Susan Carson

Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents--second edition.

Author Affiliations Patrick M. Kochanek, MD, FCCM, Professor and Vice Chair, Department of Critical Care Medicine, University of Pittsburgh School of Medicine Nancy Carney, PhD, Associate Professor, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University P. David Adelson, MD, FACS, FAAP, Director, Barrow Neurological Institute at Phoenix Children’s Hospital, Chief, Pediatric Neurosurgery/ Children’s Neurosciences Stephen Ashwal, MD, Distinguished Professor of Pediatrics and Neurology, Chief of the Division of Child Neurology, Department of Pediatrics, Loma Linda University School of Medicine Michael J. Bell, MD, Associate Professor of Critical Care Medicine, University of Pittsburgh School of Medicine Susan Bratton, MD, MPH, FAAP, Professor of Pediatric Critical Care Medicine, University of Utah School of Medicine Susan Carson, MPH, Senior Research Associate, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University Randall M. Chesnut, MD, FCCM, FACS, Professor of Neurological Surgery, Orthopedics and Sports Medicine, University of Washington School of Medicine Jamshid Ghajar, MD, PhD, FACS, Clinical Professor of Neurological Surgery, Weill Cornell Medical College, President of the Brain Trauma Foundation Brahm Goldstein, MD, FAAP, FCCM, Senior Medical Director, Clinical Research, Ikaria, Inc., Professor of Pediatrics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School Gerald A. Grant, MD, Associate Professor of Surgery and Pediatrics, Duke University School of Medicine Niranjan Kissoon, MD, FAAP, FCCM, Professor of Paediatrics and Emergency Medicine, British Columbia’s Children’s Hospital, University of British Columbia Kimberly Peterson, BSc, Research Associate, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University Nathan R. Selden, MD, PhD, FACS, FAAP, Campagna Professor and Vice Chair of Neurological Surgery, Oregon Health & Science University Robert C. Tasker, MBBS, MD, FRCP, Chair and Director, Neurocritical Care, Children’s Hospital Boston, Professor of Neurology and Anesthesia, Harvard Medical School Karen A. Tong, MD, Associate Professor of Radiology, Loma Linda University Monica S. Vavilala, MD, Professor of Anesthesiology and Pediatrics, University of Washington School of Medicine Mark S. Wainwright, MD, PhD, Director, Pediatric Neurocritical Care, Associate Professor of Pediatrics, Northwestern University Feinberg School of Medicine Craig R. Warden, MD, MPH, MS, Professor of Emergency Medicine and Pediatrics, Chief, Pediatric Emergency Services, Oregon Health & Science University/Doernbecher Children’s Hospital

Hypothermia Treatment for Traumatic Brain Injury: A Systematic Review and Meta-Analysis

In this study, we conducted an updated meta-analysis of the effects of hypothermia therapy on mortality, favorable neurologic outcome, and associated adverse effects in adults with traumatic brain injury (TBI) for use by Brain Trauma Foundation (BTF)/American Association of Neurological Surgeons (AANS) task force to develop evidence-based treatment guidelines. Our data sources relied on handsearches of four previous good-quality systematic reviews, which all conducted electronic searches of primarily MEDLINE (OVID), EMBASE, and Cochrane Library. An independent, supplemental electronic search of MEDLINE was undertaken as well (last searched June 2007). Only English-language publications of randomized controlled trials of therapeutic hypothermia in adults with TBI were selected for analysis. Two reviewers independently abstracted data on trial design, patient population, hypothermia and cointervention protocols, patient outcomes, and aspects of methodological quality. Pooled relative risks (RR) and associated 95% confidence intervals (CIs) were calculated for each outcome using random-effects models. In the current study, only 13 trials met eligibility criteria, with a total of 1339 randomized patients. Sensitivity analyses revealed that outcomes were influenced by variations in methodological quality. Consequently, main analyses were conducted based on eight trials that demonstrated the lowest potential for bias (n = 781). Reductions in risk of mortality were greatest (RR 0.51; 95% CI 0.33, 0.79) and favorable neurologic outcomes much more common (RR 1.91; 95% CI 1.28, 2.85) when hypothermia was maintained for more than 48 h. However, this evidence comes with the suggestion that the potential benefits of hypothermia may likely be offset by a significant increase in risk of pneumonia (RR 2.37; 95% CI 1.37, 4.10). In sum, the present studys updated meta-analysis supports previous findings that hypothermic therapy constitutes a beneficial treatment of TBI in specific circumstances. Accordingly, the BTF/AANS guidelines task force has issued a Level III recommendation for optional and cautious use of hypothermia for adults with TBI.

A systematic review of the efficacy and safety of atypical antipsychotics in patients with psychological and behavioral symptoms of dementia

Although the Food and Drug Administration (FDA) has not approved atypical antipsychotics for use in patients with dementia, they are commonly prescribed in this population. Recent concerns about increased risk of cerebrovascular events and mortality have led to warnings. A systematic review was conducted to assess the benefits and harms of atypical antipsychotics when used in patients with behavioral and psychological symptoms of dementia. Electronic searches (through March 2005) of the Cochrane Library, Medline, Embase, and PsycINFO were supplemented with hand searches of reference lists, dossiers submitted by pharmaceutical companies, and a review of the FDA Website and industry‐sponsored results database. Using predetermined criteria, each study was assessed for inclusion, and data about study design, population, interventions, and outcomes were abstracted. An overall quality rating (good, fair, or poor) was assigned based on internal validity.

Gabapentin Versus Tricyclic Antidepressants for Diabetic Neuropathy and Post-Herpetic Neuralgia: Discrepancies Between Direct and Indirect Meta-Analyses of Randomized Controlled Trials

BackgroundPrevious systematic reviews concluded that tricyclics antidepressants are superior to gabapentin for neuropathic pain, but were based on indirect comparisons from placebo-controlled trials.PurposeTo evaluate gabapentin versus tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia, using direct and indirect comparisons.Data SourcesMEDLINE (1966 to March Week 4 2008), the Cochrane central register of controlled trials (1st quarter 2008), and reference lists.Study SelectionWe selected randomized trials directly comparing gabapentin versus tricyclic antidepressants or comparing either of these medications versus placebo.Data ExtractionStudies were reviewed, abstracted, and quality-rated by two independent investigators using predefined criteria.Data SynthesisWe performed a meta-analysis of head-to-head trials using a random effects model and compared the results to an adjusted indirect analysis of placebo-controlled trials.ResultsIn three head-to-head trials, there was no difference between gabapentin and tricyclic antidepressants for achieving pain relief (RR 0.99, 95% CI 0.76 to 1.29). In adjusted indirect analyses, gabapentin was worse than tricyclic antidepressants for achieving pain relief (RR = 0.41, 95% CI 0.23 to 0.74). The discrepancy between direct and indirect analyses was statistically significant (p = 0.008). Placebo-controlled tricyclic trials were conducted earlier than the gabapentin trials, reported lower placebo response rates, had more methodological shortcomings, and were associated with funnel plot asymmetry.ConclusionsThough direct evidence is limited, we found no difference in likelihood of achieving pain relief between gabapentin and tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia. Indirect analyses that combine data from sets of trials conducted in different eras can be unreliable.

Systematic review of hyperbaric oxygen therapy for cerebral palsy: the state of the evidence

A systematic review of the evidence was conducted on the benefits and adverse effects of hyperbaric oxygen treatment (HBOT) for cerebral palsy (CP). Studies of any HBOT regimen in patients with CP were included except for case reports and case series. Electronic databases (e.g. MEDLINE, EMBASE), professional society databases, and reference lists were searched to identify studies. Study quality was assessed using predefined criteria relevant to the study design. Two randomized controlled trials and four observational studies were identified. Best evidence came from a randomized controlled trial which found that HBOT at 1.75 atmospheres (atm) and 1.3atm of room air resulted in similar improvements in motor function (5–6%). Other outcomes also indicated no difference between the HBOT and room air. Observational studies reported improvements in motor function to a similar degree. Other evidence was insufficient to clarify the benefits and/or adverse effects of HBOT for CP. Both HBOT and pressurized room air resulted in improvements in motor function compared with baseline. Similar improvements were seen in the observational studies. Children undergoing HBOT were reported to experience adverse events, including seizures and the need for ear pressure equalization tube placement, but the incidence was unclear. Future research is needed to determine the efficacy of pressurized room air or non‐pressurized oxygen in equivalent amounts by mask, compared with standard treatments.

Hyperbaric oxygen therapy for stroke: a systematic review of the evidence

Objective: To identify the benefits and harms of using hyperbaric oxygen therapy to treat acute or subacute stroke or the chronic effects of a stroke. We aimed to identify any gaps in the evidence to provide guidance for future research. Design: A systematic review of the evidence. Search strategy: We searched MEDLINE, EMBASE, the Cochrane Library, HealthSTAR, CINAHL, MANTIS, bibliographic databases from professional societies and hyperbaric oxygen therapy practitioners, and reference lists. Databases were searched from inception to December 2003. Inclusion criteria: Studies: Controlled clinical trials and observational studies published in English. Participants: Patients with ischaemic stroke in any inpatient or outpatient setting. Outcomes: Mortality, functional health outcomes and adverse events. Data collection and analysis: Using predetermined criteria, two reviewers assessed each study for inclusion, and abstracted data about study design, population, interventions, and outcomes. We assigned an overall quality rating (good, fair, or poor) based on internal validity. Results: We identified only four randomized controlled trials and one controlled clinical trial. The best evidence shows no benefit to hyperbaric oxygen therapy in patients with stroke, but because the stage of patients enrolled (acute, subacute, or chronic), the documentation of type and severity of stroke, and the dosage of hyperbaric oxygen therapy given varied considerably, the generalizability of these results is limited. We identified 17 observational studies; all were poor quality. Conclusions: The overall evidence is insufficient to determine the effectiveness of hyperbaric oxygen therapy in any subgroup of stroke patients. To determine if hyperbaric oxygen therapy for stroke provides any benefit and that these outweigh potential harms, good quality studies are needed.

Methods for the Drug Effectiveness Review Project

The Drug Effectiveness Review Project was initiated in 2003 in response to dramatic increases in the cost of pharmaceuticals, which lessened the purchasing power of state Medicaid budgets. A collaborative group of state Medicaid agencies and other organizations formed to commission high-quality comparative effectiveness reviews to inform evidence-based decisions about drugs that would be available to Medicaid recipients. The Project is coordinated by the Center for Evidence-based Policy (CEbP) at Oregon Health & Science University (OHSU), and the systematic reviews are undertaken by the Evidence-based Practice Centers (EPCs) at OHSU and at the University of North Carolina. The reviews adhere to high standards for comparative effectiveness reviews. Because the investigators have direct, regular communication with policy-makers, the reports have direct impact on policy and decision-making, unlike many systematic reviews. The Project was an innovator of methods to involve stakeholders and continues to develop its methods in conducting reviews that are highly relevant to policy-makers. The methods used for selecting topics, developing key questions, searching, determining eligibility of studies, assessing study quality, conducting qualitative and quantitative syntheses, rating the strength of evidence, and summarizing findings are described. In addition, our on-going interactions with the policy-makers that use the reports are described.

Comparative Effectiveness of Pioglitazone and Rosiglitazone in Type 2 Diabetes, Prediabetes,and the Metabolic Syndrome: A Meta-Analysis

OBJECTIVE To assess the comparative efficacy and safety of pioglitazone and rosiglitazone. RESEARCH DESIGN AND METHODS Multiple electronic databases were searched for randomized, controlled trials (RCTs) of efficacy or effectiveness and for studies of any design which reported adverse events. Pooled estimates were calculated using a random effects model. RESULTS Eighty-seven RCTs fulfilled our inclusion criteria for efficacy or effectiveness and 42 studies examined safety or tolerability. Two head-to-head RCTs of type 2 diabetes demonstrated significant improvements in A1c in both groups at follow-up with no significant difference between groups; a third study found no significant change in A1c in either group. The pooled estimate of effect on A1c for pioglitazone compared to placebo was -0.99% (95% confidence interval [CI], -1.18, -0.81) and for rosiglitazone was -0.92% (95% CI, -1.2, -0.64). Indirect comparison revealed no significant difference in A1c (between-drug difference -0.07% [95% CI, -0.41, 0.27]). Rosiglitazone increased total cholesterol compared to pioglitazone (net between-drug effect 13.91 mg/dl [95% CI, 1.20 to 26.62]). Both drugs increased weight by 2 to 3 kg and rates of adverse events were similar for the two drugs. Data were insufficient to assess comparative effects on health outcomes such as cardiovascular events. CONCLUSIONS Based largely on indirect evidence, the two thiazolidinediones appear to have similar effects on glycemic control and similar side-effect profiles. Rosiglitazone may increase total cholesterol compared to pioglitazone. Studies are needed which provide direct comparisons between the two drugs, particularly for long-term health outcomes.

Pegylated interferons for chronic hepatitis C virus infection: an indirect analysis of randomized trials

Summary.  Dual therapy with pegylated interferon and ribavirin is recommended for patients with chronic hepatitis C virus infection who meet criteria for treatment, but it is unclear whether pegylated interferon alfa‐2a or pegylated interferon alfa‐2b is more effective or associated with fewer adverse events. Because data from head‐to‐head trials of pegylated interferon regimens are sparse, we performed adjusted indirect analysis using trials comparing dual therapy with pegylated interferon alfa‐2a or pegylated interferon alfa‐2b vs dual therapy with non‐pegylated interferon. We searched for potentially relevant randomized controlled trials using electronic databases and reference lists. A total of 16 trials met inclusion criteria. Adjusted indirect comparisons found no statistically significant differences between dual therapy with pegylated interferon alfa‐2a and dual therapy with pegylated interferon alfa‐2b on the outcomes sustained virologic response [relative risk (RR) = 1.59, 95% CI: 0.56–4.46], withdrawal due to adverse events (RR = 0.86, 95% CI: 0.29–2.55), anaemia (RR = 1.67, 95% CI: 0.32–8.84), depression (RR = 1.09, 95% CI: 0.41–2.90) or flu‐like symptoms (RR = 1.10, 95% CI: 0.53–2.29). Adjusting for potential publication bias and stratifying analyses by indicators of methodological quality, human immunodeficiency virus infection status, hepatitis C virus genotype, dose of ribavirin or dose of pegylated interferon did not change conclusions. There is insufficient evidence to support conclusions that dual therapy with one pegylated interferon is superior to the other. However, because estimates are imprecise, our results also do not rule out a clinically significant difference. Head‐to‐head trials are needed to verify the results of indirect analyses and provide additional guidance on optimal treatment choices.

Routine Vitamin Supplementation To Prevent Cardiovascular Disease: A Summary of the Evidence for the U.S. Preventive Services Task Force

Study Selection: The researchers selected English-language reports of randomized trials and cohort studies that assessed vitamin supplementation in western populations and reported incidence of or death from cardiovascular events. They also included reports of good- or fair-quality clinical trials of primary and secondary prevention and good- or fair-quality prospective cohort studies. Studies that examined only dietary nutrients or did not provide separate estimates for supplements were not included. Data Extraction: Two reviewers abstracted descriptive information and data on cardiovascular outcomes and mortality from included studies. The researchers assessed study quality using predetermined criteria. Data Synthesis: Evidence tables were constructed to summarize data from included studies. The researchers summarized the strength, level, and quality of the overall evidence for the effectiveness of each of the vitamin supplements in preventing or treating cardiovascular disease. Conclusions: Some good-quality cohort studies have reported an association between the use of vitamin supplements and lower risk for cardiovascular disease. Randomized, controlled trials of specific supplements, however, have failed to demonstrate a consistent or significant effect of any single vitamin or combination of vitamins on incidence of or death from cardiovascular disease. Understanding the sources of these differences will permit researchers to better analyze the cohort study data and to better design long-term clinical trials.