Validation study of cause of death statistics in Cape Town, South Africa, found poor agreement.

OBJECTIVE: The validity of the underlying cause of death on death notification forms was assessed by comparing it to the underlying cause determined independently from medical records. STUDY DESIGN AND SETTING: Retrospective study of 703 deaths in two suburbs of Cape Town, South Africa. Two medical doctors completed a medical review death certificate to validate the registration death certificate for each decedent. Agreement, sensitivity, and positive predictive value were measured for underlying causes of death using the World Health Organization (WHO) mortality tabulation list 1. RESULTS: Agreement was poor, with only 55.3% (95% confidence interval [CI]: 51.7, 59.0) of diagnoses matching at WHO mortality tabulation list 1 level. Validity of reported causes of death was poor for HIV, cardiovascular diseases, and diabetes. With correct reporting, the cause-specific mortality fraction for HIV increased from 11.9% to 18.3% (53.6%; 95% CI: 36.9, 77.6), for ischemic heart disease from 3.3% to 7.3% (121.7%; 95% CI: 53.5, 228.7), and for hypertensive diseases from 3.3% to 5.7% (73.9%; 95% CI: 14.4, 167.8). For diabetes, the mortality fraction decreased from 6.0% to 2.3% (-64.3%; 95% CI: -77.1, -37.8) and for ill-defined deaths from 7.4% to 2.3% (-69.2%; 95% CI: -81.0, -51.6). CONCLUSION: Current cause-specific mortality levels should be cautiously interpreted. Death certification training is required to improve the validity of mortality data.

Associations with virologic treatment failure in adults on antiretroviral therapy in South Africa.

OBJECTIVES: Highly active antiretroviral therapy (HAART) has been available in government facilities in the Western Cape Province of South Africa since 2001. We aimed to investigate factors associated with virologic treatment failure in this setting. DESIGN: Case-control study, matched on facility and on starting date and duration of HAART. METHODS: Cases and controls were identified from clinic registers from May 2001 to June 2006. Cases were patients who switched to second-line therapy after confirmed virologic failure (2 consecutive viral loads above 1000 copies/mL). Controls were on first-line treatment with viral load <400 copies per milliliter at the time of case incidence. RESULTS: One hundred thirty cases and 238 controls were selected from 8 clinics (median 16.6 months on HAART, interquartile range: 12.2-24.6). Treatment interruptions [adjusted odds ratio (AOR) 8.6, 95% confidence interval: 3.6 to 20.8], prior nevirapine-based prevention of mother-to-child transmission (PMTCT) treatment (AOR: 9.6, 95% confidence interval: 2.9 to 32.2), a baseline CD4 count less than 50 cells per microliter or from 50-150 cells per microliter (AOR: 6.6, 95% confidence interval: 2.3 to 18.8 and AOR: 5.8, 95% confidence interval: 2.1 to 16.3 compared with a baseline CD4 count of more than 150 cells/microL), and the use of nevirapine in the initial regimen (AOR: 2.5, 95% confidence interval: 1.4 to 4.7) were all independently associated with virologic treatment failure. CONCLUSIONS: In this setting, nevirapine in the initial HAART regimen or for PMTCT treatment is associated with virologic treatment failure, together with low CD4 count at ART initiation. Earlier initiation of HAART and access to improved triple therapy and PMTCT regimens are priorities for HIV programs in Southern Africa.

Indices of body and brain size at birth and at the age of 2 years: relations to cognitive outcome at the age of 16 years in low birth weight infants.

OBJECTIVE: To determine in low birth weight infants the relations of being small for gestational age at birth, microcephalic at birth, low weight for age at 2 years, and microcephalic at 2 years to full scale intelligence quotient (FSIQ) at the age of 16 years. METHODS: A prospective observational study of 422 of 837 eligible nondisabled low birth weight (<2000 g) adolescents from the newborn brain hemorrhage cohort with weight and head circumference at birth and at the age of 2 years in whom FSIQ was assessed with the Wechsler Abbreviated Scales of Intelligence at the age of 16 years. RESULTS: In a multiple regression analysis, being small for gestational age (beta = -0.14, p = .02) and microcephalic at 2 years (beta = -0.18, p < .001), but not low weight for age at 2 years or microcephaly at birth, had significant independent effects on 16-year FSIQ. After adjusting for pre-, peri-, and postnatal risk factors for poor cognitive performance, the independent effects of being small for gestational age (beta = -0.13, p = .004) and microcephalic at 2 years (beta = -0.13, p = .01) persisted. In this analysis, birth social risk had the largest significant independent effect on 16-year FSIQ (beta = -0.28, p < .001). CONCLUSIONS: Being small for gestational age at birth, but not low weight for age at 2 years, and microcephaly at 2 years, but not at birth, were independently related to FSIQ of nondisabled low birth weight adolescents, both with and without control for pre-, peri-, and postnatal risk factors.

Cardiovascular disease risk factors and women prisoners in the UK: the impact of imprisonment.

Cardiovascular disease (CVD) is a leading cause of death throughout the world. In high income countries, the greatest burden of disease is seen in those from lower socio-economic groups. It is therefore likely that CVD is an important issue for prisoners in the UK, the majority of whom were either unemployed or in non-skilled employment prior to imprisonment. However, there is little research examining this issue. The aim of this study was to examine the prevalence of five modifiable cardiovascular risk factors (smoking, physical activity, diet, body mass index and hypertension) in women prisoners on entry to prison and then 1 month after imprisonment. This was a prospective longitudinal study involving 505 women prisoners in England. Participants completed a questionnaire containing questions about health-related behaviours within 72 h of entering prison. The researchers measured their blood pressure, height and weight. They followed up all participants who were still imprisoned 1 month later and invited them to participate again. The results showed that women prisoners were at high risk of CVD in the future; 85% smoked cigarettes, 87% were insufficiently active to benefit their health, 86% did not eat at least five portions of fruit and vegetables each day and 30% were overweight or obese. After 1 month, there were few improvements in risk factors. This may in part reflect the fact that, unlike prisons in other high income countries, there are currently no systematic approaches which address these health issues within UK women's prisons.

Deaths caused by HIV disease under-reported in South Africa.

Modelling of trends in age-specific death rates in South Africa suggests that deaths attributable to HIV are often misclassified on death notification forms. We compared the underlying cause of death from death notification forms with that based on scrutiny of medical records for 683 deaths in Cape Town. Of 129 deaths caused by HIV according to medical records, only 35 (27.1%) were ascribed to HIV on the death notification form using strict coding and 83 (64.3%) using interpretive coding.

Changes in women's use of illicit drugs following imprisonment.

AIM: To provide data on changes in illegal drug use in women following imprisonment. DESIGN: Prospective cohort study. SETTING: Recruitment took place in two prisons in the Midlands and South-East England and follow-up in 13 prisons across England. PARTICIPANTS: A total of 505 women prisoners participated, a response rate of 82%. Measurements Questions about drug use were contained within a questionnaire which examined broad aspects of health. On entry into prison, women answered questions about daily drug use and injecting drug use prior to imprisonment. One month later the questionnaires examined drug use during this period of imprisonment. FINDINGS: Prior to imprisonment, 53% [95% confidence interval (CI): 49-58%] of women took at least one illegal drug daily and 38% (CI: 34-42%) said they had ever injected drugs. Following imprisonment, some women continued to use drugs; 14% (CI: 10-20%) of women reported using at least one illegal drug daily and 2% (CI: 0.7-5%) of women had injected drugs. There were important changes in the types of drugs used; there was a change in use from crack and heroin to benzodiazepines and opiate substitutes. Prior to imprisonment, women most commonly used crack and heroin, but in prison the two most commonly used illegal drugs were benzodiazepines and opiate substitutes. CONCLUSIONS: The study provides quantitative evidence of the impact of imprisonment on drug use among women. It highlights the need for enhanced drug treatment services and stronger measures to reduce the availability of illegal drugs to women in prison.

Impact of self monitoring of blood glucose in the management of patients with non-insulin treated diabetes: open parallel group randomised trial.

OBJECTIVE: To determine whether self monitoring, alone or with instruction in incorporating the results into self care, is more effective than usual care in improving glycaemic control in non-insulin treated patients with type 2 diabetes. DESIGN: Three arm, open, parallel group randomised trial. SETTING: 48 general practices in Oxfordshire and South Yorkshire. PARTICIPANTS: 453 patients with non-insulin treated type 2 diabetes (mean age 65.7 years) for a median duration of three years and a mean haemoglobin A1c level of 7.5%. INTERVENTIONS: Standardised usual care with measurements of HbA1c every three months as the control group (n=152), blood glucose self monitoring with advice for patients to contact their doctor for interpretation of results, in addition to usual care (n=150), and blood glucose self monitoring with additional training of patients in interpretation and application of the results to enhance motivation and maintain adherence to a healthy lifestyle (n=151). MAIN OUTCOME MEASURE: HbA1c level measured at 12 months. RESULTS: At 12 months the differences in HbA1c level between the three groups (adjusted for baseline HbA1c level) were not statistically significant (P=0.12). The difference in unadjusted mean change in HbA1c level from baseline to 12 months between the control and less intensive self monitoring groups was -0.14% (95% confidence interval -0.35% to 0.07%) and between the control and more intensive self monitoring groups was -0.17% (-0.37% to 0.03%). CONCLUSIONS: Evidence is not convincing of an effect of self monitoring blood glucose, with or without instruction in incorporating findings into self care, in improving glycaemic control compared with usual care in reasonably well controlled non-insulin treated patients with type 2 diabetes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47464659.

Cluster randomized pilot controlled trial of an occupational therapy intervention for residents with stroke in UK care homes.

BACKGROUND AND PURPOSE: A pilot evaluation of an occupational therapy intervention to improve self-care independence for residents with stroke-related disability living in care homes was the basis of this study. METHODS: A cluster randomized controlled trial with care home as the unit of randomization was undertaken in Oxfordshire, UK. Twelve homes (118 residents) were randomly allocated to either intervention (6 homes, 63 residents) or control (6 homes, 55 residents). Occupational therapy was provided to individuals but included carer education. The control group received usual care. Assessments were made at baseline, postintervention (3 months) and at 6-months to estimate change using the Barthel Activity of Daily Living Index (BI) scores, "poor global outcome", (defined as deterioration in BI score, or death) and the Rivermead Mobility Index. RESULTS: At 3 months BI score in survivors had increased by 0.6 (SD 3.9) in the intervention group and decreased by 0.9 (2.2) in the control group; a difference of 1.5 (95% CI allowing for cluster design, -0.5 to 3.5). At 6 months the difference was 1.9 (-0.7 to 4.4). Global poor outcome was less common in the intervention group. At 3 months, 20/63 (32%) were worse/dead in the intervention group compared with 31/55 (56%) in the control group, difference -25% (-51% to 1%). At 6 months the difference was similar, -26% (-48% to -3%). Between-group changes in Rivermead Mobility Index scores were not significantly different. CONCLUSIONS: Residents who received an occupational therapy intervention were less likely to deteriorate in their ability to perform activities of daily living.

Behavioral and emotional adjustment of teenagers in mainstream school who were born before 29 weeks' gestation.

OBJECTIVES: To investigate behavioral and emotional problems and positive adjustment of 15-to 16-year-olds who were born at extremely low gestational age (ELGA), from the perspective of parents, teachers, and teenagers. METHODS: Prospective follow-up was conducted of birth cohorts, with classroom control subjects. All infants who were born before 29 weeks in 1983-1984 (mean gestational age: 27 weeks) to mothers who resided in 3 regions of the United Kingdom were studied. A total of 82% (179 of 218) of survivors were traced at age 15 to 16. The 150 in mainstream school were compared with age- and gender-matched classroom control subjects (n = 108). Behavioral and emotional problems, delinquency, peer relations, self-esteem, and hobbies, were assessed by standardized, well-validated instruments, including the Strengths and Difficulties Questionnaire, administered by mail to parents, teenagers, and teachers. RESULTS: Parents were more likely to rate ELGA teenagers than control subjects as in the "abnormal" range for hyperactivity (8% vs 1%; difference: 7%; (95% confidence interval [CI]: 2-12), peer relationship problems (19% vs 5%; difference: 14%; 95% CI: 6-21), and emotional problems (18% vs 7%; difference: 11%; 95% CI: 3-19), but not conduct problems (10% vs 5%; difference: 5%; 95% CI: -1 to 12)). Teachers reported a similar pattern. In contrast, compared with control subjects, ELGA teenagers did not rate themselves as having more problems with peers, hyperactivity, conduct, depression, or low self-esteem. They reported more emotional problems but less delinquency, alcohol, cannabis, and other drug use. CONCLUSIONS: Compared with mainstream classmates, children who are born extremely early continue to have higher levels of parent- and teacher-reported emotional, attentional, and peer problems well into their teens. However, despite these problems, they do not show signs of more serious conduct disorders, delinquency, drug use, or depression.

Genetic variation in dopaminergic pathways and short-term effectiveness of the nicotine patch.

Polymorphisms in the dopamine D2 receptor (DRD2 C/T and DRD2 A/G) and in dopamine beta hydroxylase (DBH A/G) have been implicated in modulation of smoking and other reward-seeking behaviours. We hypothesized that these alleles would predict the outcome of nicotine patch therapy for smoking cessation. In 1991-93, we performed a randomized controlled trial of the nicotine patch on 1686 heavy smokers (> or = 15 cigarettes/day). In 1999-2000, we contacted 1532 of the 1612 subjects still available; 767 (50%) completed a questionnaire and gave a blood sample. In the 755 cases in which DNA was successfully genotyped, we examined associations between the polymorphisms in DRD2 and DBH, and smoking cessation. At 1 week, the patch was more effective for smokers with DRD2 CT/TT genotype [patch/placebo odds ratio (OR) 2.8, 95% confidence interval (CI) 1.7-4.6] than with CC (OR 1.4, 0.9-2.1; P for difference in ORs 0.04). Smokers with both DRD2 CT/TT and DBH GA/AA genotypes had an OR of 3.6 (2.0-6.5) compared to 1.4 (1.0-2.1) for others (P = 0.01). At 12 weeks, the ORs for these genotypic groups were 3.6 (1.7-7.8) and 1.4 (0.9-2.3), respectively (P = 0.04). There was no association between patch effectiveness and DRD2 exon 8. Short-term effectiveness of the nicotine patch may be related to dopamine beta-hydroxylase and dopamine D2 receptor genotype. Our results support the need for further investigation into personalized therapies for smoking cessation based on individual genotype.

Reporting the cost-effectiveness of interventions with nonsignificant effect differences: example from a trial of secondary prevention of coronary heart disease.

OBJECTIVES: This study reports the cost-effectiveness of interventions with nonsignificant differences in effect, and considers reporting of cost-effectiveness in situations where nonsignificant differences arise in some but not all end points. METHODS: Data on costs and effects associated with three end points (adequate assessment, risk factors, and life-years) were derived from a trial of methods to promote secondary prevention of coronary heart disease. Incremental cost per life-year gained figures were calculated, and the uncertainty around these was displayed on cost-effectiveness planes in the form of ellipses. RESULTS: There was a significant difference in one of the intermediate end points (adequate assessment) but nonsignificant differences in the other intermediate end point (risk factors) and the final end point (life-years). Estimation of cost per life-year figures revealed the cost-effectiveness of the interventions to be unfavorable. CONCLUSIONS: Cost-effectiveness ratios based on final end points should be calculated even in situations where nonsignificant differences in life-years arise, to avoid publication bias and to provide decision makers with useful information. Uncertainty in the incremental cost-effectiveness ratios should be estimated and presented graphically.

No association between functional catechol O-methyl transferase 1947A>G polymorphism and smoking initiation, persistent smoking or smoking cessation.

Nicotine stimulates dopamine release and activates dopaminergic reward neurones in central pathways giving rise to dependence. Catechol O-methyl transferase (COMT) inactivates extraneuronally released dopamine and is present in dopaminergic brain regions. A functional polymorphism (COMT 1947A>G) resulting in increased enzyme activity has been associated with alcoholism and polysubstance abuse. We examined the relationship between the COMT 1947A>G polymorphism and smoking initiation, smoking persistence and smoking cessation. We genotyped 266 current smokers, 270 ex-smokers and 265 lifetime non-smokers (never smokers), matched for age and gender, for the COMT 1947A>G polymorphism. Smoking status was ascertained by self-report. There was no difference in genotype frequencies between never smokers and ever smokers (current + ex-smokers); between non-smokers (never + ex-smokers) and current smokers; or between current smokers and ex-smokers. These data suggest that the COMT 1947A>G polymorphism is not associated with smoking initiation, smoking persistence or smoking cessation.