Lisa Riste

Aortic Pulse-Wave Velocity and Its Relationship to Mortality in Diabetes and Glucose Intolerance. An Integrated Index of Vascular Function?

Background—Arterial distensibility measures, generally from pulse-wave velocity (PWV), are widely used with little knowledge of relationships to patient outcome. We tested whether aortic PWV predicts cardiovascular and all-cause mortality in type 2 diabetes and glucose-tolerance–tested (GTT) multiethnic population samples. Methods and Results—Participants were randomly sampled from (1) a type 2 diabetes outpatient clinic and (2) primary care population registers, from which nondiabetic control subjects were given a GTT. Brachial blood pressures and Doppler-derived aortic PWV were measured. Mortality data over 10 years’ follow-up were obtained. At any level of systolic blood pressure (SBP), aortic PWV was greater in subjects with diabetes than in controls. Mortality risk doubled in subjects with diabetes (hazard ratio 2.34, 95% CI 1.5 to 3.74) and in those with glucose intolerance (2.12, 95% CI 1.11 to 4.0) compared with controls. For all groups combined, age, sex, and SBP predicted mortality; the addition of PWV independently predicted all-cause and cardiovascular mortality (hazard ratio 1.08, 95% CI 1.03 to 1.14 for each 1 m/s increase) but displaced SBP. Glucose tolerance status and smoking were other independent contributors, with African-Caribbeans experiencing reduced mortality risk (hazard ratio 0.41, 95% CI 0.25 to 0.69). Conclusions—Aortic PWV is a powerful independent predictor of mortality in both diabetes and GTT population samples. In displacing SBP as a prognostic factor, aortic PWV is probably further along the causal pathway for arterial disease and may represent a useful integrated index of vascular status and hence cardiovascular risk.

Close relation of fasting insulin-like growth factor binding protein-1 (IGFBP-1) with glucose tolerance and cardiovascular risk in two populations.

Aims/hypothesis. Insulin resistance/hyperinsulinaemia is implicated in the development of cardiovascular disease and diabetes but its role and causal pathways are not clear. We tested the hypothesis that the insulin-like growth factor system is independently associated with cardiovascular risk within susceptible populations based on previous reports of the links between low circulating insulin-like growth factor binding protein-1 concentrations and increased macrovascular disease in Type II (non-insulin-dependent) diabetes mellitus. Methods. In a population-based study 272 subjects (142 subjects of European and 130 Pakistani of origin) underwent a 75 g oral glucose tolerance test and standardised anthropometry. Fasting concentrations of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II), intact insulin and lipids were measured and were related to 2-h glucose tolerance test status. Insulin sensitivity was calculated using the homeostasis model assessment (HOMA). Results. Insulin-like growth factor binding protein-1 was significantly lower in subjects with impaired glucose tolerance when compared with normal glucose tolerance in both ethnic groups (Europeans F = 6.7, p = 0.002 and Pakistanis F = 4.4, p = 0.01). Multiple linear regression modelling showed that insulin-like growth factor binding protein-1 was independently associated with 2-h glucose (β = 0.16, p = 0.009) and logistic regression indicated a 40 % reduction in risk of impaired glucose tolerance for every 2.7 ng/ml increase in the insulin-like growth factor binding protein-1 concentration [odds ratio 0.6 (CI = 0.49–0.71), p = 0.001)]. In addition, insulin-like growth factor binding protein-1 was significantly correlated negatively with several established cardiovascular factors, and positively with insulin sensitivity. Conclusion/interpretation. Insulin-like growth factor binding protein-1 is closely related to risk factors for diabetes and cardiovascular disease in people of European and Pakistani origin. It has potential use as a marker of (hepatic) insulin resistance in clinical intervention studies and further implicates the insulin-like growth factor system in the development of macrovascular disease. [Diabetologia (2001) 44: 333–339]

Hypertension in four African-origin populations : current 'Rule of Halves', quality of blood pressure control and attributable risk of cardiovascular disease

Objective To assess the public health burden from high blood pressure and the current status of its detection and management in four African-origin populations at emerging or high cardiovascular risk. Design Cross-site comparison using standardized measurement and techniques. Setting Rural and urban Cameroon; Jamaica; Manchester, Britain. Subjects Representative population samples in each setting. African-Caribbeans (80% of Jamaican origin) and a local European sample in Manchester. Main outcome measures Cross-site age-adjusted prevalence; population attributable risk. Results Among 1587 men and 2087 women, age-adjusted rates of blood pressure ⩾ 160 or 95 mmHg or its treatment rose from 5% in rural to 17% in urban Cameroon, despite young mean ages, to 21% in Jamaica and 29% in Caribbeans in Britain. Treatment rates reached 34% in urban Cameroon, and 69% in Jamaican- and British- Caribbean-origin women. Sub-optimal blood pressure control (> 140 and 90 mmHg) on treatment reached 88% in European women. Population attributable risks (or fractions) indicated that up to 22% of premature all-cause, and 45% of stroke mortality could be reduced by appropriate detection and treatment. Additional benefit on just strokes occurring on treatment could be up to 47% (e.g. in both urban Cameroon men and European women) from tighter blood pressure control on therapy. Cheap, effective therapy is available. Conclusion With mortality risk now higher from non-communicable than communicable diseases in sub-Saharan Africa and elsewhere, systematic measurement, detection and genuine control of hypertension once treated can go hand-in-hand with other adult health programmes in primary care. Cost implications are not great. The data from this collaborative study suggest that such efforts should be well rewarded.

Nutrient intake trends among African-Caribbeans in Britain: a migrant population and its second generation.

OBJECTIVE To explore British African-Caribbean (AfC) nutrient intake by migration status (place of birth), diet (traditional Caribbean or more European) and age and relate this ecologically to coronary heart disease (CHD) mortality rates. DESIGN Cross-sectional. SETTING Inner-city Manchester, UK. SUBJECTS Two hundred and fifty-five adults of AfC origin aged 25-79 years, randomly sampled from population registers. RESULTS Caribbean-born people (mean age 56, and mean time in Britain 30 years) had significantly lower per cent energy from total and saturated fat than younger British-born AfC people (mean age 29 years) (31.3% vs. 35%, difference in total fat 3.7%, 95%CI 2-5%; in saturated fat 10.9% vs. 12.6%, difference 1.7%, 95%CI 1-2.5%). The Caribbean-born group also ate more fruit (+84g/day-1, 95%CI 36-132g/day-1) and green vegetables (+26 g/day-1, 95%CI 3-49 g/day-1). Men following a traditional diet (> or = 5 days week-1) similarly had a lower per cent energy from fat, at 30.4%, than less traditional eaters, at 33.1% (difference 2.7%, 95%CI 0.7-4.8%). African-Caribbean women, at relatively greater CHD risk than AfC men, had higher body mass indices (BMIs) than AfC men. Compared with national data, AfC subjects consumed some 7% and 5% less energy from total fat and saturated fat, respectively, with over 9% more from carbohydrate. However, there was marked convergence towards the national average in the youngest AfC groups aged 25-34 years, whatever their place of birth. CONCLUSIONS Caribbean birthplace has an independent effect on total fat intake and percentage of energy from fat. Together with higher fruit and vegetable intake, these results are consistent with the dietary fat/antioxidant/CHD hypothesis.

Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial

Objective To evaluate the effectiveness of home delivered pragmatic rehabilitation—a programme of gradually increasing activity designed collaboratively by the patient and the therapist—and supportive listening—an approach based on non-directive counselling—for patients in primary care with chronic fatigue syndrome/myalgic encephalomyelitis or encephalitis (CFS/ME). Design Single blind, randomised, controlled trial. Setting 186 general practices across the north west of England between February 2005 and May 2007. Participants 296 patients aged 18 or over with CFS/ME (median illness duration seven years) diagnosed using the Oxford criteria. Interventions Participants were randomly allocated to pragmatic rehabilitation, supportive listening, or general practitioner treatment as usual. Both therapies were delivered at home in 10 sessions over 18 weeks by one of three adult specialty general nurses who had received four months’ training, including supervised practice, in each of the interventions. GP treatment as usual was unconstrained except that patients were not to be referred for systematic psychological therapies during the treatment period. Main outcome measures The primary clinical outcomes were fatigue and physical functioning at the end of treatment (20 weeks) and 70 weeks from recruitment compared with GP treatment as usual. Lower fatigue scores and higher physical functioning scores denote better outcomes. Results A total of 257 (87%) of the 296 patients who entered the trial were assessed at 70 weeks, the primary outcome point. Analysis was on an intention to treat basis, with robust treatment effects estimated after adjustment for missing data using probability weights. Immediately after treatment (at 20 weeks), patients allocated to pragmatic rehabilitation (n=95) had significantly improved fatigue (effect estimate -1.18, 95% confidence interval -2.18 to -0.18; P=0.021) but not physical functioning (-0.18, 95% CI -5.88 to +5.52; P=0.950) compared with patients allocated to treatment as usual (n=100). At one year after finishing treatment (70 weeks), there were no statistically significant differences in fatigue or physical functioning between patients allocated to pragmatic rehabilitation and those on treatment as usual (-1.00, 95% CI -2.10 to +0.11; P=0.076 and +2.57, 95% CI 3.90 to +9.03; P=0.435). At 20 weeks, patients allocated to supportive listening (n=101) had poorer physical functioning than those allocated to treatment as usual (-7.54, 95% CI -12.76 to -2.33; P=0.005) and no difference in fatigue. At 70 weeks, patients allocated to supportive listening did not differ significantly from those allocated to treatment as usual on either primary outcome. Conclusions For patients with CFS/ME in primary care, pragmatic rehabilitation delivered by trained nurse therapists improves fatigue in the short term compared with unconstrained GP treatment as usual, but the effect is small and not statistically significant at one year follow-up. Supportive listening delivered by trained nurse therapists is not an effective treatment for CFS/ME. Trial registration International Standard Randomised Controlled Trial Number IRCTN74156610.

Habitual diet in four populations of African origin: a descriptive paper on nutrient intakes in rural and urban Cameroon, Jamaica and Caribbean migrants in Britain.

BACKGROUND The prevalence of chronic diseases is increasing in West Africa, the Caribbean and its migrants to Britain. This trend may be due to the transition in the habitual diet, with increasing (saturated) fat and decreasing fruit and vegetable intakes, both within and between countries. OBJECTIVE We have tested this hypothesis by comparing habitual diet in four African-origin populations with a similar genetic background at different stages in this transition. DESIGN The study populations included subjects from rural Cameroon urban Cameroon Jamaica and African-Caribbeans in Manchester, UK all aged 25-74 years. Habitual diet was assessed by a food-frequency questionnaire, specifically developed for each country separately. RESULTS Total energy intake was greatest in rural Cameroon and lowest in Manchester for all age/sex groups. A tendency towards the same pattern was seen for carbohydrates, protein and total fat intake. Saturated and polyunsaturated fat intake and alcohol intake were highest in rural Cameroon, and lowest in Jamaica, with the intakes in the UK lower than those in urban Cameroon. The percentage of energy from total fat was higher in rural and urban Cameroon than in Jamaica and the UK for all age/sex groups. The opposite was seen for percentage of energy from carbohydrate intake, the intake being highest in Jamaica and lowest in rural Cameroon. The percentage of energy from protein increased gradually from rural Cameroon to the UK. CONCLUSIONS These results do not support our hypothesis that carbohydrate intake increased, while (saturated) fat intake decreased, from rural Cameroon to the UK.

Overcoming the barriers to the diagnosis and management of chronic fatigue syndrome/ME in primary care: a meta synthesis of qualitative studies

BackgroundThe NICE guideline for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) emphasises the need for an early diagnosis in primary care with management tailored to patient needs. However, GPs can be reluctant to make a diagnosis and are unsure how to manage people with the condition.MethodsA meta synthesis of published qualitative studies was conducted, producing a multi-perspective description of barriers to the diagnosis and management of CFS/ME, and the ways that some health professionals have been able to overcome them. Analysis provided second-order interpretation of the original findings and developed third-order constructs to provide recommendations for the medical curriculum.ResultsTwenty one qualitative studies were identified. The literature shows that for over 20 years health professionals have reported a limited understanding of CFS/ME. Working within the framework of the biomedical model has also led some GPs to be sceptical about the existence of the condition. GPs who provide a diagnosis tend to have a broader, multifactorial, model of the condition and more positive attitudes towards CFS/ME. These GPs collaborate with patients to reach agreement on symptom management, and use their therapeutic skills to promote self care.ConclusionsIn order to address barriers to the diagnosis and management of CFS/ME in primary care, the limitations of the biomedical model needs to be recognised. A more flexible bio-psychosocial approach is recommended where medical school training aims to equip practitioners with the skills needed to understand, support and manage patients and provide a pathway to refer for specialist input.

Implementing resources to support the diagnosis and management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in primary care: A qualitative study

BackgroundNICE guidelines emphasise the need for a confident, early diagnosis of Chronic Fatigue Syndrome/ Myalgic Encephalitis (CFS/ME) in Primary Care with management tailored to the needs of the patient. Research suggests that GPs are reluctant to make the diagnosis and resources for management are currently inadequate. This study aimed to develop resources for practitioners and patients to support the diagnosis and management of CFS/ME in primary care.MethodsSemi structured interviews were conducted with patients, carers, GPs, practice nurses and CFS/ME specialists in North West England. All interviews were audio recorded, transcribed and analysed qualitatively using open explorative thematic coding. Two patient involvement groups were consulted at each stage of the development of resources to ensure that the resources reflect everyday issues faced by people living with CFS/ME.ResultsPatients and carers stressed the importance of recognising CFS/ME as a legitimate condition, and the need to be believed by health care professionals. GPs and practice nurses stated that they do not always have the knowledge or skills to diagnose and manage the condition. They expressed a preference for an online training package. For patients, information on getting the most out of a consultation and the role of carers was thought to be important. Patients did not want to be overloaded with information at diagnosis, and suggested information should be given in steps. A DVD was suggested, to enable information sharing with carers and family, and also for those whose symptoms act as a barrier to reading.ConclusionRather than use a top-down approach to the development of training for health care practitioners and information for patients and carers, we have used data from key stakeholders to develop a patient DVD, patient leaflets to guide symptom management and a modular e-learning resource which should equip GPs to diagnose and manage CFS/ME effectively, meet NICE guidelines and give patients acceptable, evidence-based information.

Cost-effectiveness of supported self-management for CFS/ME patients in primary care.

BackgroundNurse led self-help treatments for people with chronic fatigue syndrome/myalgic encephalitis (CFS/ME) have been shown to be effective in reducing fatigue but their cost-effectiveness is unknown.MethodsCost-effectiveness analysis conducted alongside a single blind randomised controlled trial comparing pragmatic rehabilitation (PR) and supportive listening (SL) delivered by primary care nurses, and treatment as usual (TAU) delivered by the general practitioner (GP) in North West England. A within trial analysis was conducted comparing the costs and quality adjusted life years (QALYs) measured within the time frame of the trial. 296 patients aged 18 and over with CFS/ME diagnosed using the Oxford criteria were included in the cost-effectiveness analysis.ResultsTreatment as usual is less expensive and leads to better patient outcomes compared with Supportive Listening. Treatment as usual is also less expensive than Pragmatic Rehabilitation. PR was effective at reducing fatigue in the short term, but the impact of the intervention on QALYs was uncertain. However, based on the results of this trial, PR is unlikely to be cost-effective in this patient population.ConclusionsThis analysis does not support the introduction of SL. Any benefits generated by PR are unlikely to be of sufficient magnitude to warrant recommending PR for this patient group on cost-effectiveness grounds alone. However, dissatisfaction with current treatment options means simply continuing with ‘treatment as usual’ in primary care is unlikely to be acceptable to patients and practitioners.Trial registrationThe trial registration number is IRCTN74156610

Clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder (PARADES): a pragmatic, multicentre, observer-blind, randomised controlled superiority trial.

BACKGROUND Group psychoeducation is a low-cost National Institute for Health and Care Excellence-recommended treatment for bipolar disorder. However, the clinical effectiveness and acceptability of this intervention are unclear compared with unstructured peer support matched for delivery and aim of treatment, and for previous bipolar history. We aimed to assess the clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder. METHODS We did this pragmatic, multicentre, parallel-group, observer-blind, randomised controlled superiority trial at eight community sites in two regions in England. Participants aged 18 years or older with bipolar disorder and no episode in the preceding 4 weeks were recruited via self-referral or secondary care referral. Participants were individually randomly assigned (1:1), via a computer-generated stochastic allocation sequence, to attend 21 2-h weekly sessions of either structured group psychoeducation or optimised unstructured peer support. Randomisation was minimised by number of previous episodes (one to seven, eight to 19, or ≥20) and stratified by clinical site. Outcome assessors were masked to group allocation. The primary outcome was time from randomisation to next bipolar episode, with planned moderator analysis of number of previous bipolar episodes and qualitative interview of participant experience. We did analysis by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN62761948. FINDINGS Between Sept 28, 2009, and Jan 9, 2012, we randomly assigned 304 participants to receive psychoeducation (n=153) or peer support (n=151); all (100%) participants had complete primary outcome data. Attendance at psychoeducation groups was higher than at peer-support groups (median 14 sessions [IQR three to 18] vs nine sessions [two to 17]; p=0·026). At 96 weeks, 89 (58%) participants in the psychoeducation group had experienced a next bipolar episode compared with 98 (65%) participants in the peer-support group; time to next bipolar episode did not differ between groups (hazard ratio [HR] 0·83, 95% CI 0·62-1·11; p=0·217). Planned moderator analysis showed that psychoeducation was most beneficial in participants with few (one to seven) previous bipolar episodes (χ2; HR 0·28, 95% CI 0·12-0·68; p=0·034). Four (1%) participants (one in the psychoeducation group and three in the peer-support group) died during follow-up; these deaths were deemed unrelated to the study interventions or procedures. INTERPRETATION Structured group psychoeducation was no more clinically effective than similarly intensive unstructured peer support, but was more acceptable and improved outcome in participants with fewer previous bipolar episodes. Optimum provision of structured psychological interventions, such as group psychoeducation, early in the course of bipolar disorder might have important benefits on the course of illness, and merits further research. FUNDING National Institute for Health Research.