Effects of C-reactive protein rapid testing and communication skills training on antibiotic prescribing for acute cough. A cluster factorial randomised controlled trial.

This cluster randomised clinical trial carried out in 20 primary care centres in Barcelona was aimed at assessing the effect of a continuous intervention focused on C-reactive protein (CRP) rapid testing and training in enhanced communication skills (ECS) on antibiotic consumption for adults with acute cough due to lower respiratory tract infection (LRTI). The interventions consisted of general practitioners and nurses' use of CRP point-of-care and training in ECS separately and combined, and usual care. The primary outcomes were antibiotic consumption and variation of the quality-adjusted life years during a 6-week follow-up. The difference in the overall antibiotic prescribing between the winter seasons before and after the intervention was calculated. The sample size calculated could not be reached due to the COVID-19 outbreak. A total of 233 patients were recruited. Compared to the usual care group (56.7%) antibiotic consumption among patients assigned to professionals in the ECS group was significantly lower (33.9%, adjusted odds ratio [aOR] 0.38, 95% CI 0.15-0.94, p = 0.037), whereas patients assigned to CRP consumed 43.8% of antibiotics (aOR 0.70, 95% CI 0.29-1.68, p = 0.429) and 38.4% in the combined intervention group (aOR 0.45, 95% CI, 0.17-1.21; p = 0.112). The overall antibiotic prescribing rates in the centres receiving training were lower after the intervention compared to those assigned to usual care, with significant reductions in ß-lactam rates. Patient recovery was similar in all groups. Despite the limited power due to the low number of patients included, we observed that continuous training achieved reductions in antibiotic consumption.

Antimicrobial Agent Use for Urinary Tract Infection in Long-Term Care Facilities in Spain: Results from a Retrospective Analytical Cohort Analysis.

Urinary tract infections (UTIs) are highly prevalent in long-term care facilities, constituting the most common infection in this setting. Our research focuses on analyzing clinical characteristics and antimicrobial prescriptions for UTIs in residents across nursing homes (NH) in Spain. This is a retrospective analytical cohort analysis using a multifaceted approach based on the normalization process theory to improve healthcare quality provided by nursing staff in 34 NHs in Spain. In this study, we present the results of the first audit including 719 UTI cases collected between February and April 2023, with an average age of 85.5 years and 74.5% being women. Cystitis and pyelonephritis presented distinct symptom patterns. Notably, 6% of asymptomatic bacteriuria cases were treated. The prevalence of dipstick usage was 83%, and that of urine culture was only 16%, raising concerns about overreliance, including in the 46 asymptomatic cases, leading to potential overdiagnosis and antibiotic overtreatment. Improved diagnostic criteria and personalized strategies are crucial for UTI management in NHs, emphasizing the need for personalized guidelines on the management of UTIs to mitigate indiscriminate antibiotic use in asymptomatic cases.

Urinary Tract Infections in Men in Primary Care in Catalonia, Spain.

Antimicrobial resistance is a major global problem that is primarily driven by the excessive and inappropriate utilization of antibiotics. Urinary tract infections (UTIs) are frequent in primary health care (PHC) and are typically treated with antibiotics. There is ample evidence on the management of this condition in women but not in men. The aim of this study was to describe the epidemiology of UTIs in men in Catalonia, Spain. We conducted a population-based observational cohort study that included male patients diagnosed with UTI within our SIDIAP and CMBD database during the period from 2012 to 2021. UTI diagnoses were grouped into five main groups (cystitis, prostatitis, orchitis and epididymitis, urethritis, and pyelonephritis). Of the 316,762 men with at least one recorded UTI episode, the majority were registered with a diagnosis of cystitis in PHC (212,958 patients). Quinolones were the most commonly recorded treatment for UTIs (between 18.3% and 38.6%, depending on the group), except for urethritis in which a combination of antibiotics (36.7%) was most frequently used. The treatment duration period was between 9 days and 18 days, except for the prostatitis group, in which treatment was extended to 21 days. Urine cultures were documented in up to 30% in the cystitis group. Pyelonephritis was the category linked to most septicemia cases (3.0%). Conclusions: This is the first study to assess UTIs in men using a large PHC database in Spain. The sociodemographic characteristics of our sample are similar to other studies in the literature. In our setting, the use of quinolones for the treatment of UTIs is the most registered, and its duration was between 9 days and 18 days, despite the fact that resistance to quinolones exceeds 20% of the strains in our area.

Longitudinal treatment patterns in patients recently diagnosed with type 2 diabetes mellitus in Catalonia.

AIM: To investigate initial and subsequent treatments prescribed to newly diagnosed type 2 diabetes mellitus (T2DM) patients. METHODS: Data from SIDIAP (Information System for Research in Primary Care) including all recorded incident T2DM patients in primary care between 2015 and 2020. We used descriptive statistics and different graphical techniques to describe the most frequent longitudinal patterns. RESULTS: A total of 86,854 patients were included. 78.3 % of the patients began treatment with a single metformin medication and 21.7 % began with a combination therapy (CT). Metformin was the most frequent treatment as first and third-line therapy, while the CT of metformin with DPP4i or sulfonylurea was more prevalent as second-line. Most common first to third-line pattern was initial metformin for 15 months, adding a second antidiabetic in the second line, staying in CT for 6 months, and switching back to single metformin. Treatment patterns varied depending on HbA1c levels, with higher levels (>8 %) being associated with changes to CT and lower levels with switches to monotherapy or temporary discontinuation. CONCLUSION: The study described in detail the different treatment patterns in incident T2DM patients in Catalonia, its adherence to the guidelines, and how the changes are associated to the HbA1c dynamics.

Impact of Second-Line Combination Treatment for Type 2 Diabetes Mellitus on Disease Control: A Population-Based Cohort Study.

BACKGROUND: Type 2 diabetes mellitus is a chronic disease affecting millions of people worldwide. Achieving and maintaining glycemic control is essential to prevent or delay complications and different strategies are available as second-line treatment options for patients with type 2 diabetes who do not achieve glycemic control with metformin monotherapy. OBJECTIVE: The aim of this work is to describe the impact of initiating a combination treatment to reduce glycated hemoglobin in patients with type 2 diabetes with insufficient glycemic control. METHODS: We included patients with a type 2 diabetes diagnosis between 2015 and 2020 at the Information System for Research in Primary Care (SIDIAP) database in Catalonia, Spain. The primary outcome was the time to glycated hemoglobin control (≤ 7%) during the first 720 days, expressed as the restricted mean survival time. Adjusted differences of the restricted mean survival time were compared to analyze the performance of each treatment versus the combination with a sulfonylurea. Adherence was calculated as the medication possession ratio using an algorithm to model treatment exposure. RESULTS: A total of 28,425 patients were analyzed. The most frequent combinations were those with sulfonylureas and dipeptidyl peptidase-4 inhibitors. All treatments reduced glycated hemoglobin and the restricted mean survival time for the sulfonylurea treatment was 455 (451-459) days although combinations with glucagon-like peptide-1 and insulin reached glycemic control earlier, - 126 days (- 152 to - 100, p < 0.001) and - 69 days (- 88 to - 50, p < 0.001), respectively. Adherence was high in all groups apart from the insulin combination and had a significant effect in reducing glycated hemoglobin except in sodium-glucose cotransporter type 2 inhibitors and insulin. Glucagon-like peptide-1 and sodium-glucose cotransporter type 2 inhibitors showed significant reductions in weight. CONCLUSIONS: Patients achieved the glycated hemoglobin goal with second-line treatments. Glucagon-like peptide-1 and insulin combinations achieved the goal earlier than sulfonylurea combinations. Adherence significantly reduced the time to glycated hemoglobin control except for the combination with sodium-glucose cotransporter type 2 inhibitors.

Mycobacterium manresensis induces trained immunity in vitro.

The COVID-19 pandemic posed a global health crisis, with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants weakening vaccine-driven protection. Trained immunity could help tackle COVID-19 disease. Our objective was to analyze whether heat-killed Mycobacterium manresensis (hkMm), an environmental mycobacterium, induces trained immunity and confers protection against SARS-CoV-2 infection. To this end, THP-1 cells and primary monocytes were trained with hkMm. The increased secretion of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1ß, and IL-10, metabolic activity, and changes in epigenetic marks suggested hkMm-induced trained immunity in vitro. Healthcare workers at risk of SARS-CoV-2 infection were enrolled into the MANRECOVID19 clinical trial (NCT04452773) and were administered Nyaditum resae (NR, containing hkMm) or placebo. No significant differences in monocyte inflammatory responses or the incidence of SARS-CoV-2 infection were found between the groups, although NR modified the profile of circulating immune cell populations. Our results show that M. manresensis induces trained immunity in vitro but not in vivo when orally administered as NR daily for 14 days.

Diagnostic and Therapeutic Management of Urinary Tract Infections in Catalonia, Spain: Protocol for an Observational Cohort Study.

BACKGROUND: Antibiotic resistance is an individual and public health problem; multidrug-resistant infections could cause an estimated 10 million deaths worldwide by 2050. Unnecessary use of antimicrobials is the most important cause of resistance generation in the community, and an estimated 80% of antimicrobials are prescribed in primary health care, frequently for urinary tract infections (UTIs). OBJECTIVE: This paper presents the protocol for the first phase of the Urinary Tract Infections in Catalonia (Infeccions del tracte urinari a Catalunya) project. We aim to examine the epidemiology of the different types of UTIs in Catalonia (an autonomous community in Spain) and their diagnostic and therapeutic management by health professionals. Furthermore, we aim to evaluate the correlation between types and total consumption of antibiotics for recurrent UTIs in 2 cohorts of women with the presence and severity of infectious complications of urological origin, especially pyelonephritis and sepsis, and 2 potentially serious infections: pneumonia and COVID-19. METHODS: The study is a population-based observational cohort study including adults with a diagnosis of UTI registered in the Information System for the Development of Research in Primary Care (in Catalan: Sistema d'informació per al desenvolupament de la investigació en atenció primària), the Minimum Basic Data Sets of Hospital Discharges and Emergency Departments (in Catalan: Conjunt mínim bàsic de dades a l'hospitalització d'aguts i d'atenció urgent), and data from the Hospital Dispensing Medicines Register (in Catalan: Medicació hospitalària de dispensació ambulatòria) of Catalonia from the period between 2012 and 2021. We will evaluate the variables obtained from the databases to analyze the proportion of different types of UTIs, the percentage of adequate antibiotic treatments prescribed or received for recurrent UTIs according to the national guidelines, and the proportion of UTIs with complications. RESULTS: We expect to describe the epidemiology of UTIs in Catalonia from 2012 to 2021, as well as describe the diagnostic and therapeutic management of UTIs by health professionals. CONCLUSIONS: We expect to find a high percentage of UTI cases with inadequate management according to the national guidelines, considering that on many occasions UTIs are treated with second- or third-line antibiotic therapies with a preference for the longest regimens. Furthermore, the use of antibiotic suppressive therapies, or prophylaxis, in recurrent UTIs will likely be highly variable. Moreover, we aim to determine whether women with recurrent UTIs treated with antibiotic suppressive therapies have a higher incidence and severity of potentially serious future infections, with special attention to acute pyelonephritis, urosepsis, COVID-19, and pneumonia, compared to women who receive antibiotic treatment after they present with a UTI. This is an observational study of data from administrative databases that will not allow causality analysis. The limitations of the study will be handled according to the appropriate statistical methods. TRIAL REGISTRATION: European Union Electronic Register of Post-Authorisation Studies EUPAS49724; https://www.encepp.eu/encepp/viewResource.htm?id=49725. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44244.

Effectiveness of antitussives, anticholinergics, and honey versus usual care in adults with uncomplicated acute bronchitis: a multiarm randomized clinical trial.

BACKGROUND: Despite the frequent use of symptomatic therapies in cough, evidence of their benefits is lacking. OBJECTIVE: We compared the effectiveness of 3 symptomatic therapies and usual care in acute bronchitis. METHODS: Multicenter, pragmatic, multiarm parallel group, open randomized trial in primary care (ClinicalTrials.gov, Identifier: NCT03738917) was conducted in Catalonia. Patients ≥18 with uncomplicated acute bronchitis, with cough<3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough (7-point Likert scale), were randomized to usual care, dextromethorphan 15 mg t.i.d., ipratropium bromide inhaler 20 µg 2 puffs t.i.d, or 30 mg of honey t.i.d., all taken for up to 14 days. The main outcome measure was the number of days with moderate-to-severe cough. A symptom diary was given. A second visit was scheduled at days 2-3 for assessing evolution, with 2 more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance, and complications. RESULTS: We failed to achieve the sample size scheduled due to the COVID-19 pandemic. We finally recruited 194 patients. The median number of days with moderate-to-severe cough (score ≥ 3) in the usual care arm was 5 (interquartile range [IQR], 4, 8.75), 5 in the ipratropium bromide arm (IQR, 3, 8), 5 in the dextromethorphan arm (IQR, 4, 9.75), and 6 in the honey arm (IQR, 3.5, 7). The same results were obtained in the Kaplan-Meier survival analysis for the median survival time of each arm with the usual care as the reference group. CONCLUSION: The symptomatic treatment evaluated has shown to be ineffective against cough.

Cough is the most frequent symptom reported by patients with lower respiratory tract infections. Despite being a defense mechanism, cough is unpleasant and negatively affects sleep and overall well-being. Accordingly, many patients with acute cough seek medical help to mitigate symptoms and reduce their duration despite the typically self-limiting nature of the condition. In this randomized clinical trial, we explored the benefit of 3 common symptomatic treatments recommended in some guidelines for relieving this symptom during the course of uncomplicated acute bronchitis, a cough suppressant, an inhaler, and honey intake. Although the total number of patients initially expected could not be achieved due to the disruption caused by the COVID-19 pandemic, the results of our study demonstrate a lack of efficacy of these products as the number of days of severe-to-moderate cough was similar in the 3 arms and comparable to the group of patients allocated to usual care.

Best methods for urine sample collection for diagnostic accuracy in women with urinary tract infection symptoms: a systematic review.

BACKGROUND: Most guidelines recommend a midstream urine (MSU) or a midstream clean-catch (MSCC) sample for urinalysis. However, whether this sample is better than others is still controversial. OBJECTIVES: To assess the most adequate non-invasive method to collect a urine specimen for diagnosing urinary tract infections (UTI) in symptomatic non-pregnant women. METHODS: This review was conducted according to the Systematic Reviews of Diagnostic Test Accuracy guidelines (PROSPERO CRD42021241758). PubMed was searched paired sample studies and controlled trials. Studies comparing MSCC, MSU without cleaning, first-void urine, and random voiding samples were considered. Studies evaluating invasive methods were excluded. The main outcome was diagnostic accuracy of urine cultures. Contamination rates were evaluated. The risk of bias tool for systematic reviews on diagnostic accuracy (QUADAS-2) was assessed. RESULTS: Six studies including 1,010 patients were evaluated. Only two studies used paired samples. No study was considered as having low risk of bias. There was no difference in contamination for MSU specimens collected with or without cleansing and between random void urine collection and MSCC. In one study comparing first-void urine with MSU samples, the contamination rate was lower in the latter, but the gold standard of urine culture was only used for one sampling collection. CONCLUSIONS: To the best of our knowledge, this systematic review is the first to assess the evidence available from different exclusively non-invasive urine sampling. Despite being widely recommended, our review did not find consistent evidence that asking women to provide midstream samples with or without cleansing is better.

Urine is one type of specimen that can be easily collected from a patient. Urinalysis testing can give the doctor valuable information about the presence of an infection in the urine and the type of microorganism causing this infection. The physician can also use the information from urine testing to diagnose and treat other diseases. The collection of the mid-stream of the urination has always been advocated. However, this recommendation has never been proven with good quality studies, and the results of the studies carried out so far have been controversial. In a systematic review, we recently determined that the use of any specimen during urination is as good as midstream collection when patients are requested to provide a urine sample and in terms of quality even specimens collected without proper cleansing are also comparable to mid-stream collection with cleansing. In the present systematic review, we evaluated the most adequate non-invasive method to collect a urine specimen for diagnosing urinary tract infections in symptomatic non-pregnant women. We identified only six studies comparing different urine sampling techniques and we did not observe any difference regarding the quality of the urine between them.

Double-blind placebo-controlled randomized clinical trial to assess the efficacy of montelukast in mild to moderate respiratory symptoms of patients with long COVID: E-SPERANZA COVID Project study protocol.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to affect the globe. After 18 months of the SARS-CoV-2 emergence, clinicians have clearly defined a subgroup of patients with lasting, disabling symptoms. While big strides have been made in understanding the acute phase of SARS-CoV-2 infection, the pathophysiology of long COVID is still largely unknown, and evidence-based, effective treatments for this condition remain unavailable. OBJECTIVES: To evaluate the efficacy of 10 mg oral montelukast every 24 h versus placebo in improving quality of life associated with mild to moderate respiratory symptoms in patients with long COVID as measured with the COPD Assessment Test (CAT) questionnaire. The secondary objectives will evaluate the effect of montelukast versus placebo on improving exercise capacity, COVID-19 symptoms (asthenia, headache, mental confusion or brain fog, ageusia, and anosmia), oxygen desaturation during exertion, functional status, and mortality. METHODS AND ANALYSIS: Phase III, randomized, double-blind clinical trial. We will include 18- to 80-year-old patients with SARS-CoV-2 infection and mild to moderate respiratory symptoms lasting more than 4 weeks. Participants will be randomly allocated in a 1:1 ratio to the intervention (experimental treatment with 10 mg/day montelukast) or the control group (placebo group), during a 28-day treatment. Follow-up will finish 56 days after the start of treatment. The primary outcome will be health-related quality of life associated with respiratory symptoms according to the COPD Assessment Test 4 weeks after starting the treatment. The following are the secondary outcomes: (a) exercise capacity and oxygen saturation (1-min sit-to-stand test); (b) Post-COVID-19 Functional Status Scale; (c) other symptoms: asthenia, headache, mental confusion (brain fog), ageusia, and anosmia (Likert scale); (d) use of healthcare resources; (e) mortality; (f) sick leave duration in days; and (g) side effects of montelukast. ETHICS AND DISSEMINATION: This study has been approved by the Clinical Research Ethics Committee of the IDIAPJGol (reference number 21/091-C). The trial results will be published in open access, peer-reviewed journals and explained in webinars to increase awareness and understanding about long COVID among primary health professionals. TRIAL REGISTRATION: ClinicalTrials.gov NCT04695704 . Registered on January 5, 2021. EudraCT number 2021-000605-24. Prospectively registered.

Clinical effectiveness and bacteriological eradication of three different Short-COurse antibiotic regimens and single-dose fosfomycin for uncomplicated lower Urinary Tract infections in adult women (SCOUT study): study protocol for a randomised clinical trial.

INTRODUCTION: Uncomplicated lower urinary tract infections (uLUTI) are a common problem in primary care. Current local guidelines recommend the use of a single 3 g dose of fosfomycin. However, most general practitioners (GP) prefer short-course therapies to single-dose therapy. No study has compared head-to-head short-course antimicrobial agents for uLUTIs. Therefore, the aim of this randomised clinical trial is to compare three different short-course antibiotic therapies with a single-dose of fosfomycin for these infections. METHODS AND ANALYSIS: This will be a pragmatic, multicentre, parallel group, open trial. Women aged 18 or older and with symptoms of uLUTI and a positive urine dipstick analysis will be randomised to one of the following four groups: a single dose of 3 g of fosfomycin, 2 days of 3 g of fosfomycin o.d., 3 days of pivmecillinam 400 mg three times per day (t.i.d) or 5 days of nitrofurantoin 100 mg t.i.d. A total sample of 1120 patients was calculated. The primary endpoint is clinical effectiveness at day 7, defined as cure of symptoms reported by the patients in a diary including four symptoms: dysuria, urgency, frequency and suprapubic pain, which will be scored on a 4-point severity scale (not present/mild/moderate/severe). Follow-up visits are scheduled at days 7 (phone call), 14 and 28 for assessing evolution. Urine samples will be collected in the three on-site visits and urine cultures performed. If positive, antibiograms for the three antibiotics studied will be performed. Bacterial eradication will be measured at days 14 and 28. ETHICS AND DISSEMINATION: The study was approved by the Ethical Board of IDIAP Jordi Gol (reference number: 21/173-AC) and Spanish Agency of Medicines and Medical Devices. The findings of this trial will be disseminated through research conferences and peer-review journals. TRIAL REGISTRATION NUMBER: NCT04959331; EudraCT Number: 2021-001332-26. TIME SCHEDULE: January 2022 to April 2023.

A Co-Design Process to Elaborate Educational Materials to Promote Appropriate Use of Antibiotics for Acute Lower Respiratory Tract Infections in Primary Healthcare in Catalonia (Spain).

PURPOSE: Co-design processes with patients allow developing health education materials, that are adapted to the population's knowledge and use of language, to reduce inappropriate antibiotic use. PATIENTS AND METHODS: This study presents a co-design process of educational material with patients (over 18 years old) with a previous diagnosis of acute lower respiratory tract infection. The co-design was framed within a qualitative study (Phase I, interviews; Phase II, focus group) conducted in Barcelona between April and September 2019. RESULTS: Twenty-nine semi-structured interviews were conducted. Six people participated in the focus group. Based on participants' narratives, educational materials can be useful to support healthcare consultations. Materials should be designed to be accessible in terms of the content and language used. CONCLUSION: The co-design of educational materials is essential for health promotion. This study presents an example of how materials can be co-developed with patients. The material elaborated in this study is being used for the ISAAC-CAT project and may be useful for future research, practice in health services and health policy.

Autonomy, power dynamics and antibiotic use in primary healthcare: A qualitative study.

Antibiotic resistance is a global health concern. Although numerous strategies have tried to reduce inadequate antibiotic prescribing, antibiotics are still prescribed in 60% of acute lower respiratory tract infections (ALRTIs) cases in Catalonia (Spain). This study aims to explore service users' experiences of ALRTIs, the quality and access to healthcare services, and health education. Selective purposive sampling was carried out, based on a prior definition of participant characteristics. These were sex, age, ethnicity, date of the last ALRTI, number of ALRTIs in the last year, and treatments received. Participants with a previous diagnosis of ALRTIs were recruited from three primary health care centres in Barcelona and one in Tarragona. Twenty-nine interviews were conducted between April and June 2019. A content thematic analysis was performed. Three themes were identified: 1) risk perceptions and help-seeking; 2) treatment preferences and antibiotic use; and 3) relationship dynamics and communication with healthcare professionals. Accounts of service users' sense of autonomy towards their health and power dynamics within the healthcare system were apparent. Supporting service users to become reliable, subjective and agentic experts of their health and bodies could help them to voice their healthcare agendas. Power structures embedded within healthcare, political and economic institutions should be challenged so that healthcare services can be co-developed (with service users) and based on service users' autonomy and horizontal relationships. Special consideration should be paid to the intersection of social vulnerabilities. A concordance approach to prescribing could be key to improve the responsible use of antibiotics and to contribute to the prevention of AMR in primary healthcare. The marketisation of health, and the increased demands of private healthcare in Spain due to the financial pressures on public healthcare as a consequence of the financial crisis of 2008 and the COVID-19 pandemic, are a risk for promoting adequate antibiotic prescribing and use. Trial registration The ISAAC-CAT study has been registered in the NCT registry, ID: NCT03931577.

Effectiveness and cost-effectiveness of Improving clinicians' diagnostic and communication Skills on Antibiotic prescribing Appropriateness in patients with acute Cough in primary care in CATalonia (the ISAAC-CAT study): study protocol for a cluster randomised controlled trial.

BACKGROUND: Despite their marginal benefit, about 60% of acute lower respiratory tract infections (ALRTIs) are currently treated with antibiotics in Catalonia. This study aims to evaluate the effectiveness and efficiency of a continuous disease-focused intervention (C-reactive protein [CRP]) and an illness-focused intervention (enhancement of communication skills to optimise doctor-patient consultations) on antibiotic prescribing in patients with ALRTIs in Catalan primary care centres. METHODS/DESIGN: A cluster randomised, factorial, controlled trial aimed at including 20 primary care centres (N = 2940 patients) with patients older than 18 years of age presenting for a first consultation with an ALRTI will be included in the study. Primary care centres will be identified on the basis of socioeconomic data and antibiotic consumption. Centres will be randomly assigned according to hierarchical clustering to any of four trial arms: usual care, CRP testing, enhanced communication skills backed up with patient leaflets, or combined interventions. A cost-effectiveness and cost-utility analysis will be performed from the societal and national healthcare system perspectives, and the time horizon of the analysis will be 1 year. Two qualitative studies (pre- and post-clinical trial) aimed to identify the expectations and concerns of patients with ALRTIs and the barriers and facilitators of each intervention arm will be run. Family doctors and nurses assigned to the interventions will participate in a 2-h training workshop before the inception of the trial and will receive a monthly intervention-tailored training module during the year of the trial period. Primary outcomes will be antibiotic use within the first 6 weeks, duration of moderate to severe cough, and the quality-adjusted life-years. Secondary outcomes will be duration of illness and severity of cough measured using a symptom diary, healthcare re-consultations, hospital admissions, and complications. Healthcare costs will be considered and expressed in 2021 euros (year foreseen to finalise the study) of the current year of the analysis. Univariate and multivariate sensitivity analyses will be carried out. DISCUSSION: The ISAAC-CAT project will contribute to evaluate the effectiveness and efficiency of different strategies for more appropriate antibiotic prescribing that are currently out of the scope of the actual clinical guidelines. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03931577.

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.