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Pharmacological and electronic cigarette interventions for smoking cessation in adults: component network meta-analyses.

Background: Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop. There are a number of medicines licenced to help people quit globally, and e-cigarettes are used for this purpose in many countries. Typically treatments work by reducing cravings to smoke, thus aiding initial abstinence and preventing relapse. More information on comparative effects of these treatments is needed to inform treatment decisions and policies. Objectives: To investigate the comparative benefits, harms and tolerability of different smoking cessation pharmacotherapies and e-cigarettes, when used to help people stop smoking tobacco. Search methods: We identified studies from recent updates of Cochrane Reviews investigating our interventions of interest. We updated the searches for each review using the Cochrane Tobacco Addiction Group (TAG) specialised register to 29 April 2022. Selection criteria: We included randomised controlled trials (RCTs), cluster-RCTs and factorial RCTs, which measured smoking cessation at six months or longer, recruited adults who smoked combustible cigarettes at enrolment (excluding pregnant people) and randomised them to approved pharmacotherapies and technologies used for smoking cessation worldwide (varenicline, cytisine, nortriptyline, bupropion, nicotine replacement therapy (NRT) and e-cigarettes) versus no pharmacological intervention, placebo (control) or another approved pharmacotherapy. Studies providing co-interventions (e.g. behavioural support) were eligible if the co-intervention was provided equally to study arms. Data collection and analysis: We followed standard Cochrane methods for screening, data extraction and risk of bias (RoB) assessment (using the RoB 1 tool). Primary outcome measures were smoking cessation at six months or longer, and the number of people reporting serious adverse events (SAEs). We also measured withdrawals due to treatment. We used Bayesian component network meta-analyses (cNMA) to examine intervention type, delivery mode, dose, duration, timing in relation to quit day and tapering of nicotine dose, using odds ratios (OR) and 95% credibility intervals (CrIs). We calculated an effect estimate for combination NRT using an additive model. We evaluated the influence of population and study characteristics, provision of behavioural support and control arm rates using meta-regression. We evaluated certainty using GRADE. Main results: Of our 332 eligible RCTs, 319 (835 study arms, 157,179 participants) provided sufficient data to be included in our cNMA. Of these, we judged 51 to be at low risk of bias overall, 104 at high risk and 164 at unclear risk, and 118 reported pharmaceutical or e-cigarette/tobacco industry funding. Removing studies at high risk of bias did not change our interpretation of the results. Benefits We found high-certainty evidence that nicotine e-cigarettes (OR 2.37, 95% CrI 1.73 to 3.24; 16 RCTs, 3828 participants), varenicline (OR 2.33, 95% CrI 2.02 to 2.68; 67 RCTs, 16,430 participants) and cytisine (OR 2.21, 95% CrI 1.66 to 2.97; 7 RCTs, 3848 participants) were associated with higher quit rates than control. In absolute terms, this might lead to an additional eight (95% CrI 4 to 13), eight (95% CrI 6 to 10) and seven additional quitters per 100 (95% CrI 4 to 12), respectively. These interventions appeared to be more effective than the other interventions apart from combination NRT (patch and a fast-acting form of NRT), which had a lower point estimate (calculated additive effect) but overlapping 95% CrIs (OR 1.93, 95% CrI 1.61 to 2.34). There was also high-certainty evidence that nicotine patch alone (OR 1.37, 95% CrI 1.20 to 1.56; 105 RCTs, 37,319 participants), fast-acting NRT alone (OR 1.41, 95% CrI 1.29 to 1.55; 120 RCTs, 31,756 participants) and bupropion (OR 1.43, 95% CrI 1.26 to 1.62; 71 RCTs, 14,759 participants) were more effective than control, resulting in two (95% CrI 1 to 3), three (95% CrI 2 to 3) and three (95% CrI 2 to 4) additional quitters per 100 respectively. Nortriptyline is probably associated with higher quit rates than control (OR 1.35, 95% CrI 1.02 to 1.81; 10 RCTs, 1290 participants; moderate-certainty evidence), resulting in two (CrI 0 to 5) additional quitters per 100. Non-nicotine/placebo e-cigarettes (OR 1.16, 95% CrI 0.74 to 1.80; 8 RCTs, 1094 participants; low-certainty evidence), equating to one additional quitter (95% CrI -2 to 5), had point estimates favouring the intervention over control, but CrIs encompassed the potential for no difference and harm. There was low-certainty evidence that tapering the dose of NRT prior to stopping treatment may improve effectiveness; however, 95% CrIs also incorporated the null (OR 1.14, 95% CrI 1.00 to 1.29; 111 RCTs, 33,156 participants). This might lead to an additional one quitter per 100 (95% CrI 0 to 2). Harms There were insufficient data to include nortriptyline and non-nicotine EC in the final SAE model. Overall rates of SAEs for the remaining treatments were low (average 3%). Low-certainty evidence did not show a clear difference in the number of people reporting SAEs for nicotine e-cigarettes, varenicline, cytisine or NRT when compared to no pharmacotherapy/e-cigarettes or placebo. Bupropion may slightly increase rates of SAEs, although the CrI also incorporated no difference (moderate certainty). In absolute terms bupropion may cause one more person in 100 to experience an SAE (95% CrI 0 to 2). Authors' conclusions: The most effective interventions were nicotine e-cigarettes, varenicline and cytisine (all high certainty), as well as combination NRT (additive effect, certainty not rated). There was also high-certainty evidence for the effectiveness of nicotine patch, fast-acting NRT and bupropion. Less certain evidence of benefit was present for nortriptyline (moderate certainty), non-nicotine e-cigarettes and tapering of nicotine dose (both low certainty). There was moderate-certainty evidence that bupropion may slightly increase the frequency of SAEs, although there was also the possibility of no increased risk. There was no clear evidence that any other tested interventions increased SAEs. Overall, SAE data were sparse with very low numbers of SAEs, and so further evidence may change our interpretation and certainty. Future studies should report SAEs to strengthen certainty in this outcome. More head-to-head comparisons of the most effective interventions are needed, as are tests of combinations of these. Future work should unify data from behavioural and pharmacological interventions to inform approaches to combined support for smoking cessation.

The Cochrane database of systematic reviews · systematic review · 114 citationsread the source →

evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease.

Background: Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for the treatment of type 2 diabetes and obesity and has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms including neuroinflammatory, vascular, and other AD-related processes. Large randomized controlled trials are needed to assess the efficacy and safety of semaglutide in early-stage symptomatic AD. Methods: evoke and evoke+ are randomized, double-blind, placebo-controlled phase 3 trials investigating the efficacy, safety, and tolerability of once-daily oral semaglutide versus placebo in early-stage symptomatic AD. Eligible participants were men or women aged 55-85 years with mild cognitive impairment or mild dementia due to AD with confirmed amyloid abnormalities (assessed by positron emission tomography or cerebrospinal fluid [CSF] analysis). After a maximum 12-week screening phase, an anticipated 1840 patients in each trial are randomized (1:1) to semaglutide or placebo for 156 weeks (104-week main treatment phase and 52-week extension). Randomized participants follow an 8-week dose escalation regimen (3 mg [weeks 0-4], 7 mg [weeks 4-8], and 14 mg [weeks 8-156]). The primary endpoint is the semaglutide-placebo difference on change from baseline to week 104 in the Clinical Dementia Rating - Sum of Boxes score. Analyses of plasma biomarkers, collected from all participants, and a CSF sub-study (planned n = 210) will explore semaglutide effects on AD biomarkers and neuroinflammation. Results: Enrollment was undertaken between May 18, 2021, and September 8, 2023. Completion of the trials' main phase is expected in September 2025, and the 52-week extension (in which participants and investigators remain blinded to treatment assignment) will continue to October 2026. Conclusion: evoke and evoke+ are the first large-scale trials to investigate the disease-modifying potential of semaglutide in participants with early-stage symptomatic AD, including exploration of effects on AD biomarkers and neuroinflammation. The trials will provide data on the potential disease-modifying effects of semaglutide and will be important in evaluating its utility in the treatment of early-stage symptomatic AD. Trial registration: Clinicaltrials.gov, NCT04777396 and NCT04777409. Date: 02/03/2021.

Alzheimer's research & therapy · randomised controlled trial · 111 citationsread the source →

Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial.

Importance: A significant need exists for new antipsychotic medications with different mechanisms of action, greater efficacy, and better tolerability than existing agents. Xanomeline is a dual M1/M4 preferring muscarinic receptor agonist with no direct D2 dopamine receptor blocking activity. KarXT combines xanomeline with the peripheral muscarinic receptor antagonist trospium chloride with the goal of reducing adverse events due to xanomeline-related peripheral muscarinic receptor activation. In prior trials, xanomeline-trospium chloride was effective in reducing symptoms of psychosis and generally well tolerated in people with schizophrenia. Objective: To evaluate the efficacy and safety of xanomeline-trospium vs placebo in adults with schizophrenia. Design, setting, and participants: EMERGENT-3 (NCT04738123) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 5-week trial of xanomeline-trospium in people with schizophrenia experiencing acute psychosis, conducted between April 1, 2021, and December 7, 2022, at 30 inpatient sites in the US and Ukraine. Data were analyzed from February to June 2023. Interventions: Participants were randomized 1:1 to receive xanomeline-trospium chloride (maximum dose xanomeline 125 mg/trospium 30 mg) or placebo for 5 weeks. Main outcomes and measures: The prespecified primary end point was change from baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcome measures were change from baseline to week 5 in PANSS positive subscale score, PANSS negative subscale score, PANSS Marder negative factor score, Clinical Global Impression-Severity score, and proportion of participants with at least a 30% reduction in PANSS total score. Safety and tolerability were also evaluated. Results: A total of 256 participants (mean [SD] age, 43.1 [11.8] years; 191 men [74.6%]; 156 of 256 participants [60.9%] were Black or African American, 98 [38.3%] were White, and 1 [0.4%] was Asian) were randomized (125 in xanomeline-trospium group and 131 in placebo group). At week 5, xanomeline-trospium significantly reduced PANSS total score compared with placebo (xanomeline-trospium , -20.6; placebo, -12.2; least squares mean difference, -8.4; 95% CI, -12.4 to -4.3; P < .001; Cohen d effect size, 0.60). Discontinuation rates due to treatment-emergent adverse events (TEAEs) were similar between the xanomeline-trospium (8 participants [6.4%]) and placebo (7 participants [5.5%]) groups. The most common TEAEs in the xanomeline-trospium vs placebo group were nausea (24 participants [19.2%] vs 2 participants [1.6%]), dyspepsia (20 participants [16.0%] vs 2 participants [1.6%]), vomiting (20 participants [16.0%] vs 1 participant [0.8%]), and constipation (16 participants [12.8%] vs 5 participants [3.9%]). Measures of extrapyramidal symptoms, weight gain, and somnolence were similar between treatment groups. Conclusions and relevance: Xanomeline-trospium was efficacious and well tolerated in people with schizophrenia experiencing acute psychosis. These findings, together with the previously reported and consistent results from the EMERGENT-1 and EMERGENT-2 trials, support the potential of xanomeline-trospium to be the first in a putative new class of antipsychotic medications without D2 dopamine receptor blocking activity. Trial registration: ClinicalTrials.gov Identifier: NCT04738123.

JAMA psychiatry · randomised controlled trial · 128 citationsread the source →

An online healthy relationship tool and safety decision aid for women experiencing intimate partner violence (I-DECIDE): a randomised controlled trial.

Background: Evidence for online interventions to help women experiencing intimate partner violence is scarce. We assessed whether an online interactive healthy relationship tool and safety decision aid (I-DECIDE) would increase women's self-efficacy and improve depressive symptoms compared with an intimate partner violence information website. Methods: In this two-group pragmatic randomised controlled trial, we enrolled women who had screened positive for any form of intimate partner violence or fear of a partner in the 6 months before recruitment. Women aged 16-50 years currently residing in Australia, who had safe access to a computer and an internet connection, and who answered positively to one of the screening questions in English were eligible for inclusion. Participants were randomly assigned (1:1) by computer to receive either the intervention or control website. The intervention website consisted of modules on healthy relationships, abuse and safety, and relationship priority setting, and a tailored action plan. The control website was a static intimate partner violence information website. As the initial portion of the website containing the baseline questions was identical for both groups, there was no way for women to tell which group they had been allocated to, and the research team were also masked to participant allocation until after analysis of the 12-month data. Data were collected at baseline, immediately after completion of the website, at 6 months, and 12 months. Primary outcomes were mean general self-efficacy score (immediately after website completion, and at 6 months and 12 months) and mean depression score (at 6 months and 12 months). Data analyses were done according to intention-to-treat principles, accounting for missing data, and adjusted for outcome baseline scores. This trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN 12614001306606. Findings: Between Jan 16, and Aug 28, 2015, 584 patients registered for the study and were assessed for eligibility. 422 eligible participants were randomly allocated to the intervention group (227 patients) or control group (195 patients). 179 (79%) participants in the intervention group and 156 (80%) participants in the control group completed 12-month follow-up. Mean self-efficacy at 6 months and 12 months was lower for participants in the intervention group than for participants in the control group, although this did not meet the prespecified mean difference (6 months: 27·5 [SD 5·1] vs 28·1 [4·4], imputed mean difference 1·3 [95% CI 0·3 to 2·3]; 12 months: 27·8 [SD 5·4] vs 29·0 [5·0], imputed mean difference 1·6 [95% CI 0·5 to 2·7]). We found no difference between groups in depressive symptoms at 6 months or 12 months (6 months: 22·5 [SD 17·1] vs 24·2 [17·2], imputed mean difference -0·3 [95% CI -3·5 to 3·0]; 12 months: 21·9 [SD 19·3] vs 21·5 [19·3], imputed mean difference -1·9 [95% CI -5·6 to 1·7]). Qualitative findings indicated that participants found the intervention supportive and a motivation for action. Interpretation: Our findings highlight the need for further research, development, and refinement of online interventions for women experiencing intimate partner violence, particularly into the duration needed for interventions. Although we detected no meaningful differences between groups, our qualitative results indicated that some women find an online tool a helpful source of motivation and support. Funding: Australian Research Council.

The Lancet. Public health · randomised controlled trial · 43 citationsread the source →

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

Background: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. Methods: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. Findings: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. Interpretation: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. Funding: National Institute for Health Research, Health Technology Assessment programme.

The lancet. Psychiatry · randomised controlled trial · 192 citationsread the source →

Internet-based intervention for smoking cessation (StopAdvisor) in people with low and high socioeconomic status: a randomised controlled trial.

Background: Internet-based interventions for smoking cessation could help millions of people stop smoking at very low unit costs; however, long-term biochemically verified evidence is scarce and such interventions might be less effective for smokers with low socioeconomic status than for those with high status because of lower online literacy to engage with websites. We aimed to assess a new interactive internet-based intervention (StopAdvisor) for smoking cessation that was designed with particular attention directed to people with low socioeconomic status. Methods: We did this online randomised controlled trial between Dec 6, 2011, and Oct 11, 2013, in the UK. Participants aged 18 years and older who smoked every day were randomly assigned (1:1) to receive treatment with StopAdvisor or an information-only website. Randomisation was automated with an unseen random number function embedded in the website to establish which treatment was revealed after the online baseline assessment. Recruitment continued until the required sample size had been achieved from both high and low socioeconomic status subpopulations. Participants, and researchers who obtained data and did laboratory analyses, were masked to treatment allocation. The primary outcome was 6 month sustained, biochemically verified abstinence. The main secondary outcome was 6 month, 7 day biochemically verified point prevalence. Analysis was by intention to treat. Homogeneity of intervention effect across the socioeconomic subsamples was first assessed to establish whether overall or separate subsample analyses were appropriate. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN99820519. Findings: We randomly assigned 4613 participants to the StopAdvisor group (n=2321) or the control group (n=2292); 2142 participants were of low socioeconomic status and 2471 participants were of high status. The overall rate of smoking cessation was similar between participants in the StopAdvisor and control groups for the primary (237 [10%] vs 220 [10%] participants; relative risk [RR] 1·06, 95% CI 0·89-1·27; p=0·49) and the secondary (358 [15%] vs 332 [15%] participants; 1·06, 0·93-1·22; p=0·37) outcomes; however, the intervention effect differed across socioeconomic status subsamples (1·44, 0·99-2·09; p=0·0562 and 1·37, 1·02-1·84; p=0·0360, respectively). StopAdvisor helped participants with low socioeconomic status stop smoking compared with the information-only website (primary outcome: 90 [8%] of 1088 vs 64 [6%] of 1054 participants; RR 1·36, 95% CI 1·00-1·86; p=0·0499; secondary outcome: 136 [13%] vs 100 [10%] participants; 1·32, 1·03-1·68, p=0·0267), but did not improve cessation rates in those with high socioeconomic status (147 [12%] of 1233 vs 156 [13%] of 1238 participants; 0·95, 0·77-1·17; p=0·61 and 222 [18%] vs 232 [19%] participants; 0·96, 0·81-1·13, p=0·64, respectively). Interpretation: StopAdvisor was more effective than an information-only website in smokers of low, but not high, socioeconomic status. StopAdvisor could be implemented easily and made freely available, which would probably improve the success rates of smokers with low socioeconomic status who are seeking online support. Funding: National Prevention Research Initiative.

The Lancet. Respiratory medicine · randomised controlled trial · 99 citationsread the source →

Clinical and cost-effectiveness of cognitive behaviour therapy for health anxiety in medical patients: a multicentre randomised controlled trial.

Background: Health anxiety has been treated by therapists expert in cognitive behaviour therapy with some specific benefit in some patients referred to psychological services. Those in hospital care have been less often investigated. Following a pilot trial suggesting efficacy we carried out a randomised study in hospital medical clinics. Methods: We undertook a multicentre, randomised trial on health anxious patients attending cardiac, endocrine, gastroenterological, neurological, and respiratory medicine clinics in secondary care. We included those aged 16-75 years, who satisfied the criteria for excessive health anxiety, and were resident in the area covered by the hospital, were not under investigation for new pathology or too medically unwell to take part. We used a computer-generated random scheme to allocate eligible medical patients to an active treatment group of five-to-ten sessions of adapted cognitive behaviour therapy (CBT-HA group) delivered by hospital-based therapists or to standard care in the clinics. The primary outcome was change in health anxiety symptoms measured by the Health Anxiety Inventory at 1 year and the main secondary hypothesis was equivalence of total health and social care costs over 2 years, with an equivalence margin of £150. Analysis was by intention to treat. The study is registered with controlled-trials.com, ISRCTN14565822. Findings: Of 28,991 patients screened, 444 were randomly assigned to receive either adapted cognitive behaviour therapy (CBT-HA group, 219 participants) or standard care (standard care group, 225), with 205 participants in the CBT-HA group and 212 in the standard care group included in the analyses of the primary endpoints. At 1 year, improvement in health anxiety in the patients in the CBT-HA group was 2·98 points greater than in those in the standard care group (95% CI 1·64-4·33, p<0·0001), and twice as many patients receiving cognitive behaviour therapy achieved normal levels of health anxiety compared with those in the control group (13·9% vs 7·3%; odds ratio 2·15, 95% CI 1·09-4·23, p=0·0273). Similar differences were observed at 6 months and 2 years, and there were concomitant reductions in generalised anxiety and, to a lesser extent, depression. Of nine deaths, six were in the control group; all were due to pre-existing illness. Social functioning or health-related quality of life did not differ significantly between groups. Equivalence in total 2-year costs was not achieved, but the difference was not significant (adjusted mean difference £156, 95% CI -1446 to 1758, p=0·848). Interpretation: This form of adapted cognitive behaviour therapy for health anxiety led to sustained symptomatic benefit over 2 years, with no significant effect on total costs. It deserves wider application in medical care. Funding: National Institute for Health Research Health Technology Assessment Programme.

Lancet (London, England) · randomised controlled trial · 96 citationsread the source →

Effectiveness of the IDEFICS intervention on objectively measured physical activity and sedentary time in European children.

Background: This paper reports on the effectiveness of the prevention of dietary- and lifestyle-induced health effects in children and infants (IDEFICS) intervention on objectively measured physical activity (PA) and sedentary time (ST) in 2- to 9.9-year-old European boys and girls. Methods: The intervention was evaluated after 2 years through a non-randomized cluster-controlled trial in eight European countries (one control and one intervention community per country). All children in the intervention group received a culturally adapted childhood obesity prevention programme through the community, schools/kindergartens and family. A random sub-sample of children participating in the IDEFICS study wore an accelerometer at baseline and follow-up for at least 3 days (n = 9,184). Of this sample, 81% provided valid accelerometer data at baseline (n = 7,413; 51% boys; 6.21 ± 1.76 years; boys: 617 ± 170 cpm day(-1) ; girls 556 ± 156 cpm day(-1) ) and 3,010 children provided valid accelerometer data at baseline and during the follow-up survey 2 years later. Results: In boys and girls, no significant differences in PA and ST were found between intervention and control groups over 2 years. Strong temporal effects were found in the total sample of boys and girls: the percentage of time spent in light PA per day decreased by 4 percentage points in both boys and girls between baseline and follow-up (both: p < 0.001), while time spent in ST per day increased by 4 percentage points in both sexes over time (both: p < 0.001). Percentage of time spent in moderate-to-vigorous PA per day remained stable over time in boys and girls. Conclusion: Despite the socio-ecological approach and implementation of a culturally adapted intervention in each country, no effects of the IDEFICS intervention were found on children's objectively measured PA and ST. Behavioural interventions for children may need to enhance specificity and intensity at the family level using other behaviour change techniques and more direct strategies to reach parents.

Obesity reviews : an official journal of the International Association for the Study of Obesity · 22 citationsread the source →