Special Intervention Group Research Articles

Multidimensional Impact of Regular Physical Activity on Adolescent Mental Health, Integrating Neurobiological and Psychosocial Mechanisms

Background: Frequent exercise promotes social connection, increases neuroplasticity, and regulates neurotransmitters to enhance teenage mental health by lowering anxiety, improving depression, and improving cognitive performance. Objectives: The purpose of this study was to assess the impact of exercise on mental health status among youths aged 12–18 in terms of depression, anxiety, and self-esteem. Methodology: This study employed a cross-sectional survey design whereby 300 adolescents were selected and divided into control group and the special intervention group. The structured physical activities were 3 times per week for 12 months for the subjects in the intervention group. Physical Activity, Mental Health, Neurobiological and Psychosocial Parameters were measured regularly and collected raw data were represented through SPSS version 26.0 by applying t-tests analyses. p≤0.05 was considered statistically significant. Results: Depression scores were significantly reduced among adolescents in the intervention group which stood at 8.4 points less than those in the control group (p<0. 01). Also, self esteem increased by 12 percent in the intervention group while only 3% for the control group, p= 0.02 The existence of a positive connection between PA and better mental health was consistent even when statistical control was made for covariates. Conclusion: Physical exercise is proven to have a positive effect and to decrease the level of depression and anxiety in adolescents and to increase self-esteem. These results therefore support the recommendation of physical activity in mental health care approaches for this age bracket.

Latinos understanding the need for adherence in diabetes (LUNA-D): a randomized controlled trial of an integrated team-based care intervention among Latinos with diabetes.

We developed and tested a culturally appropriate, team-based, integrated primary care and behavioral health intervention in low income, Spanish-speaking Latinos with type 2 diabetes, at a federally qualified health center. This pragmatic randomized controlled trial included 456 Latino adults, 23-80 years, 63.7% female, with diabetes [recruitment glycosylated hemoglobin (HbA1c) ≥ 7.0%/53.01 mmol/mol)]. The Special Intervention occurred over 6 months and targeted improvement of HbA1c, blood pressure, and lipids. The intervention included: (i) four, same-day integrated medical and behavioral co-located visits; (ii) six group diabetes self-management education sessions addressing the cultural dimensions of diabetes and lifestyle messages; (iii) and care coordination. Usual Care participants received primary care provider led standard diabetes care, with referrals to health education and behavioral health as needed. HbA1c and lipids were obtained through electronic health records abstraction. Blood pressure was measured by trained research staff. Multi-level models showed a significant group by time interaction effect (B = -0.32, p < .01, 95% CI -0.49, -0.15), indicating statistically greater improvement in HbA1c level over 6 months in the Special Intervention group (ΔHbA1c = -0.35, p = <.01) versus Usual Care (ΔHbA1c = -0.02, p = .72). Marginally significant group by time interactions were also found for total cholesterol and diastolic blood pressure, with significant improvements in the Special Intervention group (p < .05). This culturally appropriate model of highly integrated care offers strategies that can assist with self-management goals and disease management for Latinos with diabetes in a federally qualified health center setting.

A win ratio approach to the re-analysis of Multiple Risk Factor Intervention Trial.

Composite outcomes, which combine multiple types of clinical events into a single outcome, are common in clinical trials. The usual analysis considers the time to first occurrence of any event in the composite. The major criticisms of such an approach are (1) this implicitly treats the outcomes as if they were of equal importance, but they often vary in terms of clinical relevance and severity, (2) study participants often experience more than one type of event, and (3) often less severe events occur before more severe ones, but the usual analysis disregards any information beyond that first event. A novel approach, referred to as the win ratio, which addresses the aforementioned criticisms of composite outcomes, is illustrated with a re-analysis of data on fatal and non-fatal cardiovascular disease time-to-event outcomes reported for the Multiple Risk Factor Intervention Trial. In this trial, 12,866 participants were randomized to a special intervention group (n = 6428) or a usual care (n = 6438) group. Non-fatal outcomes were ranked by risk of cardiovascular disease death up to 20 years after trial. In one approach, participants in the special intervention and usual care groups were first matched on coronary heart disease risk at baseline and time of enrollment. Each matched pair was categorized as a winner or loser depending on which one experienced a cardiovascular disease death first. If neither died of cardiovascular disease causes, they were evaluated on the most severe non-fatal outcome. This process continued for all the non-fatal outcomes. A second win ratio statistic, obtained from Cox partial likelihood, was also estimated. This statistic provides a valid estimate of the win ratio using multiple events if the marginal and conditional survivor functions of each outcome satisfy proportional hazards. Loss ratio statistics (inverse of win ratios) are compared to hazard ratios from the usual first event analysis. A larger 11-event composite was also considered. For the 7-event cardiovascular disease composite, the previously reported first event analysis based on 581 events in the special intervention group and 652 events in the usual care group yielded a hazard ratio (95% confidence interval) of 0.89 (0.79-0.99), compared to 0.86 (0.77-0.97) and 0.91 (0.81-1.02) for the severity ranked estimates. Results for the 11-event composite also confirmed the findings of the first event analysis. The win ratio analysis was able to leverage information collected past the first experienced event and rank events by severity. The results were similar to and confirmed previously reported traditional first event analysis. The win ratio statistic is a useful adjunct to the traditional first event analysis for trials with composite outcomes.

Strategies for improving postpartum contraceptive use: evidence from non-randomized studies.

Nearly two-thirds of women in their first postpartum year have an unmet need for family planning. Adolescents often have repeat pregnancies within a year of giving birth. Women may receive counseling on family planning both antepartum and postpartum. Decisions about contraceptive use made right after counseling may differ considerably from actual postpartum use. In earlier work, we found limited evidence of effectiveness from randomized trials on postpartum contraceptive counseling. For educational interventions, non-randomized studies may be conducted more often than randomized trials. We reviewed non-randomized studies of educational strategies to improve postpartum contraceptive use. Our intent was to examine associations between specific interventions and postpartum contraceptive use or subsequent pregnancy. We searched for eligible non-randomized studies until 3 November 2014. Sources included CENTRAL, PubMed, POPLINE, and Web of Science. We also sought current trials via ClinicalTrials.gov and ICTRP. For additional citations, we examined reference lists of relevant reports and reviews. The studies had to be comparative, i.e., have intervention and comparison groups. The educational component could be counseling or another behavioral strategy to improve contraceptive use among postpartum women. The intervention had to include contact within six weeks postpartum. The comparison condition could be another behavioral strategy to improve contraceptive use, usual care, other health education, or no intervention. Our primary outcomes were postpartum contraceptive use and subsequent pregnancy. Two authors evaluated abstracts for eligibility and extracted data from included studies. We computed the Mantel-Haenszel odds ratio (OR) for dichotomous outcomes and the mean difference (MD) for continuous measures, both with 95% Confidence Intervals (CI). Where studies used adjusted analyses for continuous outcomes, we presented the results as reported by the investigators. Due to differences in interventions and outcome measures, we did not conduct meta-analysis. To assess the evidence quality, we used the Newcastle-Ottawa Quality Assessment Scale. Six studies met our inclusion criteria and included a total of 5143 women. Of three studies with self-reported pregnancy data, two showed pregnancy to be less likely in the experimental group than in the comparison group (OR 0.48, 95% CI 0.27 to 0.87) (OR 0.60, 95% CI 0.41 to 0.87). The interventions included a clinic-based counseling program and a community-based communication project.All studies showed some association of the intervention with contraceptive use. Two showed that treatment-group women were more likely to use a modern method than the control group: ORs were 1.77 (95% CI 1.08 to 2.89) and 3.08 (95% CI 2.36 to 4.02). In another study, treatment-group women were more likely than control-group women to use pills (OR 1.78, 95% CI 1.26 to 2.50) or an intrauterine device (IUD) (OR 3.72, 95% CI 1.27 to 10.86) but less likely to use and injectable method (OR 0.23, 95% CI 0.05 to 1.00). One study used a score for method effectiveness. The methods of the special-intervention group scored higher than those of the comparison group at three months (MD 13.26, 95% CI 3.16 to 23.36). A study emphasizing IUDs showed women in the intervention group were more likely to use an IUD (OR 1.79, 95% CI 1.20 to 2.69) and less likely to use no method (OR 0.48, 95% CI 0.31 to 0.75). In another study, contraceptive use was more likely among women in a health service intervention compared to women in a community awareness program at four months (OR 1.79, 95% CI 1.40 to 2.30) or women receiving standard care at 10 to 12 months (OR 2.08, 95% CI 1.58 to 2.74). That study was the only one with a specific component on the lactational amenorrhea method (LAM) that had sufficient data on LAM use. Women in the health service group were more likely than those in the community awareness group to use LAM (OR 41.36, 95% CI 10.11 to 169.20). We considered the quality of evidence to be very low. The studies had limitations in design, analysis, or reporting. Three did not adjust for potential confounding and only two had sufficient information on intervention fidelity. Outcomes were self reported and definitions varied for contraceptive use. All studies had adequate follow-up periods but most had high losses, as often occurs in contraception studies.

Multiple Risk Factor Intervention Trial Revisited: A New Perspective Based on Nonfatal and Fatal Composite Endpoints, Coronary and Cardiovascular, During the Trial

BackgroundThe Multiple Risk Factor Intervention Trial evaluated a multifactor intervention on coronary heart disease (CHD) in 12 866 men. A priori defined endpoints (CHD death, CHD death or nonfatal myocardial infarction, cardiovascular disease [CVD] death, and all-cause death) did not differ significantly between the special intervention (SI) and usual care (UC) groups over an average follow-up period of 7 years. Event rates were lower than anticipated, reducing power. Other nonfatal CVD outcomes were prespecified but not considered in composite outcomes comparing SI with UC.Methods and ResultsPost-trial CVD mortality risks associated with nonfatal CVD events occurring during the trial were determined with Cox regression. Nonfatal outcomes associated with >2-fold risk of CVD death over the subsequent 20 years were combined with during-trial deaths to create 2 new composite outcomes. SI/UC hazard ratios and 95% confidence intervals were estimated for each composite outcome. Of 10 during-trial nonfatal events, 6 were associated (P<0.001) with >2-fold risk of CVD death. A CHD composite outcome (CHD death, myocardial infarction [clinical or serial ECG change], CHF, or coronary artery surgery) was experienced by 520 SI and 602 UC men (SI/UC hazard ratio = 0.86; 95% confidence interval, 0.76–0.97; P=0.01). A CVD composite outcome (CHD [as above], other CVD deaths, stroke, or renal impairment) was experienced by 581 SI and 652 UC men (hazard ratio = 0.89; 95% confidence interval, 0.79–0.99; P=0.04).ConclusionsIn post hoc analyses, composite fatal/nonfatal CHD and CVD rates over 7 years were significantly lower for SI than for UC. These findings reinforce recommendations for improved dietary/lifestyle practices, with pharmacological therapy as needed, to prevent and control major CVD risk factors.

Brief Patient-Centered Clinician-Delivered Counseling for High-Risk Drinking: 4-Year Results

The purpose of this study is to determine the effect at 48 months of a screening and brief patient-centered physician- and nurse practitioner-delivered intervention implemented during a routine primary care visit on the reduction of alcohol consumption by high-risk drinkers. Participants seen in primary care practices previously randomized to special intervention (SI) or usual care (UC) were reconsented for long-term follow-up. From the initial cohort, 63% reconsented to participate and provided follow-up at 48 months between November 1996 and March 2002. The data for this paper were analyzed in June 2004. At 48 months, SI participants maintained significant reductions in drinks per week seen at 6 and 12 months. However, there were no longer significant differences in drinks per week, binges per month, percentage of low-risk drinking, relapse rates, and new quits between the SI and UC groups at 48 months that had been seen at earlier follow-up. There was a significant effect of prior low-risk drinking status at 12 months; those who were low-risk drinkers at 12 months were more likely to stay low-risk drinkers at 48 months regardless of treatment group. With a single brief intervention, SI participants had significantly greater reductions in their drinking levels at 6 and 12 months compared to UC participants and maintained the lower-risk levels at 48 months resulting in a reduction in health risk exposure time. However, the significant group differences in treatment effect seen in earlier follow-ups were not maintained.

All Thiazide‐Like Diuretics Are Not Chlorthalidone: Putting the ACCOMPLISH Study Into Perspective

All Thiazide‐Like Diuretics Are Not Chlorthalidone: Putting the ACCOMPLISH Study Into Perspective

Using Diuretics in Practice—One Opinion

Using Diuretics in Practice—One Opinion

The Effects of a Smoking Cessation Intervention on 14.5-Year Mortality

had stopped smoking since study entry compared with 5.4% of usual care participants. After up to 14.5 years of follow-up, 731 patients died: 33% of lung cancer, 22% of cardiovascular disease, 7.8% of respiratory disease other than cancer, and 2.3% of unknown causes. All-cause mortality was significantly lower in the special intervention group than in the usual care group (8.83 per 1000 person-years vs. 10.38 per 1000 person-years; P 0.03). The hazard ratio for mortality in the usual care group compared with the special intervention group was 1.18 (95% CI, 1.02 to 1.37). Differences in death rates for both lung cancer and cardiovascular disease were greater when death rates were analyzed by smoking habit. Limitations: Results apply only to individuals with airway obstruction.

Incidence of Type 2 Diabetes in the Randomized Multiple Risk Factor Intervention Trial

Weight loss and increased physical exercise reduce the risk for diabetes in people with impaired glucose tolerance. Randomized trial evidence on the effect of these interventions on people without impaired glucose tolerance is lacking. To examine the influence of a comprehensive intervention program on the risk for developing diabetes in men without impaired glucose tolerance and in a post hoc subgroup analysis by baseline cigarette smoking status. Randomized, controlled trial. 22 clinical centers for the Multiple Risk Factor Intervention Trial (MRFIT). 12,866 men age 35 to 57 years at risk for cardiovascular disease were randomly assigned to either a special intervention or usual care group and followed for 6 to 7 years; this report focuses on 11,827 men without diabetes or impaired glucose tolerance at entry for whom follow-up glucose measurements were available. Cardiovascular disease risk factors, fasting blood glucose levels, and diabetes medication history were assessed before randomization and annually. Men in the special intervention group were counseled to change diet (reduce saturated fat, cholesterol, and calorie intake), to stop smoking, and to increase physical activity. Blood pressure was treated more intensively in the special intervention group than in the usual care group. 11.5% of the special intervention group and 10.8% of the usual care group developed diabetes over 6 years of follow-up (hazard ratio, 1.08 [95% CI, 0.96 to 1.20]). The special intervention-usual care hazard ratio for diabetes was 1.26 (CI, 1.10 to 1.45) among smokers (63%) and 0.82 (CI, 0.68 to 0.98) among nonsmokers (37%). These estimates differed significantly (P = 0.0003). Weight gain after smoking cessation and the use of antihypertensive drugs may have counterbalanced the beneficial effect of the lifestyle intervention for the special intervention group smokers, while the lifestyle intervention was beneficial among nonsmokers. Principal findings are based on a post hoc subgroup analysis. In nonsmokers, an intervention program that included nutrition counseling to produce reductions in weight, serum cholesterol, and (along with antihypertensive medication) blood pressure reduced the risk for diabetes.

The Effects of a Smoking Cessation Intervention on 14.5-Year Mortality

Randomized clinical trials have not yet demonstrated the mortality benefit of smoking cessation. To assess the long-term effect on mortality of a randomly applied smoking cessation program. The Lung Health Study was a randomized clinical trial of smoking cessation. Special intervention participants received the smoking intervention program and were compared with usual care participants. Vital status was followed up to 14.5 years. 10 clinical centers in the United States and Canada. 5887 middle-aged volunteers with asymptomatic airway obstruction. All-cause mortality and mortality due to cardiovascular disease, lung cancer, and other respiratory disease. The intervention was a 10-week smoking cessation program that included a strong physician message and 12 group sessions using behavior modification and nicotine gum, plus either ipratropium or a placebo inhaler. At 5 years, 21.7% of special intervention participants had stopped smoking since study entry compared with 5.4% of usual care participants. After up to 14.5 years of follow-up, 731 patients died: 33% of lung cancer, 22% of cardiovascular disease, 7.8% of respiratory disease other than cancer, and 2.3% of unknown causes. All-cause mortality was significantly lower in the special intervention group than in the usual care group (8.83 per 1000 person-years vs. 10.38 per 1000 person-years; P = 0.03). The hazard ratio for mortality in the usual care group compared with the special intervention group was 1.18 (95% CI, 1.02 to 1.37). Differences in death rates for both lung cancer and cardiovascular disease were greater when death rates were analyzed by smoking habit. Results apply only to individuals with airway obstruction. Smoking cessation intervention programs can have a substantial effect on subsequent mortality, even when successful in a minority of participants.

A randomized controlled trial of a public health nurse directed treatment program for rural patients with high blood cholesterol

Background Many rural residents do not have access to high-quality nutrition counseling for high blood cholesterol. The objective of this study was to assess the effectiveness of an intervention program designed to facilitate dietary counseling for hypercholesterolemia by rural public health nurses. Methods Eight health departments (216 participants) were randomized to give the special intervention (SI) and nine (252 participants) to give the minimal intervention (MI). The SI consisted of three individual diet counseling sessions given by a public health nurse, using a structured dietary intervention (Food for Heart Program), referral to a nutritionist if lipid goals were not achieved at 3-month follow-up, and a reinforcement phone call and newsletters. Diet was assessed by the Dietary Risk Assessment (DRA), a validated food frequency questionnaire, at baseline, 3-, and 12-month follow-up; blood lipids and weight were assessed at baseline, 3-, 6-, and 12-month follow-up. Results Participants were largely female (71%), older (mean age 55), and white (80%). At 3-month follow-up, the average reduction (indicating dietary improvement) in total Dietary Risk Assessment score was 3.7 units greater in the SI group (95% confidence interval [CI] 1.9 to 5.5, P = 0.0006), while both groups experienced a similar reduction in blood cholesterol, 14.1 mg/dL (0.37 mmol/L) for SI and 14.5 mg/dL (0.38 mmol/L) for minimal intervention group (difference −0.4 mg/dL [−0.010 mmol/L], 95% CI −12.5 to 11.7 [−0.32 to 0.30], P = 0.9). At 12-month follow-up, the reduction in total Dietary Risk Assessment score was 2.1 units greater in the SI group (95% CI 0.8 to 3.5, P = 0.005), while the reduction in blood cholesterol was similar in both groups, 18.4 mg/dL (0.48 mmol/L) for SI and 15.6 mg/dL (0.40 mmol/L) for minimal intervention group (difference 2.8 mg/dL [0.07 mmol/L], 95% CI −7.5 to 13.1 [−0.19 to 0.34], P = 0.6). During follow-up, weight loss was greater in the SI group; the difference between groups was statistically significant at 3 (1.9 lb [0.86 kg], 95% CI 0.3 to 3.4 [0.14 to 1.55], P = 0.022) and 6 months (2.1 lb [0.95 kg], 95% CI 0.1 to 4.1 [0.04 to 1.86], P = 0.04). At 12 months, the difference was not significant (1.6 lb [0.73 kg], 95% CI −0.05 to 3.7 [−0.02 to 1.68], P = 0.13). Conclusions Improvement in self-reported dietary intake was significantly greater in the SI group, while reduction in blood cholesterol was similar in both groups.

Transforming exercise-based cardiac rehabilitation programs into secondary prevention centers: a national imperative.

Transforming exercise-based cardiac rehabilitation programs into secondary prevention centers: a national imperative.

The effect of weight cycling on blood lipids and blood pressure in the Multiple Risk Factor Intervention Trial Special Intervention Group.

To assess whether weight cycling has adverse effects on blood lipids or blood pressure. Cohort study, six years of follow-up, comparing net change in blood lipids and blood pressure among weight cyclers and non-cyclers. Men (n = 4353), age 35-57 y, at high risk for heart disease because of smoking, high blood pressure, and elevated cholesterol concentration in the Multiple Risk Factor Intervention Trial (MRFIT)--a 22-site, multi-center collaborative primary prevention trial conducted in the US, 1973-1983. A weight cycle was defined as loss and regain of at least 5% of mean weight. Outcome measures were changes from baseline to year six in total serum cholesterol, high density lipoprotein cholesterol (HDL), the ratio of total cholesterol to HDL, and diastolic blood pressure. Analysis of covariance models were developed, with number of weight cycles as the predictor variable. The hypothesis was that men who weight cycled would experience less improvement in blood lipids and blood pressure than those who did not cycle. Adjustments were made for net weight change and other factors affecting each outcome. Men who weight cycled did not have the predicted smaller improvements in total cholesterol, HDL, the ratio of total cholesterol to HDL, or diastolic blood pressure, compared with noncyclers. An adverse effect of weight cycling on blood pressure or blood lipids was not found. The excess mortality previously reported among weight cyclers in this population can probably not be attributed to effects on these CVD risk factors.

Worksite Cholesterol and Nutrition: An Intervention Project in Colorado

The study purpose was to determine whether group intervention or an individual self help program proved to be more effective at lowering heart disease risk factors among employees in different worksites. Eight worksites and 502 employees in the Denver metropolitan area were selected for the project, with four randomized to Usual Care and four to the Special Intervention. Most worksites had < 200 employees. Employees were randomly assigned to either a control group receiving usual nutrition education or one of two special intervention groups in which employees selected to attend group nutrition education classes or complete an individual self paced nutrition education program. Results indicated that offering a choice of methods for the special nutrition education intervention was valuable, and both approaches modified behavior and certain physiological outcomes. Results suggested that enhanced nutrition education efforts in worksites may be effective and will realize greater benefits than a pamphlet or brief discussion following a worksite screening.

Levels of cotinine associated with long-term ad-libitum nicotine polacrilex use in a clinical trial

Studies of nicotine replacement by 2 mg nicotine polacrilex gum (NG) have typically found that one half to one third of plasma nicotine in recent smokers is replaced. This 5-year study sought to find the extent of nicotine replacement among ex-smokers in the longer term and to identify a mechanism for this relationship. The sample was the special intervention group ( N = 3923) in the Lung Health Study, a controlled clinical trial involving smoking cessation. The extent of nicotine replacement was assessed by levels of salivary cotinine. Cotinine levels of ex-smokers using NG after 1 year (219 ± 149 ng/ml) were similar to those in continuing smokers (290 ± 159 ng/ml). After 5 years, cotinine levels were the same for NG-using ex-smokers (316 ± 276 ng/ml), NG-using smokers (309 ± 240 ng/ml), and NG-non-using smokers (311 ± 198 ng/ml). Salivary cotinine among NG users at 1 year was only weakly correlated with baseline cotinine levels prior to smoking cessation. Although NG users appear to re-establish cotinine levels characteristic of their smoking, the mechanism by which this occurs remains unclear.

Heart rate adjustment of exercise-induced ST-segment depression identifies men who benefit from a risk factor reduction program.

Whether subjects identified as being at increased risk of coronary heart disease (CHD) death by heart rate adjustment of exercise-induced ST-segment depression will benefit from therapy aimed at reducing risk factors has not been examined. Exercise ECGs were performed in 11,880 men from the Usual Care (UC) and Special Intervention (SI) groups of the Multiple Risk Factor Intervention Trial. UC men were referred to customary sources of care in the community; SI men received counseling on smoking cessation and dietary reduction of cholesterol, and stepped-care therapy for hypertension. An abnormal ST-segment response to exercise was defined according to standard criteria as > or = 100 microV of additional horizontal or downsloping ST-segment depression and by an ST-segment/heart rate (ST/HR) index >1.60 microV/bpm. After 7 years of follow-up, CHD mortality was significantly lower in SI than UC men with an abnormal ST/HR index (2.4%, 19/786 versus 5.3%, 39/729, P=.005) but was comparable in SI and UC men with a normal ST/HR index (1.6%, 84/5154 versus 1.3%, 70/5211, P=NS). Risk reduction in SI men with an abnormal ST/HR index was independent of age and other cardiac risk factors. In contrast, there was no significant difference in CHD death rate between the smaller groups of SI and UC men with an abnormal test by standard criteria (3.6%, 7/192 versus 2.7%, 5/186, P=NS). An abnormal ST/HR index identifies men in whom therapy aimed at reducing CHD risk factors reduces the risk of CHD death by 61%. These findings support the application of heart rate adjustment of ST depression for screening of asymptomatic subjects at increased risk of CHD to identify those who will benefit most from risk factor-reduction programs.

Multiple Risk Factor Intervention Trial. Risk factor changes and mortality results. Multiple Risk Factor Intervention Trial Research Group. 1982

The Multiple Risk Factor Intervention Trial was a randomized primary prevention trial to test the effect of a multifactor intervention program on mortality from coronary heart disease (CHD) in 12,866 high-risk men aged 35 to 57 years. Men were randomly assigned either to a special intervention (SI) program consisting of stepped-care treatment for hypertension, counseling for cigarette smoking, and dietary advice for lowering blood cholesterol levels, or to their usual sources of health care in the community (UC). Over an average follow-up period of seven years, risk factor levels declined in both groups, but to a greater degree for the SI men. Mortality from CHD was 17.9 deaths per 1,000 in the SI group and 19.3 per 1,000 in the UC group, a statistically nonsignificant difference of 7.1% (90% confidence interval, -15% to 25). Total mortality rates were 41.2 per 1,000 (SI) and 40.4 per 1,000 (UC). Three possible explanations for these findings are considered: (1) the overall intervention program, under these circumstances, does not affect CHD mortality; (2) the intervention used does affect CHD mortality, but the benefit was not observed in this trial of seven years' average duration, with lower-than-expected mortality and with considerable risk factor change in the UC group; and (3) measures to reduce cigarette smoking and to lower blood cholesterol levels may have reduced CHD mortality within subgroups of the SI cohort, with a possibly unfavorable response to antihypertensive drug therapy in certain but not all hypertensive subjects. This last possibility was considered most likely, needs further investigation, and lends support to some preventive measures while requiring reassessment of others.

Lung cancer mortality after 16 years in MRFIT participants in intervention and usual-care groups

PURPOSE: The Multiple Risk Factor Intervention Trial (MRFIT), a randomized clinical trial for the primary prevention of coronary heart disease, enrolled 12,866 men (including 8194 cigarette smokers) aged 35–57 years at 22 clinical centers across the United States. Participants were randomized either to special intervention (SI), which included an intensive smoking cessation program, or to usual care (UC). After 16 years of follow-up, lung cancer mortality rates were higher in the SI than in the UC group. Since rates of smoking cessation in SI were higher than those for UC for the 6 years of the trial, and since risk of lung cancer mortality is known to decline with smoking cessation, these results were unexpected. The purpose of the present study was to investigate hypotheses that could explain the higher observed lung cancer mortality rates in the SI as compared with the UC group. METHODS: Analytic methods were employed to determine whether SI and UC participants differed either in baseline characteristics or in characteristics that changed during the trial and to determine whether these differences could explain the higher rates of lung cancer mortality among SI as compared to UC participants. Rates of mortality from coronary heart (CHD) were examined to explore the possibility that prevention of CHD death may have contributed to greater mortality due to lung cancer in the SI group. RESULTS: From randomization through December 1990, 135 SI and 117 UC participants died from lung cancer. The relative difference between the SI and U groups adjusted for age and number of cigarettes smoked per day, was 1.17 (95% CI:0.92–1.51). The greatest difference between the SI and UC groups in lung cancer mortality rates occurred among the heaviest smokers at baseline who did not achieve sustained smoking cessation by year 2. In this group the rates of death from CHD were approximately the same among the SI and UC subjects. No differences in baseline characteristics were found between SI and UC smokers who did not achieve sustained cessation by year 2, and there were no differences in follow-up characteristics between the two study groups that could explain the difference in lung cancer mortality. CONCLUSIONS: None of the hypotheses proposed to explain the unexpected higher rates of lung cancer mortality among SI as compared with UC subjects were sustained by the data. Thus we conclude that the difference observed is due to chance, and that a longer period of sustained smoking cessation plus follow-up is necessary to detect a reduction in lung cancer mortality as a result of smoking cessation intervention in a randomized clinical trial.

Nutritional adequacy of diets reported at baseline and during trial years 1–6 by the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial

This chapter addresses whether a fat-modified diet as implemented by special intervention participants in the Multiple Risk Factor Intervention Trial affected intake of vitamins and minerals, and whether nutritional adequacy was altered by this dietary intervention. Despite likely underreporting of intake, for men in the special intervention group, most mean intakes of 15 micronutrients estimated from 24-h recalls were above established recommended dietary allowances. A few means were slightly below; lowest was zinc at 77% (from 98% at baseline) followed by calcium at 79% (from 102% at baseline). Calculated as nutrient densities (per 1000 kcal), nutrients that were below indexes of nutritional quality (the corresponding standard based on nutrient density) during follow-up, although not reduced below baseline by this measure, were vitamin D, calcium, iron (marginally), and zinc. Analyses by food groups indicated that intake of these nutrients might have been improved by greater replacement of high- and medium-fat dairy products with low-fat dairy products (for vitamin D and calcium) and of high-fat meats with low-fat meats, fish, or poultry (for iron and zinc), or (because iron was adequate) by increasing consumption of vegetables and whole-grain products. The safety of the eating pattern was further confirmed by more favorable micronutrient profiles in men who adhered best to the intervention program, as measured by degree of serum cholesterol reduction and weight loss.