Search

Background: The LiGHT trial (Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial) is a multicentre randomised controlled trial of two treatment pathways for patients who are newly diagnosed with open-angle glaucoma (OAG) and ocular hypertension (OHT). The main hypothesis for the trial is that lowering intraocular pressure (IOP) with selective laser trabeculoplasty (SLT) as the primary treatment ('Laser-1st') leads to a better health-related quality of life than for those started on IOP-lowering drops as their primary treatment ('Medicine-1st') and that this is associated with reduced costs and improved tolerability of treatment. This paper describes the statistical analysis plan for the study.Methods/design: The LiGHT trial is an unmasked, multi-centre randomised controlled trial. A total of 718 patients (359 per arm) are being randomised to two groups: medicine-first or laser-first treatment. Outcomes are recorded at baseline and at 6-month intervals up to 36 months. The primary outcome measure is health-related quality of life (HRQL) at 36 months measured using the EQ-5D-5L. The main secondary outcome is the Glaucoma Utility Index. We plan to analyse the patient outcome data according to the group to which the patient was originally assigned. Methods of statistical analysis are described, including the handling of missing data, the covariates used in the adjusted analyses and the planned sensitivity analyses.Trial Registration: The trial was registered with the ISRCTN register on 23/07/2012, number ISRCTN32038223 . [ABSTRACT FROM AUTHOR]

Background: The effects of postal questionnaire burden on return rates and answers given are unclear following treatment on an intensive care unit (ICU). We aimed to establish the effects of different postal questionnaire burdens on return rates and answers given.Methods: Design: A parallel group randomised controlled trial. We assigned patients by computer-based randomisation to one of two questionnaire packs (Group A and Group B).Setting: Patients from 26 ICUs in the United Kingdom.Inclusion Criteria: Patients who had received at least 24 h of level 3 care and were 16 years of age or older. Patients did not know that there were different questionnaire burdens. The study included 18,490 patients. 12,170 were eligible to be sent a questionnaire pack at 3 months. We sent 12,105 questionnaires (6112 to group A and 5993 to group B).Interventions: The Group A pack contained demographic and EuroQol group 5 Dimensions 3 level (EQ-5D-3 L) questionnaires, making four questionnaire pages. The Group B pack also contained the Hospital Anxiety and Depression Score (HADS) and the Post-Traumatic Stress Disorder Check List-Civilian (PCL-C) questionnaires, making eight questionnaire pages in total.Main Outcome Measure: Questionnaire return rate 3 months after ICU discharge by group.Results: In group A, 2466/6112 (40.3%) participants responded at 3 months. In group B 2315/ 5993 (38.6%) participants responded (difference 1.7% CI for difference 0-3.5% p = 0.053). Group A reported better functionality than group B in the EQ-5D-3 L mobility (41% versus 37% reporting no problems p = 0.003) and anxiety/depression (59% versus 55% reporting no problems p = 0.017) domains.Conclusions: In survivors of intensive care, questionnaire burden had no effect on return rates. However, questionnaire burden affected answers to the same questionnaire (EQ-5D-3 L).Trial Registration: ISRCTN69112866 (assigned 02/05/2006). [ABSTRACT FROM AUTHOR]

Clinical trials for the treatment of schizophrenia now often include cognitive assessments in addition to clinical ratings of symptoms. Recently, these trials have included cross-national assessments. It is not clear if translated psychological tests produce consistent results across different languages. This paper presents the results of a study of the comparability of the results of cognitive assessments in different English-speaking countries and a number of countries where tests were translated into other languages. Performance on tests of executive functioning, verbal and visuo-spatial learning and memory, language skills, psychomotor speed, and vigilance was compared across the first episode patients with schizophrenia (n=301) assessed in six different languages (English, French, Finnish, German, Hebrew, and Afrikaans), including two different countries where patients were assessed in English and other languages: Canada (French) and South Africa (Afrikaans). The variance in performance across the sites tested in English was as large as the variance between English and non-English speakers when all tests were considered. Performance differences across English and other languages were found only for executive functions, vigilance, and psychomotor speed, with executive functioning differences nonsignificant when education was considered. No differences were found between English and non-English speakers in Canada. These results suggest that the translation of tests of memory and verbal skills can lead to consistent results across translated versions of the tests. Differences between countries were greater than differences between languages, suggesting the need to consider representativeness of patient samples in terms of local educational attainment. In general, these data support the validity of cross-national neuropsychological assessments. [Copyright &y& Elsevier]

Objective: To examine the feasibility of a trial to evaluate web-based physiotherapy compared to a standard home exercise programme in people with multiple sclerosis. Design: Multi-centre, randomized controlled, feasibility study. Setting: Three multiple sclerosis out-patient centres. Participants: A total of 90 people with multiple sclerosis (Expanded Disability Status Scale 4–6.5). Interventions: Participants were randomized to a six-month individualized, home exercise programme delivered via web-based physiotherapy (n = 45; intervention) or a sheet of exercises (n = 45; active comparator). Outcome measures: Outcome measures (0, three, six and nine months) included adherence, two-minute walk test, 25 foot walk, Berg Balance Scale, physical activity and healthcare resource use. Interviews were undertaken with 24 participants and 3 physiotherapists. Results: Almost 25% of people approached agreed to take part. No intervention-related adverse events were recorded. Adherence was 40%–63% and 53%–71% in the intervention and comparator groups. There was no difference in the two-minute walk test between groups at baseline (Intervention-80.4(33.91)m, Comparator-70.6(31.20)m) and no change over time (at six-month Intervention-81.6(32.75)m, Comparator-74.8(36.16)m. There were no significant changes over time in other outcome measures except the EuroQol-5 Dimension at six months which decreased in the active comparator group. For a difference of 8(17.4)m in two-minute walk test between groups, 76 participants/group would be required (80% power, P > 0.05) for a future randomized controlled trial. Conclusion: No changes were found in the majority of outcome measures over time. This study was acceptable and feasible by participants and physiotherapists. An adequately powered study needs 160 participants. [ABSTRACT FROM AUTHOR]

Background: University students have high rates of depression, and friends are often the most commonly-used source of support for emotional distress in this population. This study aimed to explore students' ability to provide effective support for their peers with depressive symptoms and the factors influencing the quality of their mental health first aid (MHFA) skills, including students' gender, course of study, and gender of student experiencing depression.Methods: Via an online survey, students at two British universities (N = 483) were quasi-randomly allocated to view a video vignette of either a male or female student depicting symptoms of depression. An open-ended question probed MHFA actions they would take to help the vignette character, which were rated using a standardised scoring scheme based on MHFA guidelines.Results: Students reported low MHFA scores (mean 2.89, out of possible 12). The most commonly reported action was provision of support and information, but only eight (1.6%) students stated an intention to assess risk of harm. Those studying clinically non-relevant degrees with limited mental health content reported poorer MHFA (p = <0.001) and were less confident about their ability to support a friend with depression (p = 0.04). There was no main effect of vignette gender, but within the group of students on non-relevant courses the male vignette received significantly poorer MHFA than the female vignette (p = 0.02). A significant three-way interaction found that male participants studying non-relevant degrees who viewed a male vignette had poorer MHFA compared to females studying non-relevant degrees who viewed the female vignette (p = 0.005).Conclusions: Most students lack the necessary MHFA skills to support friends suffering from symptoms of depression, or to help them get appropriate support and prevent risk of harm. Students on courses which do not include mental health related content are particularly ill-equipped to support male students, with male students receiving the poorest quality MHFA from fellow male students on these courses. MHFA training has the potential to improve outcomes for students with depression, and could have a valuable role in reducing the excess risk of harm seen in male students. [ABSTRACT FROM AUTHOR]

Background: Postnatal depression affects 10-15 % of all mothers in Western societies and remains a major public health concern for women from diverse cultures. British Pakistani and Indian women have a higher prevalence of depression in comparison to their white counterparts. Research has shown that culturally adapted interventions using Cognitive Behavioural Therapy (CBT) may be acceptable and may help to address the needs of this population. The aim of this study was to assess the acceptability and overall experience of the Positive Health Programme by British South Asian mothers.Methods: This was a nested qualitative study, part of an exploratory randomized controlled trial (RCT) conducted to test the feasibility and acceptability of a culturally-adapted intervention (Positive Health Programme or PHP) for postnatal depression in British South Asian women. In-depth interviews (N = 17) were conducted to determine the views of the participants on the feasibility and acceptability of the intervention.Results: The participants found the intervention acceptable and experienced an overall positive change in their attitudes, behaviour, and increased self-confidence.Conclusions: The findings suggest that the culturally adapted Positive Health Programme is acceptable to British South Asian women. These results support that culturally sensitive interventions may lead to better health outcomes and overall satisfaction.Trial Registration: Protocol registered on Clinicaltrials.gov NCT01838889. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure and preserved ejection fraction (HFpEF) have a poor prognosis, and no therapies have been proven to improve outcomes. It has been proposed that heart failure, including HFpEF, represents overlapping syndromes that may have different prognoses. We present an exploratory study of patients enrolled in the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I-PRESERVE) using latent class analysis (LCA) with validation using the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved study to identify HFpEF subgroups.Methods and Results: In total, 4113 HFpEF patients randomized to irbesartan or placebo were characterized according to 11 clinical features. The HFpEF subgroups were identified using LCA. Event-free survival and effect of irbesartan on the composite of all-cause mortality and cardiovascular hospitalization were determined for each subgroup. Subgroup definitions were applied to 3203 patients enrolled in CHARM-Preserved to validate observations regarding prognosis and treatment response. Six subgroups were identified with significant differences in event-free survival (P < 0.001). Clinical profiles and prognoses of the six subgroups were similar in CHARM-Preserved. The two subgroups with the worst event-free survival in both studies were characterized by a high prevalence of obesity, hyperlipidaemia, diabetes mellitus, anaemia, and renal insufficiency (Subgroup C) and by female predominance, advanced age, lower body mass index, and high rates of atrial fibrillation, valvular disease, renal insufficiency, and anaemia (Subgroup F).Conclusion: Using a data-driven approach, we identified HFpEF subgroups with significantly different prognoses. Further development of this approach for characterizing HFpEF subgroups is warranted. [ABSTRACT FROM AUTHOR]

Background: Patient-reported outcomes are vital in informing randomised controlled trials (RCTs) and health-care interventions and policies from the patient's perspective. However, participant non-response may introduce bias and can affect the generalisability of the trial. This study evaluates two interventions aimed at increasing response rates to postal questionnaires within a large, UK-wide RCT: pre-notification via short messenger service (SMS) text prior to sending the initial mailing of trial questionnaires versus no pre-notification; for non-responders to the initial mailing of the questionnaires, an e-mail reminder (containing a hyperlink to complete the questionnaire online) versus a postal reminder.Methods: This study is a 2 × 2 partial factorial design RCT nested within an RCT of medical expulsive therapy for ureteric stone disease. Participants who supplied a mobile telephone number were randomly assigned to receive an SMS text pre-notification of questionnaire delivery or no pre-notification. Those who supplied an e-mail address were randomly assigned to receive a questionnaire reminder by e-mail or post. Participants could be randomly assigned to the pre-notification comparison or the reminder comparison or both. The primary outcome measure was response rate at each questionnaire time point.Results: Four hundred eighteen participants were randomly assigned to the SMS pre-notification comparison (80% were male, and the mean age was 41 years with a standard deviation (SD) of 11.1). The intervention had no effect on response rate at either questionnaire time point. In subgroup analyses, SMS pre-notification increased response rates in women but only at the first questionnaire time point. One hundred nineteen participants were randomly assigned to the reminder comparison (80% were male, and the mean age was 42 years with an SD of 12.1). There was no difference in response rate in those who received an e-mail reminder compared with those who received a postal reminder.Conclusions: SMS text pre-notification of questionnaire delivery and email delivery of questionnaire reminders did not improve response rates. There was some evidence to suggest that SMS text pre-notification may be effective in women, and further studies to investigate this may be warranted. E-mail reminders for participants to return their postal questionnaire could be advantageous given that response rates were similar following either type of reminder and the low cost of delivering an e-mail compared with a postal reminder. This is a substudy of the SUSPEND trial (ISCTRN69423238) (18 Nov. 2010). [ABSTRACT FROM AUTHOR]

The article discusses a study which examined whether operative or non-operative treatment leads to better outcomes in patients with typical displaced intra-articular calcaneal fractures. Topics covered include the allocation of patients to open reduction and internal fixation with a plate and screws, the similarity of Kerr-Atkins scores for calcaneal fracture between the operative and non-operative groups and the complications experienced by patients in the operative group.

Objectives We investigated the treatment effects reported from a high-quality randomized controlled trial of cognitive behavioural therapy ( CBT) for 106 people with borderline personality disorder attending community-based clinics in the UK National Health Service - the BOSCOT trial. Specifically, we examined whether the amount of therapy and therapist competence had an impact on our primary outcome, the number of suicidal acts, using instrumental variables regression modelling. Design Randomized controlled trial. Participants from across three sites ( London, Glasgow, and Ayrshire/ Arran) were randomized equally to CBT for personality disorders ( CBTpd) plus Treatment as Usual or to Treatment as Usual. Treatment as Usual varied between sites and individuals, but was consistent with routine treatment in the UK National Health Service at the time. CBTpd comprised an average 16 sessions (range 0-35) over 12 months. Method We used instrumental variable regression modelling to estimate the impact of quantity and quality of therapy received (recording activities and behaviours that took place after randomization) on number of suicidal acts and inpatient psychiatric hospitalization. Results A total of 101 participants provided full outcome data at 2 years post randomization. The previously reported intention-to-treat ( ITT) results showed on average a reduction of 0.91 (95% confidence interval 0.15-1.67) suicidal acts over 2 years for those randomized to CBT. By incorporating the influence of quantity of therapy and therapist competence, we show that this estimate of the effect of CBTpd could be approximately two to three times greater for those receiving the right amount of therapy from a competent therapist. Conclusions Trials should routinely control for and collect data on both quantity of therapy and therapist competence, which can be used, via instrumental variable regression modelling, to estimate treatment effects for optimal delivery of therapy. Such estimates complement rather than replace the ITT results, which are properly the principal analysis results from such trials. Practitioner points Assessing the impact of the quantity and quality of therapy (competence of therapists) is complex., More competent therapists, trained in CBTpd, may significantly reduce the number of suicidal act in patients with borderline personality disorder. [ABSTRACT FROM AUTHOR]

Objectives: To quantify the change in work productivity and activities of daily living in North American women with heavy menstrual bleeding (HMB) treated with estradiol valerate/dienogest (E2V/DNG; Qlaira®/Natazia®) compared to placebo. Methods: Women in the United States and Canada, aged 20-53 years with an objective diagnosis of HMB and no recognizable anatomical pathology, were treated with E2V/DNG or placebo for seven cycles (196 days). Main outcome measures included work productivity (i.e., productivity while at work) and activities of daily living measured using a modified Work Productivity and Activity Impairment Questionnaire (mWPAI) on a Likert scale from 0 to 10 (higher values denote higher impairment levels). Results: In both countries, significant improvement was observed between baseline and end of treatment in work productivity and activities of daily living impairment. The improvements in work productivity and activities of daily living with E2V/DNG treatment relative to placebo ranged from 37.2% to 39.2% across both countries. Monthly gains due to E2V/DNG treatment (net of placebo improvement) associated with improvement in work productivity were estimated to be US$80.2 and Can$70.8 (US$58.5) and those associated with improvement in activities of daily living were estimated to be US$84.9 and Can$73.5 (US$60.7). Conclusions: E2V/DNG was shown to have a consistent positive impact on work productivity and activities of daily living in U.S. and Canadian women with HMB. In addition, these improvements in work productivity and activities of daily living were associated with a reduction in HMB-related monetary burden compared to the placebo group. [ABSTRACT FROM AUTHOR]