Richard J. Brand

Can lifestyle changes reverse coronary heart disease?: The Lifestyle Heart Trial

In a prospective, randomised, controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year, 28 patients were assigned to an experimental group (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) and 20 to a usual-care control group. 195 coronary artery lesions were analysed by quantitative coronary angiography. The average percentage diameter stenosis regressed from 40.0 (SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group. When only lesions greater than 50% stenosed were analysed, the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group. Overall, 82% of experimental-group patients had an average change towards regression. Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year, without use of lipid-lowering drugs.

Epidemiology as a guide to clinical decisions. The association between triglyceride and coronary heart disease.

The hypothesis that triglyceride is a cause of coronary heart disease, although unconfirmed and never universally accepted, has nonetheless strongly influenced the practice of preventive medicine. We have examined the epidemiologic association between triglyceride and coronary heart disease to evaluate the validity of inferring that there is a causal relation between the two. Neither the evidence from published studies nor an analysis of data from the Western Collaborative Group Study provides strong support for the causal hypothesis. Information from other scientific disciplines is also meager, contrasting with the coherence of diverse evidence supporting the hypothesis that cholesterol is a cause of coronary heart disease. These arguments fall short of disproving the belief that lowering triglyceride will prevent coronary heart disease, especially since triglyceride and cholesterol are inextricably associated through mutual lipoprotein carriers. But we propose that the ethics of preventive medicine place the burden of proof on the proponents of intervention. We therefore recommend that widespread screening and treatment of healthy persons for hypertriglyceridemia be abandoned until more persuasive evidence becomes available.

Multivariate prediction of coronary heart disease during 8.5 year follow-up in the western collaborative group study

The Western Collaborative Group Study is a prospective study of 3,154 employed men aged 39 to 59 years. Ischemic heart disease occurred in 257 subjects during 8.5 years of follow-up. Risk of coronary heart disease was studied with use of the multiple logistic risk model. The incidence of coronary heart disease had a highly significant association with serum cholesterol level, behavior pattern, cigarette smoking and systolic blood pressure in younger (39 to 49 years) and older (50 to 59 years) men and also with age and corneal arcus in the younger group. Type A behavior pattern was strongly related to the incidence of coronary disease in both age groups, independent of interrelations of behavior patterns with any other risk factor.

TYPE-A BEHAVIOR AND MORTALITY FROM CORONARY HEART-DISEASE

The relation of behavior (Type A or Type B) to the morbidity and mortality of coronary heart disease (CHD) is still debated. We studied the survival of 257 male patients with CHD from the initial, 8.5-year phase of the Western Collaborative Group Study to see whether behavior type--as assessed by a structured interview before the CHD event--was related to subsequent CHD mortality. Behavior type was not related to mortality in 26 patients who died within 24 hours of the coronary event. However, of the 231 patients who survived for 24 hours, the mortality rate associated with CHD among 160 Type A patients studied during an average 12.7 years was 19.1 per 1000 person-years. This was unexpectedly lower than the corresponding rate of 31.7 among 71 Type B patients who were followed for an average of 11.5 years (P = 0.04). In a proportional-hazards survival analysis, which controlled for variable follow-up time, the type of initial coronary event, and traditional risk variables, the relative CHD-associated mortality rate among Type A as compared with Type B patients was 0.58 (P = 0.03; 95 percent confidence interval, 0.35 to 0.96). The lower mortality among Type A subjects occurred in both younger and older subgroups but was more pronounced in patients whose initial diagnosis was symptomatic myocardial infarction rather than silent myocardial infarction or angina pectoris. This apparent advantage associated with Type A behavior is surprising and needs confirmation, but the results do indicate that patients with CHD and a Type A behavior pattern are not at increased risk for subsequent CHD mortality.

Continued CD4 cell count increases in HIV-infected adults experiencing 4 years of viral suppression on antiretroviral therapy

Objective: To determine the extent to which HIV-infected patients, including those with advanced immunodeficiency, can reverse peripheral CD4 T-cell depletion while maintaining long-term viral suppression on highly active antiretroviral therapy. Design: Cohort study. Participants: Four-hundred and twenty-three HIV-infected patients who initiated HAART prior to 1998 and achieved a viral load ⩽ 1000 copies/ml by 48 weeks were evaluated for up to 4 years or until plasma HIV RNA levels increased to > 1000 copies/ml. Main outcome measure: CD4 count changes. Results: Among patients who maintained plasma HIV RNA levels ⩽ 1000 copies/ml, CD4 counts continued to increase through year 4 of HAART. In the last year examined, from year 3 to 4 of HAART, mean CD4 count gains were +89 × 106, +86 × 106, +95 × 106, and +88 × 106/l in patients with pre-therapy CD4 counts of < 50 × 106, 50 × 106–199 × 106, 200 × 106–349 × 106, and ⩾ 350 × 106/l, respectively (all gains were significantly greater than zero; P < 0.05). Among those with a pre-therapy CD4 count of < 50 × 106/l, 88% achieved a CD4 cell count of ⩾ 200 × 106/l and 59% achieved a count of ⩾ 350 × 106/l by year 4. Factors associated with increased CD4 cell count gains from month 3 to year 4 included lower pre-therapy CD4 cell count, younger age, female sex, and infrequent low-level viremia (versus sustained undetectable viremia). Conclusions: Most patients who achieve and maintain viral suppression on HAART continue to experience CD4 T-cell gains through 4 years of therapy. The immune systems capacity for CD4 T lymphocyte restoration is not limited by low pre-therapy CD4 counts.

Tear mixing under a soft contact lens: effects of lens diameter.

PURPOSE Tear exchange under a soft contact lens is modest, and higher exchange rates may be necessary to reduce extended-wear complications; what is not known is the optimal soft lens design to increase tear mixing. We explored the effect of lens diameter on tear mixing. METHODS Twenty-three subjects wore four different soft contact lenses with diameters of 12.0, 12.5, 13.0, and 13.5 mm. Tear mixing was quantified by placing fluorescein isothiocyanate-dextran on the posterior lens surface, inserting the lens, and monitoring the changes in fluorescence intensity in the postlens tear film. Tear mixing, expressed as the percentage decrease in fluorescence intensity per blink, was estimated using an exponential model. Lens movement was videotaped and lens comfort was graded on a 50-point scale (50 = excellent comfort). Subjects reporting a comfort level of less than 35 were excluded. RESULTS The mean +/- SE tear mixing rates were 1.82% +/- 0.17%, 1.61% +/- 0.16%, 1.34% +/- 0.17%, and 1.24% +/- 0.17% per blink for the 12.0-, 12.5-, 13.0-, and 13.5-mm diameter lenses, respectively. By regression analysis we found that, on average, mixing under the 12.0-mm lens was 0.59% per blink greater than with the 13.5-mm lens (P = .0024). Lens diameter was a significant predictor of lens comfort, and adjusting for the effects of comfort weakened the relationship between diameter and tear replenishment rate, although the mean rate under the 12.0-mm lens was still 0.43% per blink greater than with the 13.5-mm lens (P = .0468). CONCLUSIONS These data suggest that smaller-diameter soft lenses provide substantially better tear mixing than larger lenses; however, even small lenses provide modest tear mixing compared with rigid contact lenses.

Doctor proactive communication, return-to-work recommendation, and duration of disability after a workers' compensation low back injury

Althoughdoctors are increasingly evaluated on the basis of return-to-work (RTW)outcomes, the effect of doctor–patient communication about the workplaceand RTW after an occupational injury has received little research attention.The effect of patient-reported doctor communication on duration of disabilitywas examined retrospectively in a 3-year cohort of 325 claimants with alost-time low back injury. Although doctor proactive communication wasassociated with a greater likelihood of RTW during the acute phase (<30days of disability), this effect disappeared when injury and workloadcharacteristics were taken into account. A positive RTW recommendation wasassociated with about a 60% higher RTW rate during the subacute/chronic phase(>30 days of disability) only. Prospective studies are needed to confirmthis effect. The impact of physician communication on RTW is largelyconfounded by injury and workplacefactors.

Recalling sexual behavior: a methodological analysis of memory recall bias via interview using the diary as the gold standard

This study examined the effect of time lag on the validity of retrospective self‐reports of sexual behavior. Seventy‐five heterosexual students (44 women, 31 men) made daily recordings of sexual behavior, condom use, and alcohol or substance use for 1 month. Ability of respondents to recall sexual behavior recorded during this period was assessed at 1, 2, and 3 months after diary completion using recall interviews (25 interviewed at each interval). For vaginal intercourse, total recall error was significantly greater at 3 months than at 1 month post‐diary. For all other variables assessed, the 2‐ and 3‐month time intervals did not produce significant increases in total recall error. Higher frequency of vaginal intercourse, orgasm, and alcohol use prior to sexual activity were associated with total recall error for some but not all behaviors and outcomes. The results provide a partial validation of the diary‐interview recall model as a method for studying recall error.

Validation of an Algorithm for Categorizing the Severity of Hospital Emergency Department Visits

Background:Differentiating between appropriate and inappropriate resource use represents a critical challenge in health services research. The New York University Emergency Department (NYU ED) visit severity algorithm attempts to classify visits to the ED based on diagnosis, but it has not been formally validated. Objective:To assess the validity of the NYU algorithm. Research Design:A longitudinal study in a single integrated delivery system from January 1999 to December 2001. Subjects:A total of 2,257,445 commercial and 261,091 Medicare members of an integrated delivery system. Measures:ED visits were classified as emergent, nonemergent, or intermediate severity, using the NYU ED algorithm. We examined the relationship between visit-severity and the probability of future hospitalizations and death using a logistic model with a general estimating equation approach. Results:Among commercially insured subjects, ED visits categorized as emergent were significantly more likely to result in a hospitalization within 1-day (odds ratio = 3.37, 95% CI: 3.31–3.44) or death within 30-days (odds ratio = 2.81, 95% CI: 2.62–3.00) than visits categorized as nonemergent. We found similar results in Medicare patients and in sensitivity analyses using different probability thresholds. ED overuse for nonemergent conditions was not related to socio-economic status or insurance type. Conclusions:The evidence presented supports the validity of the NYU ED visit severity algorithm for differentiating ED visits based on need for hospitalization and/or mortality risk; therefore, it can contribute to evidence-based policies aimed at reducing the use of the ED for nonemergencies.

Association between mothers' nutrient intake and their offspring's risk of gastroschisis

The young age of mothers of infants with gastroschisis, a congenital defect of the abdominal wall, suggested that deficient nutrition, with maternal-fetal competition for nutrients, could be a risk factor for gastroschisis. This population-based hypothesis-generating study consisted of 55 cases of gastroschisis and 182 matched controls. We assessed maternal nutrient intake during the trimester before conception with a self-reported food-frequency questionnaire and screened 38 nutrients to identify those most likely to be associated with gastroschisis. We used statistical classification trees to empirically generate cutpoints that determined the low and high levels of nutrient intakes corresponding to the risk of gastroschisis; cutpoints for most nutrients were similar to the corresponding recommended daily dietary allowances (RDAs). In univariate analysis, low intake of several nutrients emerged as the leading risk factors: carotenoids, e.g., alpha-carotene (odds ratio (OR) = 4.6; 95% confidence interval (CI) = 2.2-9.5), beta-carotene (OR = 3.1; 95% CI = 1.6-6.0); amino-acid compounds, e.g., total glutathione (OR = 3.5; 95% CI = 1.7-7.2); vitamin C (OR = 2.2; 95% CI = 1.5-7.8); vitamin E (OR = 2.3; 95% CI = 1.2-4.4); and minerals, fiber, and the fruit-and-vegetable group (OR = 3.1; 95% CI = 1.5-6.2). High intake of nitrosamines (OR = 2.4; 95% CI = 1.3-4.5) was also a good candidate. Many nutrient values were correlated and, in multivariate analysis, those most associated with gastroschisis were low alpha-carotene (OR = 4.3; 95% CI = 1.9-9.8), low total glutathione (OR = 3.3; 95% CI = 1.4-7.6), and high nitrosamines (OR = 2.6; 95% CI = 1.3-5.4). Adjusting for variables associated with gastroschisis in previous analyses of this population did not substantially alter those risks. These results suggest that maternal dietary inadequacy may be a risk factor for gastroschisis, and the three nutrients that emerged from the nutrient screening appear to be the best candidates to examine in further epidemiological analyses or biological studies.