L Rodgers

Effectiveness of mindfulness-based stress reduction and mindfulness based cognitive therapy in vascular disease: A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE To determine the effectiveness of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) on psychological and physical outcomes for people with vascular disease. DESIGN Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES AMED, CINAHL, EMBASE, British Nursing Index, Medline, Web of Science, PsycINFO, Cochrane Database of Systematic Reviews, Central, Social Sciences Citation Index, Social Policy and Practice, and HMIC from inception to January 2013. REVIEW METHODS Articles were screened for inclusion independently by two reviewers. Data extraction and quality appraisal were performed by one reviewer and checked by a second with discrepancies resolved by discussion with a third if necessary. Random-effects meta-analyses were performed. RESULTS Nine articles (from eight original randomised controlled trials) met eligibility criteria and were included in the final review. In total, 578 participants were enrolled across the trials, with participants presenting with prehypertension/hypertension (n=3 trials), type 1 or 2 diabetes (n=2), heart disease (n=2) and stroke (n=1). Meta-analyses, using standardised mean differences, showed evidence of reductions in stress (-0.36; 95% CI -0.67 to -0.09; p=0.01), depression (-0.35; 95% CI -0.53 to -0.16; p=0.003) and anxiety (-0.50; 95% CI -0.70 to -0.29; p<0.001). Effects on physical outcomes (blood pressure, albuminuria, stress hormones) were mixed. CONCLUSION Whilst populations with vascular disease appear to derive a range of psychological benefits from MBSR/MBCT intervention, the effects on physical parameters of disease are not yet established. More robust studies, with longer term follow-up, are required to ascertain full effectiveness of such intervention.

The Strengths and Difficulties Questionnaire as a Predictor of Parent-Reported Diagnosis of Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder

The Strengths and Difficulties Questionnaire (SDQ) is widely used as an international standardised instrument measuring child behaviour. The primary aim of our study was to examine whether behavioral symptoms measured by SDQ were elevated among children with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) relative to the rest of the population, and to examine the predictive value of the SDQ for outcome of parent-reported clinical diagnosis of ASD/ADHD. A secondary aim was to examine the extent of overlap in symptoms between children diagnosed with these two disorders, as measured by the SDQ subscales. A cross-sectional secondary analysis of data from the Millennium Birth Cohort (n = 19,519), was conducted. Data were weighted to be representative of the UK population as a whole. ADHD or ASD identified by a medical doctor or health professional were reported by parents in 2008 and this was the case definition of diagnosis; (ADHD n = 173, ASD n = 209, excluding twins and triplets). Study childrens ages ranged from 6.3–8.2 years; (mean 7.2 years). Logistic regression was used to examine the association between the parent-reported clinical diagnosis of ASD/ADHD and teacher and parent-reported SDQ subscales. All SDQ subscales were strongly associated with both ASD and ADHD. There was substantial co-occurrence of behavioral difficulties between children diagnosed with ASD and those diagnosed with ADHD. After adjustment for other subscales, the final model for ADHD, contained hyperactivity/inattention and impact symptoms only and had a sensitivity of 91% and specificity of 90%; (AUC) = 0.94 (95% CI, 0.90–0.97). The final model for ASD was composed of all subscales except the ‘peer problems’ scales, indicating of the complexity of behavioural difficulties that may accompany ASD. A threshold of 0.03 produced model sensitivity and specificity of 79% and 93% respectively; AUC = 0.90 (95% CI, 0.86–0.95). The results support changes to DSM-5 removing exclusivity clauses.

Adherence to Oral Glucose-Lowering Therapies and Associations With 1-Year HbA1c: A Retrospective Cohort Analysis in a Large Primary Care Database.

OBJECTIVE The impact of taking oral glucose-lowering medicines intermittently, rather than as recommended, is unclear. We conducted a retrospective cohort study using community-acquired U.K. clinical data (Clinical Practice Research Database [CPRD] and GoDARTS database) to examine the prevalence of nonadherence to treatment for type 2 diabetes and investigate its potential impact on HbA1c reduction stratified by type of glucose-lowering medication. RESEARCH DESIGN AND METHODS Data were extracted for patients treated between 2004 and 2014 who were newly prescribed metformin, sulfonylurea, thiazolidinedione, or dipeptidyl peptidase 4 inhibitors and who continued to obtain prescriptions over 1 year. Cohorts were defined by prescribed medication type, and good adherence was defined as a medication possession ratio ≥0.8. Linear regression was used to determine potential associations between adherence and 1-year baseline-adjusted HbA1c reduction. RESULTS In CPRD and GoDARTS, 13% and 15% of patients, respectively, were nonadherent. Proportions of nonadherent patients varied by the oral glucose-lowering treatment prescribed (range 8.6% [thiazolidinedione] to 18.8% [metformin]). Nonadherent, compared with adherent, patients had a smaller HbA1c reduction (0.4% [4.4 mmol/mol] and 0.46% [5.0 mmol/mol] for CPRD and GoDARTs, respectively). Difference in HbA1c response for adherent compared with nonadherent patients varied by drug (range 0.38% [4.1 mmol/mol] to 0.75% [8.2 mmol/mol] lower in adherent group). Decreasing levels of adherence were consistently associated with a smaller reduction in HbA1c. CONCLUSIONS Reduced medication adherence for commonly used glucose-lowering therapies among patients persisting with treatment is associated with smaller HbA1c reductions compared with those taking treatment as recommended. Differences observed in HbA1c responses to glucose-lowering treatments may be explained in part by their intermittent use.

Dropouts in the AB/BA crossover design

Missing data arise in crossover trials, as they do in any form of clinical trial. Several papers have addressed the problems that missing data create, although almost all of these assume that the probability that a planned observation is missing does not depend on the value that would have been observed; that is, the data are missing at random (MAR). In many applications, this assumption is likely to be untenable; in which case, the data are missing not at random (MNAR). We investigate the effect on estimates of the treatment effect that assume data are MAR when data are actually MNAR. We also propose using the assumption of no carryover treatment effect, which is usually required for this design, to permit the estimation of a treatment effect when data are MNAR. The results are applied to a trial comparing two treatments for neuropathic pain and show that the estimate of treatment effect is sensitive to the assumption of MAR.

Precision Medicine in Type 2 Diabetes: Clinical Markers of Insulin Resistance Are Associated With Altered Short- and Long-term Glycemic Response to DPP-4 Inhibitor Therapy

OBJECTIVE A precision approach to type 2 diabetes therapy would aim to target treatment according to patient characteristics. We examined if measures of insulin resistance and secretion were associated with glycemic response to dipeptidyl peptidase 4 (DPP-4) inhibitor therapy. RESEARCH DESIGN AND METHODS We evaluated whether markers of insulin resistance and insulin secretion were associated with 6-month glycemic response in a prospective study of noninsulin-treated participants starting DPP-4 inhibitor therapy (Predicting Response to Incretin Based Agents [PRIBA] study; n = 254), with replication for routinely available markers in U.K. electronic health care records (Clinical Practice Research Datalink [CPRD]; n = 23,001). In CPRD, we evaluated associations between baseline markers and 3-year durability of response. To test the specificity of findings, we repeated analyses for glucagon-like peptide 1 (GLP-1) receptor agonists (PRIBA, n = 339; CPRD, n = 4,464). RESULTS In PRIBA, markers of higher insulin resistance (higher fasting C-peptide [P = 0.03], HOMA2 insulin resistance [P = 0.01], and triglycerides [P < 0.01]) were associated with reduced 6-month HbA1c response to DPP-4 inhibitors. In CPRD, higher triglycerides and BMI were associated with reduced HbA1c response (both P < 0.01). A subgroup defined by obesity (BMI ≥30 kg/m2) and high triglycerides (≥2.3 mmol/L) had reduced 6-month response in both data sets (PRIBA HbA1c reduction 5.3 [95% CI 1.8, 8.6] mmol/mol [0.5%] [obese and high triglycerides] vs. 11.3 [8.4, 14.1] mmol/mol [1.0%] [nonobese and normal triglycerides]; P = 0.01). In CPRD, the obese, high- triglycerides subgroup also had less durable response (hazard ratio 1.28 [1.16, 1.41]; P < 0.001). There was no association between markers of insulin resistance and response to GLP-1 receptor agonists. CONCLUSIONS Markers of higher insulin resistance are consistently associated with reduced glycemic response to DPP-4 inhibitors. This finding provides a starting point for the application of a precision diabetes approach to DPP-4 inhibitor therapy.

Dropout in crossover and longitudinal studies: Is complete case so bad?

We discuss inference for longitudinal clinical trials subject to possibly informative dropout. A selection of available methods is reviewed for the simple case of trials with two timepoints. Using data from two such clinical trials, each with two treatments, we demonstrate that different analysis methods can at times lead to quite different conclusions from the same data. We investigate properties of complete-case estimators for the type of trials considered, with emphasis on interpretation and meaning of parameters. We contrast longitudinal and crossover designs and argue that for crossover studies there are often good reasons to prefer a complete case analysis. More generally, we suggest that there is merit in an approach in which no untestable assumptions are made. Such an approach would combine a dropout analysis, an analysis of complete-case data only, and a careful statement of justified conclusions.

Cohort profile for the MASTERMIND study: using the Clinical Practice Research Datalink (CPRD) to investigate stratification of response to treatment in patients with type 2 diabetes

Purpose This is a retrospective cohort study using observational data from anonymised primary care records. We identify and extract all patients with type 2 diabetes and associated clinical data from the Clinical Practice Research Datalink (CPRD) to inform models of disease progression and stratification of treatment. Participants Data were extracted from CPRD on 8 August 2016. The initial data set contained all patients (n=313 485) in the database who had received a type 2 diabetes medication. Criteria were applied to identify and exclude those with type 1 diabetes, polycystic ovarian syndrome or other forms of diabetes (n=40 204), and for data quality control (n=12). We identified 251 338 patients for inclusion in future analyses of diabetes progression and treatment response. Findings to date For 6-month response to treatment, measured by change in glycated haemoglobin (HbA1c), we have 91 765 patients with 119 785 treatment response episodes. The greatest impact on reduction of HbA1c occurs with first-line and second-line treatments, metformin and sulfonylurea. Patients moving to third-line treatments tend to have greater weights and higher body mass index. We have investigated the impact of non-adherence to commonly used glucose-lowering medications on HbA1c. For baseline-adjusted HbA1c change over 1 year, non-adherent patients had lower HbA1c reductions than adherent patients, with mean and 95% CI of −4.4 (−4.7 to −4.0) mmol/mol (−0.40 (−0.43 to −0.37) %). Future plans Findings from studies using these data will help inform future treatment plans and guidelines. Additional data are added with updates from CPRD. This will increase the numbers of patients on newer medications and add more data on those already receiving treatment. There are several ongoing studies investigating different hypotheses regarding differential response to treatment and progression of diabetes. For side effects, links to Hospital Episode Statistics data, where severe events such as hypoglycaemia will be recorded, will also be explored.

Sex and BMI Alter the Benefits and Risks of Sulfonylureas and Thiazolidinediones in Type 2 Diabetes: A Framework for Evaluating Stratification Using Routine Clinical and Individual Trial Data

OBJECTIVE The choice of therapy for type 2 diabetes after metformin is guided by overall estimates of glycemic response and side effects seen in large cohorts. A stratified approach to therapy would aim to improve on this by identifying subgroups of patients whose glycemic response or risk of side effects differs markedly. We assessed whether simple clinical characteristics could identify patients with differing glycemic response and side effects with sulfonylureas and thiazolidinediones. RESEARCH DESIGN AND METHODS We studied 22,379 patients starting sulfonylurea or thiazolidinedione therapy in the U.K. Clinical Practice Research Datalink (CPRD) to identify features associated with increased 1-year HbA1c fall with one therapy class and reduced fall with the second. We then assessed whether prespecified patient subgroups defined by the differential clinical factors showed differing 5-year glycemic response and side effects with sulfonylureas and thiazolidinediones using individual randomized trial data from ADOPT (A Diabetes Outcome Progression Trial) (first-line therapy, n = 2,725) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes) (second-line therapy, n = 2,222). Further replication was conducted using routine clinical data from GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland) (n = 1,977). RESULTS In CPRD, male sex and lower BMI were associated with greater glycemic response with sulfonylureas and a lesser response with thiazolidinediones (both P < 0.001). In ADOPT and RECORD, nonobese males had a greater overall HbA1c reduction with sulfonylureas than with thiazolidinediones (P < 0.001); in contrast, obese females had a greater HbA1c reduction with thiazolidinediones than with sulfonylureas (P < 0.001). Weight gain and edema risk with thiazolidinediones were greatest in obese females; however, hypoglycemia risk with sulfonylureas was similar across all subgroups. CONCLUSIONS Patient subgroups defined by sex and BMI have different patterns of benefits and risks on thiazolidinedione and sulfonylurea therapy. Subgroup-specific estimates can inform discussion about the choice of therapy after metformin for an individual patient. Our approach using routine and shared trial data provides a framework for future stratification research in type 2 diabetes.

'How I Feel About My School': The construction and validation of a measure of wellbeing at school for primary school children.

There is a growing focus on child wellbeing and happiness in schools, but we lack self-report measures for very young children. Three samples (N = 2345) were combined to assess the psychometric properties of the How I Feel About My School (HIFAMS) questionnaire, which was designed for children aged 4–8 years. Test–retest reliability was moderate (intraclass correlation coefficient = .62). HIFAMS assessed a single concept and had moderate internal consistency (Cronbach’s alpha values from .62 to .67). There were low correlations between scores on the child-reported HIFAMS and parent and teacher reports. Children at risk of exclusion had significantly lower HIFAMS scores than the community sample (mean difference = 2.4; 95% confidence interval (CI) = [1.6, 3.2]; p < .001). Schools contributed only 4.5% of the variability in HIFAMS score, the remaining 95.5% reflecting pupil differences within schools. Girls’ scores were 0.37 units (95% CI = [0.16, 0.57]; p < .001) higher than boys, while year group and deprivation did not predict HIFAMS score. HIFAMS is a promising measure that demonstrates moderate reliability and discriminates between groups even among very young children.

The Quality of Life Scale for Children (QoL-C)

Purpose – There is a lack of valid and reliable generic measures of Health-Related Quality of Life (HRQoL) for children under eight. The purpose of this paper is to assess the psychometric properties of the newly formulated Quality of Life Scale for Children (QoL-C), which uses a pictorial response format. Design/methodology/approach – In total, 335 primary school children completed the QoL-C on two occasions, two weeks apart. Children aged four to seven were interviewed one-to-one while children aged eight to nine completed the measure as a class activity. Test-re-test reliability, convergent validity and child-parent concordance were assessed. Findings – Only one child refused to complete the QoL-C, which suggests the measure is user-friendly. Test-re-test reliability was moderate for the measures total score (intraclass correlation coefficient =0.48, 95 percent CI 0.39, 0.57) but low to fair for individual items (K from 0.13 to 0.37). Internal consistency was moderate (α=0.42 time one, 0.53 time two)....