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Connie Marras

Publications and source records attributed to Connie Marras.

11 recordsLinked to original sources

Antipsychotic use in older adults with Parkinson's disease.

The choice of agents to treat psychotic symptoms in Parkinson's disease is important given the potential for antipsychotics to worsen Parkinsonism. The purpose of this study was to estimate the incidence of psychotic symptoms requiring treatment in individuals with Parkinson's disease after starting dopaminergic medications, and to describe the agents being selected as initial antipsychotic therapy. Using the administrative health care databases of Ontario, Canada, individuals 66 years of age or older with Parkinson's disease who were newly treated with dopaminergic agents were identified. Subsequent prescriptions for antipsychotic medications were then identified. A total of 10,347 older adults were newly started on dopaminergic agents between 1998 and 2003. The Kaplan-Meier estimate for the cumulative probability of requiring an antipsychotic at 7 years was 35%; 499 individuals (4.8%; 5.2/100 person-years) were prescribed an antipsychotic within 1 year of starting dopaminergic therapy. The proportion of initial antipsychotic prescriptions for typical antipsychotics decreased from 56% (42 of 75) in 1998 to 9% (8 of 88) in 2002. Antipsychotic use is common in individuals with Parkinsonism newly treated with dopaminergic medication. Typical antipsychotics are still commonly being chosen as first-line agents for older patients, indicating a need for interventions to improve practice.

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Unilateral versus bilateral tasks in early asymmetric Parkinson's disease: differential effects on bradykinesia.

Patients with Parkinson's disease (PD) have an impaired ability to perform two different simultaneous bimanual tasks. The differential effects of unilateral versus bilateral identical tasks on the bradykinesia scores of the more and less affected limbs in PD have not been examined. Twenty-seven patients with early and asymmetric PD underwent blinded, videotaped assessment, independently for each limb, using the bradykinesia items of the Unified Parkinson's Disease Rating Part III, Motor subscale (mUPDRS) and a Modified Bradykinesia Rating Scale (MBRS), which assessed amplitude, speed, and rhythm of movements. We found that the score for finger tapping in mUPDRS and MBRS, the score of amplitude of finger tapping in MBRS, and the lateralized scores of mUPDRS (sum of Items 23 to 25) of the most affected side significantly improved during the bimanual task. The improvement was associated with longer duration of illness, higher total scores in mUPDRS, and higher lateralized bradykinesia scores of the most affected side. There was a simultaneous deterioration of the lateralized bradykinesia scores in MBRS (sum of Items 23 to 25) and Item 25 of mUPDRS (rapid alternating movements) of the least affected side in bimanual tasks. In conclusion, identical bimanual tasks facilitate movement of the most affected side in early asymmetric PD at the cost of motor degradation in the least affected side. This observation also highlights the need to perform tasks of bradykinesia in one limb at a time for best accuracy.

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Atypical antipsychotics and parkinsonism.

BACKGROUND: Atypical antipsychotic agents are thought to be less likely than older typical agents to produce parkinsonism. This has not been well documented. We compared the risk of development of incident parkinsonism among older adults dispensed atypical relative to typical antipsychotics. METHODS: Retrospective cohort study of all adults 66 years and older in Ontario. We used Cox proportional hazards models to study the association between the type, potency, and dose of antipsychotic dispensed and the development of parkinsonism during 1 year of follow-up. RESULTS: All 25,769 older adults prescribed antipsychotics were observed for 11,573 person-years, and 449 events of parkinsonism were identified. Relative to individuals dispensed an atypical antipsychotic, those dispensed a typical agent were 30% more likely (adjusted hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.04-1.58) and those exposed to neither agent were 60% less likely (HR, 0.40; 95% CI, 0.29-0.43) to experience development of parkinsonism. Furthermore, those dispensed lower-potency typical agents were no different (HR, 0.75; 95% CI, 0.48-1.15), and those dispensed higher-potency typical antipsychotics were at close to a 50% greater risk (HR, 1.44; 95% CI, 1.13-1.84) of development of parkinsonism relative to atypical antipsychotics. Relative to those dispensed a high-dose atypical antipsychotic, those dispensed a typical antipsychotic were at similar risk for parkinsonism (Wald chi(2) = 0.14, P = .7). CONCLUSIONS: The risk of development of parkinsonism associated with the use of high-dose atypical antipsychotics was similar to that associated with the use of typical antipsychotics. Caution should be used when prescribing atypical antipsychotic therapy at high doses.

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Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study.

OBJECTIVE: To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving atypical or typical antipsychotics. DESIGN: Population based retrospective cohort study. SETTING: Ontario, Canada. Patients 32,710 older adults (< or = 65 years) with dementia (17,845 dispensed an atypical antipsychotic and 14,865 dispensed a typical antipsychotic). MAIN OUTCOME MEASURES: Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patient's admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking antipsychotics, died, or the study ended. RESULTS: After adjustment for potential confounders, participants receiving atypical antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving typical antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual atypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts. CONCLUSION: Older adults with dementia who take atypical antipsychotics have a similar risk of ischaemic stroke to those taking typical antipsychotics.

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Smell identification ability in twin pairs discordant for Parkinson's disease.

Olfactory dysfunction has been proposed to be a sign that may precede the motor features of Parkinson's disease (PD). To determine whether smell identification deficits predict subsequent PD, we studied smell identification ability using the University of Pennsylvania Smell Identification Test (UPSIT) in 62 members of male twin pairs discordant for PD at baseline. Smell identification ability was reduced at baseline in the twins with PD compared to their unaffected brothers (23 vs. 31 of 40; P = 0.001). UPSIT scores were not reduced in the twins without PD when compared to age- and gender-specific normal values. After a mean interval of 7.3 years, 28 unaffected twins were still alive and 19 agreed to a second evaluation. Two had newly developed PD. Neither twin had impaired smell identification at baseline. The average decline in UPSIT percentile scores in these 2 twins was greater than in the 17 twins who did not develop PD (-68% vs. -24%; P = 0.01). In subjects who did not meet Core Assessment Program for Intracerebral Transplantations diagnostic criteria for PD at baseline, the presence of cardinal signs of parkinsonism was not associated with lower baseline UPSIT scores nor with a subsequent decline. Smell identification ability may not be a sensitive indicator of future PD 7 or more years before the development of motor signs, even in a theoretically at-risk population.

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New thyroxine treatment in older adults beginning lithium therapy: implications for clinical practice.

OBJECTIVE: The authors sought to determine the incidence of lithium-induced hypothyroidism in a population-based cohort of older adults beginning lithium therapy and thereby to inform clinical guidelines on the frequency of monitoring necessary in this group. METHODS: The authors conducted a population-based observational cohort study using four administrative databases that contained information on over 1.3 million older adults in Ontario who receive universal healthcare coverage in terms of physician services, drugs, and hospitalizations. Over an 18-month period, they studied adults age>or=65 who were newly prescribed lithium or valproate, monitoring subjects for initiation of T4 therapy (as a proxy for hypothyroidism) while they continued their lithium use. RESULTS: The authors identified 1,705 new users of lithium and 2,406 new users of valproate with similar baseline characteristics. Lithium users were significantly more likely to be treated with T4 than were valproate users. The rate of T4 treatment per 100 person-years was 5.65 in the lithium group and 2.70 in the valproate group. CONCLUSION: T4 treatment was initiated in almost 6% of lithium-treated patients, suggesting the possibility that hypothyroidism developed twice as frequently among these patients as would be expected among a mixed-age population. Increased vigilance and continued monitoring of thyroid functioning for at least 2 years is necessary in older adults beginning lithium therapy.

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Quality of life in early Parkinson's disease: impact of dyskinesias and motor fluctuations.

The impact of dyskinesias and motor fluctuations on quality of life (QOL) at various stages in the course of Parkinson's disease (PD) is not well understood. In 301 subjects with early PD enrolled in a clinical trial (CALM-PD), we quantified the impact of motor complications on QOL and investigated how this changes over time. We also compared QOL related to demographic and treatment characteristics. The presence of dyskinesias was associated with visual analogue scale (VAS) scores 3.0 of 100 points higher (better) than those without dyskinesias in years 1 to 2, even when adjusting for Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. The positive association between dyskinesias and QOL scores was more marked in older patients. In years 3 to 4, dyskinesias no longer had a significant relationship with QOL. Younger subjects had higher VAS scores. Gender, motor fluctuations, and treatment regimen had no significant association with QOL, although a trend was found toward a small negative effect of motor fluctuations on QOL. We conclude that motor complications that occur within the first 4 years of treatment of PD do not have a significant negative effect on quality of life as measured by a visual analogue scale for most patients.

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Outcome measures for clinical trials in Parkinson's disease: achievements and shortcomings.

Three areas of intense investigation in Parkinson's disease clinical trials include symptomatic treatment of Parkinsonism, disease-modifying therapy (or neuroprotection), and the prevention and treatment of motor complications of dopaminergic therapy. Difficulty interpreting the results of many studies in recent years has been attributed to problems with the chosen outcome measures. This article reviews the most common outcome measures used, assesses their positive attributes and proposes needs for future research. The Unified Parkinson's disease Rating Scale has been extensively validated and is by far the most common outcome measure used in trials of symptomatic therapy. Ambiguities in the response scale descriptors, poor inter-rater reliability of some items and a lack of items addressing nonmotor features of the disease are being addressed in a revision of the scale. Quality of life outcomes are being used in the minority of clinical trials, and no single generic or disease-specific quality of life measure is being used most frequently. Additional work validating several of the disease-specific instruments is needed. When a generic measure is used, its validity for use in Parkinson's disease must be critically assessed despite its previously established validity in other diseases. With respect to measuring motor complications, significant unmet needs include a consensus as to the best way to define the first motor complication and validating time to the first occurrence of motor complications as a surrogate of future disability and quality of life. Measuring the effectiveness of a potential neuroprotective agent presents unique challenges, particularly since symptomatic effects of the experimental agent or concomitant treatment can obscure any neuroprotective effects. Study designs and biomarkers are being developed that may overcome this problem. Currently, neuroimaging techniques that reflect function of the dopaminergic system are the most promising biomarkers but still require additional validation.

Antiparkinson Agents↗

Predicting motor decline and disability in Parkinson disease: a systematic review.

CONTEXT: The clinical course of Parkinson disease (PD) varies from patient to patient. A number of studies investigating predictors of prognosis in patients with PD have been performed. OBJECTIVE: To summarize evidence on predicting the rate of motor decline and increasing disability in early PD. DATA SOURCES: English-language and French-language literature cited in the MEDLINE database (1966-2002). STUDY SELECTION: Cohort and case-control studies investigating associations between clinical features and subsequent motor impairment or disability were selected. DATA EXTRACTION: Study methods and results were abstracted by a single reviewer. DATA SYNTHESIS: The results of 13 studies were summarized qualitatively. Study methods were highly variable, particularly regarding the choice of outcome measure. Baseline motor impairment and cognitive impairment are probable predictors of more rapid motor decline and disability. A lack of tremor at onset and older age both appear to be predictive of increasing disability, but conflicting results exist for their association with the rate of change of motor impairment. Family history of PD does not appear to be prognostically important. The prognostic value of many other factors studied is uncertain owing to conflicting or unconfirmed results. CONCLUSIONS: Uncertainty remains about the prognostic importance of many baseline clinical features in PD. Greater baseline impairment, early cognitive disturbance, older age, and lack of tremor at onset appear to be adverse prognostic factors.

Age Factors↗