Effectiveness of antitussives, anticholinergics or honey versus usual care in adults with uncomplicated acute bronchitis : a study protocol of an open randomised clinical trial in primary care

Introduction Despite the frequent use of therapies in acute bronchitis, the evidence of their benefit is lacking, since only a few clinical trials have been published, with low sample sizes, poor methodological quality and mainly in children. The objective of this study is to compare the effectiveness of three symptomatic therapies (dextromethorphan, ipratropium or honey) associated with usual care and the usual care in adults with acute bronchitis. Methods and analysis This will be a multicentre, pragmatic, parallel group, open randomised trial. Patients aged 18 or over with uncomplicated acute bronchitis, with cough for less than 3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough on a 7-point Likert scale, will be randomised to one of the following four groups: usual care, dextromethorphan 30 mg three times a day, ipratropium bromide inhaler 20 μg two puffs three times a day or honey 30 mg (a spoonful) three times a day, all taken for up to 14 days. The exclusion criteria will be pneumonia, criteria for hospital admission, pregnancy or lactation, concomitant pulmonary disease, associated significant comorbidity, allergy, intolerance or contraindication to any of the study drugs or admitted to a long-term residence. Sample: 668 patients. The primary outcome will be the number of days with moderate-to-severe cough. All patients will be given a paper-based symptom diary to be self-administered. A second visit will be scheduled at day 2 or 3 for assessing evolution, with two more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance and complications. Patients still with symptoms at day 29 will be called 6 weeks after the baseline visit. Ethics and dissemination The study has been approved by the Ethical Board of IDIAP Jordi Gol (reference number: AC18/002). The findings of this trial will be disseminated through research conferences and peer-review journals. Trial registration number NCT03738917; Pre-results

Effectiveness of antitussives, anticholinergics or honey versus usual care in adults with uncomplicated acute bronchitis: a study protocol of an open randomised clinical trial in primary care

Introduction: Despite the frequent use of therapies in acute bronchitis, the evidence of their benefit is lacking, since only a few clinical trials have been published, with low sample sizes, poor methodological quality and mainly in children. The objective of this study is to compare the effectiveness of three symptomatic therapies (dextromethorphan, ipratropium or honey) associated with usual care and the usual care in adults with acute bronchitis. Methods and analysis: This will be a multicentre, pragmatic, parallel group, open randomised trial. Patients aged 18 or over with uncomplicated acute bronchitis, with cough for less than 3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough on a 7-point Likert scale, will be randomised to one of the following four groups: usual care, dextromethorphan 30 mg three times a day, ipratropium bromide inhaler 20 µg two puffs three times a day or honey 30 mg (a spoonful) three times a day, all taken for up to 14 days. The exclusion criteria will be pneumonia, criteria for hospital admission, pregnancy or lactation, concomitant pulmonary disease, associated significant comorbidity, allergy, intolerance or contraindication to any of the study drugs or admitted to a long-term residence. Sample: 668 patients. The primary outcome will be the number of days with moderate-to-severe cough. All patients will be given a paper-based symptom diary to be self-administered. A second visit will be scheduled at day 2 or 3 for assessing evolution, with two more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance and complications. Patients still with symptoms at day 29 will be called 6 weeks after the baseline visit. Ethics and dissemination: The study has been approved by the Ethical Board of IDIAP Jordi Gol (reference number: AC18/002). The findings of this trial will be disseminated through research conferences and peer-review journals. Trial registration: number NCT03738917; Pre-results

Rationale, design and organization of the delayed antibiotic prescription (DAP) trial: a randomized controlled trial of the eficacy 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

Prescripció diferida d’antibiòtics en les infeccions respiratòries agudes no complicades ateses en atenció primària

[cat] La prescripció antibiòtica és una de les principals causes de desenvolupar resistències antimicrobianes i en la majoria de les infeccions on s’utilitzen a l’atenció primària són innecessaris. Tot i aquesta creixent preocupació, Espanya segueix augmentant en l’ús d’antibiòtic i es troba entre els països que més en consumeixen. La prescripció diferida d’antibiòtic podria ser una estratègia efectiva per a disminuir el seu consum. OBJECTIUS: Els objectius principals d’aquesta tesi doctoral són: 1) Determinar l’eficàcia i la seguretat de 2 estratègies diferides comparades amb la prescripció antibiòtica immediata i la no prescripció antibiòtica i 2) Determinar el coneixement i la utilització de la prescripció diferida d’antibiòtic entre els professionals sanitaris de l’atenció primària. MÈTODES: S’han dut a terme dos estudis amb diferent metodologia: 1) Assaig clínic, pragmàtic, randomitzat, multicèntric i obert que compara quatre estratègies de prescripció (dues de prescripció diferida d’antibiòtic, una de prescripció immediata d’antibiòtic i una de no prescripció antibiòtica) en infeccions respiratòries agudes no complicades, i 2) Estudi transversal multicèntric mitjançant una enquesta sobre prescripció diferida d’antibiòtic entre els professionals sanitaris. RESULTATS: En l’assaig clínic hem observat una reducció important en el consum d’antibiòtics en les estratègies de prescripció diferida amb un lleuger increment en la durada de símptomes sense ser clínicament rellevant i sense diferències en els símptomes severs, amb una alta satisfacció similar en els quatre grups, però amb una percepció més alta en creure que els antibiòtics no són adequats per tractar aquest tipus d’episodis en els pacients assignats a prescripcions diferides, així com també amb menys reconsulta pel mateix procés, que el grup de prescripció antibiòtica immediata. En l’estudi on vam valorar grau de coneixement i utilització de la prescripció diferida d’antibiòtic mitjançant una enquesta, vam observar que el grau de coneixement entre els professionals sanitaris espanyols és baixa, però com més es dóna a conèixer més s’utilitza i més positives són les percepcions sobre la prescripció diferida d’antibiòtic com a eina adequada per utilitzar en les infeccions respiratòries agudes no complicades. CONCLUSIONS: Les estratègies de prescripció diferida d’antibiòtic han demostrat la seva eficàcia i seguretat, reduint de manera important el consum d’antibiòtic quan ho comparem amb la prescripció immediata d’antibiòtic, amb un discret augment en la duració de símptomes lleus (sense diferències en símptomes severs) però sense ser clínicament rellevants. La majoria dels professionals d’atenció primària a Espanya no utilitzen encara la PDA a la seva pràctica habitual. Però un cop aquests professionals la coneixen, més la utilitzen i més en prenen consciència que és una estratègia que redueix el consum d’antibiòtic, alhora que manté la satisfacció del pacient. Són necessaris més estudis que abordin limitacions per aplicar la prescripció diferida d’antibiòtic en el nostre àmbit, però amb aquests resultats obtinguts podem posar de manifest la necessitat de difondre l’estratègia diferida entre els professionals de l’atenció primer.[eng] BACKGROUND: The deferred prescription of antibiotic is one of the main causes in developing antimicrobial resistances and in the majority of the infections are unnecessary when used in primary care. Although there is a growing concern about this issue, Spain continues to show an increase in the use of antibiotics and is placed among the countries which consume the most antibiotics. The prescription of antibiotics could be an effective strategy to reduce their consumption. OBJECTIVES: The main objectives of this doctoral thesis are: 1) To determine the efficacy and safety of two deferred strategies compared with immediate prescription and no antibiotic prescription and 2) to determine the degree of knowledge and use of deferred antibiotic prescription among primary care health professionals. METHODOLOGY: Two studies with different methodology have been carried out: 1) Clinical, pragmatic, randomized, multicentre and open trial that compares four prescribing strategies (two delayed prescription of antibiotics, one with immediate antibiotic prescription and one with non-prescription antibiotics) in uncomplicated acute respiratory infections and 2) Multicentre cross-sectional study by means of a survey of delayed antibiotic prescription among health professionals. RESULTS: In the clinical trial we have observed a significant reduction in the consumption of antibiotics in the deferred prescription strategies with a discrete increase in the duration of the symptoms which weren’t clinically relevant and without differences between the severe symptoms, with a high and similar satisfaction among the four groups, but with a higher perception regarding the belief that antibiotics are not adequate to treat these types of episodes in patients assigned to deferred strategies, as well as with fewer re-visits by the same process, than in the immediate antibiotic prescription group. In second study is designed, by means of a survey, to assess the degree of knowledge and use of delayed antibiotic prescription. We observed a low percentage of knowledge among Spanish healthcare professionals, but we also observed that the more the strategy is disclosed, the more it is used, and more positive perceptions are held that deferred antibiotic prescription is an adequate strategy to be used in uncomplicated acute respiratory infections. CONCLUSIONS: Deferred antibiotic prescription strategies have demonstrated their efficacy and safety, significantly reducing antibiotic consumption when compared to the immediate prescription of antibiotics, with a slight increase in the duration of mild symptoms (without differences between severe symptoms) but without being clinically relevant. The majority of primary care professionals in Spain do not use deferred prescription in their usual practice. However, once these professionals obtain knowledge of the strategy, it is used with greater frequency, as they become aware that it reduces antibiotic consumption, while maintaining patient satisfaction. More studies are needed to address the limitations of this study so as to apply the deferred prescription of antibiotics in our area, but with these results we can highlight the need to disseminate the deferred strategy among primary care professionals

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

Abstract 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

Effectiveness of antitussives, anticholinergics or honey versus usual care in adults with uncomplicated acute bronchitis : a study protocol of an open randomised clinical trial in primary care

Introduction Despite the frequent use of therapies in acute bronchitis, the evidence of their benefit is lacking, since only a few clinical trials have been published, with low sample sizes, poor methodological quality and mainly in children. The objective of this study is to compare the effectiveness of three symptomatic therapies (dextromethorphan, ipratropium or honey) associated with usual care and the usual care in adults with acute bronchitis. Methods and analysis This will be a multicentre, pragmatic, parallel group, open randomised trial. Patients aged 18 or over with uncomplicated acute bronchitis, with cough for less than 3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough on a 7-point Likert scale, will be randomised to one of the following four groups: usual care, dextromethorphan 30 mg three times a day, ipratropium bromide inhaler 20 μg two puffs three times a day or honey 30 mg (a spoonful) three times a day, all taken for up to 14 days. The exclusion criteria will be pneumonia, criteria for hospital admission, pregnancy or lactation, concomitant pulmonary disease, associated significant comorbidity, allergy, intolerance or contraindication to any of the study drugs or admitted to a long-term residence. Sample: 668 patients. The primary outcome will be the number of days with moderate-to-severe cough. All patients will be given a paper-based symptom diary to be self-administered. A second visit will be scheduled at day 2 or 3 for assessing evolution, with two more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance and complications. Patients still with symptoms at day 29 will be called 6 weeks after the baseline visit. Ethics and dissemination The study has been approved by the Ethical Board of IDIAP Jordi Gol (reference number: AC18/002). The findings of this trial will be disseminated through research conferences and peer-review journals. Trial registration number NCT03738917; Pre-results

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 &lt; .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.</p

Delayed antibiotic prescribing for respiratory tract infections: 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.<br/

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

Abstract 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)