John Neuhaus

Long-term physical functioning in persons with knee osteoarthritis from NHANES. I: Effects of comorbid medical conditions.

This study examined the effects of comorbid medical conditions (heart disease, pulmonary disease, hypertension and obesity) on the association of radiographic knee osteoarthritis (OA) with long-term difficulty in physical function. Data are from the National Health and Nutrition Examination Survey, 1971-1975 (NHANES I), a prospective epidemiologic cohort study, and the NHANES Epidemiologic Follow-up Study, 1982-1984 (NHEFS) and included 4059 persons who were 45-74 years old and participated in the detailed examination component of NHANES I. Knee OA was ascertained by anterior-posterior bilateral radiographs of the knee and self-report of knee pain, heart and pulmonary disease by self report of disease or symptoms, and hypertension and obesity by blood pressure and weight measurements. The presence of symptomatic knee OA at NHANES I was associated with reported difficulty at NHEFS 1982-84 in functions which used the lower extremity (ambulation and transfer). The presence of coexistent chronic conditions, particularly heart disease, pulmonary disease and obesity, increased the likelihood of subsequent disability. These findings suggest that knee OA is associated with long-term physical disability, and that the presence of coexistent chronic disease may increase the amount of long-term disability from knee OA.

Recruitment and retention of healthy minority women into community-based longitudinal research.

This report examines the impact of individualized, population-based recruitment and retention approaches on the development of a subject pool, enrollment, and retention at 12 months of healthy, community-based women in three ethnic groups: African Americans, non-Hispanic European Americans, and Mexicans/Central Americans. Of 722 women contacted and screened, 346 (48%) were eligible and consented to participate. Attrition at 12 months was low (10%) compared with other published reports. The largest group of potential subjects was identified through broadcast media approaches, but this method produced the highest number of ineligible women and highest rate of attrition. Printed matter produced the next largest group of potential subjects, but ineligibility was high (53%). Face-to-face interactions enrolled the highest proportion of eligible women (84%) and lowest overall attrition (7%). Direct referral yielded fairly efficient enrollments (57%) and average attrition. Multiple approaches for recruitment can produce a diverse sample of healthy, community-based women. Face-to-face recruitment results in the highest yield of participants with the lowest attribution but is presumed to require more resources.

Comparison of family histories in FTLD subtypes and related tauopathies

Pedigrees from 269 patients with frontotemporal lobar degeneration (FTLD), including frontotemporal dementia (FTD), FTD with ALS (FTD/ALS), progressive nonfluent aphasia, semantic dementia (SD), corticobasal degeneration, and progressive supranuclear palsy were analyzed to determine the degree of heritability of these disorders. FTD/ALS was the most and SD the least heritable subtype. FTLD syndromes appear to have different etiologies and recurrence risks.

Statistical methods for longitudinal and clustered designs with binary responses

Dependent binary response data arise frequently in practice due to repeated measurements in longitudi nal studies or to subsampling primary sampling units as in fields such as teratology and ophthalmology. Several classes of approaches have recently been proposed to analyse such repeated binary outcome data. The different classes of approaches measure different effects of covariates on binary responses and address different statistical questions. This article compares the different classes of approaches in terms of parameter interpretation and magnitude, standard errors of model parameters and Wald tests for covariate effects. The results help to clarify the substantive questions which data analysts can address with each approach, as well as why the covariate effects measured by different approaches may be different. Finally, I will provide guidelines to the advantages and disadvantages of alternative approaches for analysing dependent binary responses. Simulations and example data illustrate these findings.

Obesity and osteoarthritis of the knee: Evidence from the national health and nutrition examination survey (NHANES I)

The importance of systemic/metabolic factors in the association of obesity with radiographic knee osteoarthritis (OA) was examined for 3,905 adults aged 45 to 74 from the United States National Health and Nutrition Examination Survey, 1971 to 1975 (NHANES I). Obesity was associated with both bilateral and unilateral OA, but more strongly with bilateral OA. Obesity was also associated with both symptomatic and nonsymptomatic knee OA. Controlling for age, sex, serum cholesterol, serum uric acid, diabetes, body fat distribution, bone density, and blood pressure did not significantly reduce the association between obesity and knee OA. Findings from these data are not supportive of a metabolic link between obesity and knee OA.

Language networks in semantic dementia

Cognitive deficits in semantic dementia have been attributed to anterior temporal lobe grey matter damage; however, key aspects of the syndrome could be due to altered anatomical connectivity between language pathways involving the temporal lobe. The aim of this study was to investigate the left language-related cerebral pathways in semantic dementia using diffusion tensor imaging-based tractography and to combine the findings with cortical anatomical and functional magnetic resonance imaging data obtained during a reading activation task. The left inferior longitudinal fasciculus, arcuate fasciculus and fronto-parietal superior longitudinal fasciculus were tracked in five semantic dementia patients and eight healthy controls. The left uncinate fasciculus and the genu and splenium of the corpus callosum were also obtained for comparison with previous studies. From each tract, mean diffusivity, fractional anisotropy, as well as parallel and transverse diffusivities were obtained. Diffusion tensor imaging results were related to grey and white matter atrophy volume assessed by voxel-based morphometry and functional magnetic resonance imaging activations during a reading task. Semantic dementia patients had significantly higher mean diffusivity, parallel and transverse in the inferior longitudinal fasciculus. The arcuate and uncinate fasciculi demonstrated significantly higher mean diffusivity, parallel and transverse and significantly lower fractional anisotropy. The fronto-parietal superior longitudinal fasciculus was relatively spared, with a significant difference observed for transverse diffusivity and fractional anisotropy, only. In the corpus callosum, the genu showed lower fractional anisotropy compared with controls, while no difference was found in the splenium. The left parietal cortex did not show significant volume changes on voxel-based morphometry and demonstrated normal functional magnetic resonance imaging activation in response to reading items that stress sublexical phonological processing. This study shows that semantic dementia is associated with anatomical damage to the major superior and inferior temporal white matter connections of the left hemisphere likely involved in semantic and lexical processes, with relative sparing of the fronto-parietal superior longitudinal fasciculus. Fronto-parietal regions connected by this tract were activated normally in the same patients during sublexical reading. These findings contribute to our understanding of the anatomical changes that occur in semantic dementia, and may further help to explain the dissociation between marked single-word and object knowledge deficits, but sparing of phonology and fluency in semantic dementia.

Spinal dural arteriovenous fistulae: clinical features and long-term results.

OBJECTIVEThe goals of this study were to characterize the clinical, radiological, treatment, and outcome data associated with patients diagnosed with spinal dural arteriovenous fistulae (SDAVFs) at a single tertiary care institution over a 20-year period. METHODSA 20-year retrospective study was undertaken at our university hospital. Patients with mixed intracranial and spinal dural fistulas were excluded. A literature review of articles reporting endovascular or combined treatment of SDAVFs was performed. RESULTSBetween 1984 and 2005, our institution diagnosed and treated 63 patients (mean age, 62; 13 women, 50 men) with SDAVFs. The presenting symptoms were consistent with progressive myelopathy, and included lower extremity weakness (33 patients, 52%), parasthesias (19 patients, 30%), back pain (15 patients, 24%), and urinary symptoms (four patients, 6%). Thirty-nine patients underwent an initial endovascular embolization with 27 requiring only this first procedure for complete obliteration. On the other hand, 24 patients underwent an initial surgical procedure with 20 of them treated successfully with a single operation. Endovascular patients presented at mean age 62.3 years (standard deviation [SD], 10.6), were hospitalized for an average of 3.1 days (SD, 2.6), and were followed-up for 39 months (SD, 33). Surgical patients presented at mean age of 65.8 years (SD, 10.3), were hospitalized for 9.8 days (SD, 2.7), and were followed-up for 35 months (SD, 44). A significant improvement in Aminoff-Logue scores was found in both the endovascular and surgery groups (gait, P < 0.001; micturition, P = 0.005). The endovascular group had reduced hospitalization (P = 0.0001). No differences were found in the magnitude of clinical response to treatment. CONCLUSIONSDAVFs most commonly present with progressive myelopathy, yet often remain undiagnosed for months or years. Endovascular therapies and surgical therapies are associated with significantly improved symptoms once the definitive diagnosis of SDAVF is made.

Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer's disease

Frontotemporal lobar degeneration (FTLD) often overlaps clinically with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), both of which have prominent eye movement abnormalities. To investigate the ability of oculomotor performance to differentiate between FTLD, Alzheimers disease, CBS and PSP, saccades and smooth pursuit were measured in three FTLD subtypes, including 24 individuals with frontotemporal dementia (FTD), 19 with semantic dementia (SD) and six with progressive non-fluent aphasia (PA), as compared to 28 individuals with Alzheimers disease, 15 with CBS, 10 with PSP and 27 control subjects. Different combinations of oculomotor abnormalities were identified in all clinical syndromes except for SD, which had oculomotor performance that was indistinguishable from age-matched controls. Only PSP patients displayed abnormalities in saccade velocity, whereas abnormalities in saccade gain were observed in PSP > CBS > Alzheimers disease subjects. All patient groups except those with SD were impaired on the anti-saccade task, however only the FTLD subjects and not Alzheimers disease, CBS or PSP groups, were able to spontaneously self-correct anti-saccade errors as well as controls. Receiver operating characteristic statistics demonstrated that oculomotor findings were superior to neuropsychological tests in differentiating PSP from other disorders, and comparable to neuropsychological tests in differentiating the other patient groups. These data suggest that oculomotor assessment may aid in the diagnosis of FTLD and related disorders.

Misspecifying the Shape of a Random Effects Distribution: Why Getting It Wrong May Not Matter

Statistical models that include random effects are commonly used to analyze longitudinal and correlated data, often with strong and parametric assumptions about the random effects distribution. There is marked disagreement in the literature as to whether such parametric assumptions are important or innocuous. In the context of generalized linear mixed models used to analyze clustered or longitudinal data, we examine the impact of random effects distribution misspecification on a variety of inferences, including prediction, inference about covariate effects, prediction of random effects and estimation of random effects variances. We describe examples, theoretical calculations and simulations to elucidate situations in which the specification is and is not important. A key conclusion is the large degree of robustness of maximum likelihood for a wide variety of commonly encountered situations.

The efficacy of medical abortion: a meta-analysis

Multiple clinical studies demonstrate the efficacy of medical abortion with mifepristone or methotrexate followed by a prostaglandin analogue. However, assessing predictors of success, including regimen, is difficult because of regimen variability and a lack of direct comparisons. This meta-analysis estimates rates of primary clinical outcomes of medical abortion (successful abortion, incomplete abortion, and viable pregnancy) and compares them by regimen and gestational age. We identified 54 studies published from 1991 to 1998 using mifepristone with misoprostol (18), mifepristone with other prostaglandin analogues (23), and methotrexate with misoprostol (13). Data abstracted from studies included regimen details and clinical outcomes by gestational age. We found that efficacy decreases with increasing gestational age (p<0.001), and differences by regimen are not statistically significant except at gestational age > or =57 days. For gestations < or =49 days, mean rates of complete abortion were 94-96%, incomplete abortion 2-4%, and ongoing (viable) pregnancy 1-3%. For gestations of 50-56 days, the mean rate of complete abortion was 91% (same for all regimens), incomplete abortion 5-8%, and ongoing pregnancy 3-5%. For > or =57 days, success was lower for mifepristone/misoprostol (85%, 95% confidence interval 78-91%) than for mifepristone/other prostaglandin analogues 95% (CI 91-98%, p = 0.006). For mifepristone/misoprostol, using > or =2 prostaglandin analogue doses seems to be better than a single dose for certain outcomes and gestational ages. We conclude that both mifepristone and methotrexate, when administered with misoprostol, have high levels of success at < or =49 days gestation but may have lower efficacy at longer gestation.