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Biomedical subjects

S A Grover

Publications and source records attributed to S A Grover.

At least 19 recordsLinked to original sources
PubMed1998

Estimating the benefits of modifying risk factors of cardiovascular disease: a comparison of primary vs secondary prevention.

OBJECTIVES: To compare the potential years of life saved (YOLS) associated with risk factor modification in the primary and secondary prevention of cardiovascular disease (CVD). METHODS: The CVD life expectancy model estimates the risk of death due to coronary disease, stroke, and other causes based on the levels of independent risk factors (such as age, blood pressure, and blood lipid levels) found in the cohort of the Lipid Research Clinics. The model was validated by comparing its predictions with the observed fatal outcomes of 9 randomized clinical trials. We then estimated the YOLS associated with treating hyperlipidemia or hypertension among hypothetical patient groups with and without CVD at baseline. We defined high-risk patients as those with 3 risk factors (hyperlipidemia, cigarette smoking, and hypertension) and low-risk patients as those with isolated hypertension or hyperlipidemia. RESULTS: The fatal events predicted by the model were consistent with the clinical trial results. Among men and women with hyperlipidemia without CVD, the forecasted benefits of lipid therapy were substantially greater among high-risk groups vs low-risk groups (4.74-0.78 YOLS vs 2.50-0.25 YOLS, respectively). Among those with CVD, the forecasted benefits of treatment were similar for both high-risk and low-risk groups (4.65-0.65 YOLS vs 3.84-0.58 YOLS, respectively). The results for hypertension therapy also demonstrated greater benefits for high-risk vs low-risk patients undergoing primary prevention therapy (1.34-0.29 YOLS vs 0.85-0.13 YOLS, respectively), and the forecasted benefits in secondary prevention were similar (1.26-0.23 YOLS vs 1.00-0.23 YOLS, respectively). CONCLUSIONS: The clinical approach to risk factor modification in primary prevention should be different from that in secondary prevention. The forecasted benefits of therapy among patients without CVD are greatest in the presence of other risk factors. Among those with CVD, the benefits of therapy are equivalent, thereby obviating the need to target high-risk patients.

Cardiovascular Diseases↗
PubMed1998

Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis.

RPE65 is a protein of unknown function expressed specifically by the retinal pigment epithelium. We examined all 14 exons of this gene in 147 unrelated patients with autosomal recessive retinitis pigmentosa (RP), in 15 patients with isolate RP, and in 45 patients with Leber congenital amaurosis (LCA). Sequence anomalies that were likely to be pathogenic were found in two patients with recessive RP, in one patient with isolate RP recategorized as recessive, and in seven patients with LCA. Cosegregation analysis in each available family showed that all affected individuals were either homozygotes or compound heterozygotes and that all unaffected individuals were either heterozygote carriers or homozygous wild type. In one family, there was one instance of a new mutation not present in either parent of the affected individual. In another family, affected members with recessive RP in three branches (i.e., three distinct pairs of parents) were compound heterozygotes for the same two mutations or homozygous for one of them. Based on our results, mutations in the RPE65 gene appear to account for approximately 2% of cases of recessive RP and approximately 16% of cases of LCA.

Blindness↗
PubMed1997

Flexible modeling of the effects of serum cholesterol on coronary heart disease mortality.

Current understanding of the impact of lipids and other risk factors on coronary heart disease is largely based on the results of parametric multiple regression analyses of large prospective studies. To assess the potential impact of the a priori assumption of linearity of continuous risk factors on the results of parametric analyses, the authors completed a secondary analysis of the Lipid Research Clinics Prevalence and Follow-up Studies (1972-1987) data using an assumption-free nonparametric modeling approach. The effects of total serum cholesterol and the ratio of total serum cholesterol to high density lipoprotein cholesterol, adjusted for common risk factors, were estimated using a smoothing spline method available in the generalized additive model extension of the multiple logistic regression. The data set included 2,512 men in the random sample of the Lipid Research Clinics study who did not take lipid-lowering medications. During the median follow-up of 12.6 years, 94 coronary heart disease deaths occurred. The generalized additive model fits the effects of total serum cholesterol (p < 0.01) and the ratio of total serum cholesterol to high density lipoprotein cholesterol (p < 0.02) significantly better than the parametric logistic regression. Validation studies confirmed that, among new observations arising from the same population, generalized additive model estimates predicted outcomes better than the parametric estimates. Nonlinear effects of both lipid measures were robust and may be clinically important. The authors conclude that the linearity assumption inherent in parametric models may result in biased estimates of the effects of total serum cholesterol on coronary heart disease mortality and recommend that their findings be verified in a nonparametric analysis of data from another large prospective study.

Cholesterol↗
PubMed1997

Direct and indirect medical costs incurred by Canadian patients with rheumatoid arthritis: a 12 year study.

OBJECTIVE: To perform the first prospective longitudinal study of direct (health services utilized) and indirect costs (diminished productivity represented by income loss) incurred by patients with rheumatoid arthritis (RA) in Saskatoon and Montreal, followed for up to 12 and 4 years, respectively. METHODS: 1063 patients reported on health status, health services utilization, and diminished productivity every 6 months. RESULTS: Annual direct costs were $3788 (1994 Canadian dollars) in the late 1980s and $4656 in the early 1990s. Given that the average age exceeded 60 years, few participated in labor force activities or considered themselves disabled from the labor force and their indirect costs were substantially less, $2165 in the late 1980s and $1597 in the early 1990s. Institutional stays and medications made up at least 80% of total direct costs. Lengths of stay in acute care facilities remained constant, but the rate of hospitalization increased in the early 1990s, increasing average hospital costs per patient from $1563 in the late 1980s to $2023 in the early 1990s. For nonacute care facilities, rate of admission as well as length of stay increased over time, increasing costs per patient in Saskatoon 5-fold, from $291 to $1605. Those with greater functional disability incurred substantially higher direct and those under 65 years incurred higher indirect costs. CONCLUSION: Direct costs are higher than indirect costs. The major component is due to institutional stays that, in contrast to other direct cost components, is increased in the older and more disabled. Measures to reduce longterm disability by earlier, more aggressive intervention have the potential to produce considerable cost savings. However, it is unknown which strategies will have the greatest effect on outcome and accordingly, how resources can be optimally allocated.

Aged↗
PubMed1996

Use of the emergency department for nonurgent care during regular business hours.

OBJECTIVE: To characterize the patient population seeking care for nonurgent medical problems at an emergency department during regular business hours and to determine why these patients chose the emergency department over alternative care sites. DESIGN: Patient survey (self-administered questionnaire). SETTING: Emergency department at a tertiary care hospital in Montreal. PATIENTS: All ambulatory patients presenting on weekdays between 8 am and 5 pm from Nov. 10 to Dec. 8, 1993, whose condition was determined to be nonurgent. Eligible patients had to be residents of Montreal, who did not have a pre-arranged consultation at the emergency department. Of 202 consecutive eligible patients, 200 agreed to participate. OUTCOME MEASURES: Description of events leading to the visit, including possible attempts by patients to contact their regular physician; patients' knowledge of alternative care options such as provincial CLSGs (centres locaux des services communautaires) and private walk-in clinics. RESULTS: Of the 200 patients 152 (76%) stated that they had not visited an emergency department within the previous month, and only 10 (5%) stated that they were in extreme pain. At least 70% were aware of alternative care options, however, 120 (60%) felt that the emergency department was the best place for them to receive care for their medical problem. In all, 81 patients (40%) were referred to the emergency department; 62 (77%) were referred by a health care professional, 46 (57%) by a physician. CONCLUSION: Most patients are aware of alternatives to the emergency department for care of nonurgent medical problems. Nevertheless, a large number are being referred to the emergency department during regular business hours by health care professionals. This inefficient use of expensive hospital resources requires further investigation.

Adolescent↗
PubMed1996

Relationship between dietary intake and coronary heart disease mortality: lipid research clinics prevalence follow-up study.

The diet-heart hypothesis proposes that elevated intakes of total fat, saturated fat, and dietary cholesterol raise serum cholesterol, which in turn increases the risk of developing coronary heart disease (CHD). To examine the relationship between dietary intake and 12-year CHD mortality we used data from the Lipid Research Clinics Prevalence Follow-Up Study. Dietary intake was measured at study entry using the 24-hour recall technique among 4546 North American men and women who were at least 30 years old and initially free of CHD. Proportional hazards analyses controlling for total energy intake indicated that increasing percentages of energy intake as total fat (RR 1.04, 95% CI = 1.01-1.08), saturated fat (RR 1.11, CI = 1.04-1.18), and monounsaturated fat (RR 1.08, CI = 1.01-1.16) were significant risk factors for CHD mortality among 30 to 59 year olds. The increasing percentage of energy intake from carbohydrate had a significant protective effect (RR 0.96, CI = 0.94-0.99). The strength of these associations was not diminished after adjustment for specific serum lipids, suggesting that serum lipids did not mediate the effect of diet on CHD mortality. None of the dietary components were significantly associated with CHD mortality among those aged 60-79 years. We conclude that future research must be directed toward better understanding the pathway between dietary intake and coronary disease as the current diet-lipid-heart hypothesis may be overly simplistic.

Adult↗
PubMed1995

Identifying adults at increased risk of coronary disease. How well do the current cholesterol guidelines work?

OBJECTIVE: To assess the accuracy of lipid screening strategies to identify individuals at increased risk of coronary heart disease mortality. PATIENTS: The 15% random sample of adults recruited into the Lipid Research Clinic Prevalence and Follow-up Studies, which included 3678 men and women aged 35 to 74 years. Total plasma cholesterol levels, lipoprotein fractions, and other coronary risk factors at study entry were compared with subsequent coronary heart disease mortality (mean follow-up, 12.2 years). MAIN OUTCOME MEASURES: The areas under receiver operating characteristic curves for blood lipids, lipid ratios, the screening guidelines proposed by the National National Cholesterol Education Program, those of the Canadian Consensus Conference on Cholesterol, and a coronary risk model that used Framingham data. MAIN RESULTS: The current National Cholesterol Education Program guidelines (area under the curve, 0.74) were significantly (P = .03) more accurate than the old National Cholesterol Education Program guidelines (area, 0.72). The ratio of total plasma cholesterol level to high-density lipoprotein cholesterol level (area, 0.72) was as accurate as current National Cholesterol Education Program guidelines. The coronary risk model (area, 0.85) was superior (P < .003) to all other screening maneuvers. Compared with the current National Cholesterol Education Program guidelines, the risk model demonstrated superior test sensitivity (70% vs 45%) with only slightly reduced specificity (82% vs 86%). CONCLUSION: The ratio of total plasma cholesterol level to high-density lipoprotein cholesterol level is as accurate as current American screening guidelines. Future guidelines should better incorporate high-density lipoprotein cholesterol levels and nonlipid risk factors to target high-risk individuals accurately.

Adult↗
PubMed1995

Do doctors accurately assess coronary risk in their patients? Preliminary results of the coronary health assessment study.

OBJECTIVE: To evaluate the ability of doctors in primary care to assess risk patients' risk of coronary heart disease. DESIGN: Questionnaire survey. SETTING: Continuing medical education meetings, Ontario and Quebec, Canada. SUBJECTS: Community based doctors who agreed to enroll in the coronary health assessment study. MAIN OUTCOME MEASURE: Ratings of coronary risk factors and estimates by doctors of relative and absolute coronary risk of two hypothetical patients and the "average" 40 year old Canadian man and 70 year old Canadian woman. RESULTS: 253 doctors answered the questionnaire. For 30 year olds the doctors rated cigarette smoking as the most important risk factor and raised serum triglyceride concentrations as the least important; for 70 year old patients they rated diabetes as the most important risk factor and raised serum triglyceride concentrations as the least important. They rated each individual risk factor as significantly less important for 70 year olds than for 30 year olds (all risk factors, P < 0.001). They showed a strong understanding of the relative importance of specific risk factors, and most were confident in their ability to estimate coronary risk. While doctors accurately estimated the relative risk of a specific patient (compared with the average adult) they systematically overestimated the absolute baseline risk of developing coronary disease and the risk reductions associated with specific interventions. CONCLUSIONS: Despite guidelines on targeting patients at high risk of coronary disease accurate assessment of coronary risk remains difficult for many doctors. Additional strategies must be developed to help doctors to assess better their patients' coronary risk.

Clinical Competence↗
PubMed1995

The cost-effectiveness of HMG-CoA reductase inhibitors to prevent coronary heart disease. Estimating the benefits of increasing HDL-C.

OBJECTIVE: To evaluate the lifetime cost-effectiveness of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors for treatment of high blood cholesterol levels. DESIGN: We added cost data to a validated coronary heart disease (CHD) prevention computer model that estimates the benefits of lifelong risk factor modification. The updated model takes into account the costs of cholesterol reduction, the savings in CHD health care costs attributable to intervention, the additional non-CHD costs resulting from patients' living longer, and the beneficial effects of reducing CHD risk by reducing total cholesterol and increasing high-density lipoprotein cholesterol (HDL-C). PATIENTS: Men and women aged 30 to 70 years who were free of CHD, had total cholesterol levels equal to the 90th percentile of the US distribution in their age and sex group, had HDL-C levels equal to the mean of the US distribution in their age and sex group, and were either with or without additional CHD risk factors. INTERVENTION: Use of 20 mg of lovastatin per day, which on average reduces total serum cholesterol by 17% and increases HDL-C by 7%. MAIN OUTCOME MEASURES: Cost per year of life saved after discounting benefits and costs by 5% annually. RESULTS: The increase in HDL-C associated with lovastatin lowered cost-effectiveness ratios by approximately 40%, such that the treatment of hypercholesterolemia was relatively cost-effective for men (as low as $20,882 per year of life saved at age 50 years) and women ($36,627 per year of life saved at age 60 years) with additional risk factors. Non-CHD costs resulting from longer life expectancy after intervention added at most 23% to the cost-effectiveness ratios for patients who began treatment at age 70 years, and as little as 3% for patients at age 30 years. CONCLUSION: The cost-effectiveness of HMG-CoA reductase inhibitors varied widely by age and sex and was sensitive to the presence of non-lipid CHD risk factors. The additional non-CHD costs due to increased life expectancy may be significant for the elderly. Accounting for the drug effects of raising HDL-C levels increased the proportion of the population for which medication treatment was relatively cost-effective.

Adult↗
PubMed1995

The existence of a fatigue syndrome after glandular fever.

This prospective cohort study was designed to test whether a distinct fatigue syndrome existed after the onset of glandular fever. Two hundred and fifty primary care patients, with either glandular fever or an ordinary upper respiratory tract infection (URTI) were interviewed three times in the 6 months after the clinical onset of their infection. At each interview a standardized psychiatric interview was given and physical symptoms were assessed. There were 108 subjects with and Epstein-Barr virus (EBV) infection; 83 subjects had glandular fever not caused by EBV and 54 subjects had an ordinary URTI. Five subjects were excluded because they had no evidence of an infection. Principal components analyses of symptoms supported the existence of a fatigue syndrome, particularly in the two glandular fever groups. The addition of symptoms not elicited by the standard interviews gave the full syndrome. This included physical and mental fatigue, excessive sleep, psychomotor retardation, poor concentration, anhedonia, irritability, social withdrawal, emotional lability, and transient sore throat and neck gland swelling with pain. A fatigue syndrome probably exists after glandular fever.

Animals↗
PubMed1995

The validity and reliability of the fatigue syndrome that follows glandular fever.

The validity and reliability of an empirically defined fatigue syndrome were tested in a prospective cohort study of 245 primary care patients, with glandular fever or an upper respiratory tract infection. Subjects were interviewed three times in the 6 months after onset. Subjects with the empirically defined fatigue syndrome were compared with those who were well and those who had a psychiatric disorder. The validity of the fatigue syndrome was supported, separate from psychiatric disorders in general and depressive disorders in particular. Only 16% of subjects with the principal component derived fatigue factor also met criteria for a psychiatric disorder (excluding pre-morbid phobias). Compared with subjects with psychiatric disorders, subjects with the operationally defined fatigue syndrome reported more severe physical fatigue, especially after exertion, were just as socially incapacitated, had fewer mental state abnormalities, and showed little overlap on independent questionnaires. A more mild fatigue state also existed. Both fatigue syndrome and state were more reliable diagnoses over time than depressive disorders. The empirically defined syndrome probably is a valid and reliable condition in the six months following glandular fever.

Cohort Studies↗
PubMed1994

Life expectancy following dietary modification or smoking cessation. Estimating the benefits of a prudent lifestyle.

OBJECTIVE: To evaluate the maximum benefits of dietary modification or smoking cessation to the life expectancy of North American adults. DESIGN: Using a computer model, we estimated the change in life expectancy for men and women following risk factor modification. We then estimated the total number of adults who would be targeted by national guidelines and the total person-years of life that would be saved. PATIENTS: Men and women aged 30 to 74 years who were free of coronary heart disease. INTERVENTIONS: Smoking cessation or serum cholesterol-reducing diets with 8% to 10% saturated fat and 240 to 300 mg of daily cholesterol, respectively. RESULTS: On average, dietary modification would reduce serum cholesterol levels from 0.45 mmol/L (17.4 mg/dL) to 0.75 mmol/L (29.1 mg/dL) in men and 0.12 mmol/L (4.6 mg/dL) to 0.55 mmol/L (21.4 mg/dL) in women, thereby increasing life expectancy by 0.03 to 0.4 year and 0.01 to 0.16 year, respectively. Smoking cessation would increase life expectancy from 2.59 to 4.43 years among men and from 2.6 to 3.68 years among women. Among adult Canadians, dietary modification would save 373,000 to 683,000 person-years of life. The majority of these benefits would occur among men who start dieting at ages 30 to 59 years. Smoking cessation would add more than 4 million person-years of life to the Canadian population. The relative impact of either intervention among American adults would be similar to these Canadian estimates. CONCLUSIONS: Younger men, aged 30 to 59 years, might live slightly longer after dietary change, but among women and older men the average benefits would be negligible. The benefits of smoking cessation are more uniform across age and sex and are substantially greater than those predicted for dietary change.

Adult↗
PubMed1994

Serum lipid screening to identify high-risk individuals for coronary death. The results of the Lipid Research Clinics prevalence cohort.

OBJECTIVE: To assess the accuracy of specific plasma lipid fractions in predicting coronary heart disease (CHD) mortality among adults. METHODS: Follow-up data for a random sample of 30- to 79-year-old men and women recruited into the Lipid Research Clinics Prevalence and Follow-up Studies were included in this analysis (n = 4499). Baseline measurements of total plasma cholesterol and lipoprotein fractions were compared with subsequent CHD mortality after a mean follow-up of 12.3 years. The areas under receiver operating characteristics curves for specific serum lipids were compared for individuals aged 30 to 59 and 60 to 79 years. MAIN RESULTS: For the younger cohort, the ratio of total cholesterol to high-density lipoprotein cholesterol was a better predictor (P < .05) of CHD mortality (receiver operating characteristic curve area, 0.80 +/- 0.03) than was total cholesterol level alone (receiver operating characteristic curve area, 0.73 +/- 0.03) or any other single lipoprotein measurement. Among the older cohort, the same screening strategies performed poorly, with receiver operating characteristic curve areas ranging from 0.51 +/- 0.05 for total cholesterol to 0.64 +/- 0.05 for the ratio of low-density to high-density lipoprotein cholesterol levels. CONCLUSION: Plasma lipid levels are poor predictors of coronary death among those aged 60 to 79 years without known CHD. These data indicate the need to define better lipid screening strategies for older, asymptomatic adults. Among younger adults aged 30 to 59 years, high-density lipoprotein cholesterol measurement should be included as part of any lipid screening program, as the ratio of total to high-density lipoprotein cholesterol levels is the best lipid screening test to identify those at high risk for subsequent CHD mortality.

Adult↗
PubMed1994

Risk-benefit assessment of drug treatment to prevent coronary heart disease. Estimating the benefits of risk factor modification.

Risk factor modification to prevent the development of coronary heart disease (CHD) is a rapidly growing concern of physicians interested in disease prevention. Drug treatments to reduce hypertension and hyperlipidaemia are 2 important interventions for CHD primary prevention. The benefits of these interventions have been demonstrated in short term clinical trials by reducing the incidence of stroke and coronary events. While the short term benefits may appear modest, the long term changes in life expectancy and disease morbidity may be substantial for carefully targeted groups of patients. Computer models are therefore increasingly being used to estimate the long term benefits of risk factor modification among selected patients. A review of published CHD models demonstrates that predictions among the different models are usually consistent. Moreover, the results of randomised clinical trials can be accurately forecasted using the CHD Primary Prevention Model.

Adult↗
PubMed1993

Modifying serum lipids to prevent coronary heart disease: do we have a consensus?

Despite the importance of hyperlipidemia as an independent coronary risk factor and the positive results of recent lipid intervention trials to prevent coronary disease, there remain many unanswered questions regarding the benefits and risks of treating hyperlipidemia. Critical review of epidemiologic studies and clinical trials suggest that the benefits of cholesterol reduction may vary depending on the patient's age, sex, and the presence of other coronary risk factors. Furthermore, one must recognize that there is a small but consistent increase in noncoronary deaths among patients receiving cholesterol-lowering medications that remains unexplained but requires further evaluation. These data underscore the importance of weighing both the risks and benefits of modifying serum lipids. Accordingly, careful evaluation of the underlying risk of developing coronary disease and the potential long-term benefits of intervention are necessary to identify appropriate high-risk patients for treatment among whom the predicted benefits will outweigh the risks.

Cholesterol, HDL↗