Bone marrow stromal cell therapy for ischemic stroke: A meta-analysis of randomized control animal trials.

Background Results of animal studies assessing efficacy of bone marrow stromal cell therapy for ischemic stroke remain inconsistent. Aims The aims are to assess efficacy of bone marrow stromal cell therapy for ischemic stroke in animal studies. Methods Randomized controlled animal trials assessing efficacy of bone marrow stromal cell therapy were eligible. Stroke therapy academic industry round table was used to assess methodologic quality of included studies. Primary outcomes were total infarction volume and modified Neurological Severity Score. Multiple prespecified sensitivity analyses and subgroup analyses were conducted. Random effects models were used for meta-analysis. Results Thirty-three randomized animal trials were included with a total of 796 animals. The median quality score was 6 (interquartile range, 5-7). Bone marrow stromal cell therapy decreased total infarction volume (standardized mean difference, 0.897; 95% confidence interval, 0.553-1.241; P < .001) at follow-up. Overall standardized mean difference between animals treated with bone marrow stromal cell and controls was 2.47 (95% confidence interval, 1.84-3.11; P < .001) for modified Neurological Severity Score; 1.27 (95% confidence interval, 0.72-1.82; P < .001) for adhesive removal test; and 2.13 (95% confidence interval, 0.65-3.61; P < .001) for rotarod test. Significant heterogeneity among studies was observed. Effect of all outcomes stayed significant in various sensitivity analyses and subgroup analyses, except in a few subgroup analyses with small sample size or with short time follow-up. No significant difference between groups was observed except for study location, in which significantly larger estimates were found in Asian countries. On the basis of this meta-analysis, larger sample sizes are warranted for future animal studies. Conclusions Bone marrow stromal cell therapy significantly decreased total infarction volume and increased neural functional recovery in randomized controlled animal models of ischemic stroke.

International consensus diagnostic criteria for neuromyelitis optica spectrum disorders.

Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS.

IVIG Versus PLEX in the Treatment of Worsening Myasthenia Gravis: What is the Evidence?: A Critically Appraised Topic.

BACKGROUND: Immune therapies such as intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) are first line in the treatment of worsening myasthenia gravis. Although PLEX is favored in myasthenic crisis, IVIG is increasingly used in exacerbations due to cost and ease of administration. OBJECTIVES: To review and critically assess current evidence on the effects of IVIG and PLEX on functional outcomes in patients with worsening myasthenia gravis. METHODS: A structured critical appraisal was conducted on the objective topic. This included a creation of a structured question based on a clinical scenario, comprehensive literature search, selection of evidence for review, and critical appraisal of selected evidence. Evidence was summarized and commentary provided. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of neuromuscular neurology. RESULTS: A single-blinded, randomized-controlled trial that compared IVIG and PLEX in 84 patients with worsening myasthenia gravis was selected for review. Primary outcome measure was functional status at 14 days after treatment, as assessed by the Quantitative Myasthenia Gravis Score. Change in Quantitative Myasthenia Gravis Score at day 14 for all subjects was 4.0, without statistically significant differences between IVIG and PLEX groups. CONCLUSIONS: IVIG and PLEX are equally effective in worsening myasthenia gravis. Treatment decisions may depend on several variables, including presence of respiratory distress, medical comorbidities, access to medication, and cost. PLEX will likely remain the treatment of choice in true myasthenic crisis.

Physical activity level and future risk of mild cognitive impairment or dementia: a critically appraised topic.

BACKGROUND: The relationships between physical activity, cognition, and development of neurodegenerative diseases represent an area of intense research interest. Meta-analyses and prospective cohort studies show that greater levels of physical activity are associated with lower dementia risk. Most studies, however, depend on self-report data that are subject to recall and other biases. Obtaining objective and quantitative physical activity data could strengthen observational study validity. OBJECTIVE: To examine the association between objectively measured daytime activity and mild cognitive impairment (MCI) or Alzheimer disease (AD). METHODS: The objective was addressed through the development of a structured, critically appraised topic. We incorporated a clinical scenario, background information, a structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, clinical epidemiologists, a medical librarian, and behavioral neurology and neuropsychiatry content experts. RESULTS: We selected a prospective, single-center cohort study of 716 cognitively normal elderly participants followed for 3.5 years. Greater levels of physical activity, as measured using wrist actigraphy, were associated with a lower risk of incident MCI or AD (hazard ratio, 0.477; 95% confidence interval, 0.273-0.832). CONCLUSIONS: Objective measurement confirms that greater levels of physical activity are associated with decreased risk of a future diagnosis of MCI or AD. Further studies are needed to confirm the temporal association of exercise and future cognitive health and understand the relevant underlying biological mechanisms.

Amantadine for patients with severe traumatic brain injury: a critically appraised topic.

BACKGROUND: Research into traumatic brain injury (TBI) has increased significantly. Diagnostic testing and therapeutics for patients with severe TBI are 2 areas on which there is increasing focus. Amantadine hydrochloride is one treatment considered to have potential therapeutic value in this patient population. OBJECTIVE: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the disciplines of neurocritical care and physical medicine and rehabilitation. RESULTS: A multicenter, placebo-controlled, double-blind, randomized controlled trial was selected for review. The trial compared the rate of recovery, as determined by the overall Disability Rating Scale score, in a total of 184 patients with severe TBI. Patients were randomized to either receive amantadine (87) or visually identical placebo (97) over the 4-week study interval. The rate of recovery, as measured by the Disability Rating Scale, was found to be greater in the treatment arm as compared with the placebo arm (difference in slope -0.24 points/wk, P=0.007) over the 4-week treatment interval. CONCLUSIONS: The results from this study demonstrated that amantadine hydrochloride accelerates recovery in patients with severe TBI.

Burnout in inpatient-based versus outpatient-based physicians: a systematic review and meta-analysis.

BACKGROUND: Burnout is a syndrome affecting the entirety of work life and characterized by cynicism, detachment, and inefficacy. Despite longstanding concerns about burnout in hospital medicine, few data about burnout in hospitalists have been published. PURPOSE: A systematic review of the literature on burnout in inpatient-based and outpatient-based physicians worldwide was undertaken to determine whether inpatient physicians experience more burnout than outpatient physicians. DATA SOURCES: Five medical databases were searched for relevant terms with no language restrictions. Authors were contacted for unpublished data and clarification of the practice location of study subjects. STUDY SELECTION: Two investigators independently reviewed each article. Included studies provided a measure of burnout in inpatient and/or outpatient nontrainee physicians. DATA EXTRACTION: Fifty-four studies met inclusion criteria, 15 of which provided direct comparisons of inpatient and outpatient physicians. Twenty-eight studies used the same burnout measure and therefore were amenable to statistical analysis. DATA SYNTHESIS: Outpatient physicians reported more emotional exhaustion than inpatient physicians. No statistically significant differences in depersonalization or personal accomplishment were found. Further comparisons were limited by the heterogeneity of instruments used to measure burnout and the lack of available information about practice location in many studies. CONCLUSIONS: The existing literature does not support the widely held belief that burnout is more frequent in hospitalists than outpatient physicians. Better comparative studies of hospitalist burnout are needed.

Systematic review of teleneurology: neurohospitalist neurology.

The use of 2-way audiovisual telemedicine technology for the delivery of acute stroke care is well established in the literature and is a growing practice. The use of such technology for neurologic consultation outside the cerebrovascular specialty has been reported to a variable extent across most disciplines within the field of neurology, including that of the neurohospitalist medicine. A systematic review of these reports is lacking. Hence, the main purpose of this study was to conduct a systematic review of the literature on teleneurologic consultation in hospital neurology. The databases Ovid MEDLINE, EMBASE, PsychINFO, CINAHL, and Cochrane were used as data sources and were searched with key words "teleneurology" and its numerous synonyms and cognates. These key words were cross-referenced with subspecialties of neurology. The studies were included for further review only if the title or the abstract indicated that the study made use of 2-way audiovisual communication to address a neurologic indication. This search yielded 6625 abstracts. By consensus between the 2 investigators, 688 publications met the criteria for inclusion and further review. Four of those citations directly pertained to the inpatient hospital neurologic consultation. Each of the 4 relevant articles was scored with a novel rubric scoring functionality, application, technology, and evaluation phase. A subspecialty category score was calculated by averaging those scores. The use of 2-way audiovisual technology for general neurologic consultation of hospital inpatients, beyond stroke-related care, is promising, but the evidence supporting its routine use is weak. Further studies on reliability, validity, safety, efficacy, and cost-effectiveness are encouraged.

Role of telemedicine in providing tertiary neurological care.

OPINION STATEMENT: Remote consultation via telemedicine for neurologic indications is in the mainstream. This holds most true for cerebrovascular concerns such as acute stroke, but its use has extended into most of the breadth of neurologic subspecialty practice. This is ostensibly a major advance for enhancing access to neurologic specialty care and a path toward better outcomes overall. Currently, there is a lack of randomized controlled trials and health economic analyses to support this conclusion. The continued use and expansion of teleneurologic practice is encouraged, so long as it is accompanied by clinical data tracking and leads to more randomized controlled trials. A solid evidence base should be established for its use such that future trials and monetary investments can be made with a better understanding of what teleneurology has to offer patients and society.

Systematic review of telestroke for post-stroke care and rehabilitation.

Telemedicine for acute stroke care is supported by a literature base. It remains unclear whether or not the use of telemedicine for other phases of stroke care is beneficial. The authors conducted a systematic review of the published literature on telemedicine for the purposes of providing post-stroke care. Studies were included if the title or abstract expressed use of two-way audio/video communication for post-stroke care. From an initial yield of 1,405 potentially eligible hits, two reviewers ultimately identified 24 unique manuscripts to undergo functionality, application, technology, and evaluative (F.A.T.E.) scoring. Each article was classified using a scoring rubric to assess the functionality, application, technology, and evaluative stage. It was found that most post-stroke telemedicine studies evaluated rehabilitation of adults. All primary data manuscripts were small and preliminary in scope and evaluative phase, and median F.A.T.E. score for primary data was 2. The use of telemedicine for post-stroke care is nascent and is primarily focused on post-stroke rehabilitation.

A systematic review of telestroke.

BACKGROUND: The use of 2-way audiovisual (AV) technology for delivery of acute stroke evaluation and management, termed "telestroke," is supported by a rapidly growing literature base. A systematic review that provides a comprehensive, easily digestible overview of telestroke science and practice is lacking. PURPOSE: To conduct a systematic review of the published literature on telemedical consultation for the purposes of providing acute stroke evaluation and management. DATA SOURCES: The Ovid Medline, Embase, PsychINFO, CINAHL, PubMed, and Cochrane databases were searched with numerous keywords relevant to telestroke from January 1996 through July 2012. STUDY SELECTION: Studies were included if the title or abstract expressed use of 2-way AV communication for acute stroke evaluation and management. DATA EXTRACTION: Each article was classified using a novel scoring rubric to assess the level of Functionality, Application, Technology, and Evaluative stage (FATE). DATA ANALYSIS: The search yielded 1405 potentially eligible articles, which were independently reviewed by 2 investigators. There were 344 unique studies that met eligibility criteria and underwent full-text review. Ultimately, 145 unique studies underwent FATE assessment and scoring. RESULTS: Most telestroke studies evaluated functionality in the context of acute stroke assessment of adults in emergency departments. Nearly half of all published articles on telestroke were narrative reviews. After exclusion of these reviews, the median FATE score for telestroke primary data was 4. CONCLUSION: Telestroke technology is now part of mainstream clinical stroke practice in North America and internationally. Telestroke reliability, validity, efficacy, safety, clinical, and cost-effectiveness studies reflect maturity in the field, and new post-implementation studies in the pre-hospital setting present welcome and sophisticated advancements in the field.

The effect of selective serotonin reuptake inhibitors on the frequency of psychogenic nonepileptic seizures: a critically appraised topic.

BACKGROUND: Psychogenic nonepileptic seizures (PNES) are commonly encountered problem in neurological practice and usually are accompanied by other psychiatric comorbidities. Despite its prevalence and profound impact on patients and families, there have been few trials addressing treatment. Cognitive behavioral therapy may be effective but the role of pharmacologic therapy remains unclear. OBJECTIVE: To critically evaluate evidence that PNES frequency may be reduced by treatment with selective serotonin reuptake inhibitors. METHODS: The objective was addressed through the development of a structured, critically appraised topic. We incorporated a clinical scenario, background information, a structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, epileptology, and psychiatry content experts. RESULTS: A pilot randomized control clinical trial was selected for critical appraisal. Thirty-eight PNES patients were randomized to flexible-dose sertraline (target dose, 200 mg/d) or placebo. Only 68% of patients contributed data to the primary analysis and baseline PNES frequency was notably dissimilar. Twelve-week seizure frequency rates, as compared with baseline, were 45% lower in the sertraline group (P=0.03) but unchanged in the placebo group (8% increase; P=0.78). After adjustment for baseline differences, between-treatment group comparison revealed a trend toward lower event frequency in the sertraline group (risk ratio 0.51; 95% confidence interval, 0.25-1.05; P=0.29). Psychosocial and quality of life measures did not differ between treatment groups. CONCLUSIONS: There is insufficient evidence to recommend routine treatment with sertraline to reduce PNES event frequency but these pilot data suggest a possible benefit worthy of further exploration.

Systematic review of teleneurology: methodology.

BACKGROUND: The use of two-way audio-visual technology for delivery of acute stroke is supported by a well established literature base. The use of telemedicine for general neurologic consultation has been reported across most subspecialties within the field, but a comprehensive systematic review of these reports is lacking. PURPOSE: To conduct a systematic review of the published literature on teleneurologic consultation beyond stroke. DATA SOURCES: Databases Ovid MEDLINE, EMBASE, PsychINFO, CINAHL, and Cochrane were searched with keywords, "teleneurology," and numerous synonyms and cross-referenced with neurology subspecialties. The search yielded 6,615 potentially eligible hits, which were independently reviewed by two investigators. Ultimately 375 unique studies met eligibility criteria and were included in the review. STUDY SELECTION: Studies were included if the title or abstract expressed use of two-way AV communication for a clinical neurologic indication other than stroke. DATA EXTRACTION: Each article was classified using a novel scoring rubric to assess the level of functionality, application, technology, and evaluative stage. DATA ANALYSIS: Articles were hierarchized within a subspecialty category. Overall subspecialty scores were assigned based on aggregate of scores across papers in each category. CONCLUSION: Use of telemedicine for general and most subspecialty neurologic consultation, beyond stroke, appears very promising but the clinical science is nascent.

Disrupted daytime activity and altered sleep-wake patterns may predict transition to mild cognitive impairment or dementia: a critically appraised topic.

BACKGROUND: There is a well-known relationship between neurodegenerative disease, disrupted sleep, and cognition. Pathologic and imaging studies have shown that regions in the brain shown to regulate sleep and circadian rhythm are abnormal in Alzheimer disease. Most of these studies have been cross-sectional, and often look at patients already with dementia. This leaves uncertainty with regard to the temporal relationship of circadian disruption and cognitive decline. OBJECTIVE: To determine whether disrupted daytime activity and altered sleep patterns predict development of mild cognitive impairment (MCI) or dementia. METHODS: The objective was addressed through the development of a structured, critically-appraised topic. We incorporated a clinical scenario, background information, a structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, and behavioral neurology and sleep medicine content experts. RESULTS: A prospective cohort study of 1282 cognitively normal women demonstrated that when peak circadian activity, as measured by wrist actigraphy, occurred later than average, there was an increased risk of MCI or dementia [odds ratio (OR), 1.83; 95% confidence interval (CI), 1.29-2.61]. Increased odds for dementia or MCI also existed for those with decreased circadian rhythm amplitude (OR, 1.57; 95% CI, 1.09-2.25) and robustness (OR, 1.57; 95% CI, 1.29-2.61). CONCLUSIONS: Disrupted circadian rhythm measures, including lower amplitude, a less robust rhythm, and delayed timing of peak activity on wrist actigraphy, were predictive of future development of MCI or dementia in cognitively normal women.

Collaboration, collegiality, and cooperation: consumer health library services and the American Cancer Society navigator role.

Patients and family members are overwhelmed by the diagnosis of cancer and often do not know where to look for answers, information on the treatment options, or community resources for support during the cancer journey. A unique relationship was forged with a patient and health education librarian at the Mayo Clinic in Arizona and an American Cancer Society navigator, which encouraged collaboration to better meet the informational and supportive healthcare needs of patients. This article addresses the background of the project, the steps taken to establish the relationship, space allocation, and need for confidentiality. The innovations produced by this partnership also are discussed, including development of cancer pathfinders and cancer communication blogs for patients, as well as comarketing of services.

Determination of hemispheric language dominance in the surgical epilepsy patient: diagnostic properties of functional magnetic resonance imaging.

BACKGROUND: Presurgical evaluation for refractory epilepsy typically includes assessment of cognitive and language functions. The reference standard for determination of hemispheric language dominance has been the intracarotid amobarbital test (IAT) but functional magnetic resonance imaging (fMRI) is increasingly used. OBJECTIVE: To critically assess current evidence regarding the diagnostic properties of fMRI in comparison with the IAT for determination of hemispheric language dominance. METHODS: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the fields of epilepsy and neurosurgery. RESULTS: A systematic review and meta-analysis that compared the sensitivity and specificity of fMRI to IAT-determined language lateralization was selected for critical appraisal. The review included data from 23 articles (n=442); study methodology varied widely. fMRI was 83.5% sensitive and 88.1% specific for detection of hemispheric language dominance. CONCLUSIONS: There are insufficient data to support routine use of fMRI for the purpose of determining hemispheric language dominance in patients with intractable epilepsy. Larger, well-designed studies of fMRI for language and other cognitive outcomes as part of the presurgical and postsurgical evaluation of epilepsy patients are necessary.

New-onset atrial fibrillation in severe sepsis and risk of stroke and death: a critically appraised topic.

BACKGROUND: Severe sepsis has been associated with an increased risk of new-onset arrhythmias, namely atrial fibrillation (AF). Single-center and small-center studies suggest that new-onset AF is associated with higher mortality and prolonged hospitalization during severe sepsis. However, the relationship between new-onset AF in severe sepsis to prognosis is unknown. OBJECTIVE: To determine whether new-onset AF increases the risk of stroke and death in severe sepsis. METHODS: The objective was addressed through the development of a structured, critically appraised topic. This incorporated a clinical scenario, background information, a structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and fellow-level neurologists, a medical librarian, clinical epidemiologists, and context experts in the fields of vascular neurology, hospital neurology, critical care medicine, and cardiovascular medicine. RESULTS: A recent retrospective, population-based cohort study was selected and appraised to address this prognostic question. Patients were obtained from the California State Inpatient Database administrative claims data from nonfederal acute care hospitals from January 1 through December 31, 2007. Of the 3,144,787 patients, 49,082 (1.56%) had severe sepsis, defined by the validated International Classification of Disease, 9th Revision, Clinical Modification code 995.92. The a priori outcome measures included in-hospital ischemic stroke and mortality. New-onset AF occurred in 5.9% of patients with severe sepsis versus 0.65% of patients without severe sepsis [odds ratio, 6.82; 95% confidence interval (CI), 6.52-7.11; P<0.001]. Compared with severe sepsis patients without new-onset AF, patients with new-onset AF during severe sepsis had greater risks of in-hospital ischemic stroke (2.6% vs. 0.6% strokes; adjusted odds ratio, 2.70; 95% CI, 2.05-3.57; P<0.001) and in-hospital mortality (56% vs. 39% deaths; adjusted relative risk, 1.07; 95% CI, 1.04-1.11; P<0.001). Findings were robust across 2 separate definitions of severe sepsis and multiple sensitivity analyses. CONCLUSIONS: In patients with severe sepsis, new-onset AF seems to increase the risk of in-hospital stroke and mortality compared with patients with no or preexisting AF.

Therapeutic hypothermia for severe traumatic brain injury: a critically appraised topic.

BACKGROUND: Traumatic brain injury (TBI) is common and confers a high rate of disability and mortality. Current treatments are primarily supportive. Therapeutic hypothermia has been proposed for severe TBI because of its ability to reduce intracranial pressure and putative neuroprotective effects. OBJECTIVE: To critically appraise the current evidence concerning the efficacy of therapeutic hypothermia in the treatment of severe TBI. METHODS: The objective was addressed through the development of a structured, critically appraised topic. This incorporated a clinical scenario, background information, a structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and critical care and neurocritical care content experts. RESULTS: A recent multicenter randomized controlled trial was selected for critical assessment; meta-analyses were also reviewed. Subjects with severe TBI were randomized to either rapid cooling to 33°C for 48 hours (treatment, n=52) or normothermia (control, n=45). Outcome assessments included mortality and disability at 6 months as measured by the Glasgow Outcome Scale. Initiation of hypothermia began within 2.5 hours of injury and patients were rewarmed over a mean of 17.2 hours. The study was terminated for futility; no difference in outcome or mortality was detected between treatment groups. Post hoc subgroup analysis showed that among subjects who required hematoma evacuation, hypothermia was associated with a lower rate of poor clinical outcome (number needed to treat=2.8; 95% confidence interval, 1.4-78.3, P=0.02) and a trend toward a decrease in mortality (P=0.16). CONCLUSIONS: Current cumulative evidence does not support general use of therapeutic hypothermia for acute severe TBI. However, further investigation of the role of therapeutic hypothermia may be warranted for specific TBI subgroups.

Assessing inpatient glycemic control: what are the next steps?

Despite the emergence of glucometrics (i.e., systematic analysis of data on blood glucose levels of inpatients) as a subject of high interest, there remains a lack of standardization on how glucose parameters are measured and reported. This dilemma must be resolved before a national benchmarking process can be developed that will allow institutions to track and compare inpatient glucose control performance against established guidelines and that can also be supported by quality care organizations. In this article, we review some of the questions that need to be resolved through consensus and review of the evidence, and discuss some of the limitations in analyzing and reporting inpatient glucose data that must be addressed (or at least accepted as limitations) before hospitals can commit resources to gathering, compiling, and presenting inpatient glucose statistics as a health care quality measure. Standards must include consensus on which measures to report, the unit of analysis, definitions of targets for hyperglycemia treatment, a definition of hypoglycemia, determination of how data should be gathered (from chart review or from laboratory information systems), and which type of sample (blood or point of care) should be used for analysis of glycemic control. Hospitals and/or their representatives should be included in the discussion. For inpatient glucose control to remain a focus of interest, further dialogue and consensus on the topic are needed.

Is dabigatran cost effective compared with warfarin for stroke prevention in atrial fibrillation? A critically appraised topic.

BACKGROUND: Warfarin has provided protection against cardioembolic stroke in the setting of nonvalvular atrial fibrillation (NVAF) for the past 60 years. Dabigatran, the first oral direct thrombin inhibitor to be approved in the United States, promises to provide the same or better stroke protection with reduced risk of intracranial hemorrhage. However, it remains to be seen whether grand-scale adoption of dabigatran will be cost effective. OBJECTIVE: To critically assess current evidence regarding the cost effectiveness of dabigatran for preventing stroke in patients with NVAF compared with warfarin. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of vascular neurology. RESULTS: A cost-effectiveness analysis (CEA) that followed a hypothetical cohort of NVAF patients 65 years of age or older and CHADS2≥1 over their lifetime comparing dabigatran with adjusted-dose warfarin was reviewed. Assuming a willingness to pay a threshold of $50,000 per quality-adjusted life year (QALY), base case results favored high-dose (150 mg bid) dabigatran as a cost-effective alternative to warfarin. Sensitivity analysis asserted that the cost effectiveness of dabigatran improved if it could be obtained for ≤$13/d or if it was used in populations with high risk of stroke or intracranial hemorrhage. CONCLUSIONS: Dabigatran 150 mg bid ($12,286 per QALY) is a cost-effective alternative to International Normalized Ratio-adjusted warfarin for the prevention of ischemic stroke in patients 65 years of age or older with NVAF.

Is donepezil effective for multiple sclerosis-related cognitive dysfunction? A critically appraised topic.

BACKGROUND: Cognitive dysfunction affects approximately half of the patients with multiple sclerosis (MS). Cholinesterase inhibitor drugs are approved to treat cognitive dysfunction associated with degenerative dementia. OBJECTIVE: To critically assess current evidence regarding the efficacy of the cholinesterase inhibitor, donepezil in the treatment of MS-associated cognitive impairment. METHODS: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the fields of behavioral neurology and MS. RESULTS: A randomized control trial was selected for critical appraisal. This trial randomized MS patients to receive donepezil 10 mg daily or placebo for treatment of MS-related cognitive dysfunction. There was no significant treatment effect found between the 2 groups on either the primary outcome of memory or any of the secondary cognitive measures. Post hoc analyses suggested a trend favoring donepezil in subjects with greater baseline cognitive dysfunction. CONCLUSIONS: Donepezil 10 mg daily for 24 weeks is not superior to placebo in improving MS-related cognitive dysfunction.