Search PubMed⌕ Search

Biomedical subjects

C Wolfson

Publications and source records attributed to C Wolfson.

At least 37 records · Page 2Linked to original sources

Review of outcome measurement instruments in Alzheimer's disease drug trials: introduction.

This article introduces a four-part series on outcome scales used in Alzheimer's disease drug trials. First, it discusses the division of scales into four domains: cognition, functional ability/quality of life, behavior/mood, and global. Within each domain, the shortcomings of existing literature reviews are outlined, and the need for a more coherent view of the psychometric properties of the scales is emphasized. Second, the key concepts of reliability, validity, and responsiveness to change are defined and explained. This explanation also provides an overview of the statistical techniques used to assess measurement properties. Finally, the methods used to select the scales for review in the subsequent articles are explained, and each article is briefly introduced.

Aged↗

Review of outcome measurement instruments in Alzheimer's disease drug trials: psychometric properties of functional and quality of life scales.

The psychometric properties of functional and quality of life outcome measures that were used for the purpose of showing changes in antidementia drug trials for Alzheimer's disease are described and critiqued. The seven functional scales reviewed for reliability, validity, and responsiveness to change included the Geriatric Evaluation by Relative's Rating Instrument, the Physical Self-Maintenance Scale, the Instrumental Activities of Daily Living, the Blessed Dementia Scale, Part 1 and its revised version, the Interview for Deterioration in Daily Living with Dementia, the Unified Activities of Daily Living, and the Dependence Scale. The Progressive Deterioration Scale and Quality of Life Assessment were classified as quality of life scales. The majority of the scales were found to exhibit serious limitations, such as incomplete reliability and validity assessment for the intended uses. The most pervasive problem was a lack of data on responsiveness to change. It is recommended that further research be conducted to develop new tools or enhance existing measures for the assessment of both quality of life and functional ability.

Aged↗

Review of outcome measurement instruments in Alzheimer's disease drug trials: psychometric properties of behavior and mood scales.

This article reviews the reliability and validity of eight scales for behavior and mood problems that were identified in a comparative analysis of Alzheimer's disease (AD) drug trials. The scales are the Brief Psychiatric Rating Scale, the Alzheimer's Disease Assessment Scale-noncognitive, the Relative's Assessment of Global Symptomatology, the Consortium to Establish a Registry for Alzheimer's Disease-Behavior Rating Scale for Dementia, the Dementia Behavior Disturbance scale, the Neuropsychiatric Inventory, and two scales for depressive symptoms, the Cornell Scale for Depression in Dementia and the Dementia Mood Assessment Scale. This article also examines methodological limitations in the way the published literature has assessed the psychometric properties of these scales. The aim is to help clinicians and potential trial investigators select appropriate measurement instruments with which to assess behavior and mood problems in AD and to assist AD researchers in the evaluation of the psychometric properties of such scales.

Affective Symptoms↗

Review of outcome measurement instruments in Alzheimer's disease drug trials: psychometric properties of global scales.

The use of global outcome measures with strong psychometric properties in Alzheimer's disease (AD) drug trials is encouraged. This article focuses on Clinician Global Impression of Change scales, the Clinical Dementia Rating, and the Global Deterioration Scale to provide (1) a review of psychometric properties, (2) a critique of how these properties are assessed in the literature, and (3) a basis for evaluating, from the standpoint of psychometric properties, the appropriateness of using a given global scale in a drug trial. Reported reliability and validity estimates for the aforementioned scales range from fair to very good, but small sample sizes and/or inappropriate measures of correlation weaken the quality of the evidence. There is also a dearth of published information on responsiveness to change. Researchers planning AD drug trials should consider these issues, along with the interval between test administrations for test-retest reliability, to help select appropriate global outcome measurement instruments.

Aged↗

Elements of mobility as predictors of survival in elderly patients with dementia: findings from the Canadian Study of Health and Aging.

In order to identify elements of mobility that predict survival in elderly people with dementia, we conducted a two-year follow-up of a cohort of dementia subjects from the population-based Canadian Study of Health and Aging. There were 749 prevalent cases of Alzheimer's disease (AD) and 208 prevalent cases of vascular dementia. Elements of mobility that predicted death during the two-year follow-up period included difficulty in dressing (OR = 2.08, 95% CI 1.41 3.07), difficulty in getting about (OR = 1.69, 95% CI 1.18 2.40), history of falls (OR = 1.43, 95% CI 1.05 1.94), abnormal gait (OR = 1.61, 95% CI 1.08 2.40) and abnormal motor strength (OR = 1.51, 95% CI 1.07 2.15). Sociodemographic factors such as older age and male sex were also significant predictors of decreased survival. These associations are potentially useful to clinicians and health professionals by providing prognostic information to supply to families and suggesting areas in which interventions to improve survival might be focused

Activities of Daily Living↗

Predictors of five-year mortality in older Canadians: the Canadian Study of Health and Aging.

OBJECTIVE: Based on the Canadian Study of Health and Aging (CSHA), to determine the importance of cognitive status, sociodemographic factors, functional status, and other health related factors as predictors of 5-year overall mortality in older Canadians. DESIGN, SETTING AND PARTICIPANTS: Two partially overlapping groups from the Canadian Study of Health and Aging (1991) were identified: (1) older people living in the community (n = 8949) who had a screening interview (larger sample, fewer variables) and (2) older people who underwent an extensive clinical examination (smaller sample, more objective variables; n = 2914). Deaths in the subsequent 5 years were determined from death certificates and interviews with the caregivers. Multivariate logistic regression models, with death within 5 years as the outcome, were developed separately for men and women. Predictor variables were introduced in the following groups: sociodemographic factors, physical and cognitive status, and physical illnesses and life style factors. Parallel models were developed for the screening sample and for the clinical sample. RESULTS AND DISCUSSION: Five-year mortality ranged from 10.0% (women aged 65-74 living in the community) to 88.1% (men aged 85 and older living in institutions). Multivariate models showed that the odds of death within 5 years increased with age. This effect remained after adjustment for all other variables. Odds of death increased with institutionalization and with increasing cognitive and physical impairment. Although vision and hearing problems and the presence of heart disease, stroke, and diabetes were all strongly related to 5-year mortality in univariate, unadjusted analyses, their contributions were minimal in the multivariate analyses. Increased Body Mass Index was associated with lower mortality in both univariate and multivariate analyses. CONCLUSIONS: This population-based study supported the importance of gender, age, functional status, cognition, and health status in predicting 5-year mortality, and after accounting for cognitive status, physical status, and specific disease variables, the difference in mortality between older people in the community and in institutions was reduced. Knowledge about survival and prognosis is important not only for the planning of long-term facilities and home care, but it can also be helpful for clinical decision-making and for family and caregivers.

Aged↗

Imaging axonal damage of normal-appearing white matter in multiple sclerosis.

The current study was designed to determine the relative distribution of decreases of N-acetylasparate (NAA), a marker of axonal damage, between lesions and normal-appearing white matter of patients with established multiple sclerosis and to test for associations between changes in the ratio of NAA to creatine/phosphocreatine (NAA:Cr) in those compartments and changes in disability. Data were collected from a 30-month longitudinal study of 28 patients with either a relapsing course with partial remissons and no progression between attacks (relapsing/remitting) (11 patients) or a course of progressively increasing disability, following a period of relapsing/remitting disease (secondary progressive) (17 patients). Proton magnetic resonance spectroscopic imaging (MRSI) and conventional MRI examinations were performed at 6-8-month intervals with concurrent clinical assessments of disability. General linear models were used to test associations between MRSI, MRI, lesion volume and clinical data. Analysis confirmed that the NAA:Cr ratio is lower in lesions than in the normal-appearing white matter (-15.3% in relapsing/remitting multiple sclerosis and -8.8% in secondary progressive multiple sclerosis). The lower NAA:Cr ratio per unit lesion volume previously observed for secondary progressive relative to relapsing/remitting patients was found to result from a lower ratio (8.2%, P < 0.01) in the normal-appearing white matter rather than from any differences within lesions. The importance of changes in the normal-appearing white matter was emphasized further with the observation that the NAA:Cr ratio in the normal-appearing white matter accounted for most of the observed 15.6% (P < 0.001) decrease in the NAA:Cr ratio in the brains of relapsing/remitting patients over the period of study. The decrease in the NAA:Cr ratio in normal-appearing white matter correlated strongly (P < 0.001) with changes in disability in the relapsing/remitting subgroup. These results add to data suggesting that axonal damage or loss may be responsible for functional impairments in multiple sclerosis. The accumulation of secondary axonal damage in the normal-appearing white matter may be of particular significance for understanding chronic disability in this disease.

Aspartic Acid↗

Randomised trial of home-based psychosocial nursing intervention for patients recovering from myocardial infarction.

BACKGROUND: Increases in life stress have been linked to poor prognosis, after myocardial infarction (MI). Previous research suggested that a programme of monthly screening for psychological distress, combined with supportive and educational home nursing interventions for distressed patients, may improve post-MI survival among men. Our study assessed this approach for both men and women. We aimed to find out whether the programme would reduce 1-year cardiac mortality for women and men. METHODS: We carried out a randomised, controlled trial of 1376 post-MI patients (903 men, 473 women) assigned to the intervention programme (n = 692) or usual care (n = 684) for 1 year. All patients completed a baseline interview that included assessment of depression and anxiety. Survivors were also interviewed at 1 year. FINDINGS: The programme had no overall survival impact. Preplanned analyses showed higher cardiac (9.4 vs 5.0%, p = 0.064) and all-cause mortality (10.3 vs 5.4%, p = 0.051) among women in the intervention group. There was no evidence of either benefit or harm among men (cardiac mortality 2.4 vs 2.5%, p = 0.94; all-cause mortality 3.1 vs 3.1%, p = 0.93). The programme's impact on depression and anxiety among survivors was small. INTERPRETATION: Our results do not warrant the routine implementation of programmes that involve psychological-distress screening and home nursing intervention for patients recovering from MI. The poorer overall outcome for women, and the possible harmful impact of the intervention on women, underline the need for further research and the inclusion of adequate numbers of women in future post-MI trials.

Aged↗

HM-PAO (CERETEC) SPECT brain scanning in the diagnosis of Alzheimer's disease.

OBJECTIVE: To evaluate the accuracy of Single Photon Emission Computed Tomography (SPECT) scanning in the diagnosis of Alzheimer's Disease (AD) and its capacity to improve the diagnostic accuracy of conventional clinical evaluation. DESIGN: Comparison of SPECT scanning of AD and normal subjects with the criterion standard of clinical diagnosis confirmed by 1-year repeated evaluation. SETTING: A memory clinic in a tertiary care university hospital. PATIENTS: One hundred twenty patients were evaluated upon entering the Jewish General Hospital (McGill University) Memory Clinic. Fifty-eight patients were diagnosed as having AD and 17 as having vascular dementia. Twenty unmatched controls (recruited mainly through newspaper advertisements) were normal, and 25 had cognitive impairment without dementia (not included in the statistical analysis). MAIN OUTCOME MEASURES: Comparison of visual inspection of SPECT, based on the system of classification developed by Holman et al., using B pattern alone as positive or B (bilateral posterior temporal and/or parietal cortex deficits) or C (bilateral posterior temporal and/or parietal deficits with additional defects) pattern and B or C or D (unilateral posterior temporal and/or parietal defects with or without additional defects) as positive compared with clinical diagnosis after repeated evaluations. Sensitivity and specificity, as well as positive predictive value (PPV) and negative predictive value (NPV) based on the prevalence of AD in a memory clinic setting of 30% or 50%, were calculated. RESULTS: With B pattern as positive, the sensitivity of SPECT was 21% whereas the specificity was 80%. With B or C as positive, the sensitivity was 29% and the specificity was 75%. With B or C or D as positive, the sensitivity was 55% and the specificity was 65%. With a 30% prevalence, the PPV with B pattern as positive was 31% whereas the NPV was 30%. The PPV with B or C as positive was 33% while the NPV was 29%, and the PPV with B or C or D as positive was 40% whereas the NPV was 23%. With a 50% prevalence, the PPV with B pattern as positive was 51% and the NPV 49.6%; the PPV with B or C as positive was 54% and the NPV 48.6%; the PPV with B or C or D as positive was 61% while NPV was 41%. CONCLUSION: The sensitivity and specificity were too low for SPECT to be useful as a diagnostic test for AD. The poor positive and negative predictive values in our tertiary care clinic mean that SPECT is not useful in "ruling-in" or "ruling-out" AD in that setting. In fact, clinical evaluation is more accurate.

Aged↗

Statistics for investigation of multimodal MR imaging data and an application to multiple sclerosis patients.

Magnetic resonance spectroscopy can image axonal damage specifically based on changes in N-acetyl aspartate (NAA), a neuronal marker. We have developed statistical methods for multimodal analysis of MR spectroscopic images. These methods, which are extensions of mixed-effect models, have allowed us to quantify differences in images from different subgroups of patients with multiple sclerosis (MS) and to determine the dependence of chemical pathology on clinical disability, duration of disease and lesions on T2-weighted MRI. Statistical power was improved by using all reliable resonance intensities in the spectroscopic images while taking into consideration the intra-subject correlations. We studied 17 normal subjects, 14 patients with relapsing remitting (RR) MS and 21 patients with chronic progressive (CP) MS. The ratio of resonance intensities of N-acetylaspartate over creatine (Cr) was found to be significantly lower than normal in normal appearing white matter (NAWM) of both RR and CP patients (19.6% in RR, 28.8% in CP), NAA/Cr was decreased even more in MS plaques than in NAWM (44.2% in RR, 17.7% in CP), NAA/Cr was correlated with clinical disability (p < 0.02) and disease duration (p < 0.1). Our results suggest that, in this setting, MRS reflects accumulated neuronal loss or damage and can be used as a measure of disease severity. The methods developed provide opportunities to evaluate the relationship between inflammation, demyelination, axonal loss and clinical disability in future studies.

Aspartic Acid↗

Prevalence of Bartonella henselae bacteremia, the causative agent of cat scratch disease, in an Australian cat population.

In order to determine the prevalence of Bartonella henselae becteremia in an Australian cat population we examined blood cultures on a group of Sydney cats. Cats referred to the Concord Animal Hospital for euthanasia were selected randomly for blood culture and serum sampling. Blood samples were lysed and centrifuged and then cultured for up to five weeks. Suspicious colonies were identified biochemically as probable B. henselae. Selected isolates were confirmed as B. henselae using the polymerase chain reaction. Of the cats accrued throughout Sydney, 27/77 (35%) were culture positive for B. henselae, of these 24/59 (40%) were feral cats and 3/18 (16%) were domestic. Most cats in the study were younger than one year (mean 9.9 months). Our study demonstrates that bacteremia with B. henselae is common in the metropolitan cat population and suggests that it is particularly prevalent among feral animals. By contrast Cat Scratch Disease (CSD) is a relatively uncommon clinical diagnosis in the Australian population. Explanations for this discrepancy may include poor transmission, low bacterial virulence and underdiagnosis. It is possible that feral animals are a greater potential risk source for this infection than domestic cats.

Animals↗

Assessment of lesion pathology in multiple sclerosis using quantitative MRI morphometry and magnetic resonance spectroscopy.

Quantitative measurement of MRI-defined brain lesions can provide an index of the extent and activity of disease in multiple sclerosis patients. However, the relationships between these indices and clinical features are not well-understood. Heterogeneity of the pathological changes underlying MRI lesions may be an important factor determining the correlation between MRI lesion volumes and clinical measures. Recent studies have suggested that with magnetic resonance spectroscopy (MRS), it may be possible to define chemical changes that better reflect the pathological changes in multiple sclerosis. Here we report results of combined quantitative brain T2-weighted MRI lesion volume and proton MRS examinations that demonstrate heterogeneity of the chemical pathology underlying brain lesions in patients selected on the basis of similar clinical disability but differing with respect to the presence or absence of clinical relapses. We examined 29 patients with disease characterized by either clear relapses with at least partial remissions (RR) or secondary, chronic progression after an earlier history of a more relapsing and remitting course (SP). Total hemispheric lesion volume was greater (P < 0.04) in the RR (32.5 +/- 20.9 cm3) than in the SP (16.2 +/- 9.0 cm3) patients, despite the longer duration of disease in the latter group. Central brain N-acetyl aspartate: creatine (NAA:Cr) ratios were reduced relative to normal controls (4.0 +/- 0.3, n = 19) by similar amounts in the two patients groups (RR, 3.1 +/- 0.5; SP, 3.2 +/- 0.4; P < 0.0001). The ratio lesion volume:(NAA:Cr) was greater for the RR group (11.7 +/- 9.3 cm3) than for the SP group (5.4 +/- 3.3 cm3, P < 0.05), implying a greater average degree of axonal loss per unit lesion volume defined by MRI for subjects in the SP group or, alternatively, a greater proportion of lesions without axonal damage or loss in the RR group. Our results emphasize a limitation of using T2-weighted MRI lesion volume alone and suggest that combined analysis of MR-based chemical and imaging data might allow improved non-invasive assessment of lesion pathology in order to better understand its relationship to clinical features of multiple sclerosis.

Adult↗

Organic solvents and multiple sclerosis: a synthesis of the current evidence.

To evaluate the possible relation between exposure to organic solvents and the development of multiple sclerosis, we carried out a best-evidence synthesis of the available information. We found 13 studies with varying methodology that included information on solvent exposure. In 10 of the studies, there were indications of an increased risk of multiple sclerosis in relation to solvent exposure. We made three selections of studies for both pooled analyses and meta-analyses. The relative risk point estimates that we obtained varied from 1.7 to 2.6. Our evaluation is consistent with the hypothesis that organic solvents may be a cause of multiple sclerosis.

Case-Control Studies↗

The Etest for antimicrobial susceptibility testing of Bartonella henselae.

The in-vitro susceptibility of 10 isolates of Bartonella henselae was assessed using the Etest. The organisms, one reference human strain and nine feline isolates, were grown on chocolate agar and the Etests read at days 5, 8 and 11. Six antibiotics, erythromycin, azithromycin, doxycycline, ciprofloxacin, rifampicin and vancomycin were evaluated. The results correlated well with published results using agar dilution. The results confirmed the high in-vitro susceptibility of B. henselae to erythromycin, azithromycin, doxycycline and rifampicin and to a lesser extent ciprofloxacin. The majority of isolates were resistant to vancomycin. Although in-vitro results of B. henselae susceptibility testing may not necessarily correlate with clinical response, the Etest may be a simpler way for laboratories to monitor for the development of resistance particularly in the setting of relapsing infection.

Animals↗