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David Oakes

Publications and source records attributed to David Oakes.

18 recordsLinked to original sources
PubMed2006

A randomized controlled trial of etilevodopa in patients with Parkinson disease who have motor fluctuations.

BACKGROUND: Motor fluctuations are a common complication in patients with Parkinson disease (PD) receiving long-term levodopa therapy. Slowed gastric emptying and poor solubility of levodopa in the gastrointestinal tract may delay the onset of drug benefit after dosing. Etilevodopa is an ethyl-ester prodrug of levodopa that has greater gastric solubility, passes quickly into the small intestine, is rapidly hydrolyzed to levodopa, and has a shortened time to maximum levodopa concentration. OBJECTIVE: To determine the efficacy, safety, and tolerability of etilevodopa in patients with PD who have motor fluctuations. DESIGN: A double-blind, randomized, comparative clinical trial. SETTING: Forty-four sites in the United States and Canada. PATIENTS: Three hundred twenty-seven patients with PD who had a latency of at least 90 minutes total daily time to "on" (TTON) after levodopa dosing. INTERVENTION: Treatment with either etilevodopa-carbidopa or levodopa-carbidopa for 18 weeks. MAIN OUTCOME MEASURE: Change from baseline in total daily TTON as measured using home diaries. RESULTS: The reduction in mean total daily TTON from baseline to treatment was 0.58 hour in the etilevodopa-carbidopa group and 0.79 hour in the levodopa-carbidopa group (P = .24). There was no significant difference between the etilevodopa-carbidopa and levodopa-carbidopa groups in the reduction of response failures (-6.82% vs -4.69%; P = .20). Total daily "off" time improved in the etilevodopa-carbidopa (-0.85 hour) and levodopa-carbidopa (-0.87 hour) groups without an increase in on time with troublesome dyskinesias. CONCLUSION: Despite the theoretical pharmacokinetic advantage of etilevodopa, there was no improvement in TTON, response failures, or off time compared with levodopa.

Aged↗
PubMed2006

Preparing for preventive clinical trials: the Predict-HD study.

BACKGROUND: The optimal design and outcome measures for preventive clinical trials in neurodegenerative diseases are unknown. OBJECTIVE: To examine measures that may be associated with disease in the largest cohort ever recruited of prediagnosed individuals carrying the gene expansion for Huntington disease (HD). DESIGN: The Predict-HD study is a multicenter observational research study in progress at 17 sites in the United States, 4 in Canada, and 3 in Australia. SETTING: Genetics and HD outpatient clinics. PARTICIPANTS: Five hundred five at-risk individuals who had previously undergone elective DNA analyses for the CAG expansion in the HD gene (predictive testing) and did not currently have a clinical diagnosis of HD. MAIN OUTCOME MEASURES: Basal ganglia volumes on magnetic resonance images, estimated probability of diagnosis (based on CAG repeat length), performances on 21 standardized cognitive tasks, total scores on 3 scales of psychiatric distress, and motor diagnosis based on the Unified Huntington's Disease Rating Scale. RESULTS: Several variables showed progressive decline as the diagnostic ratings advanced toward manifest disease. Estimated probability of diagnosis was associated with Unified Huntington's Disease Rating Scale prediagnostic stages and varied from 15% in persons with no motor abnormalities to nearly 40% in those with abnormalities suggestive of probable disease. Striatal volumes, cognitive performances, and even psychiatric ratings declined significantly with motor manifestations of disease. CONCLUSIONS: The documentation of biological and refined clinical markers suggests several clinical end points for preventive clinical trials. Longitudinal study is critical to further validate possible markers for prediagnosed HD.

Adult↗
PubMed2006

Head injury and Parkinson's disease risk in twins.

OBJECTIVE: Head injury is an inconsistently reported risk factor for Parkinson's disease (PD). Many related variables might confound this association, such as differences in childhood and adolescent lifestyles or genetically determined risk-taking behaviors. Twin studies circumvent some of these problems, because twins are genetically and environmentally much more similar than typical cases and control subjects. METHODS: We conducted a case-control study in 93 twin pairs discordant for PD ascertained from the National Academy of Sciences/National Research Council World War II Veteran Twins Cohort. RESULTS: A prior head injury with amnesia or loss of consciousness was associated with an increased risk for PD (odds ratio, 3.8; 95% confidence interval, 1.3-11; p = 0.014). Truncating observations 10 years before PD onset enhanced the association. Though less precise, the association was somewhat stronger in monozygotic than in dizygotic pairs. Risk increased further with a subsequent head injury (p trend = 0.022) and with head injuries requiring hospitalization. Duration of unconsciousness was not associated. In a subanalysis of 18 pairs concordant for PD, the twin with younger onset PD was more likely to have sustained a head injury, although numbers were small. INTERPRETATION: Our results suggest that mild-to-moderate closed head injury may increase PD risk decades later.

Adolescent↗
PubMed2006

Rasagiline improves quality of life in patients with early Parkinson's disease.

The objective of this study was to determine the effects of rasagiline as monotherapy on quality of life (QOL) in patients with early Parkinson's disease (PD). Rasagiline, a potent, second-generation, irreversible, selective monoamine oxidase B inhibitor improves PD symptoms in patients with early PD. Patients with early untreated PD were randomly assigned to once-daily rasagiline 1 mg/day, rasagiline 2 mg/day, or placebo in a 6-month, double-blind trial (n=404). At the end of 6 months, patients entered the preplanned, active-treatment phase in which those receiving 1 mg/day and 2 mg/day of rasagiline continued on their previously assigned dosages and those receiving placebo switched to rasagiline 2 mg/day, while maintaining blinding to treatment assignments. QOL was measured with the Parkinson's Disease Quality of Life questionnaire (PDQUALIF) at 0, 14, 26, and 52 weeks after randomization. Analysis of the change in PDQUALIF scores from baseline to 6 months showed adjusted treatment effects (with 95% confidence interval) favoring rasagiline over placebo of -2.91 units (-5.19, -0.64, P=0.01) for the 1 mg/day group and -2.74 units (-5.02, -0.45, P=0.02) for the 2 mg/day. Subscore analysis attributed most of this benefit to the self-image/sexuality domain. At 12 months (n=266), with all groups receiving rasagiline for at least 6 months, no significant differences in PDQUALIF scores were seen between groups. Rasagiline improved QOL compared with placebo. This QOL improvement appears to be accounted for primarily by the symptomatic benefit of rasagiline.

Aged↗
PubMed2005

Atherosclerotic risk genotypes and recurrent coronary events after myocardial infarction.

The association of a group of prespecified atherosclerotic risk genotypes with recurrent coronary events (coronary-related death, nonfatal myocardial infarction, or unstable angina) was investigated in a cohort of 1,008 patients after infarction during an average follow-up of 28 months. We used a carrier-ship approach with time-dependent survivorship analysis to evaluate the average risk of each carried genotype. Contrary to expectation, the hazard ratio for recurrent coronary events per carried versus noncarried genotype was 0.89 (95% confidence interval 0.80 to 0.99, p = 0.03) after adjustment for relevant genetic, clinical, and environmental covariates. This hazard ratio, derived from the 7 prespecified genotypes, indicated an average 11% reduction in the risk of recurrent coronary events per carried versus noncarried genotype. At 1 year after hospital discharge, the cumulative probability of recurrent coronary events was 26% in those who carried < or =1, 20% for those with 2 to 4, and 13% for those with > or =5 of these genotypes (p = 0.02). This unexpected risk reversal is a likely consequence of changes in the mix of risk factors in pre- and postinfarction populations. In conclusion, this under appreciated, population-based, risk-reversal phenomenon may explain the inconsistent associations of genetic risk factors with outcome events in previous reports involving coronary populations with different risk attributes.

Aged↗
PubMed2005

Interrater agreement in the assessment of motor manifestations of Huntington's disease.

With prospects improving for experimental therapeutics aimed at postponing the onset of illness in preclinical carriers of the Huntington's disease (HD) gene, we assessed agreement among experienced clinicians with respect to the motor manifestations of HD, a relevant outcome measure for preventive trials in this population. Seventy-five clinicians experienced in the evaluation of patients with early HD and six non-clinicians were shown a videotape compiled from the film archives of the United States-Venezuela Collaborative HD Research Project. Observers were asked to rate a 2-3-minute segment of the motor examination for each of 17 at-risk subjects. The rating scale ranged from 0 (normal) to 4 (unequivocal extrapyramidal movement disorder characteristic of HD). As measured by a weighted kappa statistic, there was substantial agreement among the 75 clinicians in the judgment of unequivocal motor abnormalities comparing scale ratings of 4 with ratings that were not 4 (weighted kappa = 0.67; standard error (SE) = 0.09). Agreement among the non-clinicians was only fair (weighted kappa = 0.28; SE = 0.10). Even under the artificial conditions of a videotape study, experienced clinicians show substantial agreement about the signs that constitute the motor manifestations of illness in subjects at risk for HD. We expect these findings to translate to a similar level of interobserver agreement in the clinical trial setting involving experienced investigators examining live patients.

Basal Ganglia Diseases↗
PubMed2004

Levodopa and the progression of Parkinson's disease.

BACKGROUND: Despite the known benefit of levodopa in reducing the symptoms of Parkinson's disease, concern has been expressed that its use might hasten neurodegeneration. This study assessed the effect of levodopa on the rate of progression of Parkinson's disease. METHODS: In this randomized, double-blind, placebo-controlled trial, we evaluated 361 patients with early Parkinson's disease who were assigned to receive carbidopa-levodopa at a daily dose of 37.5 and 150 mg, 75 and 300 mg, or 150 and 600 mg, respectively, or a matching placebo for a period of 40 weeks, and then to undergo withdrawal of treatment for 2 weeks. The primary outcome was a change in scores on the Unified Parkinson's Disease Rating Scale (UPDRS) between baseline and 42 weeks. Neuroimaging studies of 142 subjects were performed at baseline and at week 40 to assess striatal dopamine-transporter density with the use of iodine-123-labeled 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT) uptake. RESULTS: The severity of parkinsonism increased more in the placebo group than in all the groups receiving levodopa: the mean difference between the total score on the UPDRS at baseline and at 42 weeks was 7.8 units in the placebo group, 1.9 units in the group receiving levodopa at a dose of 150 mg daily, 1.9 in those receiving 300 mg daily, and -1.4 in those receiving 600 mg daily (P<0.001). In contrast, in a substudy of 116 patients the mean percent decline in the [123I]beta-CIT uptake was significantly greater with levodopa than placebo (-6 percent among those receiving levodopa at 150 mg daily, -4 percent in those receiving it at 300 mg daily, and -7.2 percent among those receiving it at 600 mg daily, as compared with -1.4 percent among those receiving placebo; 19 patients with no dopaminergic deficits on the baseline scans were excluded from the analysis) (P=0.036). The subjects receiving the highest dose of levodopa had significantly more dyskinesia, hypertonia, infection, headache, and nausea than those receiving placebo. CONCLUSIONS: The clinical data suggest that levodopa either slows the progression of Parkinson's disease or has a prolonged effect on the symptoms of the disease. In contrast, the neuroimaging data suggest either that levodopa accelerates the loss of nigrostriatal dopamine nerve terminals or that its pharmacologic effects modify the dopamine transporter. The potential long-term effects of levodopa on Parkinson's disease remain uncertain.

Aged↗
PubMed2004

(123I) beta-CIT and single-photon emission computed tomographic imaging vs clinical evaluation in Parkinsonian syndrome: unmasking an early diagnosis.

BACKGROUND: The diagnosis of Parkinson disease is currently based on clinical evaluation. Functional neuroimaging using (123I) beta-carboxymethyoxy-3-beta-(4-iodophenyl) tropane (CIT) and single-photon emission computed tomography (SPECT) provides information on the integrity of the dopaminergic system in vivo and is a promising diagnostic tool in early Parkinson disease. OBJECTIVE: To evaluate the diagnostic accuracy of dopamine transporter imaging using (123I)beta-CIT in patients with suspected parkinsonian syndrome (PS). DESIGN: Community neurologists referred patients with suspected PS for imaging evaluation. Clinical diagnoses (positive PS or negative PS) were provided by the community neurologists and 2 movement disorder experts. We performed (123I)beta-CIT and SPECT imaging, and imaging diagnoses of positive PS or negative PS were assigned. A 6-month follow-up clinical diagnosis was assigned by a movement disorder expert blind to the imaging data, which represented the "gold standard" diagnosis for the study. RESULTS: Thirty-five patients with suspected PS were referred. Diagnoses in question included essential tremor, psychogenic parkinsonism, drug-induced parkinsonism, primary dystonia, and unspecified gait disorder. Comparing the community neurologist's diagnoses at referral with the gold standard diagnosis, there was dis agreement in 25.7% (sensitivity, 0.92; specificity, 0.30). Comparing the quantitative imaging diagnoses with the gold standard, there was disagreement in 8.6% (sensitivity, 0.92; specificity, 1.00). CONCLUSION: Performing (123I)beta-CIT and SPECT imaging at baseline appears to be a useful diagnostic tool to detect patients thought to have PS at baseline but who, after follow-up, do not have PS.

Aged↗
PubMed2003

Reliability of reported age at onset for Parkinson's disease.

An individual's age at onset of Parkinson disease (PD) can be collected through a variety of sources, including medical records, family report, and clinical observation. The most common source of PD age at onset information in the research setting is family-report, which is then typically used to classify a subject as juvenile, young, or late age at onset. The reliability of the family-reported age at onset of PD has not been rigorously examined. The present study used data from individuals diagnosed with PD to evaluate the reliability of age at onset information by comparing data obtained from three sources: 1) the subject's medical records, 2) a Family History Questionnaire, and 3) a Subject History Questionnaire. Among the 149 subjects with data for all three age at onset sources, the estimated reliability was R = 0.94. Similar reliability was observed when the sample was stratified based on gender, age at examination, disease duration, first symptom of PD, and years of education. The three measures of age at onset of PD show excellent agreement, strengthening confidence in the reliability of the reported age of clinical onset for PD.

Adult↗
PubMed2003

Randomized clinical trial of pacifier use and bottle-feeding or cupfeeding and their effect on breastfeeding.

OBJECTIVE: To enhance breastfeeding practices, the World Health Organization discourages pacifiers and bottle-feeding. However, the effect of artificial nipples on breastfeeding duration is poorly defined. The effects of 2 types of artificial nipple exposure on breastfeeding duration were evaluated: 1) cupfeeding versus bottle-feeding for the provision of in-hospital supplements and 2) early (2-5 days) versus late (>4 weeks) pacifier introduction. METHODS: A total of 700 breastfed newborns (36-42 weeks, birth weight >or=2200 g) were randomly assigned to 1 of 4 intervention groups: bottle/early pacifier (n = 169), bottle/late pacifier (n = 167), cup/early pacifier (n = 185), or cup/late pacifier (n = 179). The cup/bottle intervention was invoked for infants who received supplemental feedings: cup (n = 251), bottle (n = 230). Data were collected at delivery and at 2, 5, 10, 16, 24, 38, and 52 weeks' postpartum. Intervention effects on breastfeeding duration were evaluated with logistic regression and survival analyses. RESULTS: Supplemental feedings, regardless of method (cup or bottle), had a detrimental effect on breastfeeding duration. There were no differences in cup versus bottle groups for breastfeeding duration. Effects were modified by the number of supplements; exclusive and full breastfeeding duration were prolonged in cup-fed infants given >2 supplements. Among infants delivered by cesarean, cupfeeding significantly prolonged exclusive, full, and overall breastfeeding duration. Exclusive breastfeeding at 4 weeks was less likely among infants exposed to pacifiers (early pacifier group; odds ratio: 1.5; 95% confidence interval: 1.0-2.0). Early, as compared with late, pacifier use shortened overall duration (adjusted hazard ratio: 1.22; 95% confidence interval: 1.03-1.44) but did not affect exclusive or full duration. CONCLUSIONS: There was no advantage to cupfeeding for providing supplements to the general population of healthy breastfed infants, but it may have benefitted mother-infant dyads who required multiple supplements or were delivered by cesarean. Pacifier use in the neonatal period was detrimental to exclusive and overall breastfeeding. These findings support recommendations to avoid exposing breastfed infants to artificial nipples in the neonatal period.

Adult↗
PubMed2002

Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline.

BACKGROUND: Parkinson disease (PD) is a degenerative neurological disorder for which no treatment has been shown to slow the progression. OBJECTIVE: To determine whether a range of dosages of coenzyme Q10 is safe and well tolerated and could slow the functional decline in PD. DESIGN: Multicenter, randomized, parallel-group, placebo-controlled, double-blind, dosage-ranging trial. SETTING: Academic movement disorders clinics. PATIENTS: Eighty subjects with early PD who did not require treatment for their disability. INTERVENTIONS: Random assignment to placebo or coenzyme Q10 at dosages of 300, 600, or 1200 mg/d. MAIN OUTCOME MEASURE: The subjects underwent evaluation with the Unified Parkinson Disease Rating Scale (UPDRS) at the screening, baseline, and 1-, 4-, 8-, 12-, and 16-month visits. They were followed up for 16 months or until disability requiring treatment with levodopa had developed. The primary response variable was the change in the total score on the UPDRS from baseline to the last visit. RESULTS: The adjusted mean total UPDRS changes were +11.99 for the placebo group, +8.81 for the 300-mg/d group, +10.82 for the 600-mg/d group, and +6.69 for the 1200-mg/d group. The P value for the primary analysis, a test for a linear trend between the dosage and the mean change in the total UPDRS score, was.09, which met our prespecified criteria for a positive trend for the trial. A prespecified, secondary analysis was the comparison of each treatment group with the placebo group, and the difference between the 1200-mg/d and placebo groups was significant (P =.04). CONCLUSIONS: Coenzyme Q10 was safe and well tolerated at dosages of up to 1200 mg/d. Less disability developed in subjects assigned to coenzyme Q10 than in those assigned to placebo, and the benefit was greatest in subjects receiving the highest dosage. Coenzyme Q10 appears to slow the progressive deterioration of function in PD, but these results need to be confirmed in a larger study.

Administration, Oral↗
PubMed2002

Impact of sustained deprenyl (selegiline) in levodopa-treated Parkinson's disease: a randomized placebo-controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trial.

Deprenyl (selegiline) delays the need for levodopa therapy in patients with early Parkinson's disease, but the long-term benefits of this treatment remain unclear. During 1987 to 1988, 800 patients with early Parkinson's disease were randomized in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial to receive deprenyl, tocopherol, combined treatments, or a placebo and were then placed on active deprenyl (10mg/day). A second, independent randomization was carried out in early 1993 for 368 subjects who by that time had required levodopa and who had consented to continuing the deprenyl treatment (D subjects) or changing to a matching placebo (P subjects) under double-blind conditions. The first development of wearing off, dyskinesias, or on-off motor fluctuations was the prespecified primary outcome measure. During the average 2-year follow-up, there were no differences between the treatment groups with respect to the primary outcome measure (hazard ratio, 0.87; 95% confidence interval, 0.63, 1.19; p = 0.38), withdrawal from the study, death, or adverse events. Although 34% of D subjects developed dyskinesias and only 19% of P subjects did (p = 0.006), only 16% of D subjects developed freezing of gait but 29% of P subjects did (p = 0.0003). Decline in motor performance was less in D subjects than P subjects. Levodopa-treated Parkinson's disease patients who had been treated with deprenyl for up to 7 years, compared with patients who were changed to a placebo after about 5 years, experienced slower motor decline and were more likely to develop dyskinesias but less likely to develop freezing of gait.

Aged↗
PubMed2002

Design and analysis of two-period studies of potentially disease-modifying treatments.

A number of two-period designs have been introduced in the neurological clinical trials literature to evaluate the effects of treatment on progressive diseases, using names such as withdrawal, active-extension, randomized withdrawal, randomized start, and staggered-start designs. After parallel groups complete the first period, treatment is either initiated or withdrawn in the second period in a subset of subjects. The purpose of the second period is to provide evidence of whether any effect of treatment observed during the first period is long-term ("disease-modifying") or short-term and transitory ("symptomatic"). A four-arm version, which we term a complete two-period design, has active/active, active/placebo, placebo/active and placebo/placebo respective treatment assignments in the two periods. We provide statistical models for these designs, describe some of the appropriate analyses, and investigate the relative efficiencies of various allocations and special cases. We describe extensions to full and partial factorial versions of such designs which permit efficient and simultaneous evaluation of disease-modifying and symptomatic effects of two or more treatments, along with possible interactions. Advantages and limitations of the various designs are discussed.

Alzheimer Disease↗
PubMedDate not supplied

Prevalence and penetrance of HFE mutations in 4865 unselected primary care patients.

Two HFE gene mutations, C282Y and H63D, underlie the vast majority of cases of hereditary hemochromatosis. We performed a cross-sectional primary care-based study to determine the allele frequency of the C282Y and H63D mutations and the penetrance of each of the affected genotypes defined by their presence. Patients had previously undergone transferrin saturation (TS) testing. A total of 4865 unselected frozen serum samples were analyzed to determine serum ferritin (SF) levels. Genomic DNA isolated from these samples was analyzed for the C282Y and H63D HFE mutations. Homozygotes for each mutation and compound heterozygotes were evaluated to determine clinical penetrance. The allele frequency of C282Y was 0.0507 among Caucasian and 0.0067 among African Americans; that of H63D was 0.1512 and 0.0263, respectively. TS was > or =55% in 83% of individuals with C282Y/C282Y, 14.5% of C282Y/H63D, and 5% of H63D/H63D; SF was > or =300 microG/L in 42, 9, and 5% of these genotypes, respectively. None of the 12 C282Y homozygotes had cardiac dysfunction or hepatic cirrhosis. Only 9/129 (7%) individuals with the genotypes C282Y/H63D or H63D/H63D had a SF > or =300 microG/L; many had explanations other than iron overload that accounted for this increase. Thus, the prevalence of the common HFE mutations is the same in our population as previously described. TS screening would detect most C282Y homozygotes but not the other two genotypes. The penetrance of C282Y/C282Y is significant. The biochemical penetrance of H63D/H63D and C282Y/H63D is modest and the clinical penetrance is low.

Adult↗
PubMedDate not supplied

Drug-induced psychosis in Parkinson disease: phenomenology and correlations among psychosis rating instruments.

OBJECTIVES: To describe further the phenomenology of drug-induced psychosis (DIP) in patients with Parkinson disease (PD) and assess which items on two common psychosis rating instruments-the Brief Psychiatric Rating Scale (BPRS) and the Neuropsychiatric Inventory (NPI)-are the best measure of DIP by comparing them with the Clinical Global Impression Scale (CGIS). METHODS: Baseline data from two placebo-controlled, double-blind studies of olanzapine in PD patients with DIP were collected and analyzed. RESULTS: A total of 157 of 160 patients had hallucinations, with visual hallucinations being the most common (97% of subjects), followed by auditory (48%), tactile (23%), and olfactory (16%). Seventy-six percent of subjects experienced delusions, and all types of delusions occurred with relatively equal frequency. The CGIS correlated with suspiciousness, hallucinatory behavior, unusual thought content, and hostility on the BPRS; and delusions, hallucinations, agitation, aberrant motor behavior, and sleep on the NPI. CONCLUSION: Nonvisual hallucinations and delusions may occur more frequently in DIP than previously thought. These symptoms, plus agitation and hostility, may ultimately be the best measure of DIP in patients with PD.

Aged↗