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Individuals with pacemakers are at increased risk of left ventricular systolic dysfunction (LVSD). Whether screening for and optimizing the medical management of LVSD in these individuals can improve clinical outcomes is unknown. In the present study, in a multicenter controlled trial (OPT-PACE), we randomized 1,201 patients (717 men) with a pacemaker to echocardiography screening or usual care. In the screening arm, LVSD was detected in 201 of 600 (34%) patients, who then received management in either primary care or a specialist heart failure (HF) and devices clinic. The primary outcome of the trial was the difference in a composite of time to first HF hospitalization or death. Over 31 months (interquartile range = 30–40 months), the primary outcome occurred in 106 of 600 (18%) patients receiving echocardiography screening, which was not significantly different compared with the occurrence of the primary outcome in 115 of 601 (19%) patients receiving the usual care (hazard ratio = 0.89; 95% confidence interval = 0.69, 1.17). In a prespecified, nonrandomized, exploratory analysis, patients with LVSD managed by the specialist clinic experienced the primary outcome event less frequently than those managed in primary care. The results of this trial indicate that echocardiography screening commonly identifies LVSD in individuals with pacemakers but alone does not alter outcomes. ClinicalTrials.gov registration: NCT01819662 . For individuals with pacemakers, a care pathway that includes echocardiographic screening to detect signs of heart failure did not improve cardiac outcomes, but patients flagged as having impaired heart function who were managed by a specialized heart failure clinic benefited, as compared to those managed by primary care physicians.

Objectives Duchenne muscular dystrophy (DMD) is a rare, progressive neuromuscular disease. Long-term care is primarily provided by unpaid family-caregivers. This time trade-off (TTO) study aimed to generate family-caregiver utility values associated with different stages of DMD. Methods Eight vignettes were developed to reflect the experience of caring for patients with DMD across health states (HS) defined in the Project HERCULES model. Vignettes were informed by literature and input from family-caregivers and healthcare professionals. TTO interviews were conducted online with members of the UK general public. Participants reviewed all vignettes and completed HS ranking, visual analog scale (VAS) ratings, and TTO valuation tasks. Results 200 participants (mean age 44.0 years, 51% female) completed interviews. Mean utility scores were highest for HS1 (early ambulatory: 0.717) and lowest for HS8 (no hand-to-mouth function, full-time ventilation: 0.477). VAS scores showed a similar pattern, with HS1 scoring 65.49 and HS8 scoring 31.665. Conclusions This study highlights the increasing burden on family-caregivers as DMD progresses, with declining health-related quality of life across HS. The resulting utility values support inclusion of family-caregiver outcomes in future DMD cost-effectiveness models.

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. 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. 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. 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. National Institute for Health and Care Research Health Technology Assessment Programme (grant reference 16/162/01).

Background Respiratory medicine (RM) and palliative care (PC) physicians’ management of chronic breathlessness in advanced chronic obstructive pulmonary disease (COPD), fibrotic interstitial lung disease (fILD) and lung cancer (LC), and the influence of practice guidelines was explored via an online survey. Methods A voluntary, online survey was distributed to RM and PC physicians via society newsletter mailing lists. Results 450 evaluable questionnaires (348 (77%) RM and 102 (23%) PC) were analysed. Significantly more PC physicians indicated routine use (often/always) of opioids across conditions (COPD: 92% vs. 39%, fILD: 83% vs. 36%, LC: 95% vs. 76%; all p  < 0.001) and significantly more PC physicians indicated routine use of benzodiazepines for COPD (33% vs. 10%) and fILD (25% vs. 12%) (both p  < 0.001). Significantly more RM physicians reported routine use of a breathlessness score (62% vs. 13%, p  < 0.001) and prioritised exercise training/rehabilitation for COPD (49% vs. 7%) and fILD (30% vs. 18%) (both p  < 0.001). Overall, 40% of all respondents reported reading non-cancer palliative care guidelines (either carefully or looked at them briefly). Respondents who reported reading these guidelines were more likely to: routinely use a breathlessness score ( χ 2  = 13.8; p  < 0.001), use opioids ( χ 2  = 12.58, p  < 0.001) and refer to pulmonary rehabilitation ( χ 2  = 6.41, p  = 0.011) in COPD; use antidepressants ( χ 2  = 6.25; p  = 0.044) and refer to PC ( χ 2  = 5.83; p  = 0.016) in fILD; and use a handheld fan in COPD ( χ 2  = 8.75, p  = 0.003), fILD ( χ 2  = 4.85, p  = 0.028) and LC ( χ 2  = 5.63; p  = 0.018). Conclusions These findings suggest a need for improved dissemination and uptake of jointly developed breathlessness management guidelines in order to encourage appropriate use of existing, evidence-based therapies. The lack of opioid use by RM, and continued benzodiazepine use in PC, suggest that a wider range of acceptable therapies need to be developed and trialled.

ObjectiveGeneral practitioners may not prescribe amitriptyline for irritable bowel syndrome (IBS) despite using it for other chronic conditions. The Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment (ATLANTIS) trial found low-dose titrated amitriptyline was a safe and clinically effective second-line treatment for IBS in primary care. We undertook a prespecified cost-effectiveness analysis of ATLANTIS trial data.Design/methodComplete case (CC) and a full population (FP) analysis using multiply imputed data with analyses at 6 (365 participants CC, 463 participants FP) and 12 (224 participants CC, 291 participants FP) months. As the trial was not fully randomised between 6 and 12 months, we adopted inverse probability weighting to mitigate potential impact of participants choosing to continue trial medication.ResultsAt a 6-month time horizon, CC analysis demonstrated low-dose amitriptyline was more likely to be cost-effective than not (incremental net health benefit (NHB) 0.0029 quality-adjusted life years (QALYs)/person, low-dose amitriptyline dominant, 67.3% probability cost-effective), but not FP analysis. At 12 months, all analyses demonstrated low-dose amitriptyline was more likely to be cost-effective than not (CC: incremental NHB 0.00757 QALYs/person, low-dose amitriptyline dominant, 81.7% probability cost-effective; FP: incremental NHB 0.00388 QALYs/person, low-dose amitriptyline dominant, 68.7% probability cost-effective).ConclusionIn addition to the clinical benefit, safety and acceptability of low-dose amitriptyline in patients with IBS found in the ATLANTIS trial, these results indicate this inexpensive medication is likely to be cost-effective as a second-line treatment for IBS in primary care over 12 months. This strengthens amitriptyline as a treatment option for people with ongoing IBS symptoms.Trial registration numberISRCTN48075063.