Judith Stephenson

Managing the health effects of climate change

Climate change is the biggest global health threat of the 21st century. Effects of climate change on health will affect most populations in the next decades and put the lives and wellbeing of billions of people at increased risk. During this century, earthﾒs average surface temperature rises are likely to exceed the safe threshold of 2ﾰC above preindustrial average temperature. Rises will be greater at higher latitudes, with medium-risk scenarios predicting 2ﾖ3ﾰC rises by 2090 and 4ﾖ5ﾰC rises in northern Canada, Greenland, and Siberia. In this report, we have outlined the major threatsﾗboth direct and indirectﾗto global health from climate change through changing patterns of disease, water and food insecurity, vulnerable shelter and human settlements, extreme climatic events, and population growth and migration. Although vector-borne diseases will expand their reach and death tolls, especially among elderly people, will increase because of heatwaves, the indirect effects of climate change on water, food security, and extreme climatic events are likely to have the biggest effect on global health.

Process evaluation in randomised controlled trials of complex interventions

Most randomised controlled trials focus on outcomes, not on the processes involved in implementing an intervention. Using an example from school based health promotion, this paper argues that including a process evaluation would improve the science of many randomised controlled trials

Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes

BACKGROUND Retinopathy commonly occurs in people with type 1 diabetes. Strict glycaemic control can decrease development and progression of retinopathy only partially. Blood pressure is also a risk factor for microvascular complications. Antihypertensive therapy, especially with inhibitors of angiotensin-converting enzyme (ACE), can slow progression of nephropathy, but the effects on retinopathy have not been established. We investigated the effect of lisinopril on retinopathy in type 1 diabetes. METHODS As part of a 2-year randomised double-blind placebo-controlled trial, we took retinal photographs at baseline and follow-up (24 months) in patients aged 20-59 in 15 European centres. Patients were not hypertensive, and were normoalbuminuric (85%) or microalbuminuric. Retinopathy was classified from photographs on a five-level scale (none to proliferative). FINDINGS The proportion of patients with retinopathy at baseline was 65% (117) in the placebo group and 59% (103) in the lisinopril group (p = 0.2). Patients on lisinopril had significantly lower HbA1c at baseline than those on placebo (6.9% vs 7.3 p = 0.05). Retinopathy progressed by at least one level in 21 (13.2%) of 159 patients on lisinopril and 39 (23.4%) of 166 patients on placebo (odds ratio 0.50 [95% CI 0.28-0.89], p = 0.02). This 50% reduction was the same when adjusted for centre and glycaemic control (0.55 [0.30-1.03], p = 0.06). Lisinopril also decreased progression by two or more grades (0.27 [0.07-1.00], p = 0.05), and progression to proliferative retinopathy (0.18 [0.04-0.82], p = 0.03). Progression was not associated with albuminuric status at baseline. Treatment reduced retinopathy incidence (0.69 [0.30-1.59], p = 0.4). INTERPRETATION Lisinopril may decrease retinopathy progression in non-hypertensive patients who have type 1 diabetes with little or no nephropathy. These findings need to be confirmed before changes to clinical practice can be advocated.

Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study

Summary The EURODIAB IDDM Complications Study involved the examination of 3250 randomly selected insulin-dependent diabetic patients, from 31 centres in 16 European countries. Part of the examination included an assessment of neurological function including neuropathic symptoms and physical signs, vibration perception threshold, tests of autonomic function and the prevalence of impotence. The prevalence of diabetic neuropathy across Europe was 28 % with no significant geographical differences. Significant correlations were observed between the presence of diabetic peripheral neuropathy with age (p < 0.05), duration of diabetes (p < 0.001), quality of metabolic control (p < 0.001), height (p < 0.01), the presence of background or proliferative diabetic retinopathy (p < 0.01), cigarette smoking (p < 0.001), high-density lipoprotein cholesterol (p < 0.001) and the presence of cardiovascular disease (p < 0.05), thus confirming previous associations. New associations have been identified from this study – namely with elevated diastolic blood pressure (p < 0.05), the presence of severe ketoacidosis (p < 0.001), an increase in the levels of fasting triglyceride (p < 0.001), and the presence of microalbuminuria (p < 0.01). All the data were adjusted for age, duration of diabetes and HbA1c. Although alcohol intake correlated with absence of leg reflexes and autonomic dysfunction, there was no overall association of alcohol consumption and neuropathy. The reported problems of impotence were extremely variable between centres, suggesting many cultural and attitudinal differences in the collection of such information in different European countries. In conclusion, this study has identified previously known and new potential risk factors for the development of diabetic peripheral neuropathy. [Diabetologia (1996) 39: 1377–1384]

MICROVASCULAR AND ACUTE COMPLICATIONS IN IDDM PATIENTS - THE EURODIAB IDDM COMPLICATIONS STUDY

SummaryThe prevalence of microvascular and acute diabetic complications, and their relation to duration of diabetes and glycaemic control were examined in a cross-sectional study of 3250 IDDM patients in Europe (EURODIAB IDDM Complications Study). Mean (SD) duration of diabetes was 14.7 (9.3) years. HbA1c and AER were measured centrally. Retinopathy was assessed by centrally graded retinal photography. Autonomic neuropathy was measured by heart rate and blood pressure responses to standing up. Sensory neuropathy was measured by biothesiometry. Normal HbA1c was found in 16% of patients. An AER of 20 μg/min or higher was found in 30.6% (95% CI 29.0%, 32.2%) of all patients, and 19.3% (15.6%, 23.0%) of those with diabetes for 1 to 5 years. The prevalence of retinopathy (46% in all patients; 82% after 20 or more years) was substantially lower than in comparable studies. Of all patients 5.9% (5.1%, 6.7%) had postural hypotension, 19.3% (17.9%, 20.7%) had abnormal heart rate variability, 32.2% (30.6%, 33.8%) reported one or more severe hypoglycaemic attacks during the last 12 months and 8.6% (7.6%, 9.6%) reported hospital admission for ketosis over the same period. Microvascular and acute complications were clearly related to duration of diabetes and to glycaemic control. However, the relation of glycaemic control to raised albuminuria differed qualitatively from its relation to retinopathy.

Retinopathy and Vision Loss in Insulin-dependent Diabetes in Europe: The EURODIAB IDDM Complications Study

PURPOSE To assess the frequency of retinopathy and vision loss in patients with insulin-dependent diabetes mellitus and their relations to potentially modifiable risk factors. METHODS The authors conducted a multicenter cross-sectional study of diabetic complications and their risk factors using standardized methods of assessment. The sample was comprised of 3250 insulin-dependent diabetic patients (1668 men, 1582 women) aged 15 to 60 years with mean (standard deviation) duration of diabetes of 14.7 (9.3) years from 31 European diabetes centers; 2991 of the patients were eligible for retinal photography. Visual acuity was measured using the Snellen chart. Retinopathy was evaluated by retinal photographs (two fields per eye) graded at a central facility. Glycated hemoglobin (HbA1c), cholesterol, triglyceride, fibrinogen, von Willebrand factor, and urinary albumin excretion rate were assessed at a single location. RESULTS Corrected visual acuity was greater than or equal to 1.0 in both eyes in 69.7% of patients and less than or equal to 0.1 in the best eye in 2.3%. Factors significantly related to vision loss were age, duration of diabetes, glycated hemoglobin (HbA1c), and level of retinopathy. Mild nonproliferative retinopathy was found in 25.8% of the patients, moderate-severe nonproliferative retinopathy in 9.8% of the patients, and proliferative retinopathy in 10.6% of the patients. After adjustment for age, duration of diabetes, HbA1c, and albumin excretion rate, significant risk factors for moderate-severe nonproliferative retinopathy were blood pressure and triglyceride, and risk factors for proliferative retinopathy were triglyceride and fibrinogen. CONCLUSION Vision loss is a common complication of patients with insulin-dependent diabetes, with diabetic retinopathy an important cause. Apart from poor glycemic control, several other potentially modifiable risk factors for retinopathy may be important, including elevated blood pressure, plasma triglyceride, and fibrinogen. In view of the possible barriers to the full implementation of strict glycemic control in this type of diabetes, additional strategies for the prevention and slowing of progression of retinopathy should be investigated, such as blood pressure and lipid lowering therapies.

Pupil-led sex education in England (RIPPLE study): cluster-randomised intervention trial

BACKGROUND Improvement of sex education in schools is a key part of the UK governments strategy to reduce teenage pregnancy in England. We examined the effectiveness of one form of peer-led sex education in a school-based randomised trial of over 8000 pupils. METHODS 29 schools were randomised to either peer-led sex education (intervention) or to continue their usual teacher-led sex education (control). In intervention schools, peer educators aged 16-17 years delivered three sessions of sex education to 13-14 year-old pupils from the same schools. Primary outcome was unprotected (without condom) first heterosexual intercourse by age 16 years. Analysis was by intention to treat. FINDINGS By age 16 years, significantly fewer girls reported intercourse in the peer-led arm than in the control arm, but proportions were similar for boys. The proportions of pupils reporting unprotected first sex did not differ for girls (8.4% intervention vs 8.3% control) or for boys (6.2% vs 4.7%). Stratified estimates of the difference between arms were -0.4% (95% CI -3.7% to 2.8%, p=0.79) for girls and -1.4% (-4.4% to 1.6%, p=0.36) for boys. At follow-up (mean age 16.0 years [SD 0.32]), girls in the intervention arm reported fewer unintended pregnancies, although the difference was borderline (2.3% vs 3.3%, p=0.07). Girls and boys were more satisfied with peer-led than teacher-led sex education, but 57% of girls and 32% of boys wanted sex education in single-sex groups. INTERPRETATION Peer-led sex education was effective in some ways, but broader strategies are needed to improve young peoples sexual health. The role of single-sex sessions should be investigated further.

Why do we need randomised controlled trials to assess behavioural interventions

Merits of randomised controlled trials in behavioural and psychosocial research do not differ fundamentally from those in clinical medicine. Interventions that target behaviour are often complex and demanding, as are the requirements of good randomised controlled trials to assess their efficacy. Standardising the content and delivery of an intervention in a trial may be more challenging than justifying randomisation during informed consent. When blinding of participants and researchers to treatment allocation is impossible, it is important to minimise bias through blinded assessment of the outcome. The contribution that participant choice makes to the efficacy of an intervention is hard to measure.

Proteinuria and Mortality in Diabetes: the WHO Multinational Study of Vascular Disease in Diabetes

The relation between proteinuria and mortality was investigated in 1188 patients with Type 1 diabetes and 3234 patients with Type 2 diabetes, aged 35–55 at baseline and followed up for a mean of 9.4 ± 3.1 years in the WHO Multinational Study of Vascular Disease in Diabetes. Baseline prevalence of light or heavy proteinuria was the same (25%) in both types of diabetes after adjustment for differences in diabetes duration. Compared with patients with no proteinuria, all cause mortality ratios were 1.5 (95% confidence interval 1.1–2.0) and 2.9 (2.2–3.8) for Type 1 patients with light and heavy proteinuria, respectively, and 1.5 (1.2–1.8) and 2.8 (2.3–3.4) for Type 2 patients, after adjustment for age, duration of diabetes, blood pressure, cholesterol, and smoking. Proteinuria was associated with significantly increased mortality from renal failure, cardiovascular disease, and all other causes of death. In both types of diabetes, the association was strongest for renal deaths, and of similar magnitude for cardiovascular and all other causes of death. In conclusion, proteinuria is a common, important, and rather non‐specific risk factor for increased morbidity and mortality in diabetes. The relation of proteinuria to mortality is similar for both types of diabetes. The benefits and risks of proteinuria reduction should be examined in large randomized trials with clinical endpoints.

Effectiveness of chlamydia screening: systematic review

BACKGROUND Screening programmes are promoted to control transmission of and prevent female reproductive tract morbidity caused by genital chlamydia. The objective of this study was to examine the effectiveness of register-based and opportunistic chlamydia screening interventions. METHODS We searched seven electronic databases (Cinahl, Cochrane Controlled Trials Register, DARE, Embase, Medline, PsycINFO and SIGLE) without language restrictions from January 1990 to October 2007 and reference lists of retrieved articles to identify studies published before 1990. We included studies examining primary outcomes (pelvic inflammatory disease, ectopic pregnancy, infertility, adverse pregnancy outcomes, neonatal infection, chlamydia prevalence) and harms of chlamydia screening in men and non-pregnant and pregnant women. We extracted data in duplicate and synthesized the data narratively or used random effects meta-analysis, where appropriate. RESULTS We included six systematic reviews, five randomized trials, one non-randomized comparative study and one time trend study. Five reviews recommended screening of women at high risk of chlamydia. Two randomized trials found that register-based screening of women at high risk of chlamydia and of female and male high school students reduced the incidence of pelvic inflammatory disease in women at 1 year. Methodological inadequacies could have overestimated the observed benefits. One randomized trial showed that opportunistic screening in women undergoing surgical termination of pregnancy reduced post-abortal rates of pelvic inflammatory disease compared with no screening. We found no randomized trials showing a benefit of opportunistic screening in other populations, no trial examining the effects of more than one screening round and no trials examining the harms of chlamydia screening. CONCLUSION There is an absence of evidence supporting opportunistic chlamydia screening in the general population younger than 25 years, the most commonly recommended approach. Equipoise remains, so high-quality randomized trials of multiple rounds of screening with biological outcome measures are still needed to determine the balance of benefits and harms of chlamydia screening.