Communication training for general practitioners aimed at improving antibiotic prescribing: a controlled before-after study in multicultural Dutch cities.

Introduction: Suboptimal doctor-patient communication drives inappropriate prescribing of antibiotics. We evaluated a communication intervention for general practitioners (GPs) in multicultural Dutch cities to improve antibiotic prescribing for respiratory tract infections (RTI). Methods: This was a non-randomized controlled before-after study. The study period was pre-intervention November 2019 ­ April 2020 and post-intervention November 2021 ­ April 2022. The intervention consisted of a live training (organized between September and November 2021), an E-learning, and patient material on antibiotics and antibiotic resistance in multiple languages. The primary outcome was the absolute number of prescribed antibiotic courses indicated for RTIs per GP; the secondary outcome was all prescribed antibiotics per GP. We compared the post-intervention differences in the mean number of prescribed antibiotics between the intervention (N = 25) and the control group (N = 110) by using an analysis of covariance (ANCOVA) test, while adjusting for the pre-intervention number of prescribed antibiotics. Additionally, intervention GPs rated the training and their knowledge and skills before the intervention and 3 months thereafter. Results: There was no statistically significant difference in the mean number of prescribed antibiotics for RTI between the intervention and the control group, nor for mean number of overall prescribed antibiotics. The intervention GPs rated the usefulness of the training for daily practice a 7.3 (on a scale from 1­10) and there was a statistically significant difference between pre- and post-intervention on four out of nine items related to knowledge and skills. Discussion: There was no change in GPs prescription behavior between the intervention and control group. However, GPs found the intervention useful and showed some improvement on self-rated knowledge and communication skills.

Diagnosis-linked antibiotic prescribing quality indicators: demonstrating feasibility using practice-based routine primary care data, reliability, validity and their potential in antimicrobial stewardship.

BACKGROUND: Quality indicators (QIs) can be used to obtain valuable insights into prescribing quality. Five quantitative and nine diagnosis-linked QIs, aiming to provide general practitioners (GP) with feedback on their antibiotic prescribing quantity and quality, were previously developed and evaluated in a controlled study. OBJECTIVE: To confirm, in a larger non-controlled study, the feasibility of using routinely collected and extracted electronic patient records to calculate the diagnosis-linked QI outcomes for antibiotic prescribing, and their reliability and validity. METHODS: Retrospective study involving 299 Dutch general practices using routine care data (2018-2020). QIs describe total antibiotic and subgroup prescribing, prescribing percentages and first-choice prescribing for several clinical diagnoses. Practice variation in QI outcomes, inter-QI outcome correlations and sensitivity of QI outcomes to pandemic-induced change were determined. RESULTS: QI outcomes were successfully obtained for 278/299 practices. With respect to reliability, outcomes for 2018 and 2019 were comparable, between-practice variation in outcomes was similar to the controlled pilot, and inter-QI outcome correlations were as expected, for example: high prescribing of second choice antibiotics with low first-choice prescribing for clinical diagnoses. Validity was confirmed by their sensitivity to pandemic-induced change: total antibiotic prescribing decreased from 282 prescriptions/1000 registered patients in 2018 to 216 in 2020, with a decrease in prescribing percentages for upper and lower respiratory infections, from 26% to 18.5%, and from 28% to 16%. CONCLUSIONS: This study confirmed the fit-for-purpose (feasibility, reliability and validity) of the antibiotic prescribing QIs (including clinical diagnosis-linked ones) using routinely registered primary health care data as a source. This feedback can therefore be used in antibiotic stewardship programmes to improve GPs' prescribing routines.

Using microbiological data to improve the use of antibiotics for respiratory tract infections: A protocol for an individual patient data meta-analysis.

BACKGROUND: Resistance to antibiotics is rising and threatens future antibiotic effectiveness. 'Antibiotic targeting' ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence. AIM: To undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs. METHODS: A systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs. TRIAL REGISTRATION: PROSPERO Registration number: CRD42023376769.

Clinical diagnosis of SARS-CoV-2 infection: An observational study of respiratory tract infection in primary care in the early phase of the pandemic.

BACKGROUND: Early in the COVID-19 pandemic, GPs had to distinguish SARS-CoV-2 from other aetiologies in patients presenting with respiratory tract infection (RTI) symptoms on clinical grounds and adapt management accordingly. OBJECTIVES: To test the diagnostic accuracy of GPs' clinical diagnosis of a SARS-CoV-2 infection in a period when COVID-19 was a new disease. To describe GPs' management of patients presenting with RTI for whom no confirmed diagnosis was available. To investigate associations between patient and clinical features with a SARS-CoV-2 infection. METHODS: In April 2020-March 2021, 876 patients (9 countries) were recruited when they contacted their GP with symptoms of an RTI of unknown aetiology. A swab was taken at baseline for later analysis. Aetiology (PCR), diagnostic accuracy of GPs' clinical SARS-CoV-2 diagnosis, and patient management were explored. Factors related to SARS-CoV-2 infection were determined by logistic regression modelling. RESULTS: GPs suspected SARS-CoV-2 in 53% of patients whereas 27% of patients tested positive for SARS-CoV-2. True-positive patients (23%) were more intensively managed for follow-up, antiviral prescribing and advice than true-negatives (42%). False negatives (5%) were under-advised, particularly for social distancing and isolation. Older age (OR: 1.02 (1.01-1.03)), male sex (OR: 1.68 (1.16-2.41)), loss of taste/smell (OR: 5.8 (3.7-9)), fever (OR: 1.9 (1.3-2.8)), muscle aches (OR: 2.1 (1.5-3)), and a known risk factor for COVID-19 (travel, health care worker, contact with proven case; OR: 2.7 (1.8-4)) were predictive of SARS-CoV-2 infection. Absence of loss of taste/smell, fever, muscle aches and a known risk factor for COVID-19 correctly excluded SARS-CoV-2 in 92.3% of patients, whereas presence of 3, or 4 of these variables correctly classified SARS-CoV-2 in 57.7% and 87.1%. CONCLUSION: Correct clinical diagnosis of SARS-CoV-2 infection, without POC-testing available, appeared to be complicated.

Disease-Specific Quality Indicators for Outpatient Antibiotic Prescribing for Respiratory Infections (ESAC Quality Indicators) Applied to Point Prevalence Audit Surveys in General Practices in 13 European Countries.

Up to 80% of antibiotics are prescribed in the community. An assessment of prescribing by indication will help to identify areas where improvement can be made. A point prevalence audit study (PPAS) of consecutive respiratory tract infection (RTI) consultations in general practices in 13 European countries was conducted in January-February 2020 (PPAS-1) and again in 2022 (PPAS-4). The European Surveillance of Antibiotic Consumption quality indicators (ESAC-QI) were calculated to identify where improvements can be made. A total of 3618 consultations were recorded for PPAS-1 and 2655 in PPAS-4. Bacterial aetiology was suspected in 26% (PPAS-1) and 12% (PPAS-4), and an antibiotic was prescribed in 30% (PPAS-1) and 16% (PPAS-4) of consultations. The percentage of adult patients with bronchitis who receive an antibiotic should, according to the ESAC-QI, not exceed 30%, which was not met by participating practices in any country except Denmark and Spain. For patients (≥1) with acute upper RTI, less than 20% should be prescribed an antibiotic, which was achieved by general practices in most countries, except Ireland (both PPAS), Croatia (PPAS-1), and Greece (PPAS-4) where prescribing for acute or chronic sinusitis (0-20%) was also exceeded. For pneumonia in adults, prescribing is acceptable for 90-100%, and this is lower in most countries. Prescribing for tonsillitis (≥1) exceeded the ESAC-QI (0-20%) in all countries and was 69% (PPAS-1) and 75% (PPAS-4). In conclusion, ESAC-QI applied to PPAS outcomes allows us to evaluate appropriate antibiotic prescribing by indication and benchmark general practices and countries.

Initial symptoms and three months follow-up after acute COVID-19 in outpatients: An international prospective cohort study.

BACKGROUND: Most studies on long-term follow-up of patients with COVID-19 focused on hospitalised patients. No prospective study with structured follow-up has been performed in non-hospitalised patients with COVID-19. OBJECTIVES: To assess long-COVID and post-COVID (WHO definition: symptomatic at least 12 weeks), describe lingering symptoms, their impact on daily activities, and general practice visits and explore risk factors for symptom duration in outpatients. METHODS: A prospective study of adult outpatients with confirmed SARS-CoV-2 infection and symptoms consistent with COVID-19 in 11 European countries, recruited during 2020 and 2021 from primary care and the community. Structured follow-up by phone interviews (symptom rating, symptom impact on daily activities and general practice visits) was performed at weeks 2, 4, 8, and 12 by study personnel. Data was analysed descriptively by using correlation matrixes and Cox regression. RESULTS: Of 270 enrolled patients, 52% developed long-COVID and 32% post-COVID-syndrome. When only considering the presence of moderate or (very) severe symptoms at weeks 8 and 12, these percentages were 28% and 18%, respectively. Fatigue was the most often reported symptom during follow-up. The impact of lingering symptoms was most evident in sports and household activities. About half (53%) had at least one general practice contact during follow-up. Obese patients took twice as long to return to usual health (HR: 0.5, 95%CI: 0.3-0.8); no other risk profile could predict lingering symptoms. CONCLUSION: Long-COVID and post-COVID are also common in outpatients. In 32%, it takes more than 12 weeks to return to usual health.

Cost-effectiveness of adding oseltamivir to primary care for influenza-like-illness: economic evaluation alongside the randomised controlled ALIC4E trial in 15 European countries.

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.

Perspectives of Immigrants and Native Dutch on Antibiotic Use: A Qualitative Study.

Immigrants constitute large proportions of the population in many high-income countries. Knowledge about their perceptions of antibiotics, in comparison to native populations, is limited. We explored these perceptions by organizing nine homogeneous focus group discussions (FGDs) with first-generation immigrant and native Dutch participants (N = 64) from Rotterdam and Utrecht, who were recruited with the assistance of immigrant (community support) organizations. The FGDs were audio-recorded and transcribed verbatim. Inductive thematic analyses were performed with the qualitative analysis software Atlas.ti, using open and axial coding. We did not find noteworthy differences between immigrants and native Dutch participants; all participants had an overall reluctant attitude towards antibiotics. Within-group differences were larger than between-group differences. In each FGD there were, for instance, participants who adopted an assertive stance in order to receive antibiotics, who had low antibiotic-related knowledge, or who used antibiotics incorrectly. Native Dutch participants expressed similar difficulties as immigrant participants in the communication with their GP, which mainly related to time constraints. Immigrants who encountered language barriers experienced even greater communicational difficulties and reported that they often feel embarrassed and refrain from asking questions. To stimulate more prudent use of antibiotics, more attention is needed for supportive multilingual patient materials. In addition, GPs need to adjust their information, guidance, and communication for the individual's needs, regardless of the patient's migration background.

The Opportunity of Point-of-Care Diagnostics in General Practice: Modelling the Effects on Antimicrobial Resistance.

OBJECTIVES: Antimicrobial resistance (AMR) is a public health threat associated with antibiotic consumption. Community-acquired acute respiratory tract infections (CA-ARTIs) are a major driver of antibiotic consumption in primary care. We aimed to quantify the investments required for a large-scale rollout of point-of care (POC) diagnostic testing in Dutch primary care, and the impact on AMR due to reduced use of antibiotics. METHODS: We developed an individual-based model that simulates consultations for CA-ARTI at GP practices in the Netherlands and compared a scenario where GPs test all CA-ARTI patients with a hypothetical diagnostic strategy to continuing the current standard-of-care for the years 2020-2030. We estimated differences in costs and future AMR rates caused by testing all patients consulting for CA-ARTI with a hypothetical diagnostic strategy, compared to the current standard-of-care in GP practices. RESULTS: Compared to the current standard-of-care, the diagnostic algorithm increases the total costs of GP consultations for CA-ARTI by 9% and 19%, when priced at €5 and €10, respectively. The forecast increase in Streptococcus pneumoniae resistance against penicillins can be partly restrained by the hypothetical diagnostic strategy from 3.8 to 3.5% in 2030, albeit with considerable uncertainty. CONCLUSIONS: Our results show that implementing a hypothetical diagnostic strategy for all CA-ARTI patients in primary care raises the costs of consultations, while lowering antibiotic consumption and AMR. Novel health-economic methods to assess and communicate the potential benefits related to AMR may be required for interventions with limited gains for individual patients, but considerable potential related to antibiotic consumption and AMR.

Impact of Adding Oseltamivir to Usual Care on Quality-Adjusted Life-Years During Influenza-Like Illness.

OBJECTIVES: The ALIC4E trial has shown that oseltamivir reduces recovery time while increasing the risk of nausea. This secondary analysis of the ALIC4E trial aimed to determine the gain in quality-adjusted life-years (QALYs) associated with adding oseltamivir to usual primary care in patients presenting with influenza-like illness (ILI). METHODS: Patients with ILI were recruited during the influenza season (2015-2018) in 15 European countries. Patients were assigned to usual care with or without oseltamivir through stratified randomization (age, severity, comorbidities, and symptom onset). Patients' health status was valued with the EQ-5D and visual analog scale (VAS) for up to 28 days. Average EQ-5D and VAS scores over time were estimated for both treatment groups using one-inflated beta regression in children (<13 years old) and adults (≥13 years old). QALY gain was calculated as the difference between the groups. Sensitivity analysis considered the value set to convert EQ-5D answers to summary scores and the follow-up period. RESULTS: In adults, oseltamivir gained 0.0006 (95% confidence interval 0.0002-0.0010) QALYs, whereas no statistically significant gain was found in children (14-day follow-up, EQ-5D). QALY gains were statistically significant in patients aged ≥65 years, patients without relevant comorbidities, or patients experiencing symptoms for ≤48 hours. Using VAS and accounting for 28-day follow-up resulted in higher QALY gain. CONCLUSIONS: QALY gain owing to oseltamivir is limited compared with other diseases, and its clinical meaningfulness remains to be determined. Further analysis is needed to evaluate whether QALY gain and its impact on ILI treatment cost render oseltamivir cost-effective.

Clinical presentation, microbiological aetiology and disease course in patients with flu-like illness: a post hoc analysis of randomised controlled trial data.

BACKGROUND: There is little evidence about the relationship between aetiology, illness severity, and clinical course of respiratory tract infections (RTIs) in primary care. Understanding these associations would aid in the development of effective management strategies for these infections. AIM: To investigate whether clinical presentation and illness course differ between RTIs where a viral pathogen was detected and those where 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 flu-like illness in primary care (n = 3266) in 15 European countries. METHOD: Patient characteristics and their signs and symptoms of disease were registered at baseline. Nasopharyngeal (adults) or nasal and pharyngeal (children) swabs were taken for polymerase chain reaction analysis. Patients were followed up until 28 days after inclusion. Regression models and Kaplan-Meier curves were used to analyse the relationship between aetiology, clinical presentation at baseline, and course of disease including complications. RESULTS: Except for a less prominent congested nose (odds ratio [OR] 0.55, 95% confidence interval [CI] = 0.35 to 0.86) and acute cough (OR 0.42, 95% CI = 0.27 to 0.65) in patients with flu-like illness in whom a possible bacterial pathogen was isolated, there were no clear clinical differences in presentations between those with a possible bacterial aetiology compared with those with a viral aetiology. Also, course of disease and complications were not related to aetiology. CONCLUSION: Given current available microbiological tests and antimicrobial treatments, and outside pandemics such as COVID-19, microbiological testing in primary care patients with flu-like illness seems to have limited value. A wait-and-see policy in most of these patients with flu-like illness seems the best option.

Clinical prediction of laboratory-confirmed influenza in adults with influenza-like illness in primary care. A randomized controlled trial secondary analysis in 15 European countries.

BACKGROUND: Clinical findings do not accurately predict laboratory diagnosis of influenza. Early identification of influenza is considered useful for proper management decisions in primary care. OBJECTIVE: We evaluated the diagnostic value of the presence and the severity of symptoms for the diagnosis of laboratory-confirmed influenza infection among adults presenting with influenza-like illness (ILI) in primary care. METHODS: Secondary analysis of patients with ILI who participated in a clinical trial from 2015 to 2018 in 15 European countries. Patients rated signs and symptoms as absent, minor, moderate, or major problem. A nasopharyngeal swab was taken for microbiological identification of influenza and other microorganisms. Models were generated considering (i) the presence of individual symptoms and (ii) the severity rating of symptoms. RESULTS: A total of 2,639 patients aged 18 or older were included in the analysis. The mean age was 41.8 ± 14.7 years, and 1,099 were men (42.1%). Influenza was microbiologically confirmed in 1,337 patients (51.1%). The area under the curve (AUC) of the model for the presence of any of seven symptoms for detecting influenza was 0.66 (95% confidence interval [CI]: 0.65-0.68), whereas the AUC of the symptom severity model, which included eight variables-cough, fever, muscle aches, sweating and/or chills, moderate to severe overall disease, age, abdominal pain, and sore throat-was 0.70 (95% CI: 0.69-0.72). CONCLUSION: Clinical prediction of microbiologically confirmed influenza in adults with ILI is slightly more accurate when based on patient reported symptom severity than when based on the presence or absence of symptoms.

Influenza is usually diagnosed clinically. However, the accuracy of a diagnosis of influenza based on clinical features is limited because symptoms overlap considerably with those caused by other microorganisms. This study examined whether identification of the severity rather than the presence of key signs and symptoms could aid in the diagnosis of influenza, thereby helping clinicians to determine when antiviral agent use is appropriate. The authors used the database of a previous randomized clinical trial on the effectiveness of an antiviral carried out in primary care centers in 15 countries in Europe during three epidemic periods from 2015/2016 to 2017/2018. Participants with influenza symptoms were included and they were asked about the presence and severity of different symptoms during the baseline visit with their doctors and a nasopharyngeal swab was taken for microbiological analysis. Overall, only 51% of the patients aged 18 or older had a confirmed influenza infection. Clinical findings are not particularly useful for confirming or excluding the diagnosis of influenza. However, the results of our study recommend considering how intense the different symptoms are, since key symptoms rated as moderate or severe are slightly better for predicting flu rather than the presence or absence of these symptoms.

Point-of-care testing, antibiotic prescribing, and prescribing confidence for respiratory tract infections in primary care: a prospective audit in 18 European countries.

BACKGROUND: Between-country differences have been described in antibiotic prescribing for respiratory tract infection (RTI) in primary care, but not yet for diagnostic testing procedures and prescribing confidence. AIM: To describe between-country differences in RTI management, particularly diagnostic testing and antibiotic prescribing, and investigate which factors relate to antibiotic prescribing and GPs' prescribing confidence. DESIGN & SETTING: Prospective audit in 18 European countries. METHOD: An audit of GP-registered patient, clinical, and management characteristics for patients presenting with sore throat and/or lower RTI (n = 4982), and GPs' confidence in their antibiotic prescribing decision. Factors related to antibiotic prescribing and confidence were analysed using multi-level logistic regression. RESULTS: Antibiotic prescribing proportions varied considerably: <20% in four countries, and >40% in six countries. There was also considerable variation in point-of-care (POC) testing (0% in Croatia, Moldova, and Romania, and >65% in Denmark and Norway, mainly for C-reactive protein [CRP] and group A streptococcal [strep A] infection), and in laboratory or hospital-based testing (<3% in Hungary, the Netherlands, and Spain, and >30% in Croatia, Georgia, Greece, and Moldova, mainly chest X-ray and white blood cell counting). Antibiotic prescribing was related to illness severity, comorbidity, age, fever, and country, but not to having performed a POC test. In nearly 90% of consultations, GPs were confident in their antibiotic prescribing decision. CONCLUSION: Despite high confidence in decisions about antibiotic prescribing, there is considerable variation in the primary care of RTI in European countries, with GPs prescribing antibiotics overall more often than is considered appropriate. POC testing may enhance the quality of antibiotic prescribing decisions if it can safely reverse decisions confidently made on clinical grounds alone to prescribe antibiotics.

Common Infections and Antibiotic Prescribing during the First Year of the COVID-19 Pandemic: A Primary Care-Based Observational Cohort Study.

Presentation and antibiotic prescribing for common infectious disease episodes decreased substantially during the first COVID-19 pandemic wave in Dutch general practice. We set out to determine the course of these variables during the first pandemic year. We conducted a retrospective observational cohort study using routine health care data from the Julius General Practitioners' Network. All patients registered in the pre-pandemic year (n = 425,129) and/or during the first pandemic year (n = 432,122) were included. Relative risks for the number of infectious disease episodes (respiratory tract/ear, urinary tract, gastrointestinal, and skin), in total and those treated with antibiotics, and proportions of episodes treated with antibiotics (prescription rates) were calculated. Compared to the pre-pandemic year, primary care presentation for common infections remained lower during the full first pandemic year (RR, 0.77; CI, 0.76-0.78), mainly attributed to a sustained decline in respiratory tract/ear and gastrointestinal infection episodes. Presentation for urinary tract and skin infection episodes declined during the first wave, but returned to pre-pandemic levels during the second and start of the third wave. Antibiotic prescription rates were lower during the full first pandemic year (24%) as compared to the pre-pandemic year (28%), mainly attributed to a 10% lower prescription rate for respiratory tract/ear infections; the latter was not accompanied by an increase in complications. The decline in primary care presentation for common infections during the full first COVID-19 pandemic year, together with lower prescription rates for respiratory tract/ear infections, resulted in a substantial reduction in antibiotic prescribing in Dutch primary care.

Does C-reactive protein predict time to recovery and benefit from oseltamivir treatment in primary care patients with influenza-like illness? A randomized controlled trial secondary analysis.

OBJECTIVE: Recovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-reactive protein (CRP) concentration of ≥30 mg/L can predict (1) ILI disease duration, and (2) which patients are most likely to benefit from oseltamivir treatment. DESIGN: Secondary analysis of randomized controlled trial data. SETTING: Primary care in Lithuania, Sweden and Norway during three consecutive influenza seasons 2016-2018. SUBJECTS: A total of 277 ILI patients aged one year or older and symptom duration of ≤72 h. MAIN OUTCOME MEASURES: Capillary blood CRP concentration at baseline, and ILI recovery time defined as having 'returned to usual daily activity' with residual symptoms minimally interfering. RESULTS: At baseline, 20% (55/277) had CRP concentrations ≥30mg/L (range 0-210). CRP concentration ≥30 mg/L was not associated with recovery time (adjusted hazards ratio (HR) 0.80: 95% CI 0.50-1.3; p = 0.33). Interaction analysis of CRP concentration ≥30 mg/L and oseltamivir treatment did not identify which patients benefit more from oseltamivir treatment (adjusted HR 0.69: 95% CI 0.37-1.3; p = 0.23). CONCLUSION: There was no association between CRP concentration of ≥30 mg/L and recovery time from ILI. Furthermore, CRP could not predict which ILI patients benefit more from oseltamivir treatment. Hence, we do not recommend CRP testing for predicting ILI recovery time or identifying patients who will receive particular benefit from oseltamivir treatment.Key PointsPredicting disease course of influenza-like illness (ILI), and identifying which patients benefit from oseltamivir treatment is a challenge for physicians.• There was no association between CRP concentration at baseline and recovery time in patients consulting with ILI in primary care.• There was no association between CRP concentration at baseline and benefit from oseltamivir treatment.• We, therefore, do not recommend CRP testing for predicting recovery time or in decision-making concerning oseltamivir prescribing in ILI patients.

A Strong Decline in the Incidence of Childhood Otitis Media During the COVID-19 Pandemic in the Netherlands.

Introduction: Recent reports have highlighted the impact of the COVID-19 pandemic on the incidence of infectious disease illnesses and antibiotic use. This study investigates the effect of the pandemic on childhood incidence of otitis media (OM) and associated antibiotic prescribing in a large primary care-based cohort in the Netherlands. Material and Methods: Retrospective observational cohort study using routine health care data from the Julius General Practitioners' Network (JGPN). All children aged 0-12 registered in 62 practices before the COVID-19 pandemic (1 March 2019 - 29 February 2020) and/or during the pandemic (1 March 2020 - 28 February 2021) were included. Data on acute otitis media (AOM), otitis media with effusion (OME), ear discharge episodes and associated antibiotic prescriptions were extracted. Incidence rates per 1,000 child years (IR), incidence rate ratios (IRR) and incidence rate differences (IRD) were compared between the two study periods. Results: OM episodes declined considerably during the COVID-19 pandemic: IR pre-COVID-19 vs COVID-19 for AOM 73.7 vs 27.1 [IRR 0.37]; for OME 9.6 vs 4.1 [IRR 0.43]; and for ear discharge 12.6 vs 5.8 [IRR 0.46]. The absolute number of AOM episodes in which oral antibiotics were prescribed declined accordingly (IRD pre-COVID-19 vs COVID-19: -22.4 per 1,000 child years), but the proportion of AOM episodes with antibiotic prescription was similar in both periods (47% vs 46%, respectively). Discussion: GP consultation for AOM, OME and ear discharge declined by 63%, 57% and 54% respectively in the Netherlands during the COVID-19 pandemic. Similar antibiotic prescription rates before and during the pandemic indicate that the case-mix presenting to primary care did not considerably change. Our data therefore suggest a true decline as a consequence of infection control measures introduced during the pandemic.

Diagnostic performance of the Idylla™ respiratory panel for molecular detection of influenza A/B in patients presenting to primary care with influenza-like illness during 3 consecutive influenza seasons.

BACKGROUND: Influenza virus (IFV) is often encountered in primary care. Implementation of a rapid diagnostic test for its detection at the point-of-care would enable discrimination from other viral causes of influenza-like-illness (ILI) and might be helpful in individual patient management. In this study, the diagnostic performance of such a point-of-care platform was evaluated. METHODS: Respiratory samples (n = 1490) from ILI-patients in primary care in 15 European countries were collected as part of a prospective clinical trial. Both children (n = 252) and adults (n = 1238) were sampled during 3 consecutive periods of high IFV endemicity. Samples were analysed in a central laboratory, after storage at -70 °C, with the Idylla™ Respiratory Panel, detecting both IFV and RSV, on the Idylla™ platform. The Fast Track Diagnostics (FTD) Respiratory Pathogens 21 plus assay was used as reference. A subset of samples (n = 192) was analysed both fresh and after being frozen. RESULTS: The reference method detected IFV-A in 42% and IFV-B in 13% of the samples. Sensitivity of the Idylla for detection of IFV-A and IFV-B was 98.2% and 92.3% and specificity 97.7% and 98.4% respectively. False negative samples contained significantly lower viral loads than true positive samples (FTD mean Ct-value 30.7 versus 26.1 for IFV-A and 30.4 versus 25.1 for IFV-B, p < 0.001). Comparable results were obtained for Idylla analysis using fresh and frozen samples. CONCLUSIONS: The Idylla Respiratory Panel is a promising point-of-care test for detection of IFV in ILI patients due to its excellent diagnostic performance, minimal training requirements and limited hands-on time.

Direct and Indirect Costs of Influenza-Like Illness Treated with and Without Oseltamivir in 15 European Countries: A Descriptive Analysis Alongside the Randomised Controlled ALIC4E Trial.

BACKGROUND AND OBJECTIVE: Influenza-like illness (ILI) leads to a substantial disease burden every winter in Europe; however, oseltamivir is not frequently prescribed to ILI patients in the primary-care setting. An open-label, multi-country, multi-season, randomised controlled trial investigated the effectiveness of oseltamivir for treating ILI in 15 European countries. We aimed to evaluate whether patients presenting with ILI in primary care and being managed with the addition of oseltamivir to usual care had lower average direct and indirect costs compared to patients with usual care alone. METHODS: Resource use data were extracted from participants' daily diaries. Itemised country-specific unit costs were collected through official tariffs, pharmacies or literature. Costs were converted to 2018 values. The null hypothesis was tested based on one-sided credible intervals (CrIs) obtained by bootstrapping. Base-case analysis estimated direct cost and productivity losses using itemised costed resource use and the human capital approach. Scenario analyses with self-reported spending rather than itemised costing were also performed. RESULTS: Patients receiving oseltamivir (N = 1306) reported fewer healthcare visits, medication uses, hospital attendances and paid-work hours lost than the other patients (N = 1298). Excluding the oseltamivir cost, the average direct costs were lower in patients treated with oseltamivir from all perspectives, but these differences were not statistically significant (perspective of patient: €17 [0-95% Crl: 16-19] vs. €24 [5-100% Crl: 18-29]; healthcare provider: €37 [28-67] vs. €44 [25-55]; healthcare payers: €54 [45-85] vs. €68 [45-81]; and society: €423 [399-478] vs. €451 [390-478]). Scenario and age-group analyses confirmed these findings, but with some between-country differences. CONCLUSION: The average direct and indirect costs were consistently lower in patients treated with oseltamivir than in patients without from four perspectives (excluding the oseltamivir cost). However, these differences were not statistically significant.

Primary care for patients with respiratory tract infection before and early on in the COVID-19 pandemic: an observational study in 16 European countries.

OBJECTIVE: To describe primary health care (consultation characteristics and management) for patients contacting their general practitioner (GP) with a respiratory tract infection (RTI) early on in the COVID-19 pandemic in contrasting European countries, with comparison to prepandemic findings. SETTING: Primary care in 16 countries (79 practices), when no routine SARS-CoV-2 testing was generally available. DESIGN AND PARTICIPANTS: Before (n=4376) and early in the pandemic (n=3301), patients with RTI symptoms were registered in this prospective audit study. OUTCOME MEASURES: Consultation characteristics (type of contact and use of PPE) and management characteristics (clinical assessments, diagnostic testing, prescribing, advice and referral) were registered. Differences in these characteristics between countries and between pandemic and prepandemic care are described. RESULTS: Care for patients with RTIs rapidly switched to telephone/video consultations (10% in Armenia, 91% in Denmark), and when consultations were face-to-face, GPs used PPE during 97% (95% CI 96% to 98%) of contacts. Laboratory testing for SARS-CoV-2 in primary care patients with RTIs was rapidly implemented in Denmark (59%) and Germany (31%), while overall testing for C reactive protein decreased. The proportion of patients prescribed antibiotics varied considerably between countries (3% in Belgium, 48% in UK) and was lower during the pandemic compared with the months before, except for Greece, Poland and UK. GPs provided frequent and varied COVID-related advice and more frequently scheduled a follow-up contact (50%, 95% CI 48% to 52%). GPs reported a slightly higher degree of confidence in the likely effectiveness of their management in face-to-face (73% (very) confident, 95% CI 71% to 76%) than in virtual consultations (69%, 95% CI 67% to 71%). CONCLUSIONS: Despite between-country variation in consultation characteristics, access to SARS-CoV-2 laboratory testing and medication prescribing, GPs reported a high degree of confidence in managing their patients with RTIs in the emerging pandemic. Insight in the highly variable pandemic responses, as measured in this multicountry audit, can aid in fine-tuning national action and in coordinating a pan-European response during future pandemic threats.