Effect of Brain-Gut Behavioral Treatments on Abdominal Pain in Irritable Bowel Syndrome: Systematic Review and Network Meta-analysis.

BACKGROUND & AIMS: Some brain-gut behavioral treatments (BGBTs) are beneficial for global symptoms in irritable bowel syndrome (IBS). United States management guidelines suggest their use in patients with persistent abdominal pain, but their specific effect on this symptom has not been assessed systematically. METHODS: We searched the literature through December 16, 2023, for randomized controlled trials (RCTs) assessing efficacy of BGBTs for adults with IBS, compared with each other or a control intervention. Trials provided an assessment of abdominal pain resolution or improvement at treatment completion. We extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures and reporting pooled relative risks (RRs) of abdominal pain not improving with 95% confidence intervals (CIs), ranking therapies according to the P score. RESULTS: We identified 42 eligible randomized controlled trials comprising 5220 participants. After treatment completion, the BGBTs with the largest numbers of trials and patients recruited demonstrating efficacy for abdominal pain, specifically, included self-guided/minimal contact cognitive behavioral therapy (CBT) (RR, 0.71; 95% CI, 0.54-0.95; P score, 0.58), face-to-face multicomponent behavioral therapy (RR, 0.72; 95% CI, 0.54-0.97; P score, 0.56), and face-to-face gut-directed hypnotherapy (RR, 0.77; 95% CI, 0.61-0.96; P score, 0.49). Among trials recruiting only patients with refractory global IBS symptoms, group CBT was more efficacious than routine care for abdominal pain, but no other significant differences were detected. No trials were low risk of bias across all domains, and there was evidence of funnel plot asymmetry. CONCLUSIONS: Several BGBTs, including self-guided/minimal contact CBT, face-to-face multicomponent behavioral therapy, and face-to-face gut-directed hypnotherapy may be efficacious for abdominal pain in IBS, although none was superior to another.

Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting. METHODS: This randomised, double-blind, placebo-controlled trial (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment [ATLANTIS]) was conducted at 55 general practices in England. Eligible participants were aged 18 years or older, with Rome IV IBS of any subtype, and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score ≥75 points) despite dietary changes and first-line therapies, a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation. Participants were randomly assigned (1:1) to low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months, with dose titration over 3 weeks (up to 30 mg once daily), according to symptoms and tolerability. Participants, their general practitioners, investigators, and the analysis team were all masked to allocation throughout the trial. The primary outcome was the IBS-SSS score at 6 months. Effectiveness analyses were according to intention-to-treat; safety analyses were on all participants who took at least one dose of the trial medication. This trial is registered with the ISRCTN Registry (ISRCTN48075063) and is closed to new participants. FINDINGS: Between Oct 18, 2019, and April 11, 2022, 463 participants (mean age 48·5 years [SD 16·1], 315 [68%] female to 148 [32%] male) were randomly allocated to receive low-dose amitriptyline (232) or placebo (231). Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS score between groups at 6 months (-27·0, 95% CI -46·9 to -7·10; p=0·0079). 46 (20%) participants discontinued low-dose amitriptyline (30 [13%] due to adverse events), and 59 (26%) discontinued placebo (20 [9%] due to adverse events) before 6 months. There were five serious adverse reactions (two in the amitriptyline group and three in the placebo group), and five serious adverse events unrelated to trial medication. INTERPRETATION: To our knowledge, this is the largest trial of a tricyclic antidepressant in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated. General practitioners should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration, such as the self-titration document developed for this trial. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme (grant reference 16/162/01).

British Society of Gastroenterology guidelines on the management of irritable bowel syndrome.

Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. Since publication of the last British Society of Gastroenterology (BSG) guideline in 2007, substantial advances have been made in understanding its complex pathophysiology, resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder. Moreover, there has been a considerable amount of new evidence published concerning the diagnosis, investigation and management of IBS. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients. One of the strengths of this guideline is that the recommendations for treatment are based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of trial-based and network meta-analyses assessing the efficacy of dietary, pharmacological and psychological therapies in treating IBS. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence. Finally, this guideline identifies novel treatments that are in development, as well as highlighting areas of unmet need for future research.

Patients' Experiences of Telephone-Based and Web-Based Cognitive Behavioral Therapy for Irritable Bowel Syndrome: Longitudinal Qualitative Study.

BACKGROUND: Cognitive behavioral therapy (CBT) is recommended in guidelines for people with refractory irritable bowel syndrome (IBS). However, the availability of CBT is limited, and poor adherence has been reported in face-to-face CBT. OBJECTIVE: Nested within a randomized controlled trial of telephone- and web-delivered CBT for refractory IBS, this qualitative study aims to identify barriers to and facilitators of engagement over time with the interventions, identify social and psychological processes of change, and provide insight into trial results. METHODS: A longitudinal qualitative study was nested in a randomized controlled trial. Repeated semistructured interviews were conducted at 3 (n=34) and 12 months (n=25) post baseline. Participants received telephone-based CBT (TCBT; n=17 at 3 months and n=13 at 12 months) or web-based CBT (WCBT; n=17 at 3 months and n=12 at 12 months). Inductive thematic analysis was used to analyze the data. RESULTS: Participants viewed CBT as credible for IBS, perceived their therapists as knowledgeable and supportive, and liked the flexibility of web-based and telephone-based delivery; these factors facilitated engagement. Potential barriers to engagement in both groups (mostly overcome by our participants) included initial skepticism and concerns about the biopsychosocial nature of CBT, initial concerns about telephone-delivered talking therapy, challenges of maintaining motivation and self-discipline given already busy lives, and finding nothing new in the WCBT (WCBT group only). Participants described helpful changes in their understanding of IBS, attitudes toward IBS, ability to recognize IBS patterns, and IBS-related behaviors. Consistent with the trial results, participants described lasting positive effects on their symptoms, work, and social lives. Reasons and remedies for some attenuation of effects were identified. CONCLUSIONS: Both TCBT and WCBT for IBS were positively received and had lasting positive impacts on participants' understanding of IBS, IBS-related behaviors, symptoms, and quality of life. These forms of CBT may broaden access to CBT for IBS.

Talking in primary care (TIP): protocol for a cluster-randomised controlled trial in UK primary care to assess clinical and cost-effectiveness of communication skills e-learning for practitioners on patients' musculoskeletal pain and enablement.

INTRODUCTION: Effective communication can help optimise healthcare interactions and patient outcomes. However, few interventions have been tested clinically, subjected to cost-effectiveness analysis or are sufficiently brief and well-described for implementation in primary care. This paper presents the protocol for determining the effectiveness and cost-effectiveness of a rigorously developed brief eLearning tool, EMPathicO, among patients with and without musculoskeletal pain. METHODS AND ANALYSIS: A cluster randomised controlled trial in general practitioner (GP) surgeries in England and Wales serving patients from diverse geographic, socioeconomic and ethnic backgrounds. GP surgeries are randomised (1:1) to receive EMPathicO e-learning immediately, or at trial end. Eligible practitioners (eg, GPs, physiotherapists and nurse practitioners) are involved in managing primary care patients with musculoskeletal pain. Patient recruitment is managed by practice staff and researchers. Target recruitment is 840 adults with and 840 without musculoskeletal pain consulting face-to-face, by telephone or video. Patients complete web-based questionnaires at preconsultation baseline, 1 week and 1, 3 and 6 months later. There are two patient-reported primary outcomes: pain intensity and patient enablement. Cost-effectiveness is considered from the National Health Service and societal perspectives. Secondary and process measures include practitioner patterns of use of EMPathicO, practitioner-reported self-efficacy and intentions, patient-reported symptom severity, quality of life, satisfaction, perceptions of practitioner empathy and optimism, treatment expectancies, anxiety, depression and continuity of care. Purposive subsamples of patients, practitioners and practice staff take part in up to two qualitative, semistructured interviews. ETHICS APPROVAL AND DISSEMINATION: Approved by the South Central Hampshire B Research Ethics Committee on 1 July 2022 and the Health Research Authority and Health and Care Research Wales on 6 July 2022 (REC reference 22/SC/0145; IRAS project ID 312208). Results will be disseminated via peer-reviewed academic publications, conference presentations and patient and practitioner outlets. If successful, EMPathicO could quickly be made available at a low cost to primary care practices across the country. TRIAL REGISTRATION NUMBER: ISRCTN18010240.

Empathy in patient-clinician interactions when using telecommunication: A rapid review of the evidence.

Objectives: The COVID-19 pandemic accelerated the replacement of many face-to-face healthcare consultations with telephone consultations. Little is known about the extent to which empathy can be expressed in telephone consultations. Our objective is to review evidence related to empathy in telephone consultations including clinical outcomes, and patient/practitioner experiences. Methods: Searches of Medline/Ovid and PsycINFO/Ovid were undertaken. Titles and abstract screening, data extraction, and risk of bias were undertaken by two reviewers. Discrepancies were resolved in discussion with additional reviewers. Included studies were specific to tele-communications with empirical data on empathy related to patient outcomes/views, published (in English), 2010-2021. Studies that did not mention empathy explicitly were excluded. Results: Our search yielded 740 individual records and 8 studies (527 patients, 20 practitioners) met inclusion criteria: Some barriers to expression of empathy were noted, but no major obstacles were reported. However, data was sparse and most studies had a high risk of bias. Conclusion: Empathy in telephone consultations is possible, (though the loss of non-verbal cues and touch can present barriers) however the research does not yet identify how. Innovation: It is possible to establish and display empathy in telephone consultations, but future research needs to identify how this can be optimized. Funding: This work was supported by a National Institute for Health Research (NIHR) School for Primary Care Research grant (project number 389). The University of Southampton's Primary Care Department is a member of the NIHR School for Primary Care Research and supported by NIHR Research funds. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Protocol registration. PROSPERO (CRD42021238087).

Planning and developing a web-based intervention for active surveillance in prostate cancer: an integrated self-care programme for managing psychological distress.

OBJECTIVES: To outline the planning, development and optimisation of a psycho-educational behavioural intervention for patients on active surveillance for prostate cancer. The intervention aimed to support men manage active surveillance-related psychological distress. METHODS: The person-based approach (PBA) was used as the overarching guiding methodological framework for intervention development. Evidence-based methods were incorporated to improve robustness. The process commenced with data gathering activities comprising the following four components: • A systematic review and meta-analysis of depression and anxiety in prostate cancer • A cross-sectional survey on depression and anxiety in active surveillance • A review of existing interventions in the field • A qualitative study with the target audience The purpose of this paper is to bring these components together and describe how they facilitated the establishment of key guiding principles and a logic model, which underpinned the first draft of the intervention. RESULTS: The prototype intervention, named PROACTIVE, consists of six Internet-based sessions run concurrently with three group support sessions. The sessions cover the following topics: lifestyle (diet and exercise), relaxation and resilience techniques, talking to friends and family, thoughts and feelings, daily life (money and work) and information about prostate cancer and active surveillance. The resulting intervention has been trialled in a feasibility study, the results of which are published elsewhere. CONCLUSIONS: The planning and development process is key to successful delivery of an appropriate, accessible and acceptable intervention. The PBA strengthened the intervention by drawing on target-user experiences to maximise acceptability and user engagement. This meticulous description in a clinical setting using this rigorous but flexible method is a useful demonstration for others developing similar interventions. TRIAL REGISTRATION AND ETHICAL APPROVAL: ISRCTN registered: ISRCTN38893965 . NRES Committee South Central - Oxford A. REC reference: 11/SC/0355.

Clinician views on optimism and empathy in primary care consultations: a qualitative interview study.

BACKGROUND: Practitioner expressions of optimism and empathy may improve treatment engagement, adherence, and patient satisfaction but are not delivered consistently amid the challenges of everyday clinical practice. AIM: To explore primary care practitioner (PCP) views about optimistic and empathic communication in consultations; and to identify behavioural, attitudinal, and/or contextual issues likely to encourage or deter PCPs from practising such communication. DESIGN & SETTING: Qualitative interview study with 20 PCPs (GPs, practice nurses, and primary care physiotherapists). METHOD: Semi-structured telephone interviews with 20 PCPs. Data were analysed thematically. RESULTS: A conceptual mismatch between optimism and patient expectations became apparent; when asked how PCPs communicate about the likely effects of a treatment, answers were focussed around managing patient expectations. When prompted, it became clear PCPs were open to communicating optimistically with patients, but emphasised the need for realism. Concerns arose that patients may not be receptive to optimistic messages, especially when holding negative expectations. PCPs felt that expressing empathy is fundamental to all clinical consultations, noting that it can be challenging. Some PCPs worried that increasing expressions of empathy might increase their risk of clinician burnout and felt guilty about (appropriately) communicating empathy while maintaining some emotional distance. CONCLUSION: PCPs agreed expressing realistic optimism during consultations could aid communication and would constitute a novel change to practice. PCPs strive for clinical empathy but can struggle to manage emotional self-protection. Specific training to help PCPs express realistic optimism and empathy, and better utilise efficient non-verbal skills could help these issues.

Harnessing Placebo Effects in Primary Care: Using the Person-Based Approach to Develop an Online Intervention to Enhance Practitioners' Communication of Clinical Empathy and Realistic Optimism During Consultations.

Background: Empathic communication and positive messages are important components of "placebo" effects and can improve patient outcomes, including pain. Communicating empathy and optimism to patients within consultations may also enhance the effects of verum, i.e., non-placebo, treatments. This is particularly relevant for osteoarthritis, which is common, costly and difficult to manage. Digital interventions can be effective tools for changing practitioner behavior. This paper describes the systematic planning, development and optimization of an online intervention-"Empathico"-to help primary healthcare practitioners enhance their communication of clinical empathy and realistic optimism during consultations. Methods: The Person-Based Approach to intervention development was used. This entailed integrating insights from placebo and behavior change theory and evidence, and conducting primary and secondary qualitative research. Systematic literature reviews identified barriers, facilitators, and promising methods for enhancing clinical empathy and realistic optimism. Qualitative studies explored practitioners' and patients' perspectives, initially on the communication of clinical empathy and realistic optimism and subsequently on different iterations of the Empathico intervention. Insights from the literature reviews, qualitative studies and public contributor input were integrated into a logic model, behavioral analysis and principles that guided intervention development and optimization. Results: The Empathico intervention comprises 7 sections: Introduction, Empathy, Optimism, Application of Empathico for Osteoarthritis, Reflection on my Consultations, Setting Goals and Further Resources. Iterative refinement of Empathico, using feedback from patients and practitioners, resulted in highly positive feedback and helped to (1) contextualize evidence-based recommendations from placebo studies within the complexities of primary healthcare consultations and (2) ensure the intervention addressed practitioners' and patients' concerns and priorities. Conclusions: We have developed an evidence-based, theoretically-grounded intervention that should enable practitioners to better harness placebo effects of communication in consultations. The extensive use of qualitative research throughout the development and optimization process ensured that Empathico is highly acceptable and meaningful to practitioners. This means that practitioners are more likely to engage with Empathico and make changes to enhance their communication of clinical empathy and realistic optimism in clinical practice. Empathico is now ready to be evaluated in a large-scale randomized trial to explore its impact on patient outcomes.

Management of irritable bowel syndrome in primary care: feasibility randomised controlled trial of mebeverine, methylcellulose, placebo and a patient self-management cognitive behavioural therapy website. (MIBS trial).

BACKGROUND: IBS affects 10-22% of the UK population. Abdominal pain, bloating and altered bowel habit affect quality of life, social functioning and time off work. Current GP treatment relies on a positive diagnosis, reassurance, lifestyle advice and drug therapies, but many suffer ongoing symptoms.A recent Cochrane review highlighted the lack of research evidence for IBS drugs. Neither GPs, nor patients have good evidence to inform prescribing decisions. However, IBS drugs are widely used: In 2005 the NHS costs were nearly £10 million for mebeverine and over £8 million for fibre-based bulking agents. CBT and self-management can be helpful, but poor availability in the NHS restricts their use. We have developed a web-based CBT self-management programme, Regul8, based on an existing evidence based self-management manual and in partnership with patients. This could increase access with minimal increased costs. METHODS/DESIGN: The aim is to undertake a feasibility factorial RCT to assess the effectiveness of the commonly prescribed medications in UK general practice for IBS: mebeverine (anti-spasmodic) and methylcellulose (bulking-agent) and Regul8, the CBT based self-management website.135 patients aged 16 to 60 years with IBS symptoms fulfilling Rome III criteria, recruited via GP practices, will be randomised to 1 of 3 levels of the drug condition: mebeverine, methylcellulose or placebo for 6 weeks and to 1 of 3 levels of the website condition, Regul8 with a nurse telephone session and email support, Regul8 with minimal email support, or no website, thus creating 9 groups. OUTCOMES: Irritable bowel symptom severity scale and IBS-QOL will be measured at baseline, 6 and 12 weeks as the primary outcomes. An intention to treat analysis will be undertaken by ANCOVA for a factorial trial. DISCUSSION: This pilot will provide valuable information for a larger trial. Determining the effectiveness of commonly used drug treatments will help patients and doctors make informed treatment decisions regarding drug management of IBS symptoms, enabling better targeting of treatment. A web-based self-management CBT programme for IBS developed in partnership with patients has the potential to benefit large numbers of patients with low cost to the NHS. Assessment of the amount of email or therapist support required for the website will enable economic analysis to be undertaken.

Cognitive behavioural therapy for irritable bowel syndrome: 24-month follow-up of participants in the ACTIB randomised trial.

BACKGROUND: Irritable bowel syndrome (IBS) is common, affecting 10-20% of the adult population worldwide, with many people reporting ongoing symptoms despite first-line therapies. Cognitive behavioural therapy (CBT) is recommended in guidelines for refractory IBS but there is insufficient access to CBT for IBS and uncertainty about whether benefits last in the longer term. Assessing Cognitive behavioural Therapy for IBS (ACTIB) was a large, randomised, controlled trial of two forms of CBT for patients with refractory IBS. ACTIB results showed that, at 12 months, both forms of CBT for IBS were significantly more effective than treatment as usual at reducing IBS symptom severity in adults with refractory IBS. This follow-up study aimed to evaluate 24-month clinical outcomes of participants in the ACTIB trial. METHODS: In the ACTIB three-group, randomised, controlled trial, 558 adults with refractory IBS were randomly allocated to receive either therapist-delivered telephone CBT (telephone-CBT group), web-based CBT with minimal therapist support (web-CBT group), or treatment as usual (TAU group) and were followed up for 12 months. Participants were adults with refractory IBS (clinically significant symptoms for ≥12 months despite being offered first-line therapies), recruited by letter and opportunistically from 74 general practices and three gastroenterology centres in London and the south of England (UK) between May 1, 2014, and March 31, 2016. Primary outcome measures were IBS Symptom Severity Score (IBS-SSS) and Work and Social Adjustment Scale (WSAS), assessed in the intention-to-treat (ITT) population with multiple imputation. This study was a non-prespecified naturalistic follow-up and analysis of the participants of the ACTIB trial at 24 months assessing the same outcomes as the original trial. Outcome measures were completed online by participants or a paper questionnaire was posted, or telephone follow-up undertaken. The ACTIB trial is registered with the International Standard Randomised Controlled Trial Number registry, number ISRCTN44427879. FINDINGS: 24-month follow-up of outcomes was achieved for 323 (58%) of 558 participants: 119 (64%) of 186 in the telephone-CBT group, 99 (54%) of 185 in the web-CBT group, and 105 (56%) of 187 in the TAU group. At 24 months, mean IBS-SSS was 40·5 points (95% CI 15·0 to 66·0; p=0·002) lower in the telephone-CBT group and 12·9 points (-12·9 to 38·8; p=0·33) lower in the web-CBT group than in the TAU group. The mean WSAS score was 3·1 points (1·3 to 4·9; p<0·001) lower in the telephone-CBT group and 1·9 points (0·1 to 3·7; p=0·036) lower in the web-CBT group than in the TAU group. A clinically significant IBS-SSS change (≥50 points) from baseline to 24 months was found in 84 (71%) of 119 participants in the telephone-CBT group, in 62 (63%) of 99 in the web-CBT group, and in 48 (46%) of 105 in the TAU group. In total 41 adverse events were reported between 12 to 24 months: 11 in the telephone-CBT group, 15 in the web-CBT group, and 15 in the TAU group. Of these, eight were reported as gastrointestinal related, five as psychological, and six as musculoskeletal. There were no adverse events related to treatment. INTERPRETATION: At 24-month follow-up, sustained improvements in IBS were seen in both CBT groups compared with TAU, although some previous gains were reduced compared with the 12-month outcomes. IBS-specific CBT has the potential to provide long-term improvement in IBS, achievable within a usual clinical setting. Increasing access to CBT for IBS could achieve long-term patient benefit. FUNDING: UK National Institute for Health Research.

Symptom response to antibiotic prescribing strategies in acute sore throat in adults: the DESCARTE prospective cohort study in UK general practice.

BACKGROUND: A delayed or 'just in case' prescription has been identified as having potential to reduce antibiotic use in sore throat. AIM: To determine the symptomatic outcome of acute sore throat in adults according to antibiotic prescription strategy in routine care. DESIGN AND SETTING: A secondary analysis of the DESCARTE (Decision rule for the Symptoms and Complications of Acute Red Throat in Everyday practice) prospective cohort study comprising adults aged ≥16 years presenting with acute sore throat (≤2 weeks' duration) managed with treatment as usual in primary care in the UK. METHOD: A random sample of 2876 people from the full cohort were requested to complete a symptom diary. A brief clinical proforma was used to collect symptom severity and examination findings at presentation. Outcome details were collected by notes review and a detailed symptom diary. The primary outcome was poorer 'global' symptom control (defined as longer than the median duration or higher than median symptom severity). Analyses controlled for confounding by indication (propensity to prescribe antibiotics). RESULTS: A total of 1629/2876 (57%) of those requested returned a symptom diary, of whom 1512 had information on prescribing strategy. The proportion with poorer global symptom control was greater in those not prescribed antibiotics 398/587 (68%) compared with those prescribed immediate antibiotics 441/728 (61%) or delayed antibiotic prescription 116/197 59%); adjusted risk ratio (RR) (95% confidence intervals [CI]): immediate RR 0.87 (95% CI = 0.70 to 0.96), P = 0.006; delayed RR 0.88 (95% CI = 0.78 to 1.00), P = 0.042. CONCLUSION: In the routine care of adults with sore throat, a delayed antibiotic strategy confers similar symptomatic benefits to immediate antibiotics compared with no antibiotics. If a decision is made to prescribe an antibiotic, a delayed antibiotic strategy is likely to yield similar symptomatic benefit to immediate antibiotics.

A randomised controlled trial of management strategies for acute infective conjunctivitis in general practice.

OBJECTIVE: To assess different management strategies for acute infective conjunctivitis. DESIGN: Open, factorial, randomised controlled trial. SETTING: 30 general practices in southern England. PARTICIPANTS: 307 adults and children with acute infective conjunctivitis. INTERVENTION: One of three antibiotic prescribing strategies-immediate antibiotics (chloramphenicol eye drops; n = 104), no antibiotics (controls; n = 94), or delayed antibiotics (n = 109); a patient information leaflet or not; and an eye swab or not. MAIN OUTCOME MEASURES: Severity of symptoms on days 1-3 after consultation, duration of symptoms, and belief in the effectiveness of antibiotics for eye infections. RESULTS: Prescribing strategies did not affect the severity of symptoms but duration of moderate symptoms was less with antibiotics: no antibiotics (controls) 4.8 days, immediate antibiotics 3.3 days (risk ratio 0.7, 95% confidence interval 0.6 to 0.8), delayed antibiotics 3.9 days (0.8, 0.7 to 0.9). Compared with no initial offer of antibiotics, antibiotic use was higher in the immediate antibiotic group: controls 30%, immediate antibiotics 99% (odds ratio 185.4, 23.9 to 1439.2), delayed antibiotics 53% (2.9, 1.4 to 5.7), as was belief in the effectiveness of antibiotics: controls 47%, immediate antibiotics 67% (odds ratio 2.4, 1.1 to 5.0), delayed antibiotics 55% (1.4, 0.7 to 3.0), and intention to reattend for eye infections: controls 40%, immediate antibiotics 68% (3.2, 1.6 to 6.4), delayed antibiotics 41% (1.0, 0.5 to 2.0). A patient information leaflet or eye swab had no effect on the main outcomes. Reattendance within two weeks was less in the delayed compared with immediate antibiotic group: 0.3 (0.1 to 1.0) v 0.7 (0.3 to 1.6). CONCLUSIONS: Delayed prescribing of antibiotics is probably the most appropriate strategy for managing acute conjunctivitis in primary care. It reduces antibiotic use, shows no evidence of medicalisation, provides similar duration and severity of symptoms to immediate prescribing, and reduces reattendance for eye infections. TRIAL REGISTRATION: Current Controlled Trials ISRCTN32956955 [controlled-trials.com].