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L Freedman

Publications and source records attributed to L Freedman.

At least 37 records · Page 2Linked to original sources
PubMed1997

Design aspects of calibration studies in nutrition, with analysis of missing data in linear measurement error models.

Motivated by an example in nutritional epidemiology, we investigate some design and analysis aspects of linear measurement error models with missing surrogate data. The specific problem investigated consists of an initial large sample in which the response (a food frequency questionnaire, FFQ) is observed and then a smaller calibration study in which replicates of the error prone predictor are observed (food records or recalls, FR). The difference between our analysis and most of the measurement error model literature is that, in our study, the selection into the calibration study can depend on the value of the response. Rationale for this type of design is given. Two major problems are investigated. In the design of a calibration study, one has the option of larger sample sizes and fewer replicates or smaller sample sizes and more replicates. Somewhat surprisingly, neither strategy is uniformly preferable in cases of practical interest. The answers depend on the instrument used (recalls or records) and the parameters of interest. The second problem investigated is one of analysis. In the usual linear model with no missing data, method of moments estimates and normal-theory maximum likelihood estimates are approximately equivalent, with the former method in most use because it can be calculated easily and explicitly. Both estimates are valid without any distributional assumptions. In contrast, in the missing data problem under consideration, only the moments estimate is distribution-free, but the maximum likelihood estimate has at least 50% greater precision in practical situations when normality obtains. Implications for the design of nutritional calibration studies are discussed.

Aged↗
PubMed1996

Approached to monitoring the results of long-term disease prevention trials: examples from the Women's Health Initiative.

We contrast monitoring therapeutic trials with monitoring prevention trails. We argue that in monitoring prevention trials one should place more emphasis on formally defined global measures of health, not simply on a single targeted disease, particularly when an intervention may reduce the incidence of some diseases but increase the incidence of others. We describe one approach, illustrated by the Women's Health Initiative. For each of several sets of hypothetical interim results ("scenarios"), members of the Data and Safety Monitoring Committee (DSMC) were asked whether they would continue or stop the trial. In parallel with this exercise, various statistical methods of monitoring that are based on (1) the primary targeted disease, (2) a combination of various disease outcomes, or (3) a mixture of both were applied to these scenarios. One objective was to find a statistical approach that mirrors the majority view of the DSMC. A second objective was to stimulate discussion among DSMC members in preparation for their task of monitoring the trial as the real data become available. We found that no single method fully matched the majority vote of the DSMC. However, a mixed approach requiring the primary outcome to be significant and the global index to be "supportive," with separate monitoring of adverse effects, corresponded with the majority vote quite well. This approach maintains the emphasis on the primary hypothesis while assuring that broader safety and ethical issues of multiple diseases are incorporated.

Bayes Theorem↗
PubMed1996

Remacemide hydrochloride and ARL 15896AR lack abuse potential: additional differences from other uncompetitive NMDA antagonists.

This study was designed to determine the possible abuse liability and phencyclidine-like effects of the low-affinity uncompetitive N-methyl-D-aspartate (NMDA) antagonists remacemide hydrochloride [(+/-)-2-amino-N-(1-methyl-1,2-diphenylethyl)-acetamine hydrochloride] and ARL 15896AR [(+)-alpha-phenyl-2-pyridine-ethanamine dihydrochloride]. For the abuse-liability studies, in rats trained to self-administer cocaine intravenously (0.1 mg/kg/injection), doses of remacemide HCl, ARL 15896AR, phencyclidine, and saline were made available, and the number of injections self-administered was recorded. In different sets of rats, we assessed the ability of these drugs to induce phencyclidine-like stereotyped behavior. Doses of the compounds were expressed as multiples of the 50% effective dose (ED50), as determined from the maximal electroshock (MES) test by using either oral or intravenous administration. None of the remacemide hydrochloride or ARL 15896AR doses was self-administered at a level higher than that of the saline vehicle, unlike cocaine and phencyclidine, which were self-administered at high and moderate levels, respectively. Unlike that with remacemide hydrochloride and ARL 15896AR, oral administration of the high-affinity uncompetitive NMDA receptor-antagonists phencyclidine, ARL 16247 [N-(3-ethylphenyl)-N-methyl-N'-naphthylguanidine] and MK-801 engendered phencyclidine-like stereotypy at doses near their MES ED50 values. These data confirm the unusual safety of remacemide hydrochloride and ARL 15896AR and demonstrate that they do not possess reinforcing properties. As such, they are unlikely to present a drug-abuse problem in human beings.

Acetamides↗
PubMed1995

High dose rate endobronchial brachytherapy in the management of primary and recurrent bronchogenic malignancies.

BACKGROUND: The clinical, radiographic, and bronchoscopic records of patients treated with out-patient high dose rate (HDR) endobronchial brachytherapy were reviewed to determine its effectiveness in patients with malignant airway obstruction (with or without prior external beam radiation). In addition, quality of life and acute and chronic morbidity were evaluated. METHODS: From January 1, 1989 to June 30, 1993, 46 patients received 128 HDR endobronchial treatments employing a high activity Ir-192 source with a remote afterloader. Patients treated had a total of 22 primary and 17 recurrent bronchogenic carcinomas, 7 of which were metastatic nonpulmonary tumors. Three separate fractions of 7.0 Gy were prescribed to a depth of 1.0 cm. and given 1 week apart. Twelve patients (30%) received prior external beam irradiation (median dose, 58 Gy). RESULTS: Median follow-up for the entire group was 5 months (17.5 for surviving patients). Of the eight asymptomatic patients, five (62%) remained asymptomatic for the remainder of their lives. Of the 38 symptomatic patients, 28 (74%) had significant clinical improvement, and 12 of them remained improved for the duration of their lives. Of thirty-six (78%) patients examined for radiographic response, 25 (69%) had a partial or complete response to this treatment. In patients without prior irradiation, there was a tendency for a higher percentage of clinical and radiographic response. Two patients (4%) experienced mild, transient dysphagia, four patients developed self-limited radiation pneumonitis (9%), and three patients (7%) suffered fatal hemoptysis (all of these patients received prior or concurrent external beam radiotherapy). No factor (i.e., prior radiation therapy, number of catheters placed, surgery, or chemotherapy) predicted an increased risk of complications (P = NS). CONCLUSIONS: Outpatient HDR endobronchial brachytherapy is effective in both preventing and relieving endobronchial obstruction in patients with or without prior irradiation, recurrent lesions, or metastatic nonpulmonary disease. A significant proportion of patients can be rendered asymptomatic for the duration of their lives, hence were provided with improved quality of life. These treatments are well tolerated and safe, and result in minimal long term morbidity.

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PubMed1995

Sleep and agitation in agitated nursing home residents: an observational study.

An observational study was conducted to describe the physical and social environment of sleep of 16 highly agitated and cognitively impaired nursing home residents, and the relationships between manifestations of agitation and sleep. Results showed that nursing home residents were more likely to be observed asleep when alone, in their own rooms, and between 9 p.m. and 5 a.m. Considerable amounts of sleep were also observed during the day. Great individual variation was observed in the presence of sleep-related disorders, although a tendency was observed for more fragmented sleep during the day hours. Almost all the agitated behaviors observed decreased immediately after sleep. Similar to findings of objective studies, much individual variation was found in sleep patterns and sleep pathology of cognitively impaired and highly agitated nursing home residents. Findings suggest that agitation may be exacerbated by fatigue.

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PubMed1993

An epidemiologic perspective on biomarkers.

The authors discuss biological markers from an epidemiologic perspective, emphasizing the importance of integrating biomarkers into large-scale observational and intervention studies. Whereas any biologic phenomenon can be considered a biomarker, an intermediate end-point is defined as being on the causal pathway between exposure and disease. An intermediate end-point is a valid surrogate for a disease in relation to a given exposure if, and only if, that exposure causes a similar change in the occurrence of both the intermediate end-point and the disease. Cancer studies using surrogate end-points may be shorter, smaller and cheaper than those using malignancy per se as an outcome. Three types of studies may be carried out to determine whether a given biomarker is an intermediate end-point and whether it can serve as a surrogate: (i) exposure-marker studies, (ii) marker-disease studies, and (iii) studies comprising all three elements, exposure, marker, and disease. The authors discuss statistical aspects of these three types of studies and provide examples from investigations of alcohol-hormone-breast cancer, diet-epithelial proliferation markers-large bowel adenomatous polyps, and reproductive risk factors-human papillomavirus infection-cervical cancer.

Biomarkers, Tumor↗
PubMed1992

Temporal patterns of agitated nursing home residents.

Twenty-four highly agitated, cognitively impaired nursing home residents were studied in depth to determine whether they manifested temporal patterns of agitation. Results demonstrated that agitated behaviors were significantly associated with temporal factors. For instance, residents made more requests for attention during lunch than other time periods, and residents screamed most often during the night. Some agitated behaviors (e.g., aggression) were manifested more frequently in the evening than in the day, consistent with the notion of sundowning in the nursing home. Implications of temporal patterns of agitation for caregivers of severely cognitively impaired and agitated nursing home residents are discussed.

Aged↗
PubMed1992

Pure alexia and right hemiachromatopsia in posterior dementia.

A 66 year old, right handed woman presented with pure alexia and right hemiachromatopsia (PARH) in the context of a posterior dementia. PARH was accompanied by prosopagnosia, 2-D object agnosia, and environmental agnosia. Visual fields were normal to confrontation testing. The pathological anatomy of PARH involves circumscribed damage to the lingual and fusiform gyri and paraventricular white matter of the left occipital cortex, two contiguous cortical regions functionally specialised for processing colour and word form information, respectively.

Aged↗
PubMed1991

Endocranial capacity of Western Australian aboriginal crania: comparisons and association with stature and latitude.

The endocranial capacities (ECCs) of 73 Western Australian Aboriginal crania were estimated. Using water-standardised mustard seed, ECCs were (in cm3) males--means 1,239, S.D. 92.3; females--means 1,118, S.D. 77.5. The male and female mean values were smaller than those previously published for Australia as a whole; sexual dimorphism (9.7%) was also slightly lower. Comparison of the Western Australian Aboriginal sample with a large Danish sample (Pakkenberg and Voigt, 1964; Holloway, 1980) permitted analysis of factors underlying sex and population differences in ECC. In both samples about 40% of the mean sex differences in ECC could be related to stature differences; for each sex almost 2/3 of the differences between the Western Australian and Danish means appear to be associated with differences in stature and latitude. Allometric adjustments are also involved.

Body Height↗
PubMed1991

Visuospatial ability in cortical dementia.

The level and pattern of visuospatial ability were comparatively examined in patients with putative cortical dementia (CD) and acute right hemisphere (RH) injury. Visuospatial ability was evaluated using measures of block construction, spatial reasoning, hemispatial search, and visuoconstructive copy. The incidence of neglect was also determined using special index measures derived from the spatial tasks. There was no difference between the CD and RH groups on measures of block construction, visuoconstructive copy, and spatial reasoning. While the overall incidence and severity of neglect was generally equivalent between the two clinical groups, 50% of the CD patients exhibited a pattern of right spatial neglect. In addition, a strong relationship was not evident between neglect laterality in CD and corresponding asymmetric cognitive and sensory-perceptual compromise, suggesting that neglect in CD may be due to different mechanisms than those causing neglect following right hemisphere injury. The findings indicate that while patients with putative CD perform like individuals with recent right hemisphere injury with respect to mean level of visuospatial ability, many exhibit a differential pattern of compromise related to the laterality of visuospatial neglect. The relevance of these results for the clinical diagnosis of CD is discussed.

Analysis of Variance↗
PubMed1991

Two studies of pacing in the nursing home.

Two studies concerning pacing by nursing home residents are presented. The first was a cross-sectional survey of 402 residents, which found that 39% of the subjects were pacers. In comparison to residents who did not pace, the pacers had fewer medical diagnoses, better appetites, and had resided in the facility for fewer years. Additionally, pacing was positively related to cognitive impairment and to past life-threatening experiences. Results of the second study, an observational study of six cognitively impaired residents who paced frequently, showed that these residents paced more when the environmental conditions were conducive to pacing (e.g., adequate lighting, enough room within which to pace). We believe that pacing is a reflection of good health within the nursing home population and suggest that caregivers may want to encourage rather than inhibit this behavior in some nursing home residents.

Activities of Daily Living↗
PubMed1991

Posterior cortical dementia with alexia: neurobehavioural, MRI, and PET findings.

A progressive disorder of relatively focal but asymmetric biposterior dysfunction is described in a 54 year old right handed male. Initial clinical features included letter-by-letter alexia, visual anomia, acalculia, mild agraphia, constructional apraxia, and visuospatial compromise. Serial testing demonstrated relentless deterioration with additional development of transcortical sensory aphasia, Gerstmann's tetrad, and severe visuoperceptual impairment. Amnesia was not an early clinical feature. Judgment, personality, insight, and awareness remained preserved throughout most of the clinical course. Extinction in the right visual field to bilateral stimulation was the sole neurological abnormality. Early CT was normal and late MRI showed asymmetrical bioccipitoparietal atrophy with greater involvement of the left hemisphere. Results from positron emission tomography (PET) showed bilaterally asymmetric (left greater than right) occipitotemporoparietal hypometabolism. The metabolic decrement was strikingly asymmetric with a 50% reduction in glucose consumption confined to the left occipital cortex. The picture of occipitotemporoparietal compromise verified by MRI, PET, and neurobehavioural testing would be unusual for such degenerative dementias as Alzheimer's (AD) and Pick's disease, although atypical AD with predominant occipital lobe involvement cannot be excluded. This case supports the concepts of posterior cortical dementia (PCD) as a clinically distinct entity and for the first time documents its corresponding metabolic deficit using PET.

Atrophy↗
PubMed1989

Using permutation tests and bootstrap confidence limits to analyze repeated events data from clinical trials.

In clinical trials comparing treatments for superficial bladder cancer, patients are at risk of repeated recurrences of their disease. Statistical methods of analyzing such data are required. This article presents a nonparametric approach. A statistical test to compare the recurrence or tumor rates in two treatment groups, using the randomization distribution, is described. Confidence intervals for the rate ratio are determined from the bootstrap distribution. The implementation of both requires Monte Carlo methods. Computer simulations support the use of these nonparametric methods when there are more than 60 recurrences in each treatment group. An example illustrating their use is given. The strategy adopted for analysis of these data could be applied to other clinical trials where standard methodology is inappropriate.

Biometry↗