Systematic review of clinical prediction rules for neuroimaging in the evaluation of dementia.

BACKGROUND: Clinical practice guidelines for dementia do not recommend routine neuroimaging but vary in their recommended clinical prediction rules to identify patients who should undergo neuroimaging for potentially reversible causes of dementia. METHODS: Using a MEDLINE search supplemented by other strategies, we identified studies from January 1, 1983, through December 31, 1998, that evaluated the diagnostic performance of a clinical prediction rule. We calculated the sensitivity and specificity of each rule, then evaluated their diagnostic performance in a hypothetical cohort of 1000 patients with dementia, varying the prevalence of potentially reversible dementia from 1% to 15%. RESULTS: We identified 7 studies that evaluated at least 1 of 6 different clinical prediction rules. Only one rule consistently had high sensitivity (>85%) across all studies; none consistently had high specificity (>85%). Six of the 7 studies included less than 15 cases of potentially reversible dementia; thus the sensitivity and specificity for each rule had relatively wide confidence intervals. At a 5% prevalence of potentially reversible dementia, all rules had low positive predictive value (<15%) in our hypothetical cohort. Depending on the rule, our analysis predicts 6 to 44 of the 50 patients with potentially reversible dementia (5% prevalence in cohort of 1000 patients) would not undergo imaging. CONCLUSIONS: There is considerable uncertainty in the evidence underlying clinical prediction rules to identify which patients with dementia should undergo neuroimaging. Application of these rules may miss patients with potentially reversible causes of dementia.

Development of performance measures for acute ischemic stroke.

BACKGROUND AND PURPOSE: The purpose of the present study was to develop and rate performance measures for hospital-based acute ischemic stroke. METHODS: A national multidisciplinary panel of 16 individuals (2 stroke specialists, 2 general neurologists, 2 internists, 2 neuroscience nurses, 2 stroke advocacy organization representatives, 1 stroke rehabilitationist, 1 family practitioner, 1 emergency room physician, 1 neuroradiologist, 1 managed care organization director, and 1 hospital association representative) from 10 medical societies or lay organizations assisted in the development of 44 potential stroke performance measures. We developed evidence summaries for each of the performance measures and graded the level of evidence associated with each measure. The panel received a summary of the literature pertaining to each measure and rated the measures by use of a modified Delphi approach for 6 dimensions of quality, including validity of evidence, feasibility, impact on outcomes, room for improvement, plausibility, and an overall rating (little reason to do, could do, should do, and must do). RESULTS: Highly rated and agreed on performance measures for the overall rating include warfarin in atrial fibrillation, antithrombotics on hospital discharge, carotid imaging in appropriate patients, and use of stroke units. Additional measures notable for high agreement were heparins for deep-vein thrombosis prophylaxis and use of a stroke protocol. Panelists rated time-related thrombolytic measures such as head CT within 25 minutes highly on the room for improvement dimension but low on the overall dimension. Neurologists tended to rate measures lower than did nonneurologists (P<0.01) for all 9 measures pertaining to thrombolytic management. CONCLUSIONS: Highly rated and agreed on performance measures exist in all domains of hospital-based stroke care.

Carotid endarterectomy trends in the patterns and outcomes of care at academic medical centers, 1990 through 1995.

OBJECTIVE: To evaluate whether the patterns of inpatient care and patient characteristics have changed for patients undergoing a carotid endarterectomy across a group of academic medical centers from 1990 through 1995. If changes occurred, we investigated whether they had an impact on patient outcomes. DESIGN: Retrospective evaluation of patients undergoing a carotid endarterectomy using a hospital discharge data set compiled by the Academic Medical Center Consortium. SETTING: Ten academic medical centers. PATIENTS: A total of 7019 hospital admissions for patients who had 1 carotid endarterectomy performed as a principal procedure from January 1990 to December 1995. MAIN OUTCOME MEASURES: Trends in patient demographics, comorbidities, length of stay, days in the intensive care unit, and inpatient cerebral arteriogram use were determined. Patient outcomes included inpatient mortality, discharge to an institution, 30-day readmission rate, and selected diagnoses (postoperative hemorrhage, infection, or seizure; acute myocardial infarction; or cranial nerve palsy) and postprocedure diagnostic tests (computed tomography and magnetic resonance imaging of the head and electroencephalogram) indicative of complications. RESULTS: Over the 6-year study period, the number of carotid endarterectomies performed more than doubled and the percentage of hospital admissions for patients 65 years or older increased from 65% to 75%. The mean and median length of stay halved and the percentage of admissions with transfers to the intensive care unit decreased from 56% to 26% of cases. In addition, the percentage of cases with a cerebral arteriogram during the same admission but prior to the day of the carotid endarterectomy decreased from 52% to 27%. There were no trends in inpatient mortality, discharge to an institution, or 30-day readmission rate. There were no significant trends indicative of poorer quality of care as measured by the frequency of secondary diagnoses or postprocedure diagnostic test use. CONCLUSIONS: Despite dramatic changes that have occurred in patient characteristics and in hospital management practices for patients undergoing a carotid endarterectomy from 1990 to 1995, we were unable to detect any measurable impact on patient outcomes. These data have implications for monitoring and evaluating the impact of systemwide change on the overall quality of care for patients undergoing a carotid endarterectomy.

Deep brain stimulation in the treatment of Parkinson's disease: a cost-effectiveness analysis.

BACKGROUND: In treating PD, deep brain stimulation (DBS) has shown great promise in a series of uncontrolled studies. OBJECTIVE: To estimate the incremental cost effectiveness of DBS compared with the best medical management in late-stage PD. METHODS: The authors constructed a decision model to determine the lifetime incremental cost effectiveness between two options in patients with PD aged 50 years and older: 1) best medical management and 2) DBS. As the long-term efficacy of DBS (>3 years) is not known, key assumptions regarding the procedure's long-term durability were made. Costs were in US 2000 dollars, and quality-adjusted life year (QALY) was the effectiveness measure. Base assumptions were that quality of life (QOL) in patients with late-stage PD is 0.55 (0-to-1 scale, 1 is perfect health) and that DBS benefits are constant for 4 years, eroding gradually over the next 5 years until at parity with those produced by best medical management. Incremental cost-effectiveness and sensitivity analyses were performed. RESULTS: Under base-case assumptions, DBS provides an additional 0.72 QALY at an additional cost of $35,000 compared with best medical management that results in an incremental cost-effectiveness ratio (C/E) of $49,000. QOL increases of between 18 and 30% resulted in questionable cost effectiveness. QOL increases of between 6 and 18% resulted in incremental C/E ratios not usually considered cost effective (>100,000/QALY). CONCLUSIONS: The results suggest that DBS may be cost effective in treating PD if QOL improves 18% or more compared with those receiving best medical management. This underscores the need for randomized, controlled, prospective DBS experiments including QOL and economic components.

Intracranial mass lesions in acquired immunodeficiency syndrome: using decision analysis to determine the effectiveness of stereotactic brain biopsy.

We studied the effectiveness of performing a stereotactic brain biopsy in the individual with acquired immunodeficiency syndrome (AIDS) and an intracranial mass lesion who failed 2 weeks of antitoxoplasmosis therapy. We used a decision analysis to compare two different treatment strategies: biopsy and no biopsy. The analysis estimates the average life expectancy for each choice and investigates the sensitivity of these results by varying parameters within the model. In the base case analysis (diagnostic yield of biopsy, 0.89; operative mortality, 0.015; life expectancy of lymphoma untreated and treated, 42 and 120 days), the life expectancy of the biopsy strategy was 98 days compared with 67 days for the no-biopsy strategy, for a net survival benefit of 31 days. Sensitivity analyses revealed that the life expectancy of the biopsy strategy remained greater than the no-biopsy strategy for a wide range of variable specifications. The net survival benefit, however, was sensitive to the diagnostic success rate, the operative mortality, the likelihood of a lymphoma diagnosis, and the life expectancy of patients being diagnosed and treated for lymphoma. These data allow AIDS patients and physicians to learn more about the potential outcomes of the alternative management strategies when an individual fails to respond to empiric antitoxoplasmosis therapy.

Neurologists' use of ICD-9CM codes for dementia.

Neurologists' use of ICD-9CM codes in a sample of 181 consecutive, new patients evaluated for dementia by 48 of all 49 neurologists from the Rochester, NY, area over a 1-year period was examined. The specific code for AD, 331.0, was used for only 36.5% of patients judged by the neurologist to have AD as the most likely diagnosis. Other codes used were not inaccurate but would result in lower reimbursement. Variation in coding could affect validity of dementia research using claims data.

Stroke prevention: narrowing the evidence-practice gap.

Many interventions reduce stroke risk. However, the full benefits of these interventions are not realized at current levels of utilization, as nearly all evidence-based or guideline-endorsed stroke prevention services are underused. The cause for such underuse is multifactorial and includes factors relating to both patients and providers, as well as to a health care system that has de-emphasized prevention at the expense of acute, technologically based care. Much like the evidence for stroke interventions themselves, there is a growing literature to support methods of implementing research evidence into clinical practice. There is still much to learn, however, about the effectiveness of interventions aimed at achieving changes in stroke prevention practice or the delivery of stroke prevention care. Nevertheless, there are many opportunities for providers, managed care organizations, and government to close the evidence-practice gap that exists for stroke prevention services. These opportunities exist in both the inpatient and outpatient setting, and depend on the neurologist taking a leading role in emphasizing the critical importance of risk factor identification and modification in all patients at risk for stroke.

Employment-seeking experiences of residents in 1996: a window into the neurology marketplace.

OBJECTIVE: To assess career choice and employment-seeking experience of senior neurology residents in 1996. METHODS: Graduating residents in adult and pediatric neurology (n = 573) were surveyed to obtain career plans, initial job selection, health care attitudes, and demographic information. Results were compared with 1996 data on all United States neurologists and data from an American Medical Association (AMA) resident survey regarding the employment status of new physicians. RESULTS: Survey response rate was 71%. There was a significant increase in international medical graduates and women entering neurology compared with the current workforce. Seventy-four percent of graduates planned to enter a fellowship position; 19%, private practice; 5%, an academic position; and 2%, a career outside of clinical medicine. Neurology residents differ from aggregate national data because only 28% of residents responding to an AMA survey across all specialties applied to fellowships in 1996. Overall, 44% of neurology graduates planned an academic career. CONCLUSIONS: Changing demographics and career choice of recent graduates may require continued monitoring and could be important in neurology workforce planning. The high rate of fellowship training and plans for academic careers in 1996 is of interest and may reflect both resident response to new demands in the changing health care market and a need to modify residency programs to enhance academic training and competitiveness of neurology graduates.

US neurologists: attitudes on rationing.

OBJECTIVE: To assess neurologists' attitudes on rationing health care and to determine whether neurologists would set healthcare priorities in ways that are consistent with cost-effectiveness research. BACKGROUND: Cost-effectiveness research can suggest ways to maximize health benefits within fixed budgets but is currently being underused in resource allocation decisions. METHODS: The authors surveyed a random sample of neurologists practicing in the United States (response rate, 44.4%) with three hypothetical scenarios. Two scenarios were designed to address general attitudes on allocating finite resources with emphasis on formulary decisions for costly drugs. The third scenario was designed to assess whether neurologists would optimize the allocation of a fixed budget as recommended by cost-effectiveness analysis. RESULTS: Three-quarters of respondents thought that neurologists make daily decisions that effectively ration healthcare resources, and 60% felt a professional responsibility to consider the financial impact of individualized treatment decisions on other patients. Only 25% of respondents thought that there should be no restrictions placed on any of the five newer antiepileptic agents. In a 1995 survey, 75% of similarly sampled neurologists agreed that no restrictions should be placed on the availability of FDA-approved medications. Nearly half (46%) of respondents favored a less effective test and would be willing to let patients die to ensure the offering of a more equitable alternative. CONCLUSIONS: Most neurologists recognize the need to ration health care, and although they think cost-effectiveness research is one method to achieve efficient distribution of resources, many think that considerable attention should also be given to equity.

Inpatient costs of specific cerebrovascular events at five academic medical centers.

We estimated the hospital costs for patients with different cerebrovascular events and applied patient and administrative variables to explain the variance of the cost estimates with particular attention to the relationship between patient age and cost. The study sample was drawn from an administrative data set of all hospital discharges from five academic medical centers for the 1992 calendar year. Using International Classification of Diseases (ICD-9-CM) primary diagnosis codes, cases were classified into cerebrovascular subgroups: subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), ischemic cerebral infarction (ICI), and transient ischemic attack (TIA). The ICD-9-driven data file was supplemented with billing data containing inpatient charges reported in UB-82 format. Costs were imputed by applying Medicare charge-to-cost ratios and regional wage adjustments to the billing data. We estimated relationships between inpatient costs and a number of demographic and administrative variables. A statistically significant difference was found between cerebrovascular subgroups for both the mean cost per discharge (p<0.01) and the mean cost of an inpatient day (p<0.01). The mean cost per discharge for each subgroup was as follows: SAH, $39,994 (n=218); ICH, $21,535 (n=258); ICI, $9,882 (n=908); TIA, $4,653 (n=303). Likewise, the mean cost per inpatient day was as follows: SAH, $2,215; ICH, $1,396; ICI, $1,036; TIA, $1,117. Length of stay as a measure of resource use was strongly predictive of inpatient cost, explaining 72 to 82% of the variation in cost. Demographic variables (i.e., age, gender, race, insurance status), however, revealed virtually no predictive power, accounting for less than 10% of the variance in each of the four subgroups. There are substantial differences in the patient-level cost of hospital services for stroke-related events. After controlling for the type of cerebrovascular event, basic demographic variables and insurance status (including Medicare) contribute little to the total cost of inpatient care. More important factor include stroke severity, social factors, and clinical practice variations.

US neurologists in the 1990's: trends in practice characteristics.

BACKGROUND: The American Academy of Neurology (AAN) conducts periodic surveys of its members to profile and monitor changes in the characteristics of US neurologists and their practices. OBJECTIVE: To assess neurologists' characteristics, geographic distribution, practice arrangements, professional activities, practice volume, procedures performed, sources of revenue, involvement with managed care and capitation, and other selected topics. METHODS: The AAN Member Census survey was sent to US neurologists in the fall of 1996 (response rate = 89%), and the Practice Profile survey was sent to a random sample of 1,986 US neurologists in the summer of 1997 (response rate = 55%) who had completed a Member Census survey. The results of the Practice Profile survey were compared with those of two prior surveys conducted in 1991 to 1992 and 1993 to 1994. RESULTS: The mean age of US neurologists is 48 years, 18% are women, 93% are US citizens, and 24% are international medical graduates. The proportion of neurologists in solo practices, group practices, and medical schools/universities has not changed. The weekly hours worked has remained stable (58 hours), but the time spent in administrative activities has increased (p < 0.001). The average number of patient visits per week to neurologists appears to have increased (p < 0.001), as has the proportion of neurologists performing procedures (p < 0.05). The majority of neurologists have contracts with managed care organizations (82%), and a minority (32%) have capitated payment arrangements. Medicare continues to be the largest source of clinical revenue. Nearly 50% of all respondents have experience in developing clinical practice guidelines or critical pathways, and >20% of respondents employed physician extenders to assist in their practices. CONCLUSION: Neurologists are spending more time in administrative activities, are performing or interpreting more procedures, and are seeing more patients. Neurologists' involvement with capitation is comparable with that in a nationally representative sample of physicians, and they are exploring innovative ways, such as developing practice guidelines and using physician extenders, to improve the quality and efficiency of providing neurologic care.

Cost effectiveness of pramipexole in Parkinson's disease in the US.

OBJECTIVE: Pramipexole was recently approved in the US for treatment of the symptoms of idiopathic Parkinson's disease (PD). Although pramipexole has been found to be safe and efficacious when compared with placebo, little data are yet available on its cost effectiveness when compared with baseline treatment. The aim of this study was to estimate the costs and cost effectiveness (cost utility) of pramipexole compared with baseline treatment in patients with early and advanced PD. DESIGN AND SETTING: We developed a cost-effectiveness (CE) model in the US setting that linked Unified Parkinson's Disease Rating Scale (UPDRS) Part II (activities of daily life) and III (motor) scores to disease progression, costs and patient utility. Data for the model were obtained from clinical trials, a literature review and a survey of 193 patients' health resource use and utility. We used cost and quality-adjusted life-year (QALY) estimates from the model to estimate the incremental cost effectiveness of pramipexole relative to baseline treatment patterns. We performed separate analyses for patients with early and advanced PD. We also performed extensive sensitivity analyses by adding other dopamine agonists to the no-pramipexole treatment regimen and varying disease progression parameters. The study was conducted from the societal perspective, although data presentation allows interpretation of cost effectiveness from either the societal or payer perspective. MAIN OUTCOME MEASURES AND RESULTS: For patients with both early and advanced PD, treatment with pramipexole had higher costs but was more effective than baseline treatment. For patients with early onset of PD, the incremental total CE ratio for pramipexole was $US8837/QALY. For patients with advanced PD, the incremental CE ratio was $US12 294/QALY (1997 costs). These ratios were lower than the CE ratios of many widely used medical treatments. CONCLUSIONS: Subject to the inherent limitations of modelling chronic disease progression and subsequent healthcare costs and patient utility, the results suggested that pramipexole was a cost effective treatment for patients with early and advanced PD in the US.

Reversible symptomatic venous congestion after treatment of dural arteriovenous fistula using NBCA.

We treated a 73-year-old man with a dural arteriovenous fistula (AVF) with cortical venous drainage of the left mastoid region using transarterial embolization of the middle meningeal and occipital arteries with n-butyl 2-cyanoacrylate (NBCA). The patient's clinical symptoms improved dramatically. Three months after the procedure, follow-up CT showed resolution of white matter edema and follow-up angiograms showed no evidence of a recurrent AVF. This report indicates that dural AVFs without sinus drainage can be cured solely with transarterial NBCA embolization.

Cost-effectiveness of disease-modifying therapy for multiple sclerosis: a population-based study.

OBJECTIVE: To evaluate the cost-effectiveness of disease-modifying therapies (DMTs) in the United States compared to basic supportive therapy without DMT for patients with relapsing multiple sclerosis (MS). METHODS: Using data from a longitudinal MS survey, we generated 10-year disease progression paths for an MS cohort. We used first-order annual Markov models to estimate transitional probabilities. Costs associated with losses of employment were obtained from the Bureau of Labor Statistics. Medical costs were estimated using the Centers for Medicare and Medicaid Services reimbursement rates and other sources. Outcomes were measured as gains in quality-adjusted life-years (QALY) and relapse-free years. Monte Carlo simulations, resampling methods, and sensitivity analyses were conducted to evaluate model uncertainty. RESULTS: Using DMT for 10 years resulted in modest health gains for all DMTs compared to treatment without DMT (0.082 QALY or <1 quality-adjusted month gain for glatiramer acetate, and 0.126-0.192 QALY gain for interferons). The cost-effectiveness of all DMTs far exceeded $800,000/QALY. Reducing the cost of DMTs had by far the greatest impact on the cost-effectiveness of these treatments (e.g., cost reduction by 67% would improve the probability of Avonex being cost-effective at $164,000/QALY to 50%). Compared to treating patients with all levels of disease, starting DMT earlier was associated with a lower (more favorable) incremental cost-effectiveness ratio compared to initiating treatment at any disease state. CONCLUSION: Use of DMT in MS results in health gains that come at a very high cost.

Selegiline shortage: Causes and costs of a generic drug shortage.

BACKGROUND: In September 2007, shortages of generic selegiline occurred, forcing patients to either switch to more expensive alternatives or forego treatment. We sought to evaluate prescription trends of generic selegiline and to quantify the economic impact of any resulting drug substitution of more expensive alternatives. METHODS: We analyzed proprietary data from IMS Health on monthly prescriptions in the United States for selegiline and potential substitutes from February 2002 through December 2007. Linear regression was used to predict the number of expected prescriptions after August 2007 had a shortage not occurred. The main outcome measures were the changes in prescriptions filled and the economic impact of drug substitution. RESULTS: Prior to the shortage, total prescriptions filled for generic selegiline decreased 42%, and supply consolidated into one company, Apotex Inc., Toronto, Canada, whose market share increased from 41% to 83%. During the first 4 months of the shortage, Apotex Inc. filled 10,500 fewer prescriptions than projected and other selegiline manufacturers filled 7,400 more than projected for a net shortage of 3,100 prescriptions. The number of branded selegiline capsules filled during this period increased by 1,800 above projections, and 1,300 prescriptions for generic selegiline were not refilled or substituted. The societal cost of substituting generic selegiline with branded capsules was $75,000 over the first 4 months of the shortage. CONCLUSIONS: Generic drug shortages carry economic and health implications. Given ongoing consolidation in the generics drug industry, these shortages may become more common and may require heightened regulatory scrutiny of the generic drug industry.

Quantitative risk-benefit analysis of natalizumab.

OBJECTIVE: To model the long-term risks and benefits of natalizumab in individuals with relapsing multiple sclerosis (MS). METHODS: We created a Markov model to evaluate treatment effects on reducing relapses and slowing disease progression using published natural history data and clinical trial results. Health changes, measured in quality-adjusted life-years (QALYs), were based on patient health preferences. Patient cohorts treated with no disease-modifying treatment, natalizumab, subcutaneous interferon beta-1a, and a theoretical "perfect" MS treatment were modeled. Sensitivity analysis was used to explore model uncertainty, including varying risks of developing progressive multifocal leukoencephalopathy (PML). RESULTS: Treatment with natalizumab resulted in 9.50 QALYs over a 20-year time horizon, a gain of 0.80 QALYs over the untreated cohort and 0.38 QALYs over interferon beta-1a. The health loss due to PML was small (-0.06 QALYs). To offset natalizumab's incremental health gain over interferon beta-1a, the risk had to increase from 1 to 7.6 PML per 1,000 patients treated over 17.9 months. The "perfect" MS treatment accumulated 10.59 QALYs over the 20-year time horizon, 1.89 QALYs above the untreated cohort. Interferon beta-1a resulted in greater QALY gains compared with natalizumab if natalizumab's relative relapse reduction was reduced from 68% to 35% or if interferon beta-1a's relative reduction was increased from 32% to 65%. CONCLUSIONS: A more than sevenfold increase in actual risk of progressive multifocal leukoencephalopathy was required to decrease natalizumab's health gain below that of interferon beta-1a, and there remains considerable room for additional gains in health (>50%) beyond those already achieved with current therapies.