Advanced chronic kidney disease, cardiovascular events and the effect of diabetes: data from the Atherosclerosis and Folic Acid Supplementation Trial.

BACKGROUND: End-stage kidney disease registry data have reported increased mortality in patients with diabetes as compared with those without. Here we examine whether diabetes is independently associated with an increased risk of major cardiovascular events and death in patients with advanced chronic kidney disease (CKD). METHODS: Data from 315 participants with CKD in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) were assessed. Primary end-points were fatal or non-fatal cardiovascular events, including myocardial infarction, stroke, unstable angina, coronary revascularisation and peripheral vascular events assessed both jointly and separately using Cox-proportional hazard models. RESULTS: Twenty-three per cent reported diabetes. Median follow up was 3.6 years. In those with diabetes, an increased risk for major cardiovascular events was observed, crude hazard ratio (HR) 2.87 (95% confidence interval (CI) 2.11-3.90). After adjustment for age, gender, smoking, systolic blood pressure, body mass index, past ischaemic heart disease and use of preventive therapies, diabetes was associated with an HR of 1.83 (1.28-2.61) for major cardiovascular events. The risk for peripheral vascular events was also increased, adjusted HR 6.31 (2.61-15.25). For all-cause death, major coronary and stroke events, the risk in those with diabetes was not significantly increased (all-cause death, adjusted HR 1.31 (95% CI 0.80-2.14); major coronary events, adjusted HR 1.26 (95% CI 0.64-2.49); and major stroke events, adjusted HR 1.28 (95% CI 0.55-2.99)). CONCLUSIONS: Diabetes significantly increases the risk of major cardiovascular events, especially peripheral vascular events in patients with advanced CKD. Trials of multifactorial management of cardiovascular risk factors are required to determine if outcomes for this population may be improved.

Randomized, placebo-controlled trial of intramuscular vitamin B12 for the treatment of hyperhomocysteinaemia in dialysis patients.

BACKGROUND: Plasma homocysteine is elevated in patients with end-stage renal disease (ESRD) and is a risk factor for cardiovascular disease. Folic acid has been shown to partially reduce homocysteine levels in dialysis patients. It is not known whether vitamin B12 reduces homocysteine independent of folic acid in patients who are not vitamin B12 deficient. AIM: To determine whether 1 mg vitamin B12 lowers homocysteine in stable, chronic, haemodialysis patients independent of folic acid. METHODS: Twenty-eight haemodialysis patients were randomized to receive three doses of 1 mg vitamin B12 or 1 mL saline placebo in a double-blind fashion at 1-month intervals. Fasting plasma total homocysteine, folic acid, red-cell folate, vitamin B12 and haemoglobin levels were determined prior to each dose and 4 weeks after the final injection. The study was powered to detect a 30% reduction in homocysteine over the 3 months. RESULTS: Both the two groups were well matched with respect to total homocysteine levels, folic acid, red-cell folate and vitamin B12 levels. Serum vitamin B12 levels were significantly higher in the treatment group compared to placebo (217.7 pmol/L; 95% confidence interval (CI) 103.0-332.5; P < 0.001) at the end of the trial but homocysteine levels were not significantly different (3.08 micromol/L; 95% CI -4.44-10.61; P= 0.406). CONCLUSIONS: The administration of intramuscular vitamin B12 over a 3-month period does not result in any reduction of plasma homocysteine levels in haemo-dialysis patients independent of folate status, however reductions of <30% cannot be excluded by the present study. High-dose folic acid remains the treatment of choice in reducing homocysteine, but whether this results in a reduction in cardiovascular events remains to be determined.

Respiratory symptoms and lung function in bauxite miners.

OBJECTIVES: To determine whether cumulative bauxite exposure is associated with respiratory symptoms or changes in lung function in a group of bauxite miners. METHODS: Current employees at three bauxite mines in Australia were invited to participate in a survey comprising: questionnaire on demographic details, respiratory symptoms, and work history; skin prick tests for four common aeroallergens; and spirometry. A task exposure matrix was constructed for bauxite exposure in all tasks in all jobs based on monitoring data. Data were examined for associations between cumulative bauxite exposure, and respiratory symptoms and lung function, by regression analyses. RESULTS: The participation rate was 86%. Self-reported work-related respiratory symptoms were reported by relatively few subjects (1.5%-11.8%). After adjustment for age and smoking no significant differences in the prevalence of respiratory symptoms were identified between subjects, in the quartiles of cumulative bauxite exposure distribution. The forced expiratory volume in I s (FEV1) of the exposed group was found to be significantly lower than that for the unexposed group. After adjustment for age, height, and smoking there were no statistically significant differences between quartiles in FEVI, forced vital capacity (FVC) and FEVl/FVC ratio. CONCLUSIONS: These data provide little evidence of a serious adverse effect on respiratory health associated with exposure to bauxite in an open-cut bauxite mine in present day conditions.

Respiratory symptoms and lung function in alumina refinery employees.

OBJECTIVES: Employees in alumina refineries are known to be exposed to a number of potential respiratory irritants, particularly caustic mist and bauxite and alumina dusts. To examine the prevalence of work related respiratory symptoms and lung function in alumina refinery employees and relate these to their jobs. METHODS: 2964 current employees of three alumina refineries in Western Australia were invited to participate in a cross sectional study, and 89% responded. Subjects were given a questionnaire on respiratory symptoms, smoking, and occupations with additional questions on temporal relations between respiratory symptoms and work. Forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) were measured with a rolling seal spirometer. Atopy was assessed with prick skin tests for common allergens. Associations between work and symptoms were assessed with Cox's regression to estimate prevalence ratios, and between work and lung function with linear regression. RESULTS: Work related wheeze, chest tightness, shortness of breath, and rhinitis were reported by 5.0%, 3.5%, 2.5%, and 9.5% of participants respectively. After adjustment for age, smoking, and atopy, most groups of production employees reported a greater prevalence of work related symptoms than did office employees. After adjustment for age, smoking, height, and atopy, subjects reporting work related wheeze, chest tightness, and shortness of breath had significantly lower mean levels of FEV(1) (186, 162, and 272 ml respectively) than subjects without these symptoms. Prevalence of most work related symptoms was higher at refinery 2 than at the other two refineries, but subjects at this refinery had an adjusted mean FEV(1) >60 ml higher than the others. Significant differences in FVC and FEV(1)/FVC ratio, but not FEV(1), were found between different process groups. CONCLUSIONS: There were significant differences in work related symptoms and lung function between process groups and refineries, but these were mostly not consistent. Undefined selection factors and underlying population differences may account for some of these findings but workplace exposures may also contribute. The differences identified between groups were unlikely to be clinically of note.

The VECAT study: methodology and statistical power for measurement of age-related macular features. Vitamin E, Cataract, and Age-related Maculopathy Study.

PURPOSES: (1) To develop the methodology for the grading of macular one-frame stereoslides and to assess the reliability of the system. (2) To determine the prevalence of soft drusen (> 63 microm) and pigment abnormalities synonymous with age-related maculopathy (ARM) at baseline, in a clinical trial of volunteers aged between 55 and 80 years of age. (3) To ascertain the power of the study to detect the 4-year incidence and progression of ARM in vitamin E versus placebo treated participants, given the baseline prevalence. METHODS: The 1204 participants enrolled in the Vitamin E, Cataract, and Age-related Maculopathy Study (VECAT) had colour stereoslides of their fundus taken using the Nidek 3-DX mydriatic fundus camera. The stereoslides were graded by two masked graders according to the "International Classification System for ARM and AMD". Assessment of inter- and intra-observer reliability was carried out on a regular basis on 15% of randomly selected slides. Anticipated rates of incidence and progression were based on results reported by the Beaver Dam Eye Study and the Chesapeake Bay Waterman Study. Power estimations were determined using the "nQuery Advisor" software program. Analyses were carried out on the worse affected eye. RESULTS: Inter-observer reliability was moderate to substantial (Kappa 0.5-0.88) whilst intra-observer agreement was high (0.6-1.0). The prevalence of any soft drusen was 32%. Significant associations were found between soft large indistinct drusen, hypopigmentation, hyperpigmentation and age (p = 0.0001, 0.024 and 0.0001, respectively). The study has at least 87% power to detect an odds ratio equal to two for the progression of soft distinct, soft indistinct, hyperpigmentation and hypopigmentation. CONCLUSIONS: The VECAT study methodology appears to be highly reliable and to have sufficient power to detect the differences in the four-year progression of soft distinct and indistinct drusen and pigment abnormalities between the treatment groups.

The role of past intake of vitamin E in early cataract changes.

PURPOSE: We examined the association between prior supplementation of vitamin E and early cataract changes in volunteers currently enrolled in the cross-sectional VECAT study. The Vitamin E and Cataract Prevention Study (VECAT) is a clinical trial currently in progress, designed to assess the affect of vitamin E supplementation on the development and progression of cataract and age-related macular degeneration. METHODS: A history of vitamin E supplementation was ascertained through a self-administered questionnaire that was mailed to each of the 1,111 participants who were enrolled at the time in the prospective VECAT Study. RESULTS: With a 99% response rate, we found that 26% of participants reported prior supplementation of vitamin E. Only 8.8% of these participants took supplementation greater than the recommended daily intake (RDI) of 10 mg/day. Of these 26%, 57% took supplementation in the form of multivitamins as opposed to a vitamin E supplement on its own. The range of supplement intake ranged from as little as 0.1 mg/day to a maximum of 55 mg/day. A statistically significant association was found between prior supplementation and the absence of cortical opacity (OR = 0.47, 95%CI = 0.28-0.83), after adjusting for age. The levels of nuclear opacity (NO) were not statistically different between those who reported intake and those with no prior vitamin E supplementation. CONCLUSION: Prior vitamin E supplementation may protect VECAT participants from developing at least early cortical cataracts. No apparent protective role in terms of nuclear opacities and nuclear color was found regardless of the level, regularity or duration of intake.

Prospective study of factors predicting outcome of transdermal nicotine treatment in smoking cessation.

OBJECTIVE: To assess the factors associated with cessation of smoking with transdermal nicotine and brief behavioural counselling. DESIGN: Interviews, treatment, and follow up for 26 weeks. SUBJECTS: 1481 subjects recruited by mass media publicity who smoked > or = 15 cigarettes a day and were motivated to stop smoking. INTERVENTIONS: Twelve weeks' treatment with transdermal nicotine and brief behavioural counselling at monthly visits. MAIN OUTCOME MEASURE: Sustained smoking cessation for the 28 days before the visit at week 26 verified by expired carbon monoxide concentrations. The logistic regression analysis included all subjects. RESULTS: Most subjects were dependent on nicotine, and the mean (SD) number of cigarettes smoked a day was 32 (12). Overall, 316/1481 subjects (21.3%) stopped smoking. Factors associated with stopping were being male (adjusted odds ratio 2.0; 95% confidence interval 1.5 to 2.7), age > or = 40 years (1.5; 1.1 to 2.0), living with a spouse or partner (1.5; 1.1 to 2.1), motivation ("want to quit" 1.7; 1.2 to 2.3), and concern about weight gain (1.7; 1.3 to 2.2). Negative associations were smoking marijuana (0.4; 0.2 to 0.8) and the presence of other smokers in the household (0.8; 0.6 to 0.9). Almost all subjects who smoked three or more cigarettes in the first four weeks of treatment resumed smoking in the long term (525/547, 96%). CONCLUSIONS: Age, sex, marital status (living with a spouse or partner), motivation, concern about weight gain, recent marijuana smoking, and other smokers in the household were baseline factors associated with differences in outcome of smoking cessation attempts. Smoking three or more cigarettes in the first few weeks after stopping strongly predicted long term relapse.

Drug overdose--reducing the load.

OBJECTIVE: To review available information about various methods for reducing gastrointestinal absorption of a poison or drug. DATA SOURCES: Articles on overdose and accidental poisoning generated by the Australian Medlars Service and concentrating on the period between 1985 and 1990 were surveyed. Earlier studies were included if relevant. STUDY SELECTION AND DATA EXTRACTION: English language articles with an emphasis on studies using objective methods to measure individual and comparative efficacy of gastrointestinal decontamination techniques were selected. A total of 65 articles were reviewed. DATA SYNTHESIS: Gastric emptying procedures (gastric lavage or emesis caused by syrup of ipecac) are only effective if performed within one hour of drug ingestion. Gastric lavage is superior to syrup of ipecac. Oral administration of activated charcoal is more effective than either gastric emptying procedure, and is recommended for most cases of poisoning. Cathartics (sorbitol) can be used with activated charcoal. Whole bowel lavage with polyethylene glycol is indicated in selected cases of potentially lethal overdose where the toxic substance cannot be absorbed by charcoal and has passed the pylorus. CONCLUSIONS: Children--syrup of ipecac can be given at home to children older than 12 months. Most children who reach hospital can be treated by charcoal alone. ADULTS--Most patients are managed with supportive care and, in the absence of contraindications, a single dose of activated charcoal if seen within four hours of ingestion of the poison or drug. Gastric lavage is used if the patient presents within one hour of ingestion and has clinical features of toxicity.