Supplementary Online Content

Transcription

1 Supplementary Online Content de la Poza Abad M, Mas Dalmau G, Moreno Bakedano M, et al; Delayed Antibiotic Prescription (DAP) Group. Prescription strategies in acute uncomplicated respiratory infections: a randomized clinical trial. Published online December 21, JAMA Oncol. doi: /jamainternmed eappendix 1. General exclusion criteria and specific inclusion and exclusion criteria eappendix 2. Primary outcomes and secondary outcomes efigure 1. CONSORT 2010 checklist of information to include when reporting a randomised trial efigure 2. The TIDieR (Template for Intervention Description and Replication) Checklist This supplementary material has been provided by the authors to give readers additional information about their work American Medical Association. All rights reserved.

2 SUPPLEMENTAL MATERIAL eappendix 1 General exclusion criteria - Previous participation in the Delayed antibiotic prescription trial. - Patient is very affected or they have been very affected for a week (constantly) - Patient with signs and symptoms suggestive of disease o serious affectation and/or of complications (particularly pneumonia, mastoiditis, peritonsillar abscess, peritonsillar cellulitis, intraorbital or intracranial complications). - Patient at a risk high of serious complications due to a previous comorbidity. This includes serious conditions involving the heart, lungs, kidney, liver, or neuromuscular disorders, immunosuppression and cystic fibrosis. - If the patient is older than 65 with acute cough and two or more of the following criteria or older than 80 with acute cough and one or more of the following criteria: admission in the previous year, type I or II Diabetes, history of cardiac failure or current use of oral corticosteroids. Specific inclusion and exclusion criteria Acute pharyngitis - Inclusion criteria: adults presenting to the family doctor with sore throat as the main symptom and at least 2 of the Centor criteria: (1) pharyngo-tonsillar exudate, (2) history of fever or feeling of dysthermia, (3) tender anterior cervical adenopathy, and (4) absence of cough. - Exclusion criteria: other causes of sore throat (ulcers, aphthas or thrush), presence of all four Centor criteria, presence of only one or none of the Centor criteria, poor general condition, immunosuppression, antibiotic use in the previous two weeks, history of rheumatic fever, repeated pharyngotonsillitis (more than five episodes in the previous year), pregnant women, and/or use of rapid antigen techniques in the visit. Rhinosinusitis 2015 American Medical Association. All rights reserved.

3 - Inclusion criteria: acute inflammation of the mucous membrane in the nose and pharynx for more than one week, with rhinitis as the main sign and at least one symptom or sign of the sinuses: purulent rhinorrhea or sinus pain. - Exclusion criteria: symptoms for less than a week, poor general condition*, suspected pneumonia, antibiotic use in the previous two weeks and/or use of rapid C-reactive protein test in the visit.. (*) Poor general condition: Patient is very affected or they have been very affected for a week. Acute bronchitis - Inclusion criteria: adults with uncomplicated acute disease presenting with cough as the main symptom and at least one symptom or sign of lower respiratory tract involvement: expectoration, chest pain, shortness of breath or wheezing. - Exclusion criteria: suspected pneumonia (crepitant rales, bronchial murmur, asymmetrical auscultation, tachypnea, vomiting and/or severe diarrhea), bronchial asthma, other acute respiratory or chronic diseases except for mild-to-moderate chronic obstructive pulmonary disease (cystic fibrosis, tuberculosis), active cardiovascular disease, psychiatric diagnoses, dementia, poor general condition, institutionalized in care centers, prior antibiotic use in the previous two weeks, history of admission in the previous year due to respiratory infections and/or use of rapid Creactive protein test in the visit. Exacerbations of mild to moderate chronic obstructive pulmonary disease - Inclusion criteria: > 40 years old, smokers or ex-smokers of over 10 packages-year, with one of the two following diagnoses: chronic bronchitis (cough for more than 3 months, for 3 or more consecutive years), or chronic obstructive pulmonary disease diagnosed with spirometry in the last 2 years (FEV1/FVC <0.7% and FEV1 50%), with an infectious exacerbation and one or both of the following Anthonisen criteria: increased expectoration volume and/or increased shortness of breath. - Exclusion criteria: purulent expectoration, no spirometry in the previous 2 years, severe chronic obstructive pulmonary disease (FEV1 <50%), neoplasm, pregnancy, tracheotomy, poor general condition, antibiotic use in the previous two weeks, suspected pneumonia (crepitant rales, bronchial murmur, asymmetrical auscultation, tachypnea, vomiting and/or severe diarrhea) and/or use of rapid C-reactive protein test in the visit American Medical Association. All rights reserved.

4 eappendix 2 Primary outcome - Duration and severity of symptoms. Patients filled out a daily questionnaire for a maximum of 30 days. Each symptom was scored using a six-point Likert scale (0=no problem, 1=very little problem, 2=slight problem, 3=moderately bad, 4=bad, 5=very bad, 6=as bad as it could be). Symptom scores of 5 or 6 were considered severe and the symptoms scores of 3 or 4 were considered moderate. We included common symptoms such as fever, discomfort or general pain, cough, difficulty sleeping, and changes in everyday life, and specific symptoms according to the condition. Specific symptoms collected for patients with pharyngitis were: swallowing difficulties, headache, nasal mucosity and sore throat. The specific symptoms collected for patients with rhinosinusitis were: spontaneous facial pain, facial pain on touch, headache, nasal mucosity and sore throat. The specific symptoms collected for patients with bronchitis and mild-moderate chronic obstructive pulmonary disease were: expectoration or phlegm, breathlessness, chest pain on breathing and chest noises on breathing. Secondary outcomes - Antibiotic use. Patients were asked about antibiotic use during the last 30 days. - Satisfaction with health care. Patients completed a questionnaire with the Likert scale when they no longer had symptoms. - Belief in the effectiveness of antibiotics. Patients completed a questionnaire with a Likert scale when they no longer had symptoms. - Absenteeism. Patients were asked about the number of days of absence from work or doing their daily activities when they no longer had symptoms. - Risk of complications (pneumonia, abscesses or cellulitis). At 30 days, physicians assessed the complications from clinical records and patient interviews. - Risk of need for unscheduled health care. At 30 days, physicians assessed this need from clinical records and patient interviews American Medical Association. All rights reserved.

5 efigure 1 Section/Topic Title and abstract Introduction Background and objectives CONSORT 2010 checklist of information to include when reporting a randomised trial* Item No 1a 1b Checklist item Identification as a randomised trial in the title Structured summary of trial design, methods, results, and conclusions (for specific guidance see CONSORT for abstracts) 1 Reported on page No 3,4 2a Scientific background and explanation of 5,6 rationale 2b Specific objectives or hypotheses 6 Methods Trial design 3a Description of trial design (such as parallel, factorial) including allocation ratio 3b Important changes to methods after trial commencement (such as eligibility 6,7 Not criteria), with reasons Participants 4a Eligibility criteria for participants 6 and Supplement 1 4b Settings and locations where the data were collected Interventions 5 The interventions for each group with sufficient details to allow replication, including how and when they were actually administered Outcomes 6a Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed 6b Any changes to trial outcomes after the trial commenced, with reasons Sample size 7a How sample size was determined 8 7b When, explanation of any interim analyses and stopping guidelines Randomisation: Sequence 8a Method used to generate the random ,7 7 and Supplement 2 Not Not

6 generatio allocation sequence n 8b Type of randomisation; details of any restriction (such as blocking and block size) Allocation 9 Mechanism used to implement the random concealm allocation sequence (such as sequentially ent numbered containers), describing any mechanis steps taken to conceal the sequence until m interventions were assigned 10 Who generated the random allocation Implementation sequence, who enrolled participants, and who assigned participants to interventions Blinding 11a If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how 11b If relevant, description of the similarity of Statistical methods Results Participant flow (a diagram is strongly recommended) 12a 12b 13a 13b interventions Statistical methods used to compare groups for primary and secondary outcomes Methods for additional analyses, such as subgroup analyses and adjusted analyses For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome For each group, losses and exclusions after randomisation, together with reasons Not 8,9 8,9 Figure 1 Figure 1 Recruitment 14a Dates defining the periods of recruitment 6 and follow-up 14b Why the trial ended or was stopped 12 Baseline data 15 A table showing baseline demographic and clinical characteristics for each group 9 and Table 1 Numbers analysed Table 1 Outcomes and estimation 16 For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups 17a 17b For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) For binary outcomes, presentation of both absolute and relative effect sizes is recommended 9-11 and Table 2-5 Table 5

7 Ancillary analyses 18 Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory Harms 19 All important harms or unintended effects in each group (for specific guidance see CONSORT for harms) Discussion Limitations 20 Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses Generalisability 21 Generalisability (external validity, applicability) of the trial findings Interpretation 22 Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence Other information Registration 23 Registration number and name of trial registry Protocol 24 Where the full trial protocol can be accessed, if available Funding 25 Sources of funding and other support (such as supply of drugs), role of funders 9-11 and Table 2-5 9,10 12, , (ref.27) 4,9,14 *We strongly recommend reading this statement in conjunction with the CONSORT 2010 Explanation and Elaboration for important clarifications on all the items. If relevant, we also recommend reading CONSORT extensions for cluster randomised trials, non-inferiority and equivalence trials, nonpharmacological treatments, herbal interventions, and pragmatic trials. Additional extensions are forthcoming: for those and for up to date references relevant to this checklist, see

8 efigure 2 Item number The TIDieR (Template for Intervention Description and Replication) Checklist*: Information to include when describing an intervention and the location of the information Item Where located ** Primary pap (page or appe number) Other (details) BRIEF NAME 1. Provide the name or a phrase that describes the intervention. WHY 2. Describe any rationale, theory, or goal of the elements essential to the intervention. WHAT 3. Materials: Describe any physical or informational materials used in the intervention, including those provided to participants or used in intervention delivery or in training of intervention providers. Provide information on where the materials can be accessed (e.g. online appendix, URL). 4. Procedures: Describe each of the procedures, activities, and/or processes used in the intervention, including any enabling or support activities. WHO PROVIDED 5. For each category of intervention provider (e.g. psychologist, nursing assistant), describe their expertise, 1 3 and

9 background and any specific training given. HOW 6. Describe the modes of delivery (e.g. face-to-face or by some other mechanism, such as internet or telephone) of the intervention and whether it was provided individually or in a group. WHERE 7. Describe the type(s) of location(s) where the intervention occurred, including any necessary infrastructure or relevant features. 8 8 WHEN and HOW MUCH 8. Describe the number of times the 8 intervention was delivered and over what period of time including the number of sessions, their schedule, and their duration, intensity or dose. TAILORING 9. If the intervention was planned to be Not personalised, titrated or adapted, then describe what, why, when, and how. MODIFICATIONS 10. ǂ If the intervention was modified during Not the course of the study, describe the changes (what, why, when, and how). HOW WELL 11. Planned: If intervention adherence or Not

10 fidelity was assessed, describe how and by whom, and if any strategies were used to maintain or improve fidelity, describe them. 12. ǂ Actual: If intervention adherence or fidelity was assessed, describe the extent to which the intervention was delivered as planned. Not ** Authors - use N/A if an item is not for the intervention being described. Reviewers use? if information about the element is not reported/not sufficiently reported. If the information is not provided in the primary paper, give details of where this information is available. This may include locations such as a published protocol or other published papers (provide citation details) or a website (provide the URL). ǂ If completing the TIDieR checklist for a protocol, these items are not relevant to the protocol and cannot be described until the study is complete. * We strongly recommend using this checklist in conjunction with the TIDieR guide (see BMJ 2014;348:g1687) which contains an explanation and elaboration for each item. * The focus of TIDieR is on reporting details of the intervention elements (and where relevant, comparison elements) of a study. Other elements and methodological features of studies are covered by other reporting statements and checklists and have not been duplicated as part of the TIDieR checklist. When a randomised trial is being reported, the TIDieR checklist should be used in conjunction with the CONSORT statement (see as an extension of Item 5 of the CONSORT 2010 Statement. When a clinical trial protocol is being reported, the TIDieR checklist should be used in conjunction with the SPIRIT statement as an extension of Item 11 of the SPIRIT 2013 Statement (see For alternate study designs, TIDieR can be used in conjunction with the appropriate checklist for that study design (see