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.

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 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.

Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial.

BACKGROUND: Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups. METHODS: We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921. FINDINGS: Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1·29, 95% Bayesian credible interval [BCrI] 1·20-1·39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1·13 to 1·72. The estimated absolute mean benefit from oseltamivir was 1·02 days (95% [BCrI] 0·74-1·31) overall, and in the prespecified subgroups, ranged from 0·70 (95% BCrI 0·30-1·20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3·20 (95% BCrI 1·00-5·50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group. INTERPRETATION: Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2-3 days sooner. FUNDING: European Commission's Seventh Framework Programme.

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.

Is C-reactive protein associated with influenza A or B in primary care patients with influenza-like illness? A cross-sectional study.

OBJECTIVE: Identifying influenza A or B as cause of influenza-like illness (ILI) is a challenge due to non-specific symptoms. An accurate, cheap and easy to use biomarker might enhance targeting influenza-specific management in primary care. The aim of this study was to investigate if C-reactive protein (CRP) is associated with influenza A or B, confirmed with PCR testing, in patients presenting with ILI. DESIGN: Cross-sectional study. SETTING: Primary care in Lithuania, Norway and Sweden. SUBJECTS: A total of 277 patients at least 1 year of age consulting primary care with ILI during seasonal influenza epidemics. MAIN OUTCOME MEASURES: Capillary blood CRP analysed as a point-of-care test and detection of influenza A or B on nasopharyngeal swabs in adults, and nasal and pharyngeal swabs in children using PCR. RESULTS: The prevalence of positive tests for influenza A among patients was 44% (121/277) and the prevalence of influenza B was 21% (58/277). Patients with influenza A infection could not be identified based on CRP concentration. However, increasing CRP concentration in steps of 10 mg/L was associated with a significantly lower risk for influenza B with an adjusted odds ratio of 0.42 (0.25-0.70; p<.001). Signs of more severe symptoms like shortness of breath, sweats or chills and dizziness were associated with higher CRP. CONCLUSIONS: There was no association between CRP and influenza A. Increased concentration of CRP was associated with a lower risk for having influenza B, a finding that lacks clinical usefulness. Hence, CRP testing should be avoided in ILI, unless bacterial pneumonia is suspected. Key points Identifying influenza A or B as cause of influenza-like illness (ILI) is a challenge due to non-specific symptoms. There was no association between concentration of CRP and influenza A. Increased concentration of CRP was associated with a lower risk for having influenza B, a finding that lacks clinical usefulness. A consequence is that CRP testing should be avoided in ILI, unless bacterial pneumonia or similar is suspected.

Cost-effectiveness analysis of a GP- and parent-directed intervention to reduce antibiotic prescribing for children with respiratory tract infections in primary care.

OBJECTIVES: We evaluated costs and effects of the RAAK (RAtional Antibiotic use Kids) intervention (GP online training and information booklets for parents), aiming to reduce antibiotic prescribing for children with respiratory tract infection (RTI). METHODS: We conducted a trial-based cost-effectiveness analysis from a societal perspective. We included children consulting the GP with RTI for whom parents kept a 2 week (cost) diary. The antibiotic prescribing rate was the percentage of children receiving an antibiotic prescription at the index consultation and during the 2 weeks of follow-up. The cost difference between the intervention and usual care groups per percentage decrease in antibiotic prescribing was calculated. Bootstrapping was used to assess uncertainty surrounding the outcomes. RESULTS: Costs and effects of 153 children in the intervention group and 107 children in the usual care group were available for analysis. Antibiotic prescribing was 12% lower in the intervention group and costs were €10.27 higher in the intervention group compared with the usual care group. This resulted in an incremental cost-effectiveness ratio of €0.85 per percentage decrease in antibiotic prescribing. The probability that the intervention was more effective, but more expensive, was 53%, whereas the probability that the intervention was more effective and less expensive compared with usual care was 41%. CONCLUSIONS: The online training for GPs and the information booklet for parents resulted in a decrease in antibiotic prescribing in children with RTI, at very low cost, and should therefore be considered for implementation in primary care.

Consecutive antibiotic use in the outpatient setting: an extensive, longitudinal descriptive analysis of antibiotic dispensing data in the Netherlands.

INTRODUCTION: Taking consecutive antibiotic use into account is of importance to obtain insight in treatment within disease episodes, use of 2nd- and 3rd-choice antibiotics, therapy failure and/or side effects. Nevertheless, studies dealing with consecutive antibiotic use are scarce. We aimed at evaluating switch patterns in antibiotic use in the outpatient setting in the Netherlands. METHODS: Outpatient antibiotic dispensing data was processed to antibiotic treatment episodes consisting of single prescriptions or consecutive prescriptions (2006 to 2014). Consecutive prescriptions were categorised into prolongations and switches. Switches were further analysed to obtain antibiotic switch percentages and trends over time. Outcomes were compared with recommendations of Dutch guidelines. RESULTS: A total of 43,179,867 antibiotic prescriptions were included in the analysis, consisting of single prescriptions (95%), prolongations (2%) and switches (3%). The highest switch percentages were found for trimethoprim (7.6%) and nitrofurantoin (5.4%). For fosfomycin, ciprofloxacin, flucloxacillin and trimethoprim we found the highest yearly increase in switching. Amoxicillin/clavulanic acid was most often used as second antibiotic in a switch. A surprisingly high number of 2nd- and 3rd-choice antibiotics are prescribed as first antibiotic in a treatment. CONCLUSIONS: Although the actual reason for a switch is unknown, switch patterns can reveal problems concerning treatment failure and guideline adherence. In general, switch percentages of antibiotics in the Netherlands are low. The data contributes to the knowledge regarding antibiotic switch patterns in the outpatient setting.

Impetigo incidence and treatment: a retrospective study of Dutch routine primary care data.

BACKGROUND: There is a lack of recently published data on impetigo presentation incidence and treatment practices in the routine Western European primary care setting. OBJECTIVES: To investigate impetigo incidence, treatments and recurrence in primary care in the Netherlands. METHODS: A retrospective, observational study. Electronic records of patients treated for impetigo in 2015 at 29 general practices in Utrecht and surrounds were reviewed. An episode of impetigo was defined as one or more patient-doctor contacts within 8 weeks of the index consultation. Within an episode, patient demographics and prescribing patterns were analysed including number of treatments, and the category and sequence of individual medicines. RESULTS: A total of 1761 impetigo episodes were managed, with an incidence rate of 13.6 per 1000 person years. Impetigo peaked in summer. Most patients, the majority children, experienced a single episode (93%), and 25% had eczema as comorbidity. Topical antibiotics (primarily fusidic acid) were the most prescribed initial treatments (85%), followed by oral antibiotics (14%). Topical antibiotics were progressively used less over subsequent treatments, while there was an inverse increase in oral antibiotic use. Topical fusidic acid as the most common first line treatment seemed satisfactory as only 12% of initial treatments with this drug received further therapy. Repeat treatments generally occurred within 7 days. CONCLUSION: This study of impetigo prescribing patterns in primary care highlighted that Dutch general practitioners were generally adherent to national treatment guidelines. Topical treatment, and if needed systemic small-spectrum antibiotic treatment, appeared satisfactory; these findings aid in antimicrobial stewardship.

Effectiveness of general practitioner online training and an information booklet for parents on antibiotic prescribing for children with respiratory tract infection in primary care: a cluster randomized controlled trial.

Objectives: Antibiotics are too often prescribed in childhood respiratory tract infection (RTI), despite limited effectiveness, potential side effects and bacterial resistance. We aimed to reduce antibiotic prescribing for children with RTI by online training for general practitioners (GPs) and information for parents. Methods: A pragmatic cluster randomized controlled trial in primary care. The intervention consisted of online training for GPs and an information booklet for parents. The primary outcome was the antibiotic prescription rate for children presenting with RTI symptoms, as registered by GPs. Secondary outcomes were number of reconsultations within the same disease episode, consultations for new episodes, hospital referrals and pharmacy-dispensed antibiotic courses for children. This trial was registered at the Dutch Trial Register (NTR), registration number: NTR4240. Results: After randomization, GPs from a total of 32 general practices registered 1009 consultations. An antibiotic was prescribed in 21% of consultations in the intervention group, compared with 33% in the usual care group, controlled for baseline prescribing (rate ratio 0.65, 95% CI 0.46-0.91). The probability of reconsulting during the same RTI episode did not differ significantly between the intervention and control groups, and nor did the numbers of consultations for new episodes and hospital referrals. In the intervention group antibiotic dispensing was 32 courses per 1000 children/year lower than the control group, adjusted for baseline prescribing (rate ratio 0.78, 95% CI 0.66-0.92). The numbers and proportion of second-choice antibiotics did not differ significantly. Conclusions: Concise, feasible, online GP training, with an information booklet for parents, showed a relevant reduction in antibiotic prescribing for children with RTI.

Antibiotic management of children with infectious diseases in Dutch Primary Care.

Background: Childhood infections are common in general practice. Although clinical guidelines recommend restrictive antibiotic use for children, antibiotics are too often prescribed. Objective: The aim of this study was to obtain insight in antibiotic prescribing for children related to clinical diagnoses. This is pivotal to define improvement strategies in the antibiotic management. Methods: In this observational study, we used consultation data collected from 45 general practices in the Netherlands in 2012. Infectious disease episode incidences, the number of antibiotic prescriptions per 1000 person-years, the proportion of episodes with an antibiotic prescription and the choice of antibiotic subclass were analysed for the most relevant diagnoses over different ages. Results: A total of 262 antibiotic courses were prescribed per 1000 person-years on average, with the highest number among children of 1 year (714/1000 person-years). Antibiotics were prescribed in 24% of infectious disease episodes. Acute upper respiratory tract infection (RTI) was the most common reason to visit the GP (173/1000 person-years), and the second most frequent indication to prescribe antibiotics. Antibiotics were most often prescribed for acute otitis media (58/1000 person-years). Amoxicillin dominated prescribing (55%), followed by macrolides (14%) and amoxicillin/clavulanate (10%), prescribing of narrow-spectrum antibiotics was low (10%). Conclusion: This detailed insight in antibiotic management of childhood infections shows targets for Dutch improvement strategies: (i) prevent antibiotic prescribing for acute upper RTI and bronchitis; (ii) stimulate the use of narrow-spectrum antibiotics; and (iii) reduce the use of macrolides and amoxicillin/clavulanate. Furthermore, this information is helpful to compare antibiotic policy between countries.

Improving antibiotic prescribing quality by an intervention embedded in the primary care practice accreditation: the ARTI4 randomized trial.

OBJECTIVES: Antibiotic overprescribing is a significant problem. Multifaceted interventions improved antibiotic prescribing quality; their implementation and sustainability, however, have proved difficult. We analysed the effectiveness of an intervention embedded in the quality cycle of primary care practice accreditation on quantity and quality of antibiotic prescribing for respiratory tract and ear infections (RTIs). METHODS: This was a pragmatic, cluster-randomized intervention trial in 88 Dutch primary care practices. The intervention (physician education and audit/feedback on antibiotic prescribing quantity and quality) was integrated in practice accreditation by defining an improvement plan with respect to antibiotic prescribing for RTIs. Numbers and types of dispensed antibiotics were analysed from 1 year prior to the intervention to 2 years after the intervention (pharmacy data). Overprescribing, underprescribing and non-first-choice prescribing for RTIs were analysed at baseline and 1 year later (self-registration). RESULTS: There were significant differences between intervention and control practices in the changes in dispensed antibiotics/1000 registered patients (first year: -7.6% versus -0.4%, P = 0.002; second year: -4.3% versus +2%, P = 0.015), which was more pronounced for macrolides and amoxicillin/clavulanate (first year: -12.7% versus +2.9%, P = 0.001; second year: -7.8% versus +6.7%, P = 0.005). Overprescribing for RTIs decreased from 44% of prescriptions to 28% (P < 0.001). Most general practitioners (GPs) envisaged practice accreditation as a tool for guideline implementation. CONCLUSIONS: GP education and an audited improvement plan around antibiotics for RTIs as part of primary care practice accreditation sustainably improved antibiotic prescribing. Tools should be sought to further integrate and facilitate education and audit/feedback in practice accreditation.

Usefulness of quality indicators for antibiotic use: case study for the Netherlands.

QUALITY PROBLEM: Inappropriate antibiotic use drives development of antimicrobial resistance. Worldwide, guideline adherence for antibiotic treatment of infectious disease is far from optimal. Insight in prescribing quality is pivotal for healthcare professionals and policy makers to intervene appropriately. INITIAL ASSESSMENTS: European countries uniformly monitor antibiotic use, which is reported yearly by the European Centre for Disease Prevention and Control. Unfortunately, this has not had enough impact to decrease prescribing and resistance levels. CHOICE OF SOLUTION: Quality indicators (QIs) could provide better insight in prescribing quality and enable benchmarking to other countries; this could trigger action to improve antimicrobial prescribing. European Surveillance of Antimicrobial Consumption (ESAC) proposed 12 antibiotic QIs. IMPLEMENTATION: Trends in use of antibiotic subgroups and the 12 ESAC QI values were determined for Dutch primary care (2004-2013); outcomes were compared to other European countries. Dutch antibiotic use is low within the European context. Nitrofurantoin use is higher than the European average, use of small-spectrum antibiotics lowers. Use of macrolides, quinolones and amoxicillin/clavulanate declined, which was not supported by the broad/narrow QI results. EVALUATION: QIs expressing antibiotic subgroup use in Defined Daily Doses/1000 inhabitants/day, particularly small-spectrum and non-first choices, provide proper insight in prescribing quality and are useful for benchmarking purposes. QIs measuring percentages were not considered useful. The broad/narrow ratio could be more informative when adjusted to national guidelines, or when more antibiotic subgroups are included based on better European consensus. LESSONS LEARNT: Benchmarking the above mentioned Dutch QI values to other countries provides direction for three specific strategies to further improve Dutch antibiotic prescribing practice.

Inappropriate antibiotic prescription for respiratory tract indications: most prominent in adult patients.

BACKGROUND: Numerous studies suggest overprescribing of antibiotics for respiratory tract indications (RTIs), without really authenticating inappropriate prescription; the strict criteria of guideline recommendations were not taken into account as information on specific diagnoses, patient characteristics and disease severity was not available. OBJECTIVE: The aim of this study is to quantify and qualify inappropriate antibiotic prescribing for RTIs. METHODS: This is an observational study of the (antibiotic) management of patients with RTIs, using a detailed registration of RTI consultations by general practitioners (GPs). Consultations of which all necessary information was available were benchmarked to the prescribing guidelines for acute otitis media (AOM), acute sore throat, rhinosinusitis or acute cough. Levels of overprescribing for these indications and factors associated with overprescribing were determined. RESULTS: The overall antibiotic prescribing rate was 38%. Of these prescriptions, 46% were not indicated by the guidelines. Relative overprescribing was highest for throat (including tonsillitis) and lowest for ear consultations (including AOM). Absolute overprescribing was highest for lower RTIs (including bronchitis). Overprescribing was highest for patients between 18 and 65 years of age, when GPs felt patients' pressure for an antibiotic treatment, for patients presenting with fever and with complaints longer than 1 week. Underprescribing was observed in <4% of the consultations without a prescription. CONCLUSION: Awareness of indications and patient groups provoking antibiotic overprescribing can help in the development of targeted strategies to improve GPs' prescribing routines for RTIs.

Antibiotic use in Dutch primary care: relation between diagnosis, consultation and treatment.

OBJECTIVES: Countries generally present their overall use of antibiotics as an indicator of antibiotic prescribing quality. Additional insight is urgently needed for targeted improvement recommendations: first, data on specific clinical indications for which antibiotics are used, and second, on distinguishing whether changes in patient consultation or changes in physician prescribing drive changing antibiotic use for particular indications. The aim of this study was to describe the antibiotic management of infectious diseases in the clinical context, by analysing prescribing by physicians and patient consultation incidences per indication over time. METHODS: A database with all contact data for infectious diseases from 45 primary care practices in the Netherlands (2007-10) was used. Consultation incidences, prescribing rates and choice of antibiotic were analysed per International Classification of Primary Care (ICPC) chapter and relevant ICPC codes. RESULTS: Antibiotics were prescribed in ∼25% of infectious disease episodes, mainly respiratory infections, urinary infections and ear and skin infections. Overall, this resulted in 300 prescribed courses of antibiotics per 1000 patient-years. Given a stable prescription rate, a 19% increase in the number of consultations explained the increased antibiotic prescribing for urinary tract infections. Given a stable consultation incidence, an 8% reduction in prescribing rate explained the decreased antibiotic prescribing for respiratory tract infections. Macrolides were predominantly prescribed for respiratory disease (∼66%), amoxicillin/clavulanate for respiratory disease (∼42%) and urinary illness (∼25%), and fluoroquinolones for urinary and genital indications. CONCLUSIONS: Insight into the reasons for the decreased prescribing for respiratory tract infections and the increased prescribing for urinary tract infections was provided by a detailed analysis of incidences and prescribing rates. For respiratory disease, the second- and third-choice antibiotics were overused. Complete data on infectious disease management, with respect to patient and physician behaviour, are crucial for understanding changes in antibiotic use, and in defining strategies to reduce inappropriate antibiotic use.

Cystitis: antibiotic prescribing, consultation, attitudes and opinions.

BACKGROUND: Despite stable overall antibiotic use between 2007 and 2011 in The Netherlands, use of nitrofurantoin and trimethoprim increased by 32%. The background of this increased antibiotic use against uropathogens is unknown. OBJECTIVES: To determine whether increased use of urinary tract infection antibiotics is caused by changes in patients' consultation or physicians' prescribing behaviour and to investigate attitudes and opinions of women with respect to cystitis management and antibiotics. METHODS: Consultation and prescribing for International Classification of Primary Care (ICPC) codes U01 (dysuria), U02 (frequency), U05 (other urination problems), U70 (pyelonephritis) and U71 (cystitis) were determined from 2007 to 2010, using routinely collected primary health care data. Separately, behaviour of women with respect to managing cystitis, consultation and opinions towards (delayed) antibiotic treatment were studied using questionnaires in 2012. RESULTS: Consultation for U02 and U71 significantly increased from 93 to 114/1000 patient-years from 2007 to 2010; proportion of episodes in which an antibiotic was prescribed remained constant. Questionnaires revealed that urination problems and pain were dominant complaints of cystitis; pain medication, however, was not adequately used. One-third of women directly consult upon first symptoms, whereas the majority awaits an average of 4 days. Sixty-six per cent of women report to be willing to postpone antibiotic use. CONCLUSION: Increased use of urinary tract infection antibiotics may be caused by increased consultation for cystitis in primary care. Future research should focus on the outcomes of adequate pain medication, enhanced diagnostic procedures and of delaying antibiotic use in cystitis management.

Patient selection for therapy reduction after long-term daily proton pump inhibitor treatment for gastro-oesophageal reflux disease: trial and error.

BACKGROUND: Proton pump inhibitor (PPI) therapy reduction after long-term daily treatment for gastro-oesophageal reflux disease (GORD) symptomatology proves difficult in primary care practice. We aimed to identify patient and/or disease characteristics in long-term daily PPI users predicting a successful switch to less than daily therapy. METHODS: GORD patients who after long-term continuous treatment were able to use less than a daily PPI dose in a placebo-controlled trial were compared to patients who persisted in a daily dosage with respect to general, lifestyle and quality of life characteristics (SF-36 Health Survey) as well as psychological factors (Symptom Check List 90), symptom control on daily PPI (Quality of Life in Reflux and Dyspepsia questionnaire), disease and medication history. RESULTS: Adequate symptom control on daily PPI use and female gender were determinants of successful therapy reduction. A prediction rule including the Quality of Life in Reflux and Dyspepsia vitality dimension and gender correctly predicted 64% of patients to both less than daily and sustained daily treatment (area under the receiver operating characteristic curve = 0.69). CONCLUSION: In the heterogeneous population of PPI users for GORD in primary care, no clinically useful, easily obtainable combination of patient characteristics was able to adequately predict eligibility for therapy reduction. Switching to less than daily therapy remains a process of trial and error in which motivation of the patient and support by the physician will be important factors for success.

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.

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.