective, oseltamivir was cost-saving in adults/adolescents, but the ICER is €8,344 in children. Large uncertainties were observed in subgroups with comorbidities, especially for children. The expected ICERs and extent of decision uncertainty varied between countries (EVPI ranged €1–€35 per patient). Conclusion Adding oseltamivir to primary usual care in Europe is likely to be cost-effective for treating adults/adolescents and children with ILI from the healthcare payers’ perspective (if willingness-to-pay per QALY gained > €22,459) and cost-saving in adults/adolescents from a societal perspective.

Expectations of how theory, empirical material, and methods should be dealt with in academic writing has not always been explicitly communicated to students. Due to a heterogeneity in student populations enrolled in higher degree courses worldwide, diversity in academic writing practices has increased. This paper explores academic writing practices among a group of students with professional, vocational backgrounds and close relationships to practical knowledge. Twelve examination papers from fifteen students within a continuing education program at a Danish university have been analysed inspired by Aristotle’s activities of theoria and praxis and Bourdieu’s concept of strategy. In this perspective, the study shows student strategies of how the students seem to retain an affinity to allow a practical approach of social and ethical evaluation when handling theory, empirical material, and methods. The analysis shows that students’ personal preferences are brought into the foreground. Background: Antibiotic overuse and misuse in primary care are common, highlighting the importance of antimicrobial stewardship (AMS) efforts in this setting. Audit and feedback (A&F) interventions can improve professional practice and performance in some settings. Objectives and methods: To leverage the expertise from international members of the Joint Programming Initiative on Antimicrobial Resistance - Primary care Antibiotic Audit and feedback Network (JPIAMR-PAAN). Network members all have experience of designing and delivering A&F interventions to reduce inappropriate antibiotic prescribing in primary care settings. We aim to introduce the network and explore ongoing A&F activities in member regions. An online survey was administered to all network members to collect regional information. Results: Fifteen respondents from 11 countries provided information on A&F activities in their country, and national/regional antibiotic stewardship programmes or policies. Most countries use electronic medical records as the primary data source, antibiotic appropriateness as the main outcome of feedback, and target GPs as the prescribers of interest. Funding sources varied across countries, which could influence the frequency and quality of A&F interventions. Nine out of 11 countries reported having a national antibiotic stewardship programme or policy, which aim to provide systematic support to ongoing AMS efforts and aid sustainability. Conclusions: The survey identified gaps and opportunities for AMS efforts that include A&F across member countries in Europe, Canada and Australia. JPIAMR-PAAN will continue to leverage its members to produce best practice resources and toolkits for antibiotic A&F interventions in primary care settings and identify research priorities.

Background: Randomised controlled trials (RCTs) investigated analgesics, herbal formulations, delayed prescription of antibiotics, and placebo to prevent overprescription of antibiotics in women with uncomplicated urinary tract infections (uUTI). Objectives: To estimate the effect of these strategies and to identify symptoms, signs, or other factors that indicate a benefit from these strategies. Data sources: MEDLINE, EMBASE, Web of Science, LILACS, Cochrane Database of Systematic Reviews and of Controlled Trials, and ClinicalTrials. Study eligibility criteria, participants and interventions: RCTs investigating any strategies to reduce antibiotics vs. immediate antibiotics in adult women with uUTI in primary care. Methods: We extracted individual participant data (IPD) if available, otherwise aggregate data (AD). Bayesian random-effects meta-analysis of the AD was used for pairwise comparisons. Candidate moderators and prognostic indicators of treatment effects were investigated using generalised linear mixed models based on IPD. Results: We analysed IPD of 3524 patients from eight RCTs and AD of 78 patients. Non-antibiotic strategies increased the rates of incomplete recovery (OR 3.0; 95% credible interval (CrI), 1.7–5.5; Bayesian p-value (p B) = 0.0017; τ = 0.6), subsequent antibiotic treatment (OR 3.5; 95% CrI, 2.1–5.8; p B = 0.0003) and pyelonephritis (OR 5.6; 95% CrI, 2.3–13.9; p B = 0.0003). Conversely, they decreased overall antibiotic use by 63%. Patients positive for urinary erythrocytes and urine culture were at increased risk for incomplete recovery (OR 4.7; 95% CrI, 2.1–10.8; p B = 0.0010), but no difference was apparent where both were negative (OR 0.8; 95% CrI, 0.3–2.0; p B = 0.667). In patients treated using non-antibiotic strategies, urinary erythrocytes and positive urine culture were independent prognostic indicators for subsequent antibiotic treatment and pyelonephritis. Conclusions: Compared to immediate antibiotics, non-antibiotic strategies reduce overall antibiotic use but result in poorer clinical outcomes. The presence of erythrocytes and tests to confirm bacteria in urine could be used to target antibiotic prescribing.

Background Antibiotics are overused in patients with acute rhinosinusitis (ARS) as it is difficult to identify those who benefit from antibiotic treatment. Aim To develop prediction models for computed tomography (CT)-confirmed ARS and cultureconfirmed acute bacterial rhinosinusitis (ABRS) in adults presenting to primary care with symptoms suggestive of ARS. Design and setting This was a systematic review and individual participant data meta-analysis. Method CT-confirmed ARS was defined as the presence of fluid level or total opacification in any maxillary sinuses, whereas culture-confirmed ABRS was defined by culture of fluid from antral puncture. Prediction models were derived using logistic regression modelling. Results Among 426 patients from three studies, 140 patients (32.9 had CT-confirmed ARS. A model consisting of seven variables: previous diagnosis of ARS, preceding upper respiratory tract infection, anosmia, double sickening, purulent nasal discharge on examination, need for antibiotics as judged by a physician, and C-reactive protein (CRP) showed an optimismcorrected c-statistic of 0.73 (95CI] = 0.69 to 0.78) and a calibration slope of 0.99 (95= 0.72 to 1.19). Among 225 patients from two studies, 68 patients (30.2 had culture-confirmed ABRS. A model consisting of three variables: pain in teeth, purulent nasal discharge, and CRP showed an optimism-corrected c-statistic of 0.70 (95CI = 0.63 to 0.77) and a calibration slope of 1.00 (95= 0.66 to 1.52). Clinical utility analysis showed that both models could be useful to rule out the target condition. Conclusion Simple prediction models for CT-confirmed ARS and culture-confirmed ABRS can be useful to safely reduce antibiotic use in adults with ARS in high-prescribing countries.

Additional file 1: Table S1. Number of subjects screened/excluded/included and reason for exclusion. Figure S1. Venn diagram showing variations in self-reported improvement in health status. Table S2. Univariate analysis of various clinical and laboratory parameters vs treatment success. Table S3. Rates of Adverse Events (AE)/Serious Adverse Event (SAE) among patients treated with pivmecillinam 400 mg QID for 1 week (ITT, n = 53).

BACKGROUND: There is little evidence about the relation between aetiology, illness severity and clinical course of respiratory tract infections (RTI) in primary care. Understanding these associations would aid to develop effective management strategies for these infections.AIM: To investigate whether the clinical presentation and illness course differ between RTI in whom a viral pathogen was detected and those in whom a potential bacterial pathogen was found.DESIGN AND SETTING: Post hoc analysis of data from a pragmatic randomised trial on the effects of oseltamivir in patients with influenza-like illness (ILI) in primary care (n=3266) in 15 European countries.METHODS: Patient characteristics, signs and symptoms were registered at baseline. Naso-pharyngeal (adults) or nasal and pharyngeal (children) swabs were taken for PCR analysis. Patients were followed up until 28 days after inclusion. Regression models and Kaplan-Meier curves were used to analyse the relation between aetiology, clinical presentation at baseline and course of disease including complications.RESULTS: Except for a less prominent congested nose (OR 0.55, CI 0.35 - 0.86) and acute cough (OR 0.52, CI 0.27 - 0.65) in ILI patients in whom a possible bacterial pathogen was isolated, there were no clear clinical differences in presentations between those with a possible bacterial aetiology than in those with a viral one. Also the course of disease and complications were not related to aetiology.CONCLUSION: Given the currently available microbiological tests and antimicrobial treatments, and outside pandemics like COVID-19, microbiological testing in primary care patients with ILI seems to have limited value.

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Table S5. Adjusted MLR showing the effects of each prognostic indicator on pain (VAS) at each study time point (based on P ≤ 0.20 from the univariate analysis). (PDF 192 kb)

Table S3. Adjusted multilevel logistic regression showing the effects of each prognostic indicator on treatment success (based on P ≤ 0.05 from the univariate analysis). (PDF 96 kb)

INTRODUCTION: Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. METHODS AND ANALYSIS: Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5 days. We aim to recruit at least 2500 participants ≥1 year presenting with influenza-like illness (ILI), with symptom duration ≤72 hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (≤48 hours/>48-72 hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. ETHICS AND DISSEMINATION: Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN27908921; Pre-results.

Introduction: Effective management of seasonal and pandemic influenza is a high priority internationally. Guidelines in many countries recommend antiviral treatment for older people and individuals with comorbidity at increased risk of complications. However, antivirals are not often prescribed in primary care in Europe, partly because its clinical and cost effectiveness has been insufficiently demonstrated by non-industry funded and pragmatic studies. Methods and analysis: Antivirals for influenza-Like Illness? An rCt of Clinical and Cost effectiveness in primary CarE is a European multinational, multicentre, open-labelled, non-industry funded, pragmatic, adaptive-platform, randomised controlled trial. Initial trial arms will be best usual primary care and best usual primary care plus treatment with oseltamivir for 5days. We aim to recruit at least 2500 participants 1year presenting with influenza-like illness (ILI), with symptom duration 72hours in primary care over three consecutive periods of confirmed high influenza incidence. Participant outcomes will be followed up to 28 days by diary and telephone. The primary objective is to determine whether adding antiviral treatment to best usual primary care is effective in reducing time to return to usual daily activity with fever, headache and muscle ache reduced to minor severity or less. Secondary objectives include estimating cost-effectiveness, benefits in subgroups according to age (64 years), severity of symptoms at presentation (low, medium and high), comorbidity (yes/no), duration of symptoms (48hours/>48-72hours), complications (hospital admission and pneumonia), use of additional prescribed medication including antibiotics, use of over-the-counter medicines and self-management of ILI symptoms. Ethics and dissemination: Research ethics committee (REC) approval was granted by the NRES Committee South Central (Oxford B) and Clinical Trial Authority (CTA) approval by The Medicines and Healthcare products Regulatory Agency. All participating countries gained national REC and CTA approval as required. Dissemination of results will be through peer-reviewed scientific journals and conference presentations.

Characteristics of selected articles using quantitative methods. (PDF 35 kb)

Characteristics of selected articles using qualitative or mixed methods. (PDF 23 kb)

BACKGROUND: Ambulatory blood pressure monitoring was introduced more than 40 years ago and is accepted as a clinically useful method to evaluate the white coat effect in patients with suspected and established hypertension. AIM: To study the differences between blood pressure readings taken in the physician's office in the primary healthcare setting, and ambulatory readings, and to find possible predictors. DESIGN OF STUDY: Prospective study. SETTING: Two primary healthcare centres in Norway. METHOD: The study included 221 patients, 107 of whom were on antihypertensive treatment, and 114 of whom were under investigation for possible hypertension. Differences between blood pressure readings taken in the physician's office and ambulatory readings were calculated. Independent predictors for the white coat effect were calculated using linear regression analysis. RESULTS: The difference between blood pressure readings taken in the office and ambulatory readings was 27 mmHg systolic and 11 mmHg diastolic. For the systolic readings, the following factors were independent predictors of the amount of the white coat effect: mean blood pressure, age, history of smoking, family history of cardiovascular disease, and antihypertensive treatment. For the diastolic readings, they were: mean blood pressure, history of smoking, and sex of the patient (with this being most significant for women). CONCLUSION: Ambulatory blood pressure measurement is of significant value in identifying patients with white coat hypertension. It can be an important supplement for use in the diagnosis and follow-up of patients with hypertension in general practice.

INTRODUCTION Uncomplicated urinary tract infection (UTI) in women is a common reason to present in general practice and is usually treated with antibiotics to reduce symptom severity and duration. Results of recent clinical trials indicate that non-antibiotic treatment approaches can also be effective. However, it remains unclear which patients would benefit from antibiotic treatment and which can effectively and safely be treated without antibiotics. This systematic review and meta-analysis aims to estimate the effect of treatment strategies to reduce antibiotic use in comparison with immediate antibiotic treatment and to identify prognostic factors and moderators of treatment effects. A further aim is to identify subgroups of patients benefiting from a specific therapy. METHODS AND ANALYSIS A systematic literature search will be performed to identify randomised controlled trials which investigated the effect of treatment strategies to reduce antibiotic use in female adults with uncomplicated UTI compared with immediate antibiotic treatment. Therefore, the primary outcome of the meta-analysis is incomplete recovery. Anonymised individual patient data (IPD) will be collected. Aggregate data will be used for pairwise comparisons of treatment strategies using meta-analysis models with random effects accounting for potential between-study heterogeneity. Potential effect moderators will be explored in meta-regressions. For IPD, generalised linear mixed models will be used, which may be adjusted for baseline characteristics. Interactions of baseline variables with treatment effects will be explored. These models will be used to assess direct comparisons of treatment, but might be extended to networks. ETHICS AND DISSEMINATION The local institutional review and ethics board judged the project a secondary analysis of existing anonymous data which meet the criteria for waiver of ethics review. Dissemination of the results will be via published scientific papers and presentations. Key messages will be promoted for example, via social media or press releases. PROSPERO REGISTRATION NUMBER CRD42019125804.