A trial-based cost-effectiveness analysis of antibiotic prescription strategies for non-complicated respiratory tract infections in children.

BACKGROUND: Antibiotic prescription for respiratory tract infections (RTIs) in children attending primary care centres is almost double that predicted according to bacterial prevalence. Delayed antibiotic prescription (DAP) is designed to deploy a more rational use of antibiotics. While studies have evaluated DAP efficacy and safety for children with RTIs, little research has been conducted on the economic implications. METHODS: Our trial compared cost-effectiveness for DAP, immediate antibiotic prescription (IAP), and no antibiotic prescription (NAP) for children aged 2-14 years with acute uncomplicated RTIs attended to in 39 primary care centres in Spain. The main outcome was the incremental cost-effectiveness ratio (ICER), measured in euros per gained quality-adjusted life days (QALDs). Net monetary benefit (NMB) was also calculated as a tool for decision making. The analysis was performed from a societal perspective for a time horizon of 30 days, and included healthcare direct costs, non-healthcare direct and indirect costs, and the antimicrobial resistance (AMR) cost. RESULTS: DAP was the most cost-effective strategy, even when the cost of AMR was included. QALD values for the three strategies were very similar. IAP compared to DAP was more costly (109.68 vs 100.90 euros) and similarly effective (27.88 vs 27.94 QALDs). DAP compared to NAP was more costly (100.90 vs 97.48 euros) and more effective (27.94 vs. 27.82 QALDs). The ICER for DAP compared to NAP was 28.84 euros per QALD. The deterministic sensitivity analysis indicated that non-healthcare indirect costs had the greatest impact on the ICER. The cost-effectiveness acceptability curve showed that DAP was the preferred option in approximately 81.75% of Monte Carlo iterations, assuming a willingness-to-pay value of 82.2 euros per gained QALD. CONCLUSIONS: When clinicians are in doubt about whether an antibiotic is needed for children with RTIs attending PC centres, those treated with the DAP strategy will have slightly better efficiency outcomes than those treated with IAP because its costs are lower than those of IAP. DAP is also the most cost-effective strategy over a time horizon of 30 days if AMR is considered, despite higher short-term costs than NAP. However, if in the long term the costs of AMR are larger than estimated, NAP could also be an alternative strategy. TRIAL REGISTRATION: This trial has been registered at www. CLINICALTRIALS: gov (identifier NCT01800747; Date: 28/02/2013 (retrospectively registered).

Perceptions and attitudes regarding delayed antibiotic prescription for respiratory tract infections: a qualitative study.

BACKGROUND: Antibiotics are overprescribed for respiratory tract infections (RTIs). However, the decision to prescribe is often complex. Delayed antibiotic prescription (DAP), a strategy designed to promote more rational antibiotic use, is still not widely used. The aim of this study was to explore perceptions and attitudes in primary care professionals, regarding antibiotic use and different DAP strategies for uncomplicated RTIs. METHODS: We conducted a qualitative study, using an inductive thematic approach to generate themes, based on focus group discussions and semi-structured interviews with professionals, recruited from 6 primary care centres (Barcelona metropolitan area, Spain). RESULTS: 26 professionals (25 family physicians and one nurse) were included in four focus group discussions and three semi-structured interviews. Participants commented that RTIs were a main reason for consultation, motivated often by patient anxiety and fear of possible complications, and this was associated with the patients' poor health-related education. Acknowledging inappropriate antibiotic use in the health system, participants attributed this, mainly to defensive medicine strategies. DAP was used when in doubt about the aetiology, and considering factors related to patient-physician interactions. The main perceived advantage of DAP was that it could reduce the need for additional visits, while the main disadvantage was uncertainty regarding proper use by the patient. CONCLUSIONS: DAP was used by participants in cases of doubt, in specific situations, and for specific patient profiles. Weak points were detected in our primary care system and its users that affect the proper use of both antibiotics and DAP, namely, time pressure on professionals, poor patient health-related education, and the lack of a patient-physician relationship in some scenarios.

Delayed antibiotic prescribing for respiratory tract infections: individual patient data meta-analysis.

OBJECTIVE: To assess the overall effect of delayed antibiotic prescribing on average symptom severity for patients with respiratory tract infections in the community, and to identify any factors modifying this effect. DESIGN: Systematic review and individual patient data meta-analysis. DATA SOURCES: Cochrane Central Register of Controlled Trials, Ovid Medline, Ovid Embase, EBSCO CINAHL Plus, and Web of Science. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials and observational cohort studies in a community setting that allowed comparison between delayed versus no antibiotic prescribing, and delayed versus immediate antibiotic prescribing. MAIN OUTCOME MEASURES: The primary outcome was the average symptom severity two to four days after the initial consultation measured on a seven item scale (ranging from normal to as bad as could be). Secondary outcomes were duration of illness after the initial consultation, complications resulting in admission to hospital or death, reconsultation with the same or worsening illness, and patient satisfaction rated on a Likert scale. RESULTS: Data were obtained from nine randomised controlled trials and four observational studies, totalling 55 682 patients. No difference was found in follow-up symptom severity (seven point scale) for delayed versus immediate antibiotics (adjusted mean difference -0.003, 95% confidence interval -0.12 to 0.11) or delayed versus no antibiotics (0.02, -0.11 to 0.15). Symptom duration was slightly longer in those given delayed versus immediate antibiotics (11.4 v 10.9 days), but was similar for delayed versus no antibiotics. Complications resulting in hospital admission or death were lower with delayed versus no antibiotics (odds ratio 0.62, 95% confidence interval 0.30 to 1.27) and delayed versus immediate antibiotics (0.78, 0.53 to 1.13). A significant reduction in reconsultation rates (odds ratio 0.72, 95% confidence interval 0.60 to 0.87) and an increase in patient satisfaction (adjusted mean difference 0.09, 0.06 to 0.11) were observed in delayed versus no antibiotics. The effect of delayed versus immediate antibiotics and delayed versus no antibiotics was not modified by previous duration of illness, fever, comorbidity, or severity of symptoms. Children younger than 5 years had a slightly higher follow-up symptom severity with delayed antibiotics than with immediate antibiotics (adjusted mean difference 0.10, 95% confidence interval 0.03 to 0.18), but no increased severity was found in the older age group. CONCLUSIONS: Delayed antibiotic prescribing is a safe and effective strategy for most patients, including those in higher risk subgroups. Delayed prescribing was associated with similar symptom duration as no antibiotic prescribing and is unlikely to lead to poorer symptom control than immediate antibiotic prescribing. Delayed prescribing could reduce reconsultation rates and is unlikely to be associated with an increase in symptoms or illness duration, except in young children. STUDY REGISTRATION: PROSPERO CRD42018079400.

Delayed Antibiotic Prescription for Children With Respiratory Infections: A Randomized Trial.

OBJECTIVES: To assess the effectiveness and safety of delayed antibiotic prescription (DAP) compared to immediate antibiotic prescription (IAP) and no antibiotic prescription (NAP) in children with uncomplicated respiratory infections. METHODS: Randomized clinical trial comparing 3 antibiotic prescription strategies. The participants were children with acute uncomplicated respiratory infections attended to in 39 primary care centers. Children were randomly assigned into prescription arms as follows: (1) DAP, (2) IAP, or (3) NAP. Primary outcomes were symptom duration and severity. Secondary outcomes were antibiotic use, parental satisfaction, parental beliefs, additional primary care visits, and complications at 30 days. RESULTS: In total, 436 children were included in the analysis. The mean (SD) duration of severe symptoms was 10.1 (6.3) for IAP, 10.9 (8.5) for NAP, and 12.4 (8.4) for DAP (P = .539), although the differences were not statistically significant. The median (interquartile range) of the greatest severity for any symptom was similar for the 3 arms (median [interquartile range] score of 3 [2-4]; P = .619). Antibiotic use was significantly higher for IAP (n = 142 [96%]) compared to DAP (n = 37 [25.3%]) and NAP (n = 17 [12.0%]) (P < .001). Complications, additional visits to primary care, and satisfaction were similar for all strategies. Gastrointestinal adverse effects were higher for IAP. CONCLUSIONS: There was no statistically significant difference in symptom duration or severity in children with uncomplicated respiratory infections who received DAP compared to NAP or IAP strategies; however, DAP reduced antibiotic use and gastrointestinal adverse effects.

Impact of the implementation of best practice guidelines on nurse's evidence-based practice and on nurses' work environment: Research protocol.

AIM: To determine the impact of the Best Practice Spotlight Organization® initiative on nurses' perception of their work environment and their attitudes to evidence-based practice. DESIGN: Quasi-experimental, multicentre study. The intervention is the participation in Best Prectice Spotilight Organizations to implement Best Practice Guidelines. METHODS: The study will include seven centres in the interventional group and 10 in the non-equivalent control group, all of them belonging to the Spanish national health system. The Practice Environment Scale of the Nursing Work Index, and the Health Sciences Evidence-Based Practice Questionnaire will be administered to a sample of 1,572 nurses at the beginning of the programme and at 1 year. This 3-year study started in April 2018 and will continue until December 2021. Statistical analyses will be carried out using the SPSS 25.0. This project was approved by the Drug Research Ethics Committee of the Parc de Salut Mar and registered in Clinical Trials. DISCUSSION: The study findings will show the current state of nurses' perception of their work environment and attitudes to evidence-based practice, and possible changes in these parameters due to the programme. IMPACT: The findings could provide a strong argument for health policymakers to scale up the Best Practice Spotlight Organization® initiative in the Spanish national health system.

Use of delayed antibiotic prescription in primary care: a cross-sectional study.

BACKGROUND: One of several strategies developed to reduce inappropriate antibiotic use in situations where the indication is not clear is delayed antibiotic prescription (DAP), defined as an antibiotic prescription issued for the patient to take only in case of feeling worse or not feeling better several days after the visit. We conducted a survey to identify DAP use in Spanish primary care settings. METHODS: We surveyed 23 healthcare centers located in 4 autonomous regions where a randomized controlled trial (RCT) on DAP was underway. The primary variable was use of DAP. Categorical and quantitative variables were analyzed by means of the chi-squared test and non-parametric tests, respectively. RESULTS: The survey was sent to 375 healthcare professionals, 215 of whom responded (57.3% response rate), with 46% of these respondents declaring that they had used DAP in routine practice before the RCT started (66.6% afterwards), mostly (91.5%) for respiratory tract infections (RTIs), followed by urinary infections (45.1%). Regarding DAP use for RTIs, the most frequent conditions were pharyngotonsillitis (88.7%), acute bronchitis (62.7%), mild chronic obstructive pulmonary disease exacerbations (59.9%), sinusitis (51.4%), and acute otitis media (45.1%). Most respondents considered that DAP reduced emergency visits (85.4%), scheduled visits (79%) and inappropriate antibiotic use (73.7%) and most also perceived patients to be generally satisfied with the DAP approach (75.6%). Having participated or not in the DAP RCT (74.1% versus 46.2%; p < 0.001), having previously used or not used DAP (86.8% versus 44.2%; p < 0.001), and being a physician versus being a nurse (81.8% versus 18.2%; p < 0.001) were factors that reflected significantly higher rates of DAP use. CONCLUSIONS: The majority of primary healthcare professionals in Spain do not use DAP. Those who use DAP believe that it reduces primary care visits and inappropriate antibiotic use, while maintaining patient satisfaction. Given the limited use of DAP in our setting, and given that its use is mainly limited to RTIs, DAP has considerable potential in terms of its implementation in routine practice.

Delayed antibiotic prescribing for respiratory tract infections: protocol of an individual patient data meta-analysis.

INTRODUCTION: Delayed prescribing can be a useful strategy to reduce antibiotic prescribing, but it is not clear for whom delayed prescribing might be effective. This protocol outlines an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) and observational cohort studies to explore the overall effect of delayed prescribing and identify key patient characteristics that are associated with efficacy of delayed prescribing. METHODS AND ANALYSIS: A systematic search of the databases Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Ovid Embase, EBSCO CINAHL Plus and Web of Science was conducted to identify relevant studies from inception to October 2017. Outcomes of interest include duration of illness, severity of illness, complication, reconsultation and patient satisfaction. Study authors of eligible papers will be contacted and invited to contribute raw IPD data. IPD data will be checked against published data, harmonised and aggregated to create one large IPD database. Multilevel regression will be performed to explore interaction effects between treatment allocation and patient characteristics. The economic evaluation will be conducted based on IPD from the combined trial and observational studies to estimate the differences in costs and effectiveness for delayed prescribing compared with normal practice. A decision model will be developed to assess potential savings and cost-effectiveness in terms of reduced antibiotic usage of delayed prescribing and quality-adjusted life years. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Southampton Faculty of Medicine Research Ethics Committee (Reference number: 30068). Findings of this study will be published in peer-reviewed academic journals as well as General Practice trade journals and will be presented at national and international conferences. The results will have important public health implications, shaping the way in which antibiotics are prescribed in the future and to whom delayed prescriptions are issued. PROSPERO REGISTRATION NUMBER: CRD42018079400.

Patients' and physicians' perceptions and attitudes about oral anticoagulation and atrial fibrillation: a qualitative systematic review.

BACKGROUND: Oral anticoagulant therapy reduces the risk of stroke in patients with atrial fibrillation, but many patients are still not prescribed this therapy. The causes of underuse of vitamin K antagonists oral anticoagulants are not clear but could be related, in part, to patients' and physicians' perceptions and attitudes towards the benefits and downsides of this treatment. The purpose of this systematic review was to evaluate and synthesize patients' and physicians' perceptions and attitudes towards the benefits and downsides of vitamin K antagonist, in order to explore potential factors related with its underuse. METHODS: We included studies that used qualitative or mixed methods and focused on patients' and/or physicians' perceptions and attitudes towards oral anticoagulation. We systematically searched PubMed, EMBASE, ISI WoK, and PsycINFO from their inception until May 2013. Two reviewers independently assessed the quality of the included studies and synthesized results using a thematic analysis approach. RESULTS: We included a total of nine studies. In four studies, the quality assessed was excellent and in five was moderate. We identified three themes that were of interest to both physicians and patients: information to reinforce anticoagulation use, balance of benefits and downsides, roles in decision-making and therapy management. Three additional themes were of interest to patients: knowledge and understanding, impact on daily life, and satisfaction with therapy. The main difficulties with the use of anticoagulant treatment according to physicians were the perceived uncertainty, need of individualised decision-making, and the feeling of delegated responsibility as their main concerns. The main factors for patients were the lack of information and understanding. CONCLUSION: Physicians' and patients' perceptions and attitudes might be potential factors in the underuse of treatment with vitamin K antagonists. Improving the quality and usability of clinical guidelines, developing tools to help with the decision-making, enhancing coordination between primary care and hospital care, and improving information provided to patients could help improve the underuse of anticoagulation.

Prescription Strategies in Acute Uncomplicated Respiratory Infections: A Randomized Clinical Trial.

IMPORTANCE: Delayed antibiotic prescription helps to reduce antibiotic use with reasonable symptom control. There are different strategies of delayed prescription, but it is not yet clear which one is the most effective. OBJECTIVE: To determine the efficacy and safety of 2 delayed strategies in acute, uncomplicated respiratory infections. DESIGN, SETTING, AND PARTICIPANTS: We recruited 405 adults with acute, uncomplicated respiratory infections from 23 primary care centers in Spain to participate in a pragmatic, open-label, randomized clinical trial. INTERVENTIONS: Patients were randomized to 1 of 4 potential prescription strategies: (1) a delayed patient-led prescription strategy; (2) a delayed prescription collection strategy requiring patients to collect their prescription from the primary care center; (3) an immediate prescription strategy; or (4) a no antibiotic strategy. Delayed prescription strategies consist of prescribing an antibiotic to take only if the symptoms worsen or if there is no improvement several days after the medical visit. MAIN OUTCOMES AND MEASURES: The primary outcomes were the duration of symptoms and severity of symptoms. Each symptom was scored using a 6-point Likert scale (scores of 3 or 4 were considered moderate; 5 or 6, severe). Secondary outcomes included antibiotic use, patient satisfaction, and patients' beliefs in the effectiveness of antibiotics. RESULTS: A total of 405 patients were recruited, 398 of whom were included in the analysis; 136 patients (34.2%) were men; mean (SD) age, 45 (17) years. The mean severity of symptoms ranged from 1.8 to 3.5 points on the Likert scale, and mean (SD) duration of symptoms described on first visit was 6 (6) days. The mean (SD) general health status on first visit was 54 (20) based on a scale with 0 indicating worst health status; 100, best status. Overall, 314 patients (80.1%) were nonsmokers, and 372 patients (93.5%) did not have a respiratory comorbidity. The presence of symptoms on first visit was similar among the 4 groups. The mean (SD) duration of severe symptoms was 3.6 (3.3) days for the immediate prescription group and 4.7 (3.6) days for the no prescription group. The median (interquartile range [IQR]) of severe symptoms was 3 (1-4) days for the prescription collection group and 3 (2-6) days for the patient-led prescription group. The median (IQR) of the maximum severity for any symptom was 5 (3-5) for the immediate prescription group and the prescription collection group; 5 (4-5) for the patient-led prescription group; and 5 (4-6) for the no prescription group. Patients randomized to the no prescription strategy or to either of the delayed strategies used fewer antibiotics and less frequently believed in antibiotic effectiveness. Satisfaction was similar across groups. CONCLUSIONS AND RELEVANCE: Delayed strategies were associated with slightly greater but clinically similar symptom burden and duration and also with substantially reduced antibiotic use when compared with an immediate strategy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01363531.

Rationale, design and organization of the delayed antibiotic prescription (DAP) trial: a randomized controlled trial of the efficacy and safety of delayed antibiotic prescribing strategies in the non-complicated acute respiratory tract infections in general practice.

BACKGROUND: Respiratory tract infections are an important burden in primary care and it's known that they are usually self-limited and that antibiotics only alter its course slightly. This together with the alarming increase of bacterial resistance due to increased use of antimicrobials calls for a need to consider strategies to reduce their use. One of these strategies is the delayed prescription of antibiotics. METHODS: Multicentric, parallel, randomised controlled trial comparing four antibiotic prescribing strategies in acute non-complicated respiratory tract infections. We will include acute pharyngitis, rhinosinusitis, acute bronchitis and acute exacerbation of chronic bronchitis or chronic obstructive pulmonary disease (mild to moderate). The therapeutic strategies compared are: immediate antibiotic treatment, no antibiotic treatment, and two delayed antibiotic prescribing (DAP) strategies with structured advice to use a course of antibiotics in case of worsening of symptoms or not improving (prescription given to patient or prescription left at the reception of the primary care centre 3 days after the first medical visit). DISCUSSION: Delayed antibiotic prescription has been widely used in Anglo-Saxon countries, however, in Southern Europe there has been little research about this topic. The DAP trial wil evaluate two different delayed strategies in Spain for the main respiratory infections in primary care. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, number http://NCT01363531.