Factors Associated With Use of Nonoral Nutrition and Hydration Support in Adult Patients With Postural Tachycardia Syndrome.

BACKGROUND: Patients with postural tachycardia syndrome (POTS) often have gastrointestinal (GI) symptoms. Occasionally, these symptoms can be so severe that nonoral nutrition/hydration support (NONHS), including intravenous fluids (IVFs), enteral nutrition (EN), and parenteral nutrition (PN), becomes necessary. METHODS: This is a retrospective cohort study of adult patients diagnosed with POTS at the Mayo Clinic Arizona from January 2010 to January 2017 with a minimum of 6 months of follow up. Demographic information, symptomatology, medications, GI testing, autonomic and autoantibody testing, and healthcare utilization data were abstracted from the electronic medical record. RESULTS: Three-hundred thirty-two patients with POTS were included, of which 32 required NONHS. Patients receiving NONHS were more likely to be female; have lower body mass index; have GI symptoms including nausea, vomiting, diarrhea, and constipation; have abdominal pain; use opiates; have delayed gastric emptying; see more specialists; and be seen in an emergency room or be hospitalized for symptoms. Of these patients, 21 (66%) required IVF, 19 (59%) required EN, and 9 (28%) required PN. Six (19%) patients required all 3 NONHS modalities at some point during their follow-up period. CONCLUSIONS: NONHS may be required in a subset of patients with POTS. Those receiving NONHS have more severe symptoms and abnormal GI motility and autonomic testing and exhibit greater healthcare utilization. Management of these patients is complex and challenging and requires a multidisciplinary approach. Further prospective studies are needed to identify optimal management strategies.

Weight Loss in Parkinson's Disease: No Evidence for Role of Small Intestinal Bacterial Overgrowth.

BACKGROUND AND OBJECTIVE: Weight loss and small intestinal bacterial overgrowth (SIBO) are common in Parkinson's disease (PD). We aimed to study the relationship between weight loss and SIBO in PD. METHODS: This was a cross-sectional study with a prospective, interventional component. Consecutive patients seen in the PD clinic who agreed to participate underwent extensive history, movement exam, SIBO breath testing and answered questionnaires. A subset of those in the weight loss group were treated with rifaximin for 14 days and returned 3 months later for an assessment of their weight, GI symptoms, quality of life and SIBO status. All analyses were adjusted for age and disease duration. RESULTS: Fifty-one patients participated in the study; 37 without weight loss and 14 with weight loss. Total energy intake including the distribution of macronutrient intake was similar between groups while physical activity was less in those with weight loss. PD severity scores did not differ between groups; however, PD-specific quality of life scores were significantly worse for the summary index and the subscales of emotional well-being, social support and communication. The prevalence of constipation, dyspepsia and abdominal pain/discomfort was higher in those with weight loss. The prevalence of SIBO was 14% in the weight loss group and was not different between groups. Eight PD patients with weight loss were treated with rifaximin; no significant change in GI symptoms, quality of life or weight was seen 3 months later. CONCLUSION: Although a number of differences were identified in quality of life and gastrointestinal symptoms between groups with and without weight loss, SIBO was not associated with weight loss in patients with PD. Given the exploratory nature and small number of patients with weight loss, however, further study is suggested.

Personality Changes During the Transition from Cognitive Health to Mild Cognitive Impairment.

BACKGROUND/OBJECTIVES: Behavioral problems in individuals with Alzheimer's disease (AD) impose major management challenges. Current prevention strategies are anchored to cognitive outcomes, but behavioral outcomes may provide another, clinically relevant opportunity for preemptive therapy. We sought to determine whether personality changes that predispose to behavioral disorders arise during the transition from preclinical AD to mild cognitive impairment (MCI). DESIGN: Longitudinal observational cohort study. SETTING: Academic medical center. PARTICIPANTS: Members of an apolipoprotein E (APOE) ɛ4 genetically enriched cohort of Maricopa County residents who were neuropsychiatrically healthy at entry (N = 277). Over a mean interval of 7 years, 25 who developed MCI and had the Neuroticism, Extraversion, and Openness Personality Inventory-Revised (NEO-PI-R) before and during the MCI transition epoch were compared with 252 nontransitioners also with serial NEO-PI-R administrations. INTERVENTION: Longitudinal administration of the NEO-PI-R and neuropsychological test battery. MEASUREMENTS: Change in NEO-PI-R factor scores (neuroticism, extraversion, openness, agreeableness, conscientiousness) from entry to the epoch of MCI diagnosis or an equivalent follow-up duration in nontransitioners. RESULTS: NEO-PI-R neuroticism T-scores increased significantly more in MCI transitioners than in nontransitioners (mean 2.9, 95% confidence interval (CI) = 0.9-4.9 vs 0, 95% CI = -0.7-0.7, P = .02), and openness decreased more in MCI transitioners than in nontransitioners (-4.8, 95% CI = -7.3 to -2.4 vs -1.0, 95% CI = -1.6 to -0.4, P < .001). Concurrent subclinical but statistically significant changes in behavioral scores worsened more in MCI transitioners than nontransitioners for measures of depression, somatization, irritability, anxiety, and aggressive attitude. CONCLUSION: Personality and subclinical behavioral changes begin during the transition from preclinical AD to incident MCI and qualitatively resemble the clinically manifest behavioral disorders that subsequently arise in individuals with frank dementia.

Behavioral Interventions to Prevent or Delay Dementia: Protocol for a Randomized Comparative Effectiveness Study.

BACKGROUND: Currently, people at risk for dementia and their caregivers are confronted with confusing choices about what behavioral interventions are most effective. OBJECTIVE: The objective of this study is to determine which empirically supported behavioral interventions most impact the outcomes highly valued by patients with mild cognitive impairment and their partners. METHODS: This protocol describes a comparative effectiveness trial targeting 300 participants with mild cognitive impairment and their study partners. The trial is being conducted at the Mayo Clinic campuses in Arizona, Florida, Minnesota, and the University of Washington in Seattle. The study examines the contribution of five behavioral interventions (yoga, memory compensation training, computerized cognitive training, support groups, and wellness education) on primary outcomes of participant and partner quality of life and self-efficacy. In this unique 10-day multicomponent intervention, groups of couples were randomized to have one of the five interventions withheld while receiving the other four. Although the longitudinal follow-up is still under way, enrollment results are available and reported. RESULTS: In total, 272 couples have been enrolled in the trial and follow-up visits continue. Outcomes will be assessed at the end-of-intervention and 6-, 12-, and 18-month follow-ups. We anticipate reporting on our primary and secondary outcomes across time points in the next 2 years. CONCLUSIONS: This paper describes the protocol for a randomized comparative effectiveness study of behavioral interventions to prevent or delay dementia. We describe of the rationale, design, power analysis, and analysis plan. Also because enrollment is complete and we are in follow-up phases of the study, we have included enrollment data from the trial. TRIAL REGISTRATION:  ClinicalTrials.gov NCT02265757; http://clinicaltrials.gov/ctsshow/ NCT02265757 (Archived by WebCite at http://www.webcitation.org/6ueRfwSYv).

Computer versus Compensatory Calendar Training in Individuals with Mild Cognitive Impairment: Functional Impact in a Pilot Study.

This pilot study examined the functional impact of computerized versus compensatory calendar training in cognitive rehabilitation participants with mild cognitive impairment (MCI). Fifty-seven participants with amnestic MCI completed randomly assigned calendar or computer training. A standard care control group was used for comparison. Measures of adherence, memory-based activities of daily living (mADLs), and self-efficacy were completed. The calendar training group demonstrated significant improvement in mADLs compared to controls, while the computer training group did not. Calendar training may be more effective in improving mADLs than computerized intervention. However, this study highlights how behavioral trials with fewer than 30-50 participants per arm are likely underpowered, resulting in seemingly null findings.

Impact of Personality on Cognitive Aging: A Prospective Cohort Study.

OBJECTIVES: The aim of this study was to assess the association between personality factors and age-related longitudinal cognitive performance, and explore interactions of stress-proneness with apolipoprotein E (APOE) ɛ4, a prevalent risk factor for Alzheimer's disease (AD). METHODS: A total of 510 neuropsychiatrically healthy residents of Maricopa County recruited through media ads (mean age 57.6±10.6 years; 70% women; mean education 15.8±2.4 years; 213 APOE ɛ4 carriers) had neuropsychological testing every 2 years (mean duration follow-up 9.1±4.4 years), and the complete Neuroticism Extraversion Openness Personality Inventory-Revised. Several tests were administered within each of the following cognitive domains: memory, executive skills, language, visuospatial skills, and general cognition. Primary effects on cognitive trajectories and APOE ɛ4 interactions were ascertained with quadratic models. RESULTS: With personality factors treated as continuous variables, Neuroticism was associated with greater decline, and Conscientiousness associated with reduced decline consistently across tests in memory and executive domains. With personality factors trichotomized, the associations of Neuroticism and Conscientiousness were again highly consistent across tests within memory and to a lesser degree executive domains. While age-related memory decline was greater in APOE ɛ4 carriers as a group than ɛ4 noncarriers, verbal memory decline was mitigated in ɛ4 carriers with higher Conscientiousness, and visuospatial perception and memory decline was mitigated in ɛ4 carriers with higher Openness. CONCLUSIONS: Neuroticism and Conscientiousness were associated with changes in longitudinal performances on tests sensitive to memory and executive skills. APOE interactions were less consistent. Our findings are consistent with previous studies that have suggested that personality factors, particularly Neuroticism and Conscientiousness are associated with cognitive aging patterns. (JINS, 2016, 22, 765-776).

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.

The neuropsychology of normal aging and preclinical Alzheimer's disease.

OBJECTIVE: A National Institute on Aging-sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD. METHODS: Seventy-one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups. RESULTS: There was a significant effect of age on all cognitive domains in both APOE ε4 carriers and noncarriers. A significant effect of APOE ε4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross-sectional comparisons did not discriminate the groups. CONCLUSIONS: Although cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory-sensitive measures and longitudinal design.

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.

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.

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.

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.

Safety and efficacy of ultrasound-enhanced thrombolysis in the treatment of acute middle cerebral artery infarction: a critically appraised topic.

BACKGROUND: Despite appropriate therapy with intravenous (IV) tissue plasminogen activator (tPA), a significant proportion of patients with acute middle cerebral artery (MCA) infarction continue to suffer residual disability or death. The therapeutic use of transcranial Doppler ultrasonography (TCD) concomitantly with IV tPA is speculated to increase recanalization rates and improve clinical outcomes in patients with acute MCA stroke. OBJECTIVE: To critically appraise the evidence concerning the safety and efficacy of the simultaneous delivery of IV tPA and continuous TCD monitoring as an acute therapy in patients with MCA territory infarction. 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, results, critical appraisal, clinical bottom line, and expert commentary from vascular neurology. RESULTS: In a multicenter phase II randomized controlled study, 126 patients with acute MCA stroke were randomized to receive treatment with IV tPA and continuous TCD monitoring or placebo monitoring. Complete recanalization or dramatic clinical recovery within 2 hours after the administration of a tPA bolus occurred in 31 patients in the target group (49%), as compared with 19 patients in the control group (30%); P=0.03. At 3 months, of the patients eligible for follow-up, 22 of 53 (42%) in the target group and 14 of 49 (29%) in the control group had favorable outcomes; P=0.20. Four symptomatic intracerebral hemorrhages were noted in each group. CONCLUSIONS: Therapeutic use of continuous TCD monitoring concomitantly with IV tPA increases recanalization rates in patients with acute MCA stroke relative to treatment with IV tPA alone without increasing the complication of intracerebral hemorrhage.

Risk of development of medication overuse headache with nonsteroidal anti-inflammatory drug therapy for migraine: a critically appraised topic.

BACKGROUND: The development of medication overuse headache (MOH) is associated with frequent use of analgesics, especially opiates, for treatment of primary headache disorders, particularly migraine. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat migraine. OBJECTIVE: To critically evaluate evidence estimating the risk of MOH associated with NSAID therapy in patients with migraine. 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 headache neurology content experts. RESULTS: The 1-year incidence of MOH was 2.5%. In patients with low (0 to 4 d monthly) to moderate (5 to 9 d monthly) baseline headache frequency, NSAIDs were not associated with progression to MOH and may be protective (odds ratio=0.31; 95% confidence interval, 0.27-0.34). However, in patients with a high baseline headache frequency (10 to 14 d monthly), NSAIDs are associated with progression to MOH (odds ratio=1.93; 95% confidence interval, 1.82-2.06). CONCLUSIONS: Acute NSAID therapy is associated with progression to MOH in migraineurs with a high baseline migraine frequency but may be protective in patients with low baseline headache frequency. However, a causal role for NSAIDs in progression from episodic to chronic headache has not been established.

A literature review on breathing retraining as a self-management strategy operationalized through Rosswurm and Larrabee's evidence-based practice model.

PURPOSE: The purpose of this article is to critically appraise and synthesize the literature on breathing retraining as a self-management strategy for individuals with chronic obstructive pulmonary disease (COPD) guided by Rosswurm and Larrabee's evidence-based practice model. DATA SOURCES: Scientific literature review, grey literature review, and hand searching. CONCLUSIONS: An exhaustive review of the literature revealed evidence that regularly practiced pursed lip breathing is an effective self-management strategy for individuals with COPD to improve their dyspnea. IMPLICATIONS FOR PRACTICE: It is expected that implementation of this non-pharmacological self-management intervention will improve perception of dyspnea, functional performance, and self-efficacy in individuals with COPD.