Palliative cancer care in Middle Eastern countries: accomplishments and challenges.

BACKGROUND: In larger parts of the Middle East palliative care is still misunderstood among health professionals, cancer patients and the public at large. One reason to that is because the term does not obviously communicate the intent of this clinical discipline, which is lending better quality of life while combating cancer. Further, culture, tradition and religion have contributed to this misgiving and confusion especially at the terminal stage of the disease. METHODS: The Middle East Cancer Consortium jointly with the American Society of Clinical Oncology, the American Oncology Nursing Society, the San Diego Hospice Center for Palliative Medicine and the Children's Hospital & Clinics of Minnesota initiated a series of training courses and workshops in the Middle East to provide updated training to physicians, nurses, social workers and psychologists from throughout the region with basic concepts of palliative care and pain managements in adults and children cancers. RESULTS: During the past 6 years hundreds of professionals took part in these educational and training activities, thereby creating the core of trained caregivers who start to make the change in their individual countries. CONCLUSIONS: The outcome of consecutive training activities can overcome geopolitical instabilities, and yield a genuine change in approach of both regulators, medical administrators, medical staff and the public; as to the important contribution of palliative care services to the welfare of the patient and his/her family.

Comparison of Postprandial Responses to a High-Fat Meal in Hypertriglyceridemic Men and Women before and after Treatment with Fenofibrate in the Genetics and Lipid Lowering Drugs and Diet Network (GOLDN) Study.

CONTEXT: The fenofibrate effect on the subclass size distribution of lipoproteins before and after a high-fat challenge is not well studied. OBJECTIVE: To characterize the baseline and post-prandial response (PPL) to a high-fat challenge following fenofibrate therapy, on changes in LDL, HDL, and VLDL particle subclasses, number, and size in 271 hypertriglyceridemic participants. METHODS: Participants from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study who conducted PPL studies both before and after three weeks of fenofibrate (160 mg/d) treatment were analyzed. Particle size distributions were determined using nuclear magnetic resonance imaging, and lipid determinations were measured at fasting (0 hr), 3.5 hours, and 6 hours after ingestion of a standardized high-fat meal. Analyses were stratified by gender. Changes in particle subclass distributions were assessed using repeated measures analysis of variance adjusted for pedigree. RESULTS: Before PPL, fenofibrate in men (adjusted for age, field center, smoking status, diabetes, and weight circumference) lowered fasting and postprandial VLDL primarily due to reductions in postprandial levels of large and medium VLDL particles (9 SE +/-0.7 to 4 +/-0.4 and 78 / -4 to 36 / -3 nmol/L both P < .0001, resp.). Fenofibrate also reduced fasting and postprandial total LDL particles, primarily a result of reduced small LDL particles (1497 = / - 37 to 1088 = / - 36 nmol/L, P < .0001). Directional changes were similar in men and women but the magnitude of change was different for some parameters. CONCLUSION: Fenofibrate treatment resulted in a lower triglyceride excursion following a high-fat meal. This investigation provides new knowledge of the magnitude and time course of fenofibrate induced attenuation of Lipoprotein subclass size distribution following a postprandial lipid challenge.

Risk factors for kidney stones in older women in the southern United States.

BACKGROUND: The occurrence of kidney stones is disproportionate in the southern region of the United States. Risk factors for the occurrence of kidney stones in this geographic area have not been reported previously. METHODS: The Women's Health Initiative (WHI) is an ongoing multicenter clinical investigation of strategies for the prevention of common causes of morbidity and mortality among postmenopausal women. A case-control ancillary study was conducted on 27,410 (white or black) women enrolled in the 9 southern WHI clinical centers. There were 1,179 cases (4.3%) of kidney stones at the baseline evaluation. Risk factors for stone formation were assessed in cases versus age- and race-matched control subjects. RESULTS: Risk factors (univariate) included low dietary potassium (2,404 versus 2,500 mg/day, P = 0.006), magnesium (243 versus 253 mg/day, P = 0.003) and oxalate (330 versus 345 mg/day, P = 0.02) intake, as well as increased body mass index (28.5 versus 27.7 kg/m2, P = 0.001) and a history of hypertension (42% versus 34%, P = 0.001). A slightly lower dietary calcium intake (683 versus 711 mg/day, P = 0.04) was noted in case subjects versus control subjects, but interpretation was confounded by the study of prevalent rather than incident cases. Supplemental calcium intake >500 mg/day was inversely associated with stone occurrence. CONCLUSION: Multivariate risk factors for the occurrence of kidney stones in postmenopausal women include a history of hypertension, a low dietary intake of magnesium, and low use of calcium supplements.

Aortic root dilatation at sinuses of valsalva and aortic regurgitation in hypertensive and normotensive subjects: The Hypertension Genetic Epidemiology Network Study .

The association of sinuses of Valsalva dilatation and aortic regurgitation with hypertension is disputed, and few data are available in population-based samples. We explored the relations of sinuses of Valsalva dilatation and aortic regurgitation to hypertension and additional clinical and echocardiographic data in 2096 hypertensive and 361 normotensive participants in the Hypertension Genetic Epidemiology Network study. Age and body surface area were used to predict aortic root diameter using published equations developed from a separated reference population. Aortic dilatation was defined as measured sinuses of Valsalva diameter exceeding the 97.5th percentile of the confidence interval of predicted diameter for age and body size. Aortic dilatation was present in 4.6% of the population. After adjustment for age and body surface area, mean aortic root diameter was larger in hypertensives with suboptimal blood pressure control than normotensives or hypertensives with optimal blood pressure control. In multivariate models, sinuses of Valsalva diameter was weakly positively related to diastolic blood pressure and to left ventricular mass independent of aortic regurgitation. Subjects with aortic dilatation were slightly older, were more frequently men, had higher left ventricular mass, and had lower left ventricular systolic chamber function independent of covariates. Sinuses of Valsalva dilatation was independently related to male gender, aortic valve fibrocalcification, and echocardiographic wall motion abnormalities but not to diastolic blood pressure (or history of hypertension in a separate model). The likelihood of aortic regurgitation increased with larger aortic root diameter, older age, female gender, presence of aortic valve fibrocalcification, and lower body mass index but not hypertension or diabetes. In a subsequent model, diastolic blood pressure was negatively related to aortic regurgitation independent of covariates. In a large population-based sample, sinuses of Valsalva diameter was only mildly larger in subjects with suboptimally controlled hypertension than in normotensives or well-controlled hypertensives, which did not result in differences in prevalence of aortic regurgitation among groups. Sinuses of Valsalva dilatation was associated with higher left ventricular mass and lower systolic function, which may contribute to higher cardiovascular risk in subjects with aortic root dilatation.

Autonomic and neurohumoral control of postprandial blood pressure in healthy aging.

BACKGROUND: Postprandial hypotension (PPH) is a common and morbid problem in elderly people that is associated with an impaired vascular response to meal digestion. Healthy aging in the absence of blood pressure elevation is associated with autonomic and neurohumoral changes that may influence the vascular response to meal ingestion. However, it is not known whether these age-related changes are associated with the development of PPH. METHODS: We measured hemodynamic (blood pressure, heart rate, and forearm vascular resistance), autonomic (power spectral analysis of heart rate and blood pressure variability), and neurohumoral (plasma norepinephrine, renin, aldosterone, and endothelin) responses to a mixed 425 kilocalorie (kcal) meal in 89 rigorously screened healthy subjects aged 20-39, 40-59, and 60-83 years. RESULTS: After the meal, supine mean arterial blood pressure fell significantly only in the middle-aged group by 5.4 +/- 7.9 mm Hg at 30 minutes (p = .02). Forearm vascular resistance fell after the meal in all age groups ( p = .0001). Older groups had higher plasma norepinephrine (p = .02), lower heart rate (p = .03), lower cardiovagal activity (p = .0001), and lower sympathetic vasomotor (p = .000) activity, but there was no difference in the response of these variables to a meal. CONCLUSION: Healthy aging, in the absence of blood pressure elevation, alters the level of autonomic activity without further impairing the ability to maintain blood pressure during meal digestion. Hemodynamic, autonomic, and neurohumoral responses to meal ingestion remain unchanged in very healthy, normotensive elderly adults.

Association between the alpha-adducin gene and hypertension in the HyperGEN Study.

This report from the HyperGEN Study, one of four networks participating in the NHLBI-sponsored Family Blood Pressure Program, presents the results of an association study based on 822 white and 572 black subjects (cases and controls) participating in the HyperGEN Network from five geographically diverse field centers. All cases met the Joint National Committee on Detection and Treatment of High Blood Pressure (JNC VI) criteria for hypertension (Stage I or higher). Each subject was clinically examined for risk factors for hypertension as well as genotyped for the point mutation Gly460Trp at the alpha-adducin locus on chromosome 4p. In the white group, the prevalence of genotypes with one or more Trp alleles was 26% in normotensives, versus 33% in hypertensives randomly selected from the population, and 39% among the multiply affected hypertensive sibships. Overall, in whites, the Trp allele significantly increased the odds of hypertension (P = .0056), with an odds ratio (OR) of 1.73 (95% confidence interval [CI] = 1.17, 2.54). The alpha-adducin gene remained a significant independent predictor of hypertension in a multivariate logistic model even after correcting for other risk factors for hypertension, including gender, age, body mass index (BMI), smoking, LDL cholesterol, triglycerides, urine sodium (Na), and urine potassium (K), (OR = 1.55, 95% CI = 1.03, 2.34). Through the use of regression trees, several gene-by-environment interactions were implicated, suggesting that alpha-adducin appears to be a particularly important risk factor (OR = 4.2) for older (age > 60.5 years), less lean (BMI < 25.8 kg/m2) subjects with moderately high triglycerides (between 145.5 and 218.5 mg/dL). In the black group, the relationship was less clear. Overall, it was protective against hypertension. The prevalence of genotypes with one or more Trp alleles was 24% among normotensive versus 11% in hypertensive black subjects randomly selected from the population, and 13% among multiply affected hypertensive sibships, resulting in an OR of 0.48 (P = .0231; 95% CI = 0.25, 0.90). However, the Trp genotype was no longer a significant independent predictor of hypertension risk in the multivariate logistic model (OR = 0.79; 95% CI = 0.37, 1.67), suggesting that it may be operating through one or more of these other factors. Thus, we conclude that the alpha-adducin gene is a significant, independent risk factor for hypertension in whites, but not in blacks, and may play a particularly important role for subjects with certain constellations of other risk factors.

Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

The objectives of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial are to determine in screenees ages 55-74 at entry whether screening with flexible sigmoidoscopy (60-cm sigmoidoscope) can reduce mortality from colorectal cancer, whether screening with chest X-ray can reduce mortality from lung cancer, whether screening men with digital rectal examination (DRE) plus serum prostate-specific antigen (PSA) can reduce mortality from prostate cancer, and whether screening women with CA125 and transvaginal ultrasound (TVU) can reduce mortality from ovarian cancer. Secondary objectives are to assess screening variables other than mortality for each of the interventions including sensitivity, specificity, and positive predictive value; to assess incidence, stage, and survival of cancer cases; and to investigate biologic and/or prognostic characterizations of tumor tissue and biochemical products as intermediate endpoints. The design is a multicenter, two-armed, randomized trial with 37,000 females and 37,000 males in each of the two arms. In the intervention arm, the PSA and CA125 tests are performed at entry, then annually for 5 years. The DRE, TVU, and chest X-ray exams are performed at entry and then annually for 3 years. Sigmoidoscopy is performed at entry and then at the 5-year point. Participants in the control arm follow their usual medical care practices. Participants will be followed for at least 13 years from randomization to ascertain all cancers of the prostate, lung, colorectum, and ovary, as well as deaths from all causes. A pilot phase was undertaken to assess the randomization, screening, and data collection procedures of the trial and to estimate design parameters such as compliance and contamination levels. This paper describes eligibility, consent, and other design features of the trial, randomization and screening procedures, and an outline of the follow-up procedures. Sample-size calculations are reported, and a data analysis plan is presented.

Heart rate and subsequent blood pressure in young adults: the CARDIA study.

The objective of the present study was to examine the hypothesis that baseline heart rate (HR) predicts subsequent blood pressure (BP) independently of baseline BP. In the multicenter longitudinal Coronary Artery Risk Development in Young Adults study of black and white men and women initially aged 18 to 30 years, we studied 4762 participants who were not current users of antihypertensive drugs and had no history of heart problems at the baseline examination (1985-1986). In each race-sex subgroup, we estimated the effect of baseline HR on BP 2, 5, 7, and 10 years later by use of repeated measures regression analysis, adjusting for baseline BP, age, education, body fatness, physical fitness, fasting insulin, parental hypertension, cigarette smoking, alcohol consumption, oral contraceptive use, and change of body mass index from baseline. The association between baseline HR and subsequent systolic BP (SBP) was explained by multivariable adjustment. However, HR was an independent predictor of subsequent diastolic BP (DBP) regardless of initial BP and other confounders in white men, white women, and black men (0.7 mm Hg increase per 10 bpm). We incorporated the part of the association that was already present at baseline by not adjusting for baseline DBP: the mean increase in subsequent DBP was 1.3 mm Hg per 10 bpm in white men, white women, and black men. A high HR may be considered a risk factor for subsequent high DBP in young persons.

Associations of race/ethnicity, education, and dietary intervention with the validity and reliability of a food frequency questionnaire: the Women's Health Trial Feasibility Study in Minority Populations.

This report describes the associations of race/ethnicity and years of education with the validity, reliability, and bias of a self-administered food frequency questionnaire (FFQ) designed to be sensitive to low-fat, regional, and ethnic dietary patterns. Data were from the Women's Health Trial Feasibility Study in Minority Populations, a randomized clinical trial conducted between 1992 and 1994 to test the feasibility of a low-fat dietary intervention that targeted low-income, black, and Hispanic women. Of 1,015 participants eligible for these analyses, 28.1% were black, 16.2% were Hispanic, and 12.3% had not completed high school. The analyses focused on percentage of energy obtained from fat, and used 4-day food records as the criterion instrument. Validity at baseline, defined as the correlation between FFQs and food records, was lower among blacks than among whites (0.26 vs. 0.49; p < 0.001), did not differ between Hispanics and whites, and was lower among women with fewer years of education (0.19, 0.35, 0.49, and 0.42 for <12, 12, 13-15, and > or =16 years of education, respectively; for trend, p < 0.05). Six months after randomization, validity increased in most race/ethnicity and education subgroups, and differences across groups became small and statistically nonsignificant. Validity increased significantly among participants receiving the dietary intervention, while increases among control women were somewhat smaller. Reliability, defined as the correlation between baseline and 6-month measures among controls, was similar across racial/ethnic and educational groups. Bias at baseline, defined as the mean value from the FFQ minus the mean from the food record, was 4.6 percentage points of energy from fat; it was lowest among blacks (p < 0.01) and did not differ by years of education. These results suggest that special protocols which address participant training may be necessary when using self-administered FFQs in minority or poorly educated populations.

Regional disparities in the incidence of elevated blood pressure among young adults: the CARDIA study.

BACKGROUND: Within the United States, little is known about regional disparities in blood pressure (BP), their changes over time, or explanations for their existence. METHODS AND RESULTS: A population-based cohort of 5115 black and white men and women, 18 to 30 years old in 1985-1986 (balanced on age, race, sex, and education), was followed up for 7 years in four centers: Birmingham, Ala; Chicago, Ill; Minneapolis, Minn; and Oakland, Calif. Differences in elevated BP (EBP) prevalence among centers at years 0, 2, 5, and 7 and in 7-year incidence of EBP were assessed. Sociodemographic and dietary variables, physical activity, weight, smoking, and alcohol were considered. At year 0, no regional differences were seen. Seven years later, there was marked variability in prevalence of EBP overall and for both black and white men, from a low in Chicago (9% for black men and 5% for white men) to a high in Birmingham (25% for black men and 14% for white men). Birmingham also had the highest 7-year incidence (11%) and overall prevalence at year 7 (14%). The adjusted odds ratios, with Birmingham as referent (95% CIs), for 7-year incidence of EBP overall were 0.38 (0.24, 0.60) for Chicago, 0.37 (0.24, 0.57) for Minneapolis, and 0.74 (0.52, 1.07) for Oakland. CONCLUSIONS: Regional disparities are absent at baseline but become apparent as the cohort ages. These differences are not fully explained by the available behavioral and sociodemographic characteristics.

Design of a multicenter trial to evaluate long-term life-style intervention in adults with high-normal blood pressure levels. Trials of Hypertension Prevention (phase II). Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

Phase II of the Trials of Hypertension Prevention (TOHP) is a multicenter, randomized trial sponsored by the National Heart, Lung, and Blood Institute designed to test whether weight loss alone, sodium reduction alone, or the combination of weight loss and sodium reduction will decrease diastolic (DBP) and systolic blood pressure (SBP) as well as the incidence of hypertension (DBP > or = 90 mm Hg, SBP > or = 140 mm Hg, and/or use of antihypertensive medications) in subjects with high-normal DBP (83 to 89 mm Hg) and SBP less than 140 mm Hg at entry. These interventions were chosen for longer-term testing with end points including hypertension prevention as well as blood pressure (BP) change based on their demonstrated short-term efficacy in reducing BP in phase I of TOHP. The phase II study population is comprised of 2382 participants (1566 men and 816 women) who are 110 to 165% of desirable body weight, allocated at random to the four treatment arms using a 2 x 2 factorial design. The trial has 80% power to detect an overall treatment effect on DBP of 1.2 mm Hg for weight loss or sodium reduction and a difference of 1.6 mm Hg between the combined intervention and placebo groups. BP observers are blinded to participant treatment assignments. Participants will be followed for 3 to 4 years. This trial may have important public policy implications concerning the ability of life-style modifications to reduce BP and prevent the development of hypertension over the long term, thereby avoiding the need for drug therapy which while effective is costly and may have side effects.

Recurrent nephrotic syndrome associated with Kimura's disease in a young non-Oriental male.

Kimura's disease (KD) is an angiolymphoid proliferative disorder of soft tissue with eosinophilia, with a predilection for head and neck regions in young Oriental men. Renal disease is rarely associated with it. We describe a young non-Oriental male with KD and relapsing steroid-responsive minimal-change nephrotic syndrome. This case of KD associated nephrotic syndrome is unique in the relapsing nature of the nephropathy and the non-Oriental origin of the patient. We comment on KD and nephrotic syndrome and on treatment strategy.

Physical activity in young black and white women. The CARDIA Study.

Total physical activity scores, based on level of participation in 13 types of activities for 2658 black and white women aged 18 to 30 years were examined in relation to demographic, health behavior, psychosocial, and obesity data to compare levels of physical activity and determine reasons for disparities between blacks and whites. Black women had lower scores than white women--geometric mean of 178 (95% confidence interval (CI): 167, 189) versus 318 (95% CI: 305, 332). After controlling for age and education, physical activity was associated with physical activity level before high school, life events score, John Henryism, and competitiveness in both groups. In white women only, it was associated with alcohol intake and need to excel, and negatively associated with number of children, number of cigarettes smoked, and fatness. Race remained a predictor of physical activity after controlling for each variable. Relationships between physical activity and age, education, cigarette smoking, and life events differed significantly by race. Black women had lower physical activity levels than white women, which may contribute to higher rates of obesity and coronary heart disease. Racial differences in physical activity remain largely unexplained by the factors examined.

Cigarette smoking and submaximal exercise test duration in a biracial population of young adults: the CARDIA study.

Symptom-limited, graded exercise treadmill testing was performed by 4,968 white and black adults, ages 18-30 yr, during the baseline examination for the Coronary Artery Risk Development in Young Adults (CARDIA) study. Compared with nonsmokers, the mean exercise test duration of smokers was 29-64 s shorter depending on race/gender group (all P < 0.001), but mean duration to heart rate 130 (beats.min-1) ranged from 20-50 s longer (P < 0.05). In each race/gender group, test duration to heart rates up to 150 was 15-35 s longer (P < 0.05) in smokers than in nonsmokers after adjustment for age, sum of skinfolds, hemoglobin, and physical activity score. The mean maximum heart rate was lower in smokers than in nonsmokers (difference ranging from 6.7 beats.min-1 in white men to 11.2 beats.min-1 lower in black women, P < 0.001), although maximum rating of perceived exertion was nearly identical in smokers and nonsmokers. Chronic smoking appears to blunt the heart rate response to exercise, so that exercise duration to submaximal heart rates is increased even though maximal performance is impaired. This may result from downloading of beta-receptors caused by smoking. Smoking status should be considered in the evaluation of physical fitness data utilizing submaximal test protocols, or else the fitness of smokers relative to nonsmokers is likely to be overestimated.

Bilateral testicular adrenal rests in a patient with 11-hydroxylase deficient congenital adrenal hyperplasia.

A 13-year-old boy was referred for investigation of hypertension, precocious puberty and giant testicles. Hormonal studies established the diagnosis of congenital adrenal hyperplasia due to 11-hydroxylase deficiency. Testicular biopsy revealed that the scrotal masses were adrenal rest tumors entirely composed of adrenocortical tissue. Primary testicular tissue was absent. The size of the tumors regressed following replacement steroid therapy together with restoration of normal blood pressure. This observation of a testicular adrenal rest tumor in a patient with 11-hydroxylase deficient congenital adrenal hyperplasia is unique.

Effect of antihypertensive therapy on weight loss. The Trial of Antihypertensive Interventions and Management Research Group.

We report the effect of weight changes of the type of antihypertensive medication prescribed in a trial of the relative efficacy of drug and dietary measures in mild hypertension. The Trial of Antihypertensive Interventions and Management studied 878 mildly hypertensive individuals randomly assigned, in a 3 x 3 design, to no diet change, weight loss, or a low sodium-high potassium diet and to placebo, 25 mg chlorthalidone, or 50 mg atenolol. The type of drug prescribed affected weight change with all diets. The drug effect on weight change, present in all groups at 6 months, was most pronounced in those randomly assigned to the weight loss diet, where the placebo group lost 4.4 kg, the atenolol group lost 3.0 kg, and the chlorthalidone group lost 6.9 kg. The group differences were attenuated but persisted at 24 months. We suggest that the antihypertensive drug prescribed affects the success of a conjoint weight loss program and speculate that the difference between the drugs may be due to their intrinsic effects on the sympathetic nervous system and related metabolic changes.

Symptom-limited graded treadmill exercise testing in young adults in the CARDIA study.

Symptom-limited, graded exercise treadmill testing was performed by 4,968 white and black adults, ages 18-30 yr, during the baseline examination for the CARDIA study. The mean estimated maximal exercise capacity by race/gender, expressed as metabolic units (METS), was: white men 13.8, black men 13.0, white women 11.1, and black women 9.4. Exercise test duration was higher in nonsmokers, positively related to physical activity score and pulmonary function (FEV1.ht-2), and inversely related to body mass index. Men had higher mean values than women for both test duration and a measure of submaximal performance, the workload 130 (WL130, the exercise test duration to a heart rate of 130 beats.min-1). Adjusted for age and education, white men had a longer mean test duration than black men (53 s longer, P less than 0.001), but nearly equal mean WL130. White women had higher mean values than black women for both test duration (114 s longer, P less than 0.001) and WL130 (36 s longer, P less than 0.001). Men had higher mean values than women for both outcome measures (P less than 0.001). Thus, in young adults significant gender and ethnic differences exist for exercise test performance, part of which can be explained by personal habits or traits.

Ten-year follow-up of quality of life in patients randomized to receive medical therapy or coronary artery bypass graft surgery. The Coronary Artery Surgery Study (CASS)

Quality of life indexes were assessed in 780 patients 10 years after randomization to medical therapy (n = 390) or coronary artery bypass graft surgery (n = 390) in the Coronary Artery Surgery Study. At 10 years, mortality was 21.8% in the medical group and 19.2% in the surgical group (p = NS), and 144 (37%) of the medical group had undergone surgery because of increasing chest pain. At study entry, 22% of medical and surgical patients were angina free; at 1 and 5 years after entry, the frequency of asymptomatic patients was 66% and 63% in the surgical group and 30% and 38% in the medical group. However, by 10 years after entry, the proportion of patients free of angina had fallen to 47% in the surgical group and to 42% in the medical group. Activity limitation and use of beta-blockers and long-acting nitrates were less in the surgical than the medical group at 1 and 5 years after entry but little different from the medical group at 10 years after entry. Throughout follow-up, recreational status, employment status, frequency of heart failure, use of other medications, and hospitalization frequency were similar between the two groups. Thus, indexes of quality of life such as angina relief, increased activity, and reduction in use of antianginal medications initially appear superior in patients with stable manifestations of ischemic heart disease assigned to surgery, but by 10 years after entry, these advantages are much less apparent. Although the observed similarities of the medically and surgically assigned groups at 10 years reflect return of symptoms in the surgical group to some extent, a more important explanation is the performance of late surgery in a large proportion of the medically assigned patients, rendering them asymptomatic.