Wilfrid J. Dixon

A Controlled Clinical Trial of a Diet High in Unsaturated Fat in Preventing Complications of Atherosclerosis

This report describes a clinical trial, with domiciled male veterans, designed to determine whether a diet which lowers serum cholesterol concentration can prevent overt complications of coronary heart disease and other manifestations of atherosclerosis. Volunteers were allocated randomly to control and experimental groups. Participants numbered 422 in the control group and 424 in the experimental group. The two groups were indistinguishable at the outset of the study in almost all observations. These included age, racial characteristics, and religious affiliation; height, weight, and blood pressure; electrocardiographic findings; prevalence of pre-existing anginal syndrome, myocardial infarction, peripheral atherosclerosis, cerebral ischemia, or cerebral infarction; cardiac decompensation; utilization of relevant medications; serum cholesterol and serum total lipid levels; and prevalence of corneal arcus and xanthelasma. One significant difference between the groups in regard to a possibly influential characteristic was that they differed slightly in patterns of cigarette smoking habits. The control diet was similar to the regular institutional diet, which is a standard American diet. It provided, by analysis, 40.1% of calories as fat, having a mean iodine value of 53.5; cholesterol intake was 262 mg/1,000 calories (653 mg/day). The experimental diet provided 38.9% of calories as fat, with an iodine value of 102.4, and had a cholesterol content of 146 mg/1,000 calories (365 mg/day). Linoleic acid content of the two diets was 10% and 38% of total fatty acid, respectively. The experimental diet was prepared to simulate conventional food. Over-all adherence expressed as percentage of total possible meals taken, from introduction into the study to termination of the study, averaged 56% for the control subjects and 49% for the experimental group. The experimental diet induced a prompt drop in serum cholesterol level and sustained a difference between the experimental and control groups amounting to 12.7% of the starting level. It is estimated from published data that the change in saturation of dietary fat accounted for five-sixths of the diet-induced lowering of serum cholesterol in the experimental group, the remaining one-sixth having been due to decreased cholesterol intake. Mean linoleic acid concentration of adipose tissue was initially 10.9%. During the latter part of the trial, which lasted eight years for some subjects, linoleic acid concentration in adipose tissue approached an asymptotic level of 33.7% among good adherers. This variable was a good measure of adherence to the diet after five or more years (r=+0.71), but not earlier. Clinical follow-up was carried out on a double-blind basis. The number of men sustaining events in major categories, in the control and experimental groups, respectively, was: definite silent myocardial infarction, 4 and 9; definite overt myocardial infarction, 40 and 27; sudden death due to coronary heart disease, 27 and 18; definite cerebral infarction, 22 and 13. The difference in the primary end point of the study-sudden death or myocardial infarction -was not statistically significant. However, when these data were pooled with those for cerebral infarction and other secondary end points, the totals were 96 in the control group and 66 in the experimental group; P=0.01. Fatal atherosclerotic events numbered 70 in the control group and 48 in the experimental group; P<0.05. Life-table analysis in general confirmed these conclusions. For all primary and secondary end points combined, eight-year incidence rates were 47.7% and 31.3% for the control and experimental groups, respectively; P value for the difference between the two incidence curves was 0.02. Stratification of the data by age demonstrated that most of the prophylactic effect occurred in the younger half of the study population, less than 65.5 years old at the start of the study. Stratification by baseline serum cholesterol concentration revealed that most of the effect was encountered in men with starting levels above the median (233 mg/dl). Stratification on the basis of pre-existing atherosclerotic complications failed to yield consistent evidence that subjects without pre-existing complications responded differently to diet than did those with prior overt disease. Deaths due to nonatherosclerotic causes numbered 71 in the control group and 85 in the experimental group. Most of the difference occurred in the latter part of the study. Consideration of causes of death in this category suggested that this difference probably did not reflect a toxic effect of the experimental diet. Gross grading of the extent of atheromata in individuals who died and were autopsied failed to reveal significant differences between the two groups of subjects. The same was true of arterial total lipid and calcium concentrations. Relative abundance of major lipid fractions in coronary atheromata and circle of Willis appeared to be independent of diet. In general, most of the varieties of lesions just cited revealed increased concentrations of linoleic acid in triglyceride, cholesterol ester, and phosphatide among the experimental subjects. In individuals on the experimental diet who died after prolonged experience in the study and high adherence to the diet, arachidonic acid concentration in atheroma phosphatide was significantly depressed. A similar but less consistent decrease was observed in arachidonic acid in cholesterol ester and free fatty acid of atheromata. Observations of other investigators suggest that these changes were due to the effects of high &agr;-tocopherol intake on the experimental diet.

Constitutional symptoms and health-related quality of life in patients with symptomatic HIV disease

PURPOSE To assess the severity of constitutional symptoms in persons with human immunodeficiency virus (HIV) infection, and their relationship to health-related quality of life (HRQOL). PATIENTS AND METHODS Two hundred five HIV-infected patients (93% male, 26% African American, 28% Latino, 39% white, 7% other ethnicity) with diarrhea, fever, or weight loss were studied at a county hospital and a Veterans Administration hospital in southern California. Consenting subjects were administered a battery that included 11 scales measuring various aspects of health-related quality of life and detailed questions about six constitutional symptoms or symptom complexes (myalgias, exhaustion, anorexia/nausea/vomiting, night sweats, fever, and weight loss) as well as about other manifestations of HIV disease. RESULTS Constitutional symptoms except weight loss were all strongly related to all measures of quality of life. On 0 (worst) to 100 (best) point scales, mean scores ranged from 34 (for individuals having all five symptoms other than weight loss) to 78 (for those with none) for physical function, 43 to 79 for emotional well-being, and 36 to 73 for social function. Adjustment for helper T-lymphocyte counts, duration of illness, and demographic characteristics did not diminish these associations. CONCLUSION The presence, number, and severity of constitutional symptoms in HIV disease is strongly related to health-related quality of life in symptomatic HIV-infected individuals. Identifying and treating these very common symptoms has the potential to improve quality of life in these patients.

Access to medical care and health-related quality of life for low-income persons with symptomatic human immunodeficiency virus.

Despite growing interest in the accessibility of medical care and health-related quality of life for persons infected with human immunodeficiency virus, an association between these variables has not been documented. The authors conducted a cross-sectional study of access to care and its association with health-related quality of life among 205 persons of low income infected with the human immunodeficiency virus with constitutional symptoms and/or diarrhea at one public and one Veterans Administration hospital, using a 9-item measure of perceived access and a 55-item health-related quality of life instrument. Problems with access were widespread: 55% traveled for longer than 30 minutes to their usual source of care (compared with 9% to 12% of general populations in national surveys), 49% had problems meeting costs of care, and 48% had problems with clinic hours (compared with 23% in national surveys). In multivariate analyses, uninsured patients reported worse access than patients with Medicaid or Veterans Administration insurance, particularly for meeting the cost of care (P < 0.01). Adjusted health-related quality of life scores in this sample were far lower (by about 1 SD) than those of subjects in a large national acquired immune deficiency syndrome clinical trial. For 8 of 11 health-related quality of life subscales, worse perceived access was significantly (P < 0.05) associated with poorer health-related quality of life, even after controlling for T-4 lymphocyte count, symptoms and other factors. Access and health-related quality of life measures similar to those used in this study may prove useful in future evaluations of medical care systems serving poor, clinically ill populations infected with human immunodeficiency virus.

Predicting individual responses to drug treatment in schizophrenia: a test dose model.

The literature and the findings from the Camarillo Schizophrenia Research Project reported in this paper indicate that a satisfactory method for predicting the response of an individual schizophrenic patient to antipsychotic drugs has yet to be devised. A test dose procedure is described which offers promise of a practical approach to selecting the most appropriate drug and dosage for a particular patient and tailoring blood concentrations to the needs of the individual case. Preliminary findings indicate that the test dose procedure is feasible; that detectable changes occur after a single test dose; and that measurements made during the test dose period may be predictive of eventual outcome. These findings are, of course, only a report of a preliminary pilot experiment, subject to important caveats about small number of cases, interpretation of large numbers of correlation coefficients, and need for cross-validation. Nevertheless, they are encouraging and suggest that the test dose approach has considerable potential for further research.

The Prospective Effect of Access to Medical Care on Health-Related Quality-of-Life Outcomes in Patients with Symptomatic HIV Disease

OBJECTIVES This study examined the prospective effect of reported access to medical care on health-related quality-of-life outcomes in patients with symptomatic human immunodeficiency virus (HIV) disease. METHODS A cohort study was designed with interviews at baseline, follow-up interviews at 3 months after baseline, mortality follow-up through 6 months after baseline, and medical record reviews for selected baseline clinical data. Participants were HIV-infected patients who were receiving ambulatory and/or hospital care at one county-run municipal and one Veterans Administration hospital in metropolitan Los Angeles and were interviewed about access to medical care (using a reliable 9-item scale assessing affordability, availability, and convenience of medical care). Access to care reported by this sample was compared with that of 2,471 patients with other chronic diseases from the Medical Outcomes Study. The main outcome measures were composite scores for physical and mental health-related quality of life 3 months after baseline, derived from a validated 56-item instrument, scored from 0 to 100, and controlling for baseline health-related quality of life. RESULTS Overall reported access to medical care in this sample was significantly poorer than that for patients with other chronic diseases (means scores were 63 and 73, respectively). The sample was categorized into tertiles of initial physical and mental health-related quality of life and into groups with initial high versus low access to care. Among those in the middle tertile of physical health-related quality of life at baseline, those with high access improved in physical health scores by 10.2 points relative to those with low access. Those in the low and middle tertiles of initial mental health improved in mental health to a significantly greater extent for those with high versus low access. There were nonsignificant trends toward similar effects for most other subgroups. The effects of access on health-related quality-of-life outcomes were generally robust in multivariate regression analyses that included CD4, hemoglobin, albumin, insurance status, and sociodemographic characteristics. CONCLUSIONS Access to care at baseline predicted better physical and mental health outcomes at 3 months for those in the middle tertile of physical health and for those in the bottom and middle tertiles of mental health at baseline. Increasing access to care for poor public hospital patients with HIV infection may help to improve health-related quality-of-life outcomes among selected persons with advanced disease.

The Growth of the Normal Aorta and of the Anastomotic Site in Infants Following Surgical Resection of Coarctation of the Aorta

Observations were made on the growth of the anastomotic site 2 to 4 years after surgical resection of coaretation of the aorta in 5 infants who were less than 2 years of age at the time of surgery. Aortic measurements were made from biplane angiocardiograms. The physiologic adequacy of the anastomotic site was demonstrated by absence of a gradient in direct pressure measurements between the upper and lower extremities. Additional observations on the normal growth of the descending thoracic aorta were made from studies in 154 subjects with other forms of heart disease. They ranged in age from 2 days to 74 years.

Validation of a new measure of diarrhea

Adequate measures of diarrheal disease are important to assess severity for clinical use and outcomes research. We developed a questionnaire to assess diarrhea severity and complications, and administered it to 205 HIV positive patients with diarrhea, fever, or weight loss. Noteworthy variations in stool form were reported by individuals and across subjects. Self-reported diarrhea correlated with the occurrence of any stool picture without form. However, verbal descriptors “loose” and “semiformed” had little value in assessment of diarrheal disease. Both verbal and pictorial stool descriptors correlated well with diarrhea complications (pain, urgency, tenesmus, incontinence, and nocturnal diarrhea). By factor analysis, discomfort and nondiscomfort diarrhea complications loaded on different factors, consistent with clinical experience that discomfort is a distinct problem in diarrheal disease. In summary we have developed an instrument to precisely characterize diarrhea severity that correlates well with clinically important events such as incontinence and abdominal pain.

Assessment of psychiatric outcome—I. Cross section analysis ☆

Abstract Cross Section Analysis is a flexible method of depicting the outcome of a patients illness from chronological series data such as post-treatment measurements. Patient status is assessed by display of outcome in terms of ‘cross point values’ at fixed ‘cross points’ in time from a pre-determined origin. The method involved interpolates or extrapolates cross point values when observations are not available at cross point times, by utilizing information from the measurements actually obtained. The necessary procedures and computations are described with illustrations from case data. The cross section method has important practical and theoretical advantages.

Assessment of psychiatric outcome. II. Simple Simon analysis

Abstract Simple Simon analysis is a method of describing the outcome of a patients illness over time in simple terms that should be meaningful to the ordinary clinician and that give some insight into process trends occurring over the selected period. It can be used to compare individual patients or subsets of patients over a given period of time. The necessary procedures, computations and tabulations are described.

TIME SHARING AND INTERACTIVE STATISTICS

Publisher Summary The terminal oriented real time operating system (TORTOS) consists of a number of modifications and extensions to the standard IBM Operating System/360 with the MVT option. TORTOS provides scheduling, memory management—with roll-in/roll-out to drum—and time sharing for four basic job priority classes: (1) real-time, (2) terminal, (3) background, and (4) batch. The full facilities of OS/360 are available to all job classes, including terminal, and an interface is provided for conversational facilities. A few conversational utilities are included as a part of the basic package; among these are conversational program entry, syntax analysis, data manipulating routines, and a conversational access method for use in the development of interactive programs. The memory management routines allocate storage to new jobs and handle roll-in/roll-out to the drum. As a job must be allocated the same memory locations from initiation to termination, it is scheduled to be rolled-out to the drum at the end of its time-slice.