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Biomedical subjects

Robert G Holloway

Publications and source records attributed to Robert G Holloway.

At least 19 recordsLinked to original sources
PubMed2006

What is the risk of developing parkinsonism following neuroleptic use?

Use of neuroleptic medications is common among elderly patients. Using multivariate models, the authors found that use of antipsychotic medications, age, and disability were strong predictors of developing self-reported Parkinson disease (PD) in the subsequent year among 1992 to 2000 Medicare Current Beneficiary Survey participants. Although more research is needed, these data suggest that 126 Medicare beneficiaries would need to be treated with neuroleptic medications to cause one additional case of self-reported PD.

Aged↗
PubMed2006

Financial anatomy of neuroscience research.

OBJECTIVE: To estimate the level of funding for neuroscience research from federal and industry sources and to examine the therapeutic advances in the neurosciences over the past decade. METHODS: We examined financing for neuroscience research over the past decade from the following principal sponsors of biomedical research: the National Institutes of Health, the pharmaceutical industry, large biotechnology firms, and large medical device firms. We also examined US Food and Drug Administration approvals for new molecular entities and medical devices for indications within the neurosciences. Neuroscience was defined to include funding and approvals for neurological and psychiatric conditions. RESULTS: Total (nominal) industry and government funding for neuroscience research increased from $4.8 billion in 1995 to $14.1 billion in 2005 and doubled after adjusting for inflation. In 2005, the pharmaceutical industry and the largest biotechnology and medical device firms accounted for 58% of total funding. The US Food and Drug Administration approved 40 new molecular entities for indications within the neurosciences from 1995 to 2005, with the annual number of approvals remaining relatively stagnant during this period. From 1995 to 2005, the US Food and Drug Administration also approved 1,679 medical devices in the neurosciences for use. INTERPRETATION: Financing for neuroscience research has increased significantly over the past decade, but new approvals for drugs in the neurosciences have not kept pace with the rapid increase in funding. This lag may represent a natural delay in realizing the return in the investment in scientific research or a decline in the productivity of neuroscience research.

Animals↗
PubMed2006

Biomarkers in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder that is largely diagnosed and managed clinically. Biomarkers, as indicators of underlying biological processes, offer the potential to identify individuals at risk for PD, screen new therapies, assist in the diagnosis and help optimize management of PD. However, to date, biomarkers, despite their considerable promise, have had limited utility in clinical trials and practice.

Biomarkers↗
PubMed2005

Prognosis and decision making in severe stroke.

CONTEXT: An increasing number of deaths following severe stroke are due to terminal extubations. Variation in withdrawal-of-care practices suggests the possibility of unnecessary prolongation of suffering or of unwanted deaths. OBJECTIVES: To review the available evidence on prognosis in mechanically ventilated stroke patients and to provide an overall framework to optimize decision making for clinicians, patients, and families. DATA SOURCES: Search of MEDLINE from 1980 through March 2005 for English-language articles addressing prognosis in mechanically ventilated stroke patients. From 689 articles identified, we selected 17 for further review. We also identified factors that influence, and decision-making biases that may result, in overuse or underuse of life-sustaining therapies, with a particular emphasis on mechanical ventilation. EVIDENCE SYNTHESIS: Overall mortality among mechanically ventilated stroke patients is high, with a 30-day death rate approximating 58% (range in literature, 46%-75%). Although data are limited, among survivors as many as one third may have no or only slight disability, yet many others have severe disability. One can further refine prognosis according to knowledge of stroke syndromes, early patient characteristics, use of clinical prediction rules, and the need for continuing interventions. Factors influencing preferences for life-sustaining treatments include the severity and pattern of future clinical deficits, the probability of these deficits, and the burdens of treatments. Decision-making biases that may affect withdrawal-of-treatment decisions include erroneous prognostic estimates, inappropriate methods of communicating evidence, misunderstanding patient values and expectations, and failing to appreciate the extent to which patients can physically and psychologically adapt. CONCLUSIONS: Although prognosis among mechanically ventilated stroke patients is generally poor, a minority do survive without severe disability. Prognosis can be assessed according to clinical presentation and patient characteristics. There is an urgent need to better understand the marked variation in the care of these patients and to reliably measure and improve the patient-centeredness of such decisions.

Communication↗
PubMed2005

Pramipexole and levodopa in early Parkinson's disease: dynamic changes in cost effectiveness.

BACKGROUND AND OBJECTIVE: In chronic disease, treatment effects and costs accumulate over time; hence, the choice of time horizon in cost-effectiveness analysis can be particularly important. In this article we analyse the dynamic changes in cumulative costs, effects and incremental cost effectiveness of two competing drug strategies in patients with early Parkinson's disease (PD). METHODS: Three hundred and one subjects with PD were randomised to initial pramipexole or levodopa and followed every 3 months over a 4-year period. Healthcare resource use was recorded in patient diaries and valued using a variety of sources at year 2002 US dollar values. Health-related quality of life (HRQoL) was measured using the EuroQoL EQ-5D. The study was conducted from a US societal perspective. Missing data were imputed using a multivariate fixed-effects model. Additional quality adjusted life years (QALY) gained by using pramipexole compared with levodopa were estimated as the area between the normalised treatment HRQoL profiles. The QALYs and costs for each treatment arm were calculated for various study horizons.The incremental cost-effectiveness ratio (ICER) and the net monetary benefit (NB) [using 50,000 US dollars, 100,000 US dollars and 150,000 US dollars as the value of a QALY] were estimated, and were bootstrapped to calculate the standard errors. Cost-effectiveness acceptability curves (CEAC) were built to estimate the probability that pramipexole was cost effective given different societal values of QALY, for various study horizons.We conducted sensitivity analyses on the ICER and the NB to test their robustness to various assumptions about missing data, for various subpopulations and under changes in the drug prices. RESULTS: Under the base-case assumptions, the ICER for pramipexole was 42,989 US dollars per QALY. Using the CEAC approach, the probability that pramipexole was cost effective relative to levodopa over the first 4 years was 0.57, 0.77 and 0.82 when a QALY was valued at 50,000 US dollars, 100,000 US dollars, and 150,000 US dollars, respectively. Over time, the ICER for pramipexole improved and uncertainty around the ICER decreased. If, after treatment withdrawal, HRQoL improved in pramipexole subjects and declined in levodopa subjects (best-case scenario for pramipexole), the probability of pramipexole being cost effective increased to 0.88, 0.96 and 0.98, respectively. Factors that improved the ICER of pramipexole were a decrease in the relative price of pramipexole and having low HRQoL or depression at baseline. CONCLUSIONS: The cost effectiveness of pramipexole compared with levodopa in the treatment of early PD increased as the time horizon of the clinical trial extended from 2 to 4 years. Our results suggest that pramipexole is more cost effective for patients with depression and low baseline HRQoL than in other patient subgroups.

Administration, Oral↗
PubMed2005

Responsiveness of life-threatening refractory emesis to gabapentin-scopolamine therapy following posterior fossa surgery. Case report.

Craniotomy-associated chronic emesis can be refractory to currently approved antiemetic therapy. The authors describe a man who suffered 4 weeks of severe refractory emesis, failure to thrive, and a 40-lb weight loss after he underwent resection of a posterior fossa cholesteatoma. The patient experienced complete resolution of emesis and anorexia in response to combined gabapentin-scopolamine therapy. This case provides anecdotal evidence for the use of gabapentin-scopolamine therapy in patients with chronic, refractory nausea and emesis, particularly following posterior fossa surgery, during which medullary nausea and emesis centers may be affected.

Amines↗
PubMed2004

Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial.

BACKGROUND: The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear. OBJECTIVE: To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes. DESIGN: Multicenter, parallel-group, double-blind, randomized controlled trial. SETTING: Academic movement disorders clinics at 22 sites in the United States and Canada. PATIENTS: Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001. INTERVENTION: Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability. MAIN OUTCOME MEASURES: Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events. RESULTS: Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups. CONCLUSIONS: Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but they are associated with different efficacy and adverse-effect profiles.

Aged↗
PubMed2004

Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations.

The Movement Disorder Society Task Force for Rating Scales for Parkinson's disease (PD) prepared a critique of the Hoehn and Yahr scale (HY). Strengths of the HY scale include its wide utilization and acceptance. Progressively higher stages correlate with neuroimaging studies of dopaminergic loss, and high correlations exist between the HY scale and some standardized scales of motor impairment, disability, and quality of life. Weaknesses include the scale's mixing of impairment and disability and its non-linearity. Because the HY scale is weighted heavily toward postural instability as the primary index of disease severity, it does not capture completely impairments or disability from other motor features of PD and gives no information on nonmotor problems. Direct clinimetric testing of the HY scale has been very limited, but the scale fulfills at least some criteria for reliability and validity, especially for the midranges of the scale (Stages 2-4). Although a "modified HY scale" that includes 0.5 increments has been adopted widely, no clinimetric data are available on this adaptation. The Task Force recommends that: (1) the HY scale be used in its original form for demographic presentation of patient groups; (2) when the HY scale is used for group description, medians and ranges should be reported and analysis of changes should use nonparametric methods; (3) in research settings, the HY scale is useful primarily for defining inclusion/exclusion criteria; (4) to retain simplicity, clinicians should "rate what you see" and therefore incorporate comorbidities when assigning a HY stage; and (5) because of the wide usage of the modified HY scale with 0.5 increments, this adaptation warrants clinimetric testing. Without such testing, however, the original five-point scales should be maintained.

Feasibility Studies↗
PubMed2004

Evidence from cost-effectiveness research.

Economic evaluations are a set of outcomes and health services research methods to inform the debate about the rising cost of health care and include cost-of-illness studies and cost-effectiveness research. Cost-effectiveness research is the comparative analysis of two or more alternative interventions in terms of their health and economic consequences, whose results are expressed as an incremental cost-effectiveness ratio, the ratio of differences in cost between a pair of medical interventions to the differences in the corresponding health effects. These research methods are particularly important to neurological diseases with debilitating natural histories, long-term courses, and a growing number of exciting, yet costly, treatment options available. The results of economic evaluations of neurological conditions influence resource allocation decisions, help set reimbursement rates, estimate future healthcare expenses, and improve the quality and efficiency of delivering neurological care. For these research methods to achieve their potential, continued methodological advances within the field are needed, as well as a more systematic integration of these methods into mainstream research to address critical questions regarding the health and well-being of patients with neurological illness.

Biomedical Research↗
PubMed2003

Development and testing of the Parkinson's disease quality of life scale.

We report on the development and results of preliminary psychometric testing of a disease specific health-related quality of life (HRQoL) scale intended for use in individuals diagnosed with idiopathic Parkinson's disease (PD). Results from an initial qualitative study provided content for item development and scale construction of the Parkinson's disease quality of life scale (PDQUALIF). The 33-item instrument includes seven domains: social/role function, self-image/sexuality, sleep, outlook, physical function, independence, and urinary function, plus one item of Global HRQoL. Initial psychometric testing of the instrument was conducted in 233 outpatient clinic attendees with physician-confirmed idiopathic PD. Factor structure, reliability and validity of the scale have been established in this cross-sectional study. Continuing development of the PDQUALIF will be directed at enhancing the psychometric properties, establishing responsiveness and determining appropriateness in culturally diverse samples.

Aged↗
PubMed2003

Surrogate endpoints in Parkinson's disease research.

Biomarkers are important tools in understanding the underlying mechanisms of causation, progression, and treatment effects in Parkinson's disease (PD). In addition, these biomarkers may be utilized as surrogate endpoints that, when used appropriately, can lead to important advances in therapeutics in a timely and cost-effective manner. This paper outlines the definition, role, validity process, and risks associated with surrogate endpoints. The use of biomarkers in recent PD clinical trials is discussed and potential shortcomings and unanswered questions related to interpreting these outcomes are reviewed. Finally, the significant challenges that lie ahead for validating and interpreting surrogate endpoints in PD are addressed.

Animals↗
PubMed2003

Burdens and benefits of placebos in antidepressant clinical trials: a decision and cost-effectiveness analysis.

OBJECTIVE: The use of placebos is a necessary, if controversial, part of determining the efficacy of new antidepressants in randomized clinical trials. Such studies need to convey accurate and useful risk-benefit information to subjects since effective treatments are withheld. The authors assessed the cost-effectiveness of entering such a trial from the perspective of potential subjects. METHOD: The choice between individualized psychiatric treatment and an 8-week placebo-controlled, randomized clinical trial was modeled by using a static model. The analysis was conducted from the perspective of a potential subject who has moderate depression, is at low risk for suicide, has no comorbid conditions, and lacks adequate insurance to pay for mental health services. The trial was assumed to be free for subjects, except for indirect costs. Model outcomes included the probability of treatment response at 8 weeks and "decremental" cost-effectiveness. Data were based on reviews of published and some unpublished clinical trials of novel antidepressants that were eventually shown to be efficacious. RESULTS: A participant in a typical antidepressant efficacy trial has a chance of treatment response almost 25% less than that with individualized treatment. An uninsured participant can expect to save just over $164 for every 10% chance of response sacrificed by entering the placebo-controlled trial. CONCLUSIONS: For placebo-controlled antidepressant trials, it is possible to derive systematic and evidence-based estimates of the burdens and potential benefits to subjects. Such information may be more useful for institutional review boards and potential subjects than an unstructured enumeration of risks and benefits.

Antidepressive Agents↗