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Biomedical subjects

M P McDermott

Publications and source records attributed to M P McDermott.

At least 19 recordsLinked to original sources
PubMed2006

Is skin biopsy a predictor of transition to symptomatic HIV neuropathy? A longitudinal study.

OBJECTIVE: To investigate whether serially assessed epidermal nerve fiber (ENF) density and quantitative sensory thresholds (QSTs) are associated with the clinical transition from HIV infection with no neuropathy or asymptomatic neuropathy to symptomatic distal sensory neuropathy (SDSP). BACKGROUND: Identifying predictors of transition to SDSP would enable identification of subjects at enhanced risk for development of HIV-SDSP and facilitate intervention studies with the ultimate goal of disease prevention. Asymptomatic signs of sensory dysfunction in the feet have been shown to be weakly predictive of SDSP; however, bedside evaluation of small sensory fibers is limited. Abnormality of these fibers may play an important role in the genesis of SDSP. METHODS: Fifty-eight HIV-infected subjects underwent serial clinical, virologic, immunologic, skin biopsy, and QST assessments. Cox proportional hazards modeling was used to examine the associations of serial ENF density and QST assessments with the risk of development of SDSP among the subset of 26 subjects who had asymptomatic or no neuropathy at study entry. RESULTS: Median follow-up was 2.9 years (range 6 months to 4.5 years) during which 19 of 26 subjects transitioned to SDSP. Using a model where ENF density and QST measures from the study visit before potential transition were examined, a lower leg ENF density, a higher cooling threshold, and a higher heat pain threshold for minimal pain (HP 0.5) were associated with a greater risk of SDSP in univariate analyses. In multiple regression analyses, leg ENF density but not QST measures were significantly associated with SDSP. A leg ENF density of 10 fibers/mm or less conferred a 14-fold greater risk of SDSP than a leg ENF density greater than 10 fibers/mm. CONCLUSIONS: Measures of small sensory fibers (leg epidermal nerve fiber density, cooling and heat pain thresholds) seem to be associated with transition to symptomatic HIV-associated distal sensory neuropathy 6 to 12 months later.

Adult↗
PubMed2006

Validity and responsiveness of generic preference-based HRQOL instruments in chronic epilepsy.

Generic, preference-based instruments are recommended for assessing health-related quality of life (HRQOL) in cost-utility analyses (CUA). We aimed to determine which instrument is the most appropriate for CUA of epilepsy care, using established psychometric criteria. We compared validity and responsiveness of EQ5D (using both UK and US preferences), visual analog scale (VAS), Health Utilities Index Mark II (HUI-2) and Mark III (HUI-3) and SF6D in 165 adults evaluated for epilepsy surgery. SF6D had the strongest or next-strongest associations with seizure severity and seizure control. It was not associated with education or IQ. Only SF6D and HUI-3 discriminated between patients with and without seizures 2 years after baseline evaluation. SF6D was most or next-most responsive to being seizure-free for 2 years, in most responsiveness analyses. VAS was also responsive, but showed less evidence of validity. The QOLIE-89, an epilepsy-targeted profile instrument, had stronger evidence for validity and responsiveness than the preference instruments. SF6D has several key psychometric advantages over four other preference instruments in CUAs of epilepsy care. This may reflect better coverage of HRQOL dimensions affected by epilepsy, greater sensitivity at the upper end of the HRQOL continuum, or both. These findings may not generalize to other chronic conditions.

Adult↗
PubMed2005

Markers of immune activation and viral load in HIV-associated sensory neuropathy.

BACKGROUND: HIV infection is associated with a painful distal sensory polyneuropathy (DSP) that can severely limit the quality of life of affected subjects. The pathogenesis of DSP is unknown, although both HIV proteins and products of immune activation triggered by HIV infection have been implicated. OBJECTIVE: To assess the association between baseline markers of immune activation and HIV RNA levels (viral load) and time to symptomatic DSP (SDSP). METHODS: A cohort of 376 subjects, most receiving highly active antiretroviral therapy (HAART), were followed semiannually for up to 48 months. Blood and CSF levels of HIV viral load, monocyte chemotactic protein-1, macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-2, and tumor necrosis factor-alpha were measured in addition to CD4 lymphocyte cell count. RESULTS: In subjects without SDSP at baseline (62.5% of the cohort), among the virologic and immunologic markers, only baseline CSF M-CSF levels were associated with time to SDSP (hazard ratio = 2.97, p = 0.05). The Kaplan-Meier estimate of the 1-year incidence of SDSP was 21%, a 15% decrease from that observed in the Dana cohort, a pre-HAART cohort enrolled with the same inclusion/exclusion criteria. CONCLUSION: Highly active retroviral therapy (HAART) has changed the natural history of HIV-associated symptomatic distal sensory polyneuropathy (SDSP), which may explain, in contrast with studies from the pre-HAART era, the lack of association between SDSP and baseline HIV viral load and CD4 cell count.

Adult↗
PubMed2005

Survival in Parkinson disease: thirteen-year follow-up of the DATATOP cohort.

OBJECTIVE: To investigate predictors of survival in Parkinson disease (PD). METHODS: Vital status was determined in 800 subjects enrolled in a clinical trial of deprenyl (selegiline) and tocopherol 13 years earlier. RESULTS: Two hundred ninety-six deaths were recorded. There was no difference in the standardized mortality ratios across gender or age group. In univariate analyses, PD-specific variables associated with mortality were increased symmetry of parkinsonism, gait dysfunction as an initial symptom, severity of parkinsonism, and rate of worsening of parkinsonism prior to study enrollment. Cumulative exposure to deprenyl was not associated with mortality. In multivariable analysis, severity of parkinsonism and rate of worsening of parkinsonism remained associated with mortality. A poorer response to levodopa was associated with increased mortality independent of disease severity or dosage of levodopa. Results were unchanged when the analysis was restricted to 747 subjects maintaining a most likely diagnosis of PD throughout 6 years of active follow-up. CONCLUSIONS: Parkinson disease did not affect survival differently across gender or age groups in this selected group of otherwise healthy clinical trial participants. Severity and rate of worsening of parkinsonism and response to levodopa are strongly related to survival.

Cohort Studies↗
PubMed2005

The prevalence of PD in a nutritionally deficient rural population in China.

OBJECTIVES: In most reports, the prevalence of PD in mainland China is lower than in western populations. To estimate PD prevalence in China, we performed a cross-sectional study in a rural population in Linxian County, China. PRIMARY OUTCOMES: Clinical diagnosis of PD. RESULTS: Among the 16,488 participants examined, the overall age- and gender-adjusted prevalence rate of PD was 522/100,000 (95% CI: 477-567) assuming no cases of PD would be found among those younger than 50 years of age. The gender-adjusted prevalence rates were 103 (95% CI: 83-123), 621 (95% CI: 572-670), 902 (95% CI: 843-961), and 1744 (95% CI: 1662-1826) per 100,000 in age groups 50-59, 60-69, 70-79, and 80 and above, respectively. CONCLUSIONS: The estimated prevalence of PD in Linxian, China is higher than most of those reported from other areas in China, and similar to those reported from non-Asian populations.

Age Distribution↗
PubMed2004

Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia.

OBJECTIVE: To evaluate whether baseline levels of plasma and CSF HIV RNA, tumor necrosis factor alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), or macrophage colony stimulating factor (M-CSF) are predictors of incident HIV-associated dementia (HIVD) in a cohort with advanced HIV infection. METHODS: A total of 203 nondemented subjects with CD4 lymphocyte counts less than 200/muL, or <300/microL but with cognitive impairment, underwent semiannual neurologic, cognitive, functional, and laboratory assessments. HIVD and minor cognitive motor disorder (MCMD) were defined using American Academy of Neurology criteria. The cumulative incidence of HIVD was estimated using Kaplan-Meier curves. Cox proportional hazards regression models were used to examine the associations between biologic variables and time to HIVD, adjusting for age, sex, years of education, duration of HIV infection, type of antiretroviral use, premorbid IQ score, and presence of MCMD. RESULTS: After a median follow-up time of 20.7 months, 74 (36%) subjects reached the HIVD endpoint. The dementia was mild in 70% of cases. The cumulative incidence of HIVD was 20% at 1 year and 33% at 2 years. Highly active antiretroviral therapy (HAART) was used by 73% of subjects at baseline. A plasma HIV RNA level was undetectable in 23% of subjects and a CSF HIV RNA level was undetectable in 48% of subjects. In adjusted analyses, neither plasma nor CSF HIV RNA levels (log10) were associated with time to HIVD; log10 levels of plasma TNFalpha (HR 3.07, p = 0.03) and CSF MCP-1 (HR = 3.36, p = 0.06) tended to be associated with time to HIVD. CONCLUSION: The lack of association between baseline plasma and CSF HIV RNA levels and incident dementia suggests highly active antiretroviral therapy may be affecting CNS viral dynamics, leading to lower HIV RNA levels, and therefore weakening the utility of baseline HIV RNA levels as predictors of HIV-associated dementia.

AIDS Dementia Complex↗
PubMed2003

Inter-rater reliability of a clinical staging of HIV-associated cognitive impairment.

OBJECTIVE: To determine the inter-rater reliability of a modification of the Memorial Sloan-Kettering (MSK) Staging for HIV-associated cognitive impairment. METHODS: Data were abstracted on neurologic, neuropsychological, and functional status on 100 individuals participating at four sites in the Northeast AIDS Dementia (NEAD) Consortium cohort study, a longitudinal study of predictors of cognitive impairment in HIV-infected individuals. Neuropsychological performance was defined 1) based on the neuropsychologist's global impression and 2) solely based on neuropsychological test scores. Raters at each site used the abstracted data to assign an MSK stage to each subject blind to any identifying information. Inter-rater reliability was assessed using kappa statistics. Agreement between computer-generated ratings and site-generated ratings was also assessed. RESULTS: Kappa statistics for pair-wise agreement among the sites regarding MSK stage ranged from 0.70-0.91, representing good to excellent agreement between sites. Agreement between computer-generated ratings and site-generated ratings was in the good to excellent range (0.62-0.79). CONCLUSIONS: The authors have modified the MSK rating scale and developed a reliable instrument that can be used in multicenter studies. This instrument will be useful in staging HIV-dementia in future longitudinal studies and will be valuable in increasing accuracy of clinicopathologic studies.

AIDS Dementia Complex↗
PubMed2002

A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment.

BACKGROUND: CPI-1189 is a compound with antioxidant properties that blocks tumor necrosis factor-alpha (TNFalpha) effects in animal models. It has neuroprotective properties in model systems for HIV-associated neurotoxicity and thus is a candidate for neuroprotective therapy in humans with HIV-associated CNS disease. OBJECTIVE: To assess the tolerability and safety of CPI-1189 in treating HIV-associated cognitive-motor impairment. METHODS: Sixty-four subjects with mild to moderate HIV-associated cognitive-motor impairment were randomized to receive either placebo or 50 or 100 mg daily of CPI-1189 in addition to optimal HIV therapy. Subjects were followed prospectively in a double-masked study for 10 weeks. The primary assessment was tolerability and safety of the compound. Secondary objectives examined neuropsychological and functional change associated with this treatment. RESULTS: The study compound was well tolerated, with 91% of CPI-1189-treated subjects and 76% of placebo-treated subjects completing the trial. Skin rash was seen equally in placebo and active arms, but the only study withdrawals due to skin rash occurred in CPI-1189-treated subjects (n = 2). One subject developed a cataract on drug (100 mg/day). CD4 lymphocyte counts and plasma HIV viral load remained stable in all groups throughout the trial. No significant treatment effects were observed on the change in composite Z-scores for eight neuropsychologic measures (NPZ-8). The Grooved Pegboard Test (nondominant) showed improved performance with CPI-1189 at 100 mg/day (p = 0.01), but no other neuropsychometric or functional measures demonstrated significant improvement. CONCLUSIONS: CPI-1189 was well tolerated in HIV subjects with cognitive-motor disorder. This study was not powered to conclusively determine efficacy and showed no consistent treatment-associated improvement in cognitive or functional measures.

AIDS Dementia Complex↗
PubMed2002

The behavioral spectrum of tic disorders: a community-based study.

BACKGROUND: Tourette syndrome (TS) and related tic disorders are commonly associated with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). It has been argued, however, that any observed association between TS and these and other psychopathologies may be due to ascertainment bias in that individuals with multiple problems are more likely to be referred for medical evaluation. METHODS: In order to overcome the potential confounding by ascertainment bias, the authors conducted a community-based study of school children using direct interviews to determine the prevalence of tic disorders and any comorbid psychopathology. A standard psychiatric interview and standardized rating scales were utilized to diagnose childhood behavioral disorders. RESULTS: Of the 1,596 children interviewed, 339 were identified as having tics. The following psychopathologies were found more commonly (p < 0.05) in the children with tics: OCD, ADHD, separation anxiety, overanxious disorder, simple phobia, social phobia, agoraphobia, mania, major depression, and oppositional defiant behavior. CONCLUSION: The behavioral spectrum of tic disorders includes OCD, other anxiety disorders, a mood disorder, and attention-deficit and disruptive behavior disorders.

Adolescent↗
PubMed2002

Incidence of and risk factors for HIV-associated distal sensory polyneuropathy.

OBJECTIVE: To assess the incidence of and risk factors for distal sensory polyneuropathy (DSP) in a cohort of HIV-infected subjects. METHODS: We followed 272 subjects semiannually for up to 30 months. DSP was diagnosed if subjects had decreased or absent ankle jerks, decreased or absent vibratory perception at the toes, or decreased pinprick or temperature in a stocking distribution. Subjects were further classified at each visit as having asymptomatic DSP (ADSP) (signs only) or symptomatic DSP (SDSP) if, in addition to the neurologic signs, paresthesias or pain was reported. RESULTS: At baseline, 45% of the subjects did not meet criteria for DSP, 20% met criteria for ADSP, and 35% met criteria for SDSP. Dideoxynucleoside therapy was used by 23% of the patients, and this treatment was independent of their neuropathy status. In longitudinal univariate analyses, history of AIDS diagnoses (hazard ratio [HR] = 1.89; p = 0.02) and lower CD4 cell count (HR = 0.69; p = 0.0006) were risk factors for incident DSP (ADSP or SDSP). However, for incident SDSP only, in addition to history of AIDS diagnoses, mood and neurologic (other than DSP) and functional abnormalities were significant risk factors. Functional abnormalities remained a significant risk factor in a multiple regression analysis. The presence of ADSP and the use of dideoxynucleosides at baseline were not significant risk factors for incident SDSP. The Kaplan-Meier estimate of the 1-year incidence of SDSP was 36%. CONCLUSION: Subjects with moderate-to-severe immunosuppression from HIV infection commonly have SDSP. However, sex, use of dideoxynucleosides, and presence of ADSP were not significant risk factors for SDSP.

Adult↗
PubMed2002

Quantitative functional measures in MS: what is a reliable change?

As a first step toward understanding which changes should be considered as meaningful, the authors assessed the reliability of quantitative functional tests on 5 consecutive days in 63 patients with MS, determining the range of measurement variability present when patients are clinically stable. Time to walk 25 feet (T25FW) and the 9-hole peg test (9HPT) varied by <20% of individual mean scores on repeated testing. Therefore, a 20% change on these tests can be considered to be the threshold that reliably indicates a true change in function for an individual.

Adult↗
PubMed2001

Prevalence of tics in schoolchildren and association with placement in special education.

BACKGROUND: Based on the knowledge that Tourette's syndrome (TS) is associated with several clinical features that can impair school function and growing evidence that the disorder is much more common than previously thought, the authors hypothesized that TS and related tic disorders would be associated with school problems in the childhood population at large. METHODS: Direct, blinded (to educational placement) interviews of 1,596 schoolchildren in Monroe County, Rochester, NY, were conducted. RESULTS: Twenty-seven percent of 341 students classified as receiving special education (SpEd) had tics compared with 19.7% (p = 0.008) of 1,255 students in regular classroom programs (RegEd). The weighted prevalence estimates for tics were 23.4% in SpEd and 18.5% in RegEd. A higher percentage of students in SpEd (7.0%) met diagnostic criteria for TS than students in RegEd (3.8%; p = 0.01). CONCLUSIONS: Although possibly influenced by selection bias, our results indicate that tic disorders are common in children and are highly associated with school dysfunction. Tics may represent an identifiable sign of an underlying brain developmental disorder that contributes to academic difficulties.

Adolescent↗
PubMed2001

Randomized, double-blind, placebo-controlled trial of albuterol in facioscapulohumeral dystrophy.

BACKGROUND/OBJECTIVES: Animal and human studies suggest that beta(2)-adrenergic agonists exert anabolic effects on muscles, inducing and preventing atrophy after a variety of insults. Based on data from an open-label trial of albuterol in 15 patients with facioscapulohumeral dystrophy (FSHD), the authors conducted a randomized, double-blind, placebo-controlled trial of sustained-release albuterol in this disease. METHODS: Ninety patients were randomized to three groups: placebo; 8.0 mg albuterol twice daily; or 16.0 mg albuterol twice daily. Patients were treated for 1 year with assessments at baseline and weeks 13, 26, and 52. The primary outcome was the 52-week change in global strength by maximum voluntary isometric contraction testing (MVICT). Secondary outcomes included changes at 52 weeks in strength by manual muscle testing (MMT), grip strength, functional testing, and muscle mass assessed by dual energy x-ray absorptiometry (DEXA). RESULTS: Eighty-four patients completed the study. The mean changes in composite MVICT scores were not significantly different between the groups (mean +/- SD: placebo 0.20 +/- 0.91; low dose -0.04 +/- 0.84; high dose 0.08 +/- 0.98). Similarly, there were no differences in the mean MMT change (placebo 0.04 +/- 0.16; low dose -0.03 +/- 0.13; high dose 0.00 +/- 0.15). Grip improved in both treatment groups compared to placebo (placebo -0.53 +/- 4.13, low dose +1.90 +/- 3.34 [p = 0.02], high dose +1.70 +/- 4.13 [p = 0.03]). The high-dose group had a significant increase in lean mass by DEXA (+1.57 +/- 1.71 kg) compared to placebo (0.25 +/- 2.24; p = 0.007). Albuterol was well tolerated; side effects included cramps, tremors, insomnia, and nervousness. CONCLUSIONS: Although albuterol did not improve global strength or function in patients with FSHD, it did increase muscle mass and improve some measures of strength.

Adrenergic beta-Agonists↗
PubMed2001

A prospective natural history study of inclusion body myositis: implications for clinical trials.

Eleven patients with untreated inclusion body myositis (IBM) were prospectively studied during a 6-month period that included muscle strength, lean body mass, and muscle mass measurements. There was an overall quantifiable mean decline in percent of predicted normal muscle strength of 4% from baseline in a 6-month period, but one third of patients showed no change or slight improvements in strength. Short-term treatment trials in IBM will require large numbers of patients to detect slowing, arrest, or even slight improvement in muscle strength.

Aged↗
PubMed2001

Freezing of gait in PD: prospective assessment in the DATATOP cohort.

OBJECTIVE: To study the development of freezing of gait in PD. BACKGROUND: Freezing of gait is a common, disabling, and poorly understood symptom in PD. METHODS: The authors analyzed data from 800 patients with early PD from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) clinical trial who were assigned either placebo, deprenyl, tocopherol, or the combination of deprenyl and tocopherol. The primary outcome measure was the time from randomization until the freezing of gait score on the Unified Parkinson's Disease Rating Scale (UPDRS) became positive. RESULTS: Fifty-seven patients (7.1%) had freezing of gait at study entry and 193 (26%) of the remaining patients experienced the symptom by the end of the follow-up period. Those with freezing of gait at baseline had significantly more advanced disease than those without the symptom, as measured by total UPDRS and Hoehn and Yahr stage. High baseline risk factors for developing freezing of gait during the follow-up period were the onset of PD with a gait disorder; higher scores of rigidity, postural instability, bradykinesia and speech; and longer disease duration. In contrast, tremor was strongly associated with a decreased risk for freezing of gait. At the end of follow-up, the signs most strongly associated with the freezing phenomenon were gait, balance, and speech disorders, not rigidity or bradykinesia. Deprenyl treatment was strongly associated with a decreased risk for developing freezing of gait; tocopherol had no effect. CONCLUSIONS: Freezing of gait is directly related to duration of PD. Risk factors at onset of disease are the absence of tremor and PD beginning as a gait disorder. The development of freezing of gait in the course of the illness is strongly associated with the development of balance and speech problems, less so with the worsening of bradykinesia, and is not associated with the progression of rigidity. These results support the concept that the freezing phenomenon is distinct from bradykinesia. Deprenyl, in the absence of L-dopa, was found to be an effective prophylactic treatment and should be considered for patients with PD who have an onset of gait difficulty.

Aged↗
PubMed2001

Clinical trials in HIV-associated cognitive impairment: cognitive and functional outcomes.

Cognitive and functional outcomes are of primary interest in the design of efficacy trials in HIV-associated cognitive impairment. In a longitudinal cohort study, weak associations were found between measures of cognitive performance and commonly used measures of daily functioning (mostly self-report measures) in HIV-infected individuals. Modifications of current functional scales or new functional instruments are needed to assess the clinical relevance of cognitive changes in clinical trials of HIV-associated cognitive impairment.

AIDS Dementia Complex↗
PubMed2001

Factors associated with incident human immunodeficiency virus-dementia.

BACKGROUND: Antecedents to human immunodeficiency virus-dementia (HIV-D) are poorly understood. OBJECTIVE: To identify risk factors for HIV-D. METHODS: Subjects who are positive for HIV who have CD4+ counts either below 200/microL or below 300/microL with evidence of cognitive impairment were enrolled in this study. Neurologic, cognitive, functional, and laboratory assessments were done semiannually for up to 30 months. Human immunodeficiency virus-dementia was diagnosed using American Academy of Neurology criteria for probable HIV-1-associated dementia complex. RESULTS: One hundred forty-six nondemented patients were enrolled, 45 of whom subsequently met criteria for incident HIV-D. In univariate analyses using the Cox proportional hazards regression model, the following variables were significantly associated with time to develop dementia: cognitive: abnormal scores on Timed Gait, Verbal Fluency, Grooved Pegboard, and Digit Symbol tests; attention-memory, psychomotor, and executive function domain scores; and the diagnosis of minor cognitive/motor disorder; neurologic and medical: increased abnormalities on the neurologic examination, extrapyramidal signs, history of HIV-related medical symptoms; functional: higher reported role or physical function difficulties. Depression was also a strong risk factor, along with sex, hematocrit, hemoglobin, and beta2-microglobulin levels. In a multivariate model that used cognitive domain scores, covariates with significant hazard ratios included depression, executive dysfunction, and the presence of minor cognitive/motor disorder. CONCLUSION: Cognitive deficits, minor cognitive/motor disorder, and depression may be early manifestations of HIV-D.

AIDS Dementia Complex↗