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Background: It is estimated that around 30% of breast cancers in post-menopausal women are related to lifestyle. The breast cancer-pooling project demonstrated that sustained weight loss of 2 to 4.5 kg is associated with an 18% lower risk of breast cancer, highlighting the importance of small changes in body weight. Our study aimed to assess the effectiveness a volunteer-delivered, community based, weight management programme (ActWELL) for women with a BMI > 25 kg/m2 attending NHS Scotland Breast Screening clinics. Methods: A multicentre, 1:1 parallel group, randomised controlled trial was undertaken in 560 women aged 50 to 70 years with BMI > 25 kg/m2. On completion of baseline measures, all participants received a breast cancer prevention leaflet. Intervention group participants received the ActWELL intervention which focussed on personalised diet advice and pedometer walking plans. The programme was delivered in leisure centres by (the charity) Breast Cancer Now volunteer coaches. Primary outcomes were changes between groups at 12 months in body weight (kg) and physical activity (accelerometer measured step count). Results: Two hundred seventy-nine women were allocated to the intervention group and 281 to the comparison group. Twelve-month data were available from 240 (81%) intervention and 227 (85%) comparison group participants. Coaches delivered 523 coaching sessions and 1915 support calls to 279 intervention participants. Mean weight change was − 2.5 kg (95% CI − 3.1 to − 1.9) in the intervention group and − 1.2 kg (− 1.8 to 0.6) in the comparison group. The adjusted mean difference was − 1.3 kg (95% CI − 2.2 to − 0.4, P = 0.003). The odds ratio for losing 5% weight was 2.20 (95% CI 1.4 to 3.4, p = 0.0005) in favour of the intervention. The adjusted mean difference in step counts between groups was 483 steps/day (95% CI − 635 to 1602) (NS). Conclusions: A community weight management intervention initiated at breast screening clinics and delivered by volunteer coaches doubled the likelihood of clinically significant weight loss at 12 months (compared with usual care) offering significant potential to decrease breast cancer risk. Trial registration: Database of registration: ISCRTN. Registration number:11057518. Date trial registered:21.07.2017. Date of enrolment of first participant: 01.09.2017. [ABSTRACT FROM AUTHOR]

Objective: To determine the effects of dapagliflozin in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) on left ventricular (LV) remodeling using cardiac MRI.Research Design and Methods: We randomized 56 patients with T2DM and HF with LV systolic dysfunction to dapagliflozin 10 mg daily or placebo for 1 year, on top of usual therapy. The primary end point was difference in LV end-systolic volume (LVESV) using cardiac MRI. Key secondary end points included other measures of LV remodeling and clinical and biochemical parameters.Results: In our cohort, dapagliflozin had no effect on LVESV or any other parameter of LV remodeling. However, it reduced diastolic blood pressure and loop diuretic requirements while increasing hemoglobin, hematocrit, and ketone bodies. There was a trend toward lower weight.Conclusions: We were unable to determine with certainty whether dapagliflozin in patients with T2DM and HF had any effect on LV remodeling. Whether the benefits of dapagliflozin in HF are due to remodeling or other mechanisms remains unknown. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease with metabolic acidosis is common in older people, but the effectiveness of oral sodium bicarbonate therapy in this group is unclear. We tested whether oral sodium bicarbonate provides net health benefit for older people with advanced chronic kidney disease and serum bicarbonate concentrations < 22 mmol/L.Methods: Pragmatic multicentre, parallel group, double-blind, placebo-controlled randomised trial. We recruited adults aged ≥ 60 years with estimated glomerular filtration rate of < 30 mL/min/1.73 m2, not receiving dialysis, with serum bicarbonate concentration < 22 mmol/L, from 27 nephrology and geriatric medicine departments in the UK. Participants received oral sodium bicarbonate (up to 3 g/day) or matching placebo given for up to 2 years, randomised in a 1:1 ratio. The primary outcome was between-group difference in the Short Physical Performance Battery (SPPB) at 12 months, adjusted for baseline values, analysed by intention to treat. Secondary outcomes included generic and disease-specific quality of life (EQ-5D and KDQoL tools), anthropometry, renal function, walk distance, blood pressure, bone and vascular health markers, and incremental cost per quality-adjusted life year gained.Results: We randomised 300 participants between May 2013 and February 2017, mean age 74 years, 86 (29%) female. At 12 months, 116/152 (76%) participants allocated to bicarbonate and 104/148 (70%) allocated to placebo were assessed; primary outcome data were available for 187 participants. We found no significant treatment effect for the SPPB: bicarbonate arm 8.3 (SD 2.5) points, placebo arm 8.8 (SD 2.2) and adjusted treatment effect - 0.4 (95% CI - 0.9 to 0.1, p = 0.15). We found no significant treatment effect for glomerular filtration rate (0.6 mL/min/1.73 m2, 95% CI - 0.8 to 2.0, p = 0.39). The bicarbonate arm showed higher costs and lower quality of life as measured by the EQ-5D-3L tool over 1 year (£564 [95% CI £88 to £1154]); placebo dominated bicarbonate under all sensitivity analyses. Adverse events were more frequent in those randomised to bicarbonate (457 versus 400).Conclusions: Oral sodium bicarbonate did not improve physical function or renal function, increased adverse events and is unlikely to be cost-effective for use by the UK NHS for this patient group.Trial Registration: European Clinical Trials Database (2011-005271-16) and ISRCTN09486651; registered 17 February 2012. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to explore the feasibility of conducting a randomized controlled trial of dynamic Lycra® orthoses as an adjunct to arm rehabilitation after stroke and to explore the magnitude and direction of change on arm outcomes. Design: This is a single-blind, two-arm parallel group, feasibility randomized controlled trial. Setting: In-patient rehabilitation. Subjects: The study participants were stroke survivors with arm hemiparesis two to four weeks after stroke receiving in-patient rehabilitation. Interventions: Participants were randomized 2:1 to wear Lycra® gauntlets for eight hours daily for eight weeks, plus usual rehabilitation (n = 27), or to usual rehabilitation only (n = 16). Main measures: Recruitment, retention, fidelity, adverse events and completeness of data collection were examined at 8 and 16 weeks; arm function (activity limitation; Action Research Arm Test, Motor Activity Log) and impairment (Nine-hole Peg Test, Motricity Index, Modified Tardieu Scale). Structured interviews explored acceptability. Results: Of the target of 51, 43 (84%) participants were recruited. Retention at 8 weeks was 32 (79%) and 24 (56%) at 16 weeks. In total, 11 (52%) intervention group participants and 6 (50%) control group participants (odds ratio = 1.3, 95% confidence interval = 0.2 to 7.8) had improved Action Research Arm Test level by 8 weeks; at 16 weeks, this was 8 (61%) intervention and 6 (75.0%) control participants (odds ratio = 1.1, 95% confidence interval = 0.1 to 13.1). Change on other measures favoured control participants. Acceptability was influenced by 26 adverse reactions. Conclusion: Recruitment and retention were low, and adverse reactions were problematic. There were no indications of clinically relevant effects, but the small sample means definitive conclusions cannot be made. A definitive trial is not warranted without orthoses adaptation. [ABSTRACT FROM AUTHOR]

Background/Aims Recruitment to trials of intervention for older people who fall is challenging. Evidence suggests that the word falls has negative connotations for older people, and this may present a barrier to engaging with trials in this area. We therefore tested whether a participant information sheet that minimised reference to falls could improve recruitment rates. Methods We conducted a study within a trial, embedded within a randomised controlled trial of vitamin K versus placebo to improve postural sway in patients aged 65 and over with a history of falls. Potential participants were identified from primary care lists in 14 practices and were randomised to receive either a standard participant information sheet or an information sheet minimising use of the word falls, instead focussing on maintenance of health, fitness and balance. The primary outcome for this embedded trial was the proportion of responses expressing interest in participating received in each arm. Secondary outcomes were the proportion of those contacted attending a screening visit, consenting at screening, and the proportion contacted who were randomised into the main trial. Results In all, 4145 invitations were sent, with an overall response rate of 444 (10.7%). In all, 2148 individuals received the new information sheet (minimising reference to falls); 1997 received the standard information sheet. There was no statistically significant difference in response rate between those individuals sent the new information sheet and those sent the standard information sheet (10.1% vs 11.4%; difference 1.3% (95% confidence interval −0.6% to 3.2%); p = 0.19). Similarly, we found no statistically significant difference between the percentage of those who attended and consented at screening in the two groups (2.1% vs 2.7%; difference 0.6% (95% confidence interval: –0.4% to 1.6%); p = 0.20), and no statistically significant difference between the percentage randomised in the two groups (2.0% vs 2.6%; difference 0.6% (95% confidence interval −0.4% to 1.6%); p = 0.20) Conclusions Use of a participant information sheet minimising reference to falls did not lead to a greater response rate in this trial targeting older people with a history of falls. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To test the effectiveness of a theoretically based text‐message intervention to reduce binge drinking among socially disadvantaged men. Design: A multi‐centre parallel group, pragmatic, individually randomized controlled trial. Setting: Community‐based study conducted in four regions of Scotland. Participants: A total of 825 men aged 25–44 years recruited from socially disadvantaged areas who had two or more episodes of binge drinking (> 8 UK units on a single occasion) in the preceding 28 days: 411 men were randomized to the intervention and 414 to the control. Intervention and comparator: A series of 112 interactive text messages was delivered by mobile phone during a 12‐week period. The intervention was structured around the Health Action Process Approach, a comprehensive model which allows integration of a range of evidence‐based behaviour change techniques. The control group received 89 texts on general health, with no mention of alcohol or use of behaviour change techniques. Measurements: The primary outcome measure was the proportion of men consuming > 8 units on three or more occasions (in the previous 28 days) at 12 months post‐intervention. Findings: The proportion of men consuming > 8 units on three or more occasions (in the previous 28 days) was 41.5% in the intervention group and 47.8% in the control group. Formal analysis showed that there was no evidence that the intervention was effective [odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.57–1.08; absolute reduction 5.7%, 95% CI = −13.3 to 1.9]. The Bayes factor for this outcome was 1.3, confirming that the results were inconclusive. The retention was high and similar in intervention (84.9%) and control (86.5%) groups. Most men in the intervention group engaged with the text messages: almost all (92%) replied to text messages and 67% replied more than 10 times. Conclusions: A theoretically based text‐messaging intervention aimed at reducing binge drinking in disadvantaged men was not found to reduce prevalence of binge drinking at 12‐month follow‐up. [ABSTRACT FROM AUTHOR]

Objective: To determine whether spironolactone could benefit older people with osteoarthritis (OA), based on a previous study showing that spironolactone improved quality of life.Methods: This parallel-group, randomized, placebo-controlled, double-blind trial randomized community-dwelling people ages ≥70 years with symptomatic knee OA to 12 weeks of 25 mg daily oral spironolactone or matching placebo. The primary outcome was between-group difference in change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores. Secondary outcomes included WOMAC stiffness and physical function subscores, EuroQol 5-domain (EQ-5D) 3L score, and mechanistic markers. Analysis was by intent to treat, using mixed-model regression, adjusting for baseline values of test variables.Results: A total of 421 people had eligibility assessed, and 86 were randomized. Mean ± SD age was 77 ± 5 years and 53 of 86 (62%) were women. Adherence to study medication was 99%, and all participants completed the 12-week assessment. No significant improvement was seen in the WOMAC pain score (adjusted treatment effect 0.5 points [95% confidence interval (95% CI) - 0.3, 1.3]; P = 0.19). No improvement was seen in WOMAC stiffness score (0.2 points [95% CI -0.6, 1.1]; P = 0.58), WOMAC physical function score (0.0 points [95% CI -0.7, 0.8]; P = 0.98), or EQ-5D 3L score (0.04 points [95% CI -0.04, 0.12]; P = 0.34). Cortisol, matrix metalloproteinase 3, and urinary C-telopeptide of type II collagen were not significantly different between groups. More minor adverse events were noted in the spironolactone group (47 versus 32), but no increase in death or hospitalization was evident.Conclusion: Spironolactone did not improve symptoms, physical function, or health-related quality of life in older people with knee OA. [ABSTRACT FROM AUTHOR]

To determine the effectiveness of a behavior change intervention (BCI) with or without a pedometer in increasing physical activity in sedentary older women. Prospective randomized controlled trial. Primary care, City of Dundee, Scotland. Two hundred four sedentary women aged 70 and older. Six months of BCI, BCI plus pedometer (pedometer plus), or usual care. Primary outcome: change in daily activity counts measured by accelerometry. Secondary outcomes: Short Physical Performance Battery, health-related quality of life, depression and anxiety, falls, and National Health Service resource use. One hundred seventy-nine of 204 (88%) women completed the 6-month trial. Withdrawals were highest from the BCI group (15/68) followed by the pedometer plus group (8/68) and then the control group (2/64). After adjustment for baseline differences, accelerometry counts increased significantly more in the BCI group at 3 months than in the control group ( P=.002) and the pedometer plus group ( P=.04). By 6 months, accelerometry counts in both intervention groups had fallen to levels that were no longer statistically significantly different from baseline. There were no significant changes in the secondary outcomes. The BCI was effective in objectively increasing physical activity in sedentary older women. Provision of a pedometer yielded no additional benefit in physical activity, but may have motivated participants to remain in the trial. Trial registration: ISRCTN26786857 [ABSTRACT FROM AUTHOR]

Background: Corticosteroids and antiviral agents are widely used to treat the early stages of idiopathic facial paralysis (i.e., Bell's palsy), but their effectiveness is uncertain. Methods: We conducted a double-blind, placebo-controlled, randomized, factorial trial involving patients with Bell's palsy who were recruited within 72 hours after the onset of symptoms. Patients were randomly assigned to receive 10 days of treatment with prednisolone, acyclovir, both agents, or placebo. The primary outcome was recovery of facial function, as rated on the House–Brackmann scale. Secondary outcomes included quality of life, appearance, and pain. Results: Final outcomes were assessed for 496 of 551 patients who underwent randomization. At 3 months, the proportions of patients who had recovered facial function were 83.0% in the prednisolone group as compared with 63.6% among patients who did not receive prednisolone (P<0.001) and 71.2% in the acyclovir group as compared with 75.7% among patients who did not receive acyclovir (adjusted P=0.50). After 9 months, these proportions were 94.4% for prednisolone and 81.6% for no prednisolone (P<0.001) and 85.4% for acyclovir and 90.8% for no acyclovir (adjusted P=0.10). For patients treated with both drugs, the proportions were 79.7% at 3 months (P<0.001) and 92.7% at 9 months (P<0.001). There were no clinically significant differences between the treatment groups in secondary outcomes. There were no serious adverse events in any group. Conclusions: In patients with Bell's palsy, early treatment with prednisolone significantly improves the chances of complete recovery at 3 and 9 months. There is no evidence of a benefit of acyclovir given alone or an additional benefit of acyclovir in combination with prednisolone. (Current Controlled Trials number, ISRCTN71548196.) N Engl J Med 2007;357:1598-607. [ABSTRACT FROM AUTHOR]

Background: Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1.Methods: We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of ≥35 on the checklist-individual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central web-based system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep-wake patterns, coping with pain, and addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10-14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0-100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with baseline scores as a covariate. Safety data were presented as descriptives. This trial is registered with ClinicalTrials.gov, number NCT02118779.Findings: Between April 2, 2014, and May 29, 2015, we randomly assigned 255 patients to treatment: 128 to cognitive behavioural therapy plus standard care and 127 to standard care alone. 33 (26%) of 128 assigned to cognitive behavioural therapy also received the graded exercise module. Follow-up continued until Oct 17, 2016. The DM1-Activ-c score increased from a mean (SD) of 61·22 (17·35) points at baseline to 63·92 (17·41) at month 10 in the cognitive behavioural therapy group (adjusted mean difference 1·53, 95% CI -0·14 to 3·20), and decreased from 63·00 (17·35) to 60·79 (18·49) in the standard care group (-2·02, -4·02 to -0·01), with a mean difference between groups of 3·27 points (95% CI 0·93 to 5·62, p=0·007). 244 adverse events occurred in 65 (51%) patients in the cognitive behavioural therapy group and 155 in 63 (50%) patients in the standard care alone group, the most common of which were falls (155 events in 40 [31%] patients in the cognitive behavioural therapy group and 71 in 33 [26%] patients in the standard care alone group). 24 serious adverse events were recorded in 19 (15%) patients in the cognitive behavioural therapy group and 23 in 15 (12%) patients in the standard care alone group, the most common of which were gastrointestinal and cardiac.Interpretation: Cognitive behavioural therapy increased the capacity for activity and social participation in patients with myotonic dystrophy type 1 at 10 months. With no curative treatment and few symptomatic treatments, cognitive behavioural therapy could be considered for use in severely fatigued patients with myotonic dystrophy type 1.Funding: The European Union Seventh Framework Programme. [ABSTRACT FROM AUTHOR]