Very early invasive strategy in higher risk non-ST-elevation acute coronary syndrome: the RAPID NSTEMI trial.

OBJECTIVE: To investigate whether a very early invasive strategy (IS)±revascularisation improves clinical outcomes compared with standard care IS in higher risk patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Multicentre, randomised, controlled, pragmatic strategy trial of higher risk patients with NSTE-ACS, defined by Global Registry of Acute Coronary Events 2.0 score of ≥118, or ≥90 with at least one additional high-risk feature. Participants were randomly assigned to very early IS±revascularisation (<90 min from randomisation) or standard care IS±revascularisation (<72 hours). The primary outcome was a composite of all-cause mortality, new myocardial infarction or hospitalisation for heart failure at 12 months. RESULTS: The trial was discontinued early by the funder due to slow recruitment during the COVID-19 pandemic. 425 patients were randomised, of whom 413 underwent an IS: 204 to very early IS (median time from randomisation: 1.5 hours (IQR: 0.9-2.0)) and 209 to standard care IS (median: 44.0 hours (IQR: 22.9-72.6)). At 12 months, there was no significant difference in the primary outcome between the early IS (5.9%) and standard IS (6.7%) groups (OR 0.93, 95% CI 0.42 to 2.09; p=0.86). The incidence of stroke and major bleeding was similar. The length of hospital stay was reduced with a very early IS (3.9 days (SD 6.5) vs 6.3 days (SD 7.6), p<0.01). CONCLUSIONS: A strategy of very early IS did not improve clinical outcomes compared with a standard care IS in higher risk patients with NSTE-ACS. However, the primary outcome rate was low and the trial was underpowered to detect such a difference. TRIAL REGISTRATION NUMBER: NCT03707314.

Structured group education programme and accompanying mHealth intervention to promote physical activity in women with a history of gestational diabetes: A randomised controlled trial.

AIMS: Assess effectiveness of a hybrid intervention targeting physical activity in women with prior gestational diabetes. METHODS: Randomised controlled trial with parallel arms. 293 women (35.1 ± 5.1 years; 40% ethnic minority) recruited from two hospitals and randomised to routine care or hybrid lifestyle intervention comprising two group sessions and access to a mobile web app. Primary outcome was a change in objectively measured physical activity at 12 months. Secondary outcomes included self-efficacy for exercise, quality of life and anxiety and depression. Linear regression compared outcome measures between groups. RESULTS: 83% of intervention participants attended at least one group session, of who 66% registered to use the app. There was a non-significant increase in physical activity at 12 months (between-group difference of 0.95 mg [95% CI: -0.46 to 2.37]), equivalent to approximately 500 steps per day. Intervention participants reported higher self-efficacy for exercise (0.54, 95% CI: 0.05 to 1.102; p = 0.029), lower anxiety (-0.91, 95% CI: -1.74 to -0.09; p = 0.031), and higher quality of life (0.05, 95% CI: 0.004 to 0.09; p = 0.032), compared to controls. CONCLUSIONS: The intervention improved confidence in exercise and quality of life. Further research is needed to improve participant engagement with physical activity interventions in multi-ethnic populations with a history of gestational diabetes.

Measuring quality of life in trials including patients on haemodialysis: methodological issues surrounding the use of the Kidney Disease Quality of Life Questionnaire.

BACKGROUND: Haemodialysis (HD) treatment causes a significant decrease in quality of life (QoL). When enrolled in a clinical trial, some patients are lost prior to follow-up because they die or they receive a kidney transplant. It is unclear how these patients are dealt with in the analysis of QoL data. There are questions surrounding the consistency of how QoL measures are used, reported and analysed. METHODS: A systematic search of electronic databases for trials measuring QoL in HD patients using any variation of the Kidney Disease Quality of Life (KDQoL) Questionnaire was conducted. The review was conducted in Covidence version 2. Quantitative analysis was conducted in Stata version 16. RESULTS: We included 61 trials in the review, of which 82% reported dropouts. The methods to account for missing data due to dropouts include imputation (7%) and complete case analysis (72%). Few trials (7%) conducted a sensitivity analysis to assess the impact of missing data on the study results. Single imputation techniques were used, but are only valid under strong assumptions regarding the type and pattern of missingness. There was inconsistency in the reporting of the KDQoL, with many articles (70%) amending the validated questionnaires or reporting only statistically significant results. CONCLUSIONS: Missing data are not dealt with according to the missing data mechanism, which may lead to biased results. Inconsistency in the use of patient-reported outcome measures raises questions about the validity of these trials. Methodological issues in nephrology trials could be a contributing factor to why there are limited effective interventions to improve QoL in this patient group. PROSPERO REGISTRATION: CRD42020223869.

The effects of empagliflozin, dietary energy restriction, or both on appetite-regulatory gut peptides in individuals with type 2 diabetes and overweight or obesity: The SEESAW randomized, double-blind, placebo-controlled trial.

AIM: To assess the impact of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin (25 mg once-daily), dietary energy restriction, or both combined, on circulating appetite-regulatory peptides in people with type 2 diabetes (T2D) and overweight or obesity. MATERIALS AND METHODS: In a double-blind, placebo-controlled trial, 68 adults (aged 30-75 years) with T2D (drug naïve or on metformin monotherapy; HbA1c 6.0%-10.0% [42-86 mmol/mol]) and body mass index of 25 kg/m2 or higher were randomized to (a) placebo only, (b) placebo plus diet, (c) empagliflozin only or (d) empagliflozin plus diet for 24 weeks. Dietary energy restriction matched the estimated energy deficit elicited by SGLT2 inhibitor therapy through urinary glucose excretion (~360 kcal/day). The primary outcome was change in postprandial circulating total peptide-YY (PYY) during a 3-hour mixed-meal tolerance test from baseline to 24 weeks. Postprandial total glucagon-like peptide-1 (GLP-1), acylated ghrelin and subjective appetite perceptions formed secondary outcomes, along with other key components of energy balance. RESULTS: The mean weight loss in each group at 24 weeks was 0.44, 1.91, 2.22 and 5.74 kg, respectively. The change from baseline to 24 weeks in postprandial total PYY was similar between experimental groups and placebo only (mean difference [95% CI]: -8.6 [-28.6 to 11.4], 13.4 [-6.1 to 33.0] and 1.0 [-18.0 to 19.9] pg/ml in placebo-plus diet, empagliflozin-only and empagliflozin-plus-diet groups, respectively [all P ≥ .18]). Similarly, there was no consistent pattern of difference between groups for postprandial total GLP-1, acylated ghrelin and subjective appetite perceptions. CONCLUSIONS: In people with T2D and overweight or obesity, changes in postprandial appetite-regulatory gut peptides may not underpin the less than predicted weight loss observed with empagliflozin therapy. CLINICAL TRIALS REGISTRATION: NCT02798744, www. CLINICALTRIALS: gov; 2015-001594-40, www.EudraCT.ema.europa.eu; ISRCTN82062639, www.ISRCTN.org.

Promoting physical activity with self-management support for those with multimorbidity: a randomised controlled trial.

BACKGROUND: Targeted self-management programmes may improve health and increase physical activity (PA) in people with multimorbidity. AIM: To investigate the impact of a structured, theoretically driven, self-management group education programme on habitual PA levels in people with multimorbidity. DESIGN AND SETTING: Individually randomised controlled trial with 12-month follow-up, involving nine primary care practices in Leicestershire, UK. METHOD: In total, 353 adults with multimorbidity (age 67.8 years [±9 years], 161 male sex) were randomised to intervention (n = 180) or control (n = 173) groups. Intervention participants were invited to attend four group-based self-management sessions, centred primarily on increasing PA, and received motivational text-message support. The primary outcome measure was change in overall volume (time and intensity) of daily PA at 12 months, as measured by the GENEActiv wrist-worn accelerometer device. RESULTS: At baseline, the total sample achieved 22 min of moderate-vigorous intensity PA per day (mean/participant). At 12 months, in the complete-case analysis, a reduction in daily mean PA volume was seen in the intervention group relative to control (-0.80 milligravity [m g]; 95% confidence interval [CI] = -1.57 to -0.03; P = 0.04). Reductions were also seen in the intervention group in time spent in moderate-vigorous PA (-3.86 min per day; 95% CI= -6.70 to -1.03; P = 0.008) and time spent at an intensity equivalent to a slow walk (-4.66 min per day; 95% CI = -8.82 to -0.51; P = 0.028). However, the per-protocol analysis (excluding participants who did not attend at least one education session) found no between-group differences in overall daily PA at 12 months (-0.65 mg; 95% CI = -1.46 to 0.15; P = 0.11). CONCLUSION: The self-management programme elicited a slight reduction in PA levels in people with multimorbidity. Future research should identify and target subgroups of those with multimorbidity in greatest need of PA promotion in order to maximise potential capacity for benefit, and also focus on refining the intervention in order to increase efficacy in increasing PA.

EXTending availability of self-management structured EducatioN programmes for people with type 2 Diabetes in low-to-middle income countries (EXTEND)-a feasibility study in Mozambique and Malawi.

BACKGROUND: Globally, there are estimated 425 million people with type 2 diabetes (T2D) with 80% from low-middle income countries (LMIC). Diabetes self-management education (DSME) programmes are a vital and core component of the treatment pathway for T2D. Despite LMIC being disproportionally affected by T2D, there are no DSME available that meet international diabetes federation criterion. METHODS: The aims were to test the feasibility of delivering a proven effective and cost-effective approach used in a UK population in two urban settings in Malawi and Mozambique by; (1) developing a culturally, contextually and linguistically adapted DSME, the EXTending availability of self-management structured EducatioN programmes for people with type 2 Diabetes in low-to-middle income countries (EXTEND) programme; (2) using a mixed-method approach to evaluate the delivery of training and the EXTEND programme to patients with T2D. RESULTS: Twelve healthcare professionals were trained. Ninety-eight participants received the DSME. Retention was high (100% in Mozambique and 94% in Malawi). At 6 months HbA1c (-0.9%), cholesterol (-0.3 mmol/L), blood pressure (-5.9 mm Hg systolic and -6.1 mm Hg diastolic) improved in addition to indicators of well-being (problem areas in diabetes and self-efficacy in diabetes). CONCLUSION: It is feasible to deliver and evaluate the effectiveness of a culturally, contextually and linguistically adapted EXTEND programme in two LMIC. The DSME was acceptable with positive biomedical and psychological outcomes but requires formal testing with cost-effectiveness. Challenges exist in scaling up such an approach in health systems that do not have resources to address the challenge of diabetes.

Physical Activity after Cardiac EventS (PACES): a group education programme with subsequent text message support designed to increase physical activity in individuals with diagnosed coronary heart disease: a randomised controlled trial.

AIM: To assess the effectiveness of a low-cost pragmatic intervention (structured education and ongoing text message support) to increase daily physical activity in participants 12-48 months after a coronary heart disease cardiac event (myocardial infarction, angina or acute coronary syndrome) diagnosis. METHODS: A single-centre randomised controlled trial of 291 adults randomised to a structured education programme (n=145) or usual care (n=146). The programme consisted of two 2.5 hour sessions delivered 2 weeks apart, followed by supplementary text message support. The GENEActiv accelerometer assessed the primary outcome at 12 months (change in overall physical activity (expressed in milli gravitational (mg) units) from baseline). Secondary outcomes included anthropometric, physical function, cardiovascular, biochemical and patient-reported outcome measures. Linear regression was used to compare outcome measures between groups on a modified intention-to-treat basis. RESULTS: Participants' mean age was 66.5±9.7 years, 84.5% males, 82.5% white British and 15.5% south Asian. At 12 months, there was no difference between the groups in terms of change in overall physical activity (-0.23 mg (95% CI -1.22 to 0.75), p=0.64) and the programme was well accepted (88% attendance). Exploratory analyses showed that average moderate to vigorous physical activity (MVPA) levels increased in individuals not meeting physical activity guidelines (≥150 min per week) on enrolment compared with those who did, by 8 minutes per day (8.04 (95% CI 0.99 to 15.10), p=0.03). CONCLUSION: The programme was well attended but showed no change in physical activity levels. Results show high baseline MVPA levels and suggest that Physical Activity after Cardiac EventS education may benefit cardiac patients not currently meeting activity guidelines. TRIAL REGISTRATION NUMBER: ISRCTN91163727.

Effectiveness of the Ready to Reduce Risk (3R) complex intervention for the primary prevention of cardiovascular disease: a pragmatic randomised controlled trial.

BACKGROUND: Cardiovascular disease is responsible for 31% of all global deaths. Primary prevention strategies are needed to improve longer-term adherence to statins and healthy lifestyle behaviours to reduce risk in people at risk of cardiovascular disease. METHODS: Pragmatic randomised controlled trial recruited between May 2016 and March 2017 from primary care practices, England. Participants (n = 212) prescribed statins for primary prevention of cardiovascular disease with total cholesterol level ≥ 5 mmol/l were randomised: 105 to the intervention group and 107 to the control group, stratified by age and sex. The 3R intervention involved two facilitated, structured group education sessions focusing on medication adherence to statins, lifestyle behaviours and cardiovascular risk, with 44 weeks of medication reminders and motivational text messages and two supportive, coaching phone calls (at approximately 2 weeks and 6 months). The control group continued with usual clinical care. Both groups received a basic information leaflet. The primary outcome was medication adherence to statins objectively measured by a biochemical urine test. Self-reported adherence and practice prescription data provided additional measures. Secondary outcomes included cholesterol profile, blood pressure, anthropometric data, cardiovascular risk score, and self-reported lifestyle behaviours and psychological measures (health/medication beliefs, quality of life, health status). All outcomes were assessed at 12 months. RESULTS: Baseline adherence to statins was 47% (control) and 62% (intervention). No significant difference between the groups found for medication adherence to statins using either the urine test (OR 1.02, 95% CI 0.34 to 3.06, P = 0.968) or other measures. This may have been due to the higher than expected adherence levels at baseline. The adjusted mean difference between the groups (in favour of the intervention group) for diastolic blood pressure (- 4.28 mmHg (95% CI - 0.98 to - 1.58, P = 0.002)) and waist circumference (- 2.55 cm (95% CI - 4.55 to - 0.55, P = 0.012)). The intervention group also showed greater perceived control of treatment and more coherent understanding of the condition. CONCLUSIONS: The 3R programme successfully led to longer-term improvements in important clinical lifestyle indicators but no improvement in medication adherence, raising questions about the suitability of such a broad, multiple risk factor approach for improving medication adherence for primary prevention of CVD. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN16863160), March 11, 2006.

Effects of an Electronic Software "Prompt" With Health Care Professional Training on Cardiovascular and Renal Complications in a Multiethnic Population With Type 2 Diabetes and Microalbuminuria (the GP-Prompt Study): Results of a Pragmatic Cluster-Randomized Trial.

OBJECTIVE: Tight, targeted control of modifiable cardiovascular risk factors can reduce cardiovascular complications and mortality in individuals with type 2 diabetes mellitus (T2DM) and microalbuminuria. The effects of using an electronic "prompt" with a treatment algorithm to support a treat-to-target approach has not been tested in primary care. RESEARCH DESIGN AND METHODS: A multicenter, cluster-randomized trial was conducted among primary care practices across Leicestershire, U.K. The primary outcome was the proportion of individuals achieving systolic and diastolic blood pressure (<130 and <80 mmHg, respectively) and total cholesterol (<3.5 mmol/L) targets at 24 months. Secondary outcomes included proportion of individuals with HbA1c <58 mmol/mol (<7.5%), changes in prescribing, change in the albumin-to-creatinine ratio, major adverse cardiovascular events, cardiovascular mortality, and coding accuracy. RESULTS: A total of 2,721 individuals from 22 practices, mean age 63 years, 41% female, and 62% from black and minority ethnic groups completed 2 years of follow-up. There were no significant differences in the proportion of individuals achieving the composite primary outcome, although the proportion of individuals achieving the prespecified outcome of total cholesterol <4.0 mmol/L (odds ratio 1.24; 95% CI 1.05-1.47; P = 0.01) increased with intensive intervention compared with control. Coding for microalbuminuria increased relative to control (odds ratio 2.05; 95% CI 1.29-3.25; P < 0.01). CONCLUSIONS: Greater improvements in composite cardiovascular risk factor control with this intervention compared with standard care were not achieved in this cohort of high-risk individuals with T2DM. However, improvements in lipid profile and coding can benefit patients with diabetes to alter the high risk of atherosclerotic cardiovascular events. Future studies should consider comprehensive strategies, including patient education and health care professional engagement, in the management of T2DM.

A Cost and Cost-Benefit Analysis of the Stand More AT Work (SMArT Work) Intervention.

This study conducted a cost and cost-benefit analysis of the Stand More AT (SMArT) Work workplace intervention, designed to reduce sitting time. The study was a cluster two-armed randomised controlled trial involving 37 office clusters (146 desk-based workers) in a National Health Service Trust. The intervention group received a height-adjustable workstation with supporting behaviour change strategies. The control group continued with usual practice. Self-report absenteeism, presenteeism and work productivity were assessed at baseline, 3, 6 and 12 months; and organisational sickness absence records 12 months prior to, and 12 months of the intervention. Mean per employee costs associated with SMArT Work were calculated. Absenteeism, presenteeism and work productivity were estimated, and employer-recorded absence data and employee wage-banding were used to provide a human-capital-based estimate of costs to the organisation. The return-on-investment (ROI) and incremental cost-efficacy ratios (ICER) were calculated. Intervention cost was £692.40 per employee. Cost-benefit estimates show a net saving of £1770.32 (95%CI £-354.40, £3895.04) per employee as a result of productivity increase. There were no significant differences in absence data compared to the control group. SMArT Work provides supporting evidence for policy-makers and employers on the cost benefits of reducing sitting time at work.

Corrigendum and Editorial Warning Regarding Use of the MMAS Scale (The Ready to Reduce Risk (3R) Study for a Group Educational Intervention With Telephone and Text Messaging Support to Improve Medication Adherence for the Primary Prevention of Cardiovascular Disease: Protocol for a Randomized Controlled Trial).

[This corrects the article DOI: 10.2196/11289.].

Incidence and severity of hypoglycaemia in type 2 diabetes by treatment regimen: A UK multisite 12-month prospective observational study.

AIMS: To determine the incidence and severity of self-reported hypoglycaemia in a primary care population with type 2 diabetes. The study also aimed to compare incidence by treatment regimen. MATERIALS AND METHODS: A prospective observational study in 17 centres throughout the UK was conducted. Recruitment was based on treatment regimen (metformin alone, sulphonylurea-, insulin- or incretin-based therapy). Participants were asked to keep a blood glucose diary and self-report hypoglycaemia episodes [non-severe (self-treated) and severe (requiring external help)] over a 12-month period. RESULTS: Three hundred and twenty-five participants were enrolled, of whom 274 (84%) returned ≥1 monthly diaries. Overall, 39% reported experiencing hypoglycaemia; 32% recorded ≥1 symptomatic, 36% ≥1 non-severe, and 7% ≥1 severe episodes. By treatment, incidence (events per person/year) for any hypoglycaemia type was 4.39 for insulin, 2.34 for sulphonylurea, 0.76 for metformin, and 0.56 for incretin-based therapy. Compared with metformin, risk of non-severe hypoglycaemia was ~3 times higher for participants on sulphonylureas and > 5 times higher for those on insulin [incidence rate ratio (IRR) 3.02 (1.76-5.18), P < 0.001, and IRR 5.96 (3.48-10.2), P < 0.001, respectively]. For severe episodes, the incidence for sulphonylurea (0.09) was similar to metformin (0.07) and incretin-based therapy (0.07); for insulin the risk remained almost 5 times higher than metformin [incidence 0.32; IRR 4.55 (1.28-16.20), P = 0.019]. CONCLUSIONS: Hypoglycaemia represents a substantial burden for people with type 2 diabetes. Sulphonylureas and insulin are both associated with a risk of reported non-severe hypoglycaemia, but only insulin with severe episodes. This suggests the importance of the continued use of sulphonylureas in appropriate patients with type 2 diabetes.

The Ready to Reduce Risk (3R) Study for a Group Educational Intervention With Telephone and Text Messaging Support to Improve Medication Adherence for the Primary Prevention of Cardiovascular Disease: Protocol for a Randomized Controlled Trial.

BACKGROUND: Poor adherence to cardiovascular medications is associated with worse clinical outcomes. Evidence for effective education interventions that address medication adherence for the primary prevention of cardiovascular disease is lacking. The Ready to Reduce Risk (3R) study aims to investigate whether a complex intervention, involving group education plus telephone and text messaging follow-up support, can improve medication adherence and reduce cardiovascular risk. OBJECTIVE: This protocol paper details the design and rationale for the development of the 3R intervention and the study methods used. METHODS: This is an open and pragmatic randomized controlled trial with 12 months of follow-up. We recruited participants from primary care and randomly assigned them at a 1:1 frequency, stratified by sex and age, to either a control group (usual care from a general practitioner) or an intervention group involving 2 facilitated group education sessions with telephone and text messaging follow-up support, with a theoretical underpinning and using recognized behavioral change techniques. The primary outcome was medication adherence to statins. The primary measure was an objective, novel, urine-based biochemical measure of medication adherence. We also used the 8-item Morisky Medication Adherence Scale to assess medication adherence. Secondary outcomes were changes in total cholesterol, blood pressure, high-density lipoprotein, total cholesterol to high-density lipoprotein ratio, body mass index, waist to hip ratio, waist circumference, smoking behavior, physical activity, fruit and vegetable intake, patient activation level, quality of life, health status, health and medication beliefs, and overall cardiovascular disease risk score. We also considered process outcomes relating to acceptability and feasibility of the 3R intervention. RESULTS: We recruited 212 participants between May 2015 and March 2017. The 12-month follow-up data collection clinics were completed in April 2018, and data analysis will commence once all study data have been collected and verified. CONCLUSIONS: This study will identify a potentially clinically useful and effective educational intervention for the primary prevention of cardiovascular disease. Medication adherence to statins is being assessed using a novel urine assay as an objective measure, in conjunction with other validated measures. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number ISRCTN16863160; http://www.isrctn.com/ISRCTN16863160 (Archived by WebCite at http://www.webcitation.org/734PqfdQw). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11289.

Effectiveness of the Stand More AT (SMArT) Work intervention: cluster randomised controlled trial.

OBJECTIVES: To evaluate the impact of a multicomponent intervention (Stand More AT (SMArT) Work) designed to reduce sitting time on short (three months), medium (six months), and longer term (12 months) changes in occupational, daily, and prolonged sitting, standing, and physical activity, and physical, psychological, and work related health. DESIGN: Cluster two arm randomised controlled trial. SETTING: National Health Service trust, England. PARTICIPANTS: 37 office clusters (146 participants) of desk based workers: 19 clusters (77 participants) were randomised to the intervention and 18 (69 participants) to control. INTERVENTIONS: The intervention group received a height adjustable workstation, a brief seminar with supporting leaflet, workstation instructions with sitting and standing targets, feedback on sitting and physical activity at three time points, posters, action planning and goal setting booklet, self monitoring and prompt tool, and coaching sessions (month 1 and every three months thereafter). The control group continued with usual practice. MAIN OUTCOME MEASURES: The primary outcome was occupational sitting time (thigh worn accelerometer). Secondary outcomes were objectively measured daily sitting, prolonged sitting (≥30 minutes), and standing time, physical activity, musculoskeletal problems, self reported work related health (job performance, job satisfaction, work engagement, occupational fatigue, sickness presenteeism, and sickness absenteeism), cognitive function, and self reported psychological measures (mood and affective states, quality of life) assessed at 3, 6, and 12 months. Data were analysed using generalised estimating equation models, accounting for clustering. RESULTS: A significant difference between groups (in favour of the intervention group) was found in occupational sitting time at 12 months (-83.28 min/workday, 95% confidence interval -116.57 to -49.98, P=0.001). Differences between groups (in favour of the intervention group compared with control) were observed for occupational sitting time at three months (-50.62 min/workday, -78.71 to -22.54, P<0.001) and six months (-64.40 min/workday, -97.31 to -31.50, P<0.001) and daily sitting time at six months (-59.32 min/day, -88.40 to -30.25, P<0.001) and 12 months (-82.39 min/day, -114.54 to -50.26, P=0.001). Group differences (in favour of the intervention group compared with control) were found for prolonged sitting time, standing time, job performance, work engagement, occupational fatigue, sickness presenteeism, daily anxiety, and quality of life. No differences were seen for sickness absenteeism. CONCLUSIONS: SMArT Work successfully reduced sitting time over the short, medium, and longer term, and positive changes were observed in work related and psychological health. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10967042.

The General Practitioner Prompt Study to Reduce Cardiovascular and Renal Complications in Patients With Type 2 Diabetes and Renal Complications: Protocol and Baseline Characteristics for a Cluster Randomized Controlled Trial.

BACKGROUND: Adherence to evidence-based cardiovascular risk factor targets in patients with type 2 diabetes and microalbuminuria has shown long-term reduction in mortality and morbidity. Strategies to achieve such adherence have been delivered at individual patient level and are not cost-effective. Health care professional-level intervention has the potential to promote better adherence at lower cost. OBJECTIVE: The aim of this study was to assess the effectiveness of a multifactorial technology-driven intervention comprising health care professional training, a software prompt installed on practice systems, clinician email support, and enhanced performance and feedback reporting. METHODS: A cluster randomized trial will be performed where the primary outcome is the proportion of eligible patients meeting tight cardiovascular risk factor targets, including systolic and diastolic blood pressure (BP; BP<130/80 mm Hg) and total cholesterol (TC; TC<3.5 mmol/L) at 24 months. Secondary outcomes include proportion of patients with glycated hemoglobin (HbA1c) <58 mmol/mol (7.5%), change in medication prescribing, changes in microalbuminuria and renal function (estimated glomerular filtration rate, eGFR), incidence of major adverse CV events and mortality, and coding accuracy. Cost-effectiveness of the intervention will also be assessed. RESULTS: Among 2721 eligible patients, mean age was 62.9 (SD 10.0) years, and duration of diabetes was 10.46 (SD 7.22) years. Mean HbA1c was 59.3 (SD 17.4) mmol/mol; mean systolic and diastolic BP (mm Hg) were 134.3 (SD 14.6) and 76.1 (SD 9.5) mm Hg, respectively; and mean TC was 4.1 (SD 0.98) mmol/L. Overall, 131 out of 2721 (4.81%) patients achieved all 3 "tight" cardiovascular risk factor targets. Cardiovascular risk factor burden increased two-fold in those with eGFR<60 mL/min/1.73 m2 compared with those with eGFR≥60 mL/min/1.73 m2. Prevalence of microalbuminuria was 22.76%. In total, 1076 out of 2721 (39.54%) patients were coded for microalbuminuria or proteinuria on their primary care medical record. CONCLUSIONS: The general practitioner prompt study is the largest UK primary care-based, technology-driven, randomized controlled trial to support intensive intervention in high-risk group of multiethnic individuals with type 2 diabetes and microalbuminuria. This paper provides contemporary estimates for prevalent cardiovascular disease and adherence to evidence-based cardiovascular risk factor targets at baseline in a population with type 2 diabetes and microalbuminuria. The main trial results, including cost-effectiveness data, will be submitted for publication in 2018. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number ISRCTN14918517; http://www.isrctn.com/ISRCTN14918517 (Archived by WebCite at http://www.webcitation.org/6zqm53wNA). REGISTERED REPORT IDENTIFIER: RR1-10.2196/9588.

Differentiating the Preterm Phenotype: Distinct Profiles of Cognitive and Behavioral Development Following Late and Moderately Preterm Birth.

OBJECTIVES: To explore patterns of comorbidity in cognitive and behavioral outcomes at 2 years' corrected age among children born late or moderately preterm (LMPT) and to identify predictors of different patterns of comorbidity. STUDY DESIGN: Geographical, prospective population-based cohort study of 1139 infants born LMPT (320/7 to 366/7 weeks' gestation) and 1255 infants born at term (370/7 to 426/7 weeks' gestation). Parent questionnaires were obtained to identify impaired cognitive and language development, behavioral problems, delayed social-emotional competence, autistic features, and clinically significant eating difficulties at 24 months corrected age for 638 (57%) children born LMPT and 765 (62%) children born at term. RESULTS: Latent class analysis revealed 2 profiles of development among the term group: optimal (84%) and a profile of social, emotional, and behavioral impairments termed "nonoptimal" (16%). These 2 profiles were also identified among the LMPT group (optimal: 67%; nonoptimal: 26%). In the LMPT group, a third profile was identified (7%) that was similar to the phenotype previously identified in infants born very preterm. Nonwhite ethnicity, socioeconomic risk, and not receiving breast milk at hospital discharge were risk factors for nonoptimal outcomes in both groups. Male sex, greater gestational age, and pre-eclampsia were only associated with the preterm phenotype. CONCLUSIONS: Among children born LMPT with parent-reported cognitive or behavioral impairments, most had problems similar to the profile of difficulties observed in children born at term. A smaller proportion of children born LMPT had impairments consistent with the "very preterm phenotype" which are likely to have arisen through a preterm pathway. These results suggest that prematurity may affect development through several etiologic pathways in the late and moderately preterm population.