A Randomised Controlled Trial to Reduce Sedentary Time in Young Adults at Risk of Type 2 Diabetes Mellitus: Project STAND (Sedentary Time ANd Diabetes)

Aims   Type 2 diabetes mellitus (T2DM), a serious and prevalent chronic disease, is traditionally associated with older age. However, due to the rising rates of obesity and sedentary lifestyles, it is increasingly being diagnosed in the younger population. Sedentary (sitting) behaviour has been shown to be associated with greater risk of cardio-metabolic health outcomes, including T2DM. Little is known about effective interventions to reduce sedentary behaviour in younger adults at risk of T2DM. We aimed to investigate, through a randomised controlled trial (RCT) design, whether a group-based structured education workshop focused on sitting reduction, with self-monitoring, reduced sitting time.  Methods   Adults aged 18–40 years who were either overweight (with an additional risk factor for T2DM) or obese were recruited for the Sedentary Time ANd Diabetes (STAND) RCT. The intervention programme comprised of a 3-hour group-based structured education workshop, use of a self-monitoring tool, and follow-up motivational phone call. Data were collected at three time points: baseline, 3 and 12 months after baseline. The primary outcome measure was accelerometer-assessed sedentary behaviour after 12 months. Secondary outcomes included other objective (activPAL) and self-reported measures of sedentary behaviour and physical activity, and biochemical, anthropometric, and psycho-social variables.  Results   187 individuals (69% female; mean age 33 years; mean BMI 35 kg/m2) were randomised to intervention and control groups. 12 month data, when analysed using intention-to-treat analysis (ITT) and per-protocol analyses, showed no significant difference in the primary outcome variable, nor in the majority of the secondary outcome measures.  Conclusions  A structured education intervention designed to reduce sitting in young adults at risk of T2DM was not successful in changing behaviour at 12 months. Lack of change may be due to the brief nature of such an intervention and lack of focus on environmental change. Moreover, some participants reported a focus on physical activity rather than reductions in sitting per se. The habitual nature of sedentary behaviour means that behaviour change is challenging

Predicting pregnancy outcomes using longitudinal biomarkers: analysis of urinary human chorionic gonadotrophin levels in normal and failing pregnancies

Early miscarriage affects approximately 25% of confirmed pregnancies and can adversely impact a woman’s body and mind. Human chorionic gonadotrophin (hCG) is used to confirm pregnancy and as a triaging tool in cases of suspected pregnancy loss. Thought its current use may be limited, the potential of hCG in the context of miscarriage is greater than is currently acknowledged. Profiles of hCG for healthy and failing pregnancies have consistently been shown to be distinct, providing motivation for quantifying the association between repeatedly observed hCG and miscarriage. Naive approaches model this association via techniques typically reserved for modelling each outcome separately. Such methods fail to consider the continuous nature of the biomarker, measurement error and appropriate estimation of uncertainty. The joint longitudinal-survival model provides a framework to simultaneously model a longitudinally observed biomarker and time-to-event outcome. In its most common incarnation, the joint model consists of a linear mixed-effects model and a proportional hazards survival submodel. The dependency between the biomarker response and survival outcome is underpinned by shared random effects, laying the groundwork for subject-specific survival predictions. The aim was to use advanced statistical models to estimate the association between miscarriage and hCG, and to extend this to predict individual outcomes. These methods were applied to data collected by SPD Development Company Ltd. The study prospectively followed women as they tried to conceive. Volunteers collected daily urine samples from the start of their cycle to up to day 60 if they conceived. The application of cutting-edge methods to this unique dataset allowed the association to be estimated using complete longitudinal profiles of hCG. Analysis extended to diary data, to establish whether timing of intercourse can alter the rate of miscarriage. A key modelling assumption of the joint models fitted in this thesis were also assessed via a simulation study.</p

Descriptive characteristics of the study population stratified by gender.

<p>Descriptive characteristics of the study population stratified by gender.</p

The association between depressive symptoms and insulin resistance, inflammation and adiposity in men and women.

INTRODUCTION: Depression has been shown to be associated with elevated leptin levels, low-grade inflammation and insulin resistance. These derangements are often measured in mixed gender cohorts despite the different body compositions and hormonal environments of men and women and gender-specific prevalence and responses to depression. METHODS: A cross-sectional analysis was carried out on a cohort of 639 participants from the ADDITION-Leicester dataset to assess differences in markers of diabetes risk, cardiovascular risk and inflammation in depressed and non-depressed individuals. Depressive symptoms were determined using the WHO (Five) well-being index. Multivariate linear and logistic regression analyses were adjusted for age, sex, ethnicity, body mass index, smoking, social deprivation and activity levels for continuous and binary variables respectively. Further analysis included stratifying the data by gender as well as assessing the interaction between depression and gender by including an interaction term in the model. RESULTS: Women with depressive symptoms had a 5.3% larger waist circumference (p = 0.003), 28.7% higher HOMA IR levels (p = 0.026), 6.6% higher log-leptin levels (p = 0.01) and 22.37% higher TNF-α levels (p = 0.015) compared with women without. Conversely, depressive symptoms in men were associated with 7.8% lower body fat % (p = 0.015) but 48.7% higher CRP levels (p = 0.031) compared to men without. However, interaction analysis failed to show a significant difference between men and women. CONCLUSIONS: Depressive symptoms are associated with metabolic derangements. Whilst women tended to show elevations in biomarkers related to an increased risk of type 2 diabetes (HOMA IR, leptin and TNF-α), men showed a marked increase in the cardiovascular disease risk biomarker CRP. However, perhaps due to the cohort size, interaction analysis did not show a significant gender difference

A comparison of participants with and without depressive symptoms, adjusted data.

<p>A comparison of participants with and without depressive symptoms, adjusted data.</p

A comparison of participants with and without depressive symptoms stratified by sex, adjusted data.

<p>A comparison of participants with and without depressive symptoms stratified by sex, adjusted data.</p

Descriptive characteristics of the study population stratified by gender.

<p>Descriptive characteristics of the study population stratified by gender.</p

The Primary-Secondary Care Partnership to Improve Outcomes in Chronic Kidney Disease (PSP-CKD) Study: A Cluster Randomized Trial in Primary Care

Background Most patients with CKD are managed in the community. Whether nurse-led CKD management programs improve outcomes in patients with CKD in primary care is unclear.Methods To assess the effect of such a program on the rate of renal function decline in patients with CKD (stages 3–5) in primary care in the United Kingdom, we conducted a cluster randomized trial, the Primary-Secondary Care Partnership to Improve Outcomes in Chronic Kidney Disease study. A software program designed for the study created a data file of patients with CKD in participating practices. In 23 intervention practices (11,651 patients), a CKD nurse practitioner worked with nominated practice leads to interpret the data file and implement guideline-based patient-level CKD management interventions. The 23 control practices (11,706 patients) received a data file but otherwise, continued usual CKD care. The primary outcome was defined at the cluster (practice) level as the change from baseline of the mean eGFR of the patients with CKD at 6-month intervals up to 42 months. Secondary outcomes included numbers of patients coded for CKD, mean BP, numbers of patients achieving National Institute for Health and Care Excellence BP targets for CKD, and proteinuria measurement.Results After 42 months, eGFR did not differ significantly between control and intervention groups. CKD- and proteinuria-related coding improved significantly along with the number of patients achieving BP targets in the intervention group versus usual care.Conclusions CKD management programs in primary care may not slow progression of CKD, but they may significantly improve processes of care and potentially decrease the cardiovascular disease burden in CKD and related costs.</div

Descriptive characteristics at baseline by randomisation group.

<p>Descriptive characteristics at baseline by randomisation group.</p