Reliability of medial temporal lobe volume measurements using reformatted 3D images.

The study assessed whether standardizing the angle of image display and controlling for head position in three planes affects the scan-rescan reliability of medial temporal lobe volume measures when very thin (1.5 mm) slices are used. Five volunteers were scanned two times on consecutive days. A three-dimensional MRI sequence acquired whole brain data in 1.4 mm thick coronal slices. The data were displayed as 1.5 mm thick images and were rated both in the originally acquired coronal plane, and after reformatting to correct for head tilt and display the brain in the coronal plane perpendicular to the long axis of the left anterior hippocampus. One rater measured five brain regions (temporal lobe, anterior and posterior hippocampus, amygdala, and temporal horn) on the left and right sides of the two non-reformatted and two reformatted scans to obtain inter-scan variance. Furthermore, most scans were remeasured, to obtain 'reread' variances. All data were log-transformed in order to produce comparable variability across brain regions of different sizes. For all the regions, except the temporal horn, the non-reformatted scans showed significantly larger scan-rescan variability than the reformatted scans. A typical standard deviation for a non-reformatted pair of scans was 0.10, corresponding to 26% error, while a typical value for a reformatted pair of scans was 0.04, corresponding to 10% error. For all the regions, the reread data (intra-rater reliability) gave similar results for both reformatted and non-reformatted images with similar standard deviations (typical value for reread standard deviation was 0.020, corresponding to 5% error). The data suggest that, even when very thin slices are acquired, volume measurement accuracy of gray matter structures in the temporal lobe is considerably improved by controlling for image orientation in three planes. For these structures, the sample size needed to detect a small (5%) within-subject volume change would be halved if reformatted images were used. Image contrast is an additional important factor since the reformatted T1 weighted images used in this study, which have suboptimal CSF/brain contrast, worsened measurement accuracy in the temporal horn.

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.

Member ratings of health care provided by 48 physician groups.

BACKGROUND: Satisfaction with health plan performance has been assessed frequently, but assessment of physician group performance is rare. OBJECTIVE: To present ratings of the care provided by physician groups to enrollees in a variety of capitated health maintenance organization plans. METHODS: A random sample was drawn of adult enrollees receiving managed health care from 48 physician groups in a group practice association. Each individual in the sample was mailed a 12-page questionnaire and 7093 were returned (59% response rate). The mean age of those returning the questionnaire was 51 years; 65% were women. RESULTS: Reliability estimates for 6 multi-item satisfaction scales were excellent, and noteworthy differences in ratings among groups were observed. In particular, ratings of overall quality ranged from a low of 28 to a high of 68 (mean, 50; SD, 10). Average scores for physician groups were strongly correlated across all scales, but no single group scored consistently highest or lowest on the different scales. Negative ratings of care were significantly related to the following: intention to switch to another physician group, difficulty in getting appointments, lengthy waiting periods in the reception area and examination room, the inability to get consistent care from one physician for routine visits, and not being informed by the office staff when there was a delay in seeing the primary care provider. CONCLUSIONS: Monitoring of health care quality at the physician group level is possible, and could be used for benchmarking, internal quality improvement, and for providing information to the public about how these physician groups will meet its needs.

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.

Staircase bioassay: the up-and-down method.

Experiments are conducted to estimate the threshold for an all-or-none response. Threshold is defined to be a point above which 50% of the subjects will respond and below which 50% of the subjects will not respond. Examples are death, death in a fixed time period, shock, fibrillation, emesis. Staircase designs, in particular up-and-down trials, produce median (ED50) estimates of given standard error with as few as one-fifth the number of subjects as the traditional designs with preset numbers of tests at each of several levels of stimulus. We discuss these estimates and their efficiency as well as procedures to estimate standard deviation and its use in designing up-and-down trails. The advantages in using several short series in factorial experiments are presented. Suggestions are given for minimizing the complications of sequential designs. Case studies indicate the efficiency of the design for various applications.

Robustness in real life: a study of clinical laboratory data.

Previous studies have evaluated the performance of robust estimators of location using computer-generated distributions. This paper describes how distributions commonly seen in biomedical research differ from the simulated distributions, and compares the performance of six families of estimators using samples from four biomedical distributions. The biomedical distributions can be asymmetric, and have shorter tails and other anomalies, such as digit preferences, which are not modeled in simulation studies. The four biomedical distributions studied differ markedly from the models previously studied, and these differences strongly affect the robust estimators. In such situations the trimmed mean provides an improvement over the sample mean, and its performance is more stable than that of estimators whose psi functions have steeply-descending tails. The central value and dispersion of each of the estimators are evaluated.

Schizophrenia. A follow-up study of the results of five forms of treatment.

Two hundred twenty-eight first-admission schizophrenic patients were randomly assigned to the following five treatments: psychotherapy alone, drug alone, psychotherapy plus drug, electroconvulsive therapy (ECT, and milieu. A there- to five-year follow-up examined their course after release from the hospital. The drug alone and ECT groups tended to have the best outcome and the psychotherapy alone group the worst. The positive effect from prior drug treatment began to dissipate after three years postadmission. For the in-hospital treatment successes, the advantage from drug treatment and the disadvantage from psychotherapy were less apparent. Overall, the follow-up outcome is far from reassuring, whatever the type of treatment. Even though a few patients may do well, much remains to be done in and out of the hospital.

Chlorpromazine levels and the outcome of treatment in schizophrenic patients.

Plasma and saliva levels of chlorpromazine hydrochloride were measured by gas chromatography-mass spectrometry, after a standard dosage had been administered to 48 newly admitted schizophrenic patients over 28 days. Other treatments were rigorously controlled. Saliva chlorpromazine concentrations were higher than plasma concentrations generally by about four to 50 times. Saliva and plasma chlorpromazine levels were significantly related. There was great variability in individuals between plasma and saliva peaks and values over time, in plasma/saliva ratios, and in change in plasma/saliva ratio over time. Chlorpromazine plasma and saliva levels at the end of fixed, sustained dosage treatment did not correlate with the amount of improvement as measured by ten criteria from the Brief Psychiatric Rating Scale and the Mobility, Affects Cooperation, and Communication Scale. Yet levels obtained in the 24 hours after the first dose did seen related to outcome, more strongly for saliva chlorpromazine than for plasma chlorpromazine levels. A reexamination is in order of our concepts of the relationships between levels of antipsychotic drugs in the body and treatment effect.

Peripheral neuropathy in arsenic smelter workers.

We conducted a double-blind controlled study of individuals exposed to arsenic trioxide in a copper-smelting factory. Subjects fell into three categories of peripheral neuropathy: none, subclinical, and clinical. The subclinical group had no symptoms or signs of numbness or reduced reflexes, but did have reduced nerve conduction velocity and amplitude measurements. Clinical neuropathy groups had signs and symptoms of neuropathy and electrophysiologic abnormalities. The clinical and subclinical groups correlated with increased content of arsenic in urine, hair and nails. The incidence of subclinical and clinical neuropathy was greater in arsenic workers than in unexposed controls.

Vestibular hyporeactivity in infants at risk for schizophrenia. Association with critical developmental disorders.

Vestibular responses to caloric stimulation were measured from birth to age 2 years in ten infants born to schizophrenic mothers. This is part of a study of evolving neurointegrative disorders that may be associated with a genetic risk for schizophrenia. Transiently decreased vestibular responses coincided with several developmental disorders that were related to psychopathology at 10 years. Absent to decreased responses were associated with (1) a "pandevelopmental retardation" involving physical growth as well as postural-motor and visual-motor development, (2) an "abnormally quiet" state in the first month, and (3) failures of bimanual integration between 4 and 6 months. The transitory nature of the decreased nystagmus rules out the possibility of an organic lesion of the vestibular system. Rather, it suggests that some covert decrease in arousal accompanied those periods when central nervous system integration was disrupted.

Mitoses in normal and psoriatic epidermis.

The morning count of mitoses in uninvolved epidermis of psoriatics is not significantly different from normal skin. The afternoon count is higher than the morning in both, and significantly higher in uninvolved than in normal epidermis. These results may be interpreted as favouring the existence of a non-cycling G2 population in human epidermis. This G2 population could be released into mitosis by the factors involved in diurnal variation, and might be larger and more labile in psoriatics than in normals. The pathogenesis and aetiology of psoriasis may be related to such a G2 population.

Movement of labelled decamethonium in muscle fibres of the rat.

1. Tritium-labelled decamethonium accumulated in diaphragm muscles of the rat in vitro with a peak at the end-plate region and the distributions were fitted by Gaussian curves. 2. Prolonged wash in physiological saline (10 hr) produced some loss in radioactivity but no detectable spread of the labelled compound along the fibres, which indicated that the decamethonium was not in a mobile form. 3. Rats injected with labelled decamethonium showed radioactivity in the diaphragm muscles after 21 days. 4. A slow spread of the labelled compound along the fibres was detected, and from the widening of the Gaussian curves the apparent diffusion coefficient was 1.2 X 10(-8) cm2sec-1, which is less than 1/500 of that in free solution.

For better or for worse? Outcome variance with psychotherapy and other treatments for schizophrenia.

It has been suggested that psychotherapy makes some persons better and some worse, and that this might account for the findings of some studies that there was no significant difference between the mean improvement scores of psychotherapy and control groups. The results of a controlled study indicate, however, that psychotherapy alone did not significantly increase outcome variance in schizophrenia by comparison to a control group. In fact, there was a nonsignificant tendency to decreased variability. Ataraxic drugs alone, psychotherapy plus ataraxic drugs, and ECT had significant variance-reducing effects. There is no convincing evidence, either in the literature or from the findings of this study, that a greater outcome variability results from psychotherapy than that resulting from hospitalization and nursing care (control). Our findings support the view that by comparison with a control group, a treatment for schizophrenia reduces outcome variance in proportion to its efficacy on the particular criterion under study.

Schizophrenia--a follow-up study of results of treatment. I. Design and other problems.

This is the first of a series of articles on a follow-up study of the results of treatment of schizophrenia, studied over a period of two to five years after first admission and first release. The study compares the follow-up outcome of five different treatment methods given to first-admission male and female schizophrenic patients in the hospital. The design of the study is used as a basis for description and discussion of the practical, ethical, and statistical problems involved. A distinction is made between follow-up and continued treatment design, and it is concluded that both pose massive problems in execution, analysis, presentation, and interpretation.