Activity-Based Therapy for Recovery of Walking in Individuals With Chronic Spinal Cord Injury: Results From a Randomized Clinical Trial

ObjectiveTo examine the effects of activity-based therapy (ABT) on neurologic function, walking ability, functional independence, metabolic health, and community participation.DesignRandomized controlled trial with delayed treatment design.SettingOutpatient program in a private, nonprofit rehabilitation hospital.ParticipantsVolunteer sample of adults (N=48; 37 men and 11 women; age, 18–66y) with chronic (≥12mo postinjury), motor-incomplete (ASIA Impairment Scale grade C or D) spinal cord injury (SCI).InterventionsA total of 9h/wk of ABT for 24 weeks including developmental sequencing; resistance training; repetitive, patterned motor activity; and task-specific locomotor training. Algorithms were used to guide group allocation, functional electrical stimulation utilization, and locomotor training progression.Main Outcome MeasuresNeurologic function (International Standards for Neurological Classification of Spinal Cord Injury); walking speed and endurance (10-meter walk test, 6-minute walk test, and Timed Up and Go test); community participation (Spinal Cord Independence Measure, version III, and Reintegration to Normal Living Index); and metabolic function (weight, body mass index, and Quantitative Insulin Sensitivity Check).ResultsSignificant improvements in neurologic function were noted for experimental versus control groups (International Standards for Neurological Classification of Spinal Cord Injury total motor score [5.1±6.3 vs 0.9±5.0; P=.024] and lower extremity motor score [4.2±5.2 vs −0.6±4.2; P=.004]). Significant differences between experimental and control groups were observed for 10-meter walk test speed (0.096±0.14m/s vs 0.027±0.10m/s; P=.036) and 6-minute walk test total distance (35.97±48.2m vs 3.0±25.5m; P=.002).ConclusionsABT has the potential to promote neurologic recovery and enhance walking ability in individuals with chronic, motor-incomplete SCI. However, further analysis is needed to determine for whom ABT is going to lead to meaningful clinical benefits.     

Bone Mass in Individuals With Chronic Spinal Cord Injury: Associations With Activity-Based Therapy,Neurologic and Functional Status,a Retrospective Study

ObjectiveTo describe the prevalence of osteoporosis and its association with functional electrical stimulation (FES) use in individuals with spinal cord injury (SCI)-related paralysis.DesignRetrospective cross-sectional evaluation.SettingClinic.ParticipantsConsecutive persons with SCI (N=364; 115 women, 249 men) aged between 18 and 80 years who underwent dual-energy x-ray absorptiometry (DXA) examinations.InterventionsNot applicable.Main Outcome MeasurePrevalence of osteoporosis defined as DXA T score ≤−2.5.ResultsThe prevalence of osteoporosis was 34.9% (n=127). Use of FES was associated with 31.2% prevalence of osteoporosis compared with 39.5% among persons not using FES. In multivariate adjusted logistic regression analysis, FES use was associated with 42% decreased odds of osteoporosis after adjusting for sex, age, body mass index, type and duration of injury, Lower Extremity Motor Scores, ambulation, previous bone fractures, and use of calcium, vitamin D, and anticonvulsant; (adjusted odds ratio [OR]=.58; 95% confidence interval [CI], .35–.99; P=.039). Duration of injury >1 year was associated with a 3-fold increase in odds of osteoporosis compared with individuals with injury <1 year; (adjusted OR=3.02; 95% CI, 1.60–5.68; P=.001).ConclusionsFES cycling ergometry may be associated with a decreased loss of bone mass after paralysis. Further prospective examination of the role of FES in preserving bone mass will improve our understanding of this association.     

Impact of Pressure Ulcers on Individuals Living With a Spinal Cord Injury

ObjectiveTo describe the impact of pressure ulcers on the ability to participate in daily and community activities, health care utilization, and overall quality of life in individuals living with spinal cord injury (SCI).DesignCross-sectional study.SettingNationwide survey.ParticipantsParticipants (N=1137) with traumatic SCI who were >1 year postinjury and living in the community were recruited. Of these, 381 (33.5%, 95% confidence interval, 30.8%–36.3%) had a pressure ulcer over the last 12 months.InterventionsNot applicable.Main Outcome MeasuresMeasures developed for the Rick Hansen Spinal Cord Injury Registry Community Follow-up Survey Version 2.0.ResultsOf the 381 individuals with pressure ulcers, 65.3% reported that their pressure ulcer reduced their activity to some extent or more. Pressure ulcers reduced the ability of individuals with SCI to participate in 19 of 26 community and daily activities. Individuals with 1 or 2 pressure ulcers were more dissatisfied with their ability to participate in their main activity than those without pressure ulcers (P=.0077). Pressure ulcers were also associated with a significantly higher number of consultations with family doctors, nurses, occupational therapists, and wound care nurses/specialists (P<.05).ConclusionsPressure ulcers have a significant impact on the daily life of individuals with SCI. Our findings highlight the importance of implementing pressure ulcer prevention and management programs for this high-risk population and require the attention of all SCI-related health care professionals.     

Reference Fitness Values in the Untrained Spinal Cord Injury Population

ObjectiveEstablish reference values of cardiorespiratory fitness applicable to the general, untrained spinal cord injury (SCI) population.DesignData were retroactively obtained from 12 studies (May 2004 to May 2012).SettingAn institution-affiliated applied physiology research laboratory.ParticipantsA total of 153 men and 26 women (age, 18–55y) with chronic SCI (N=179) were included. Participants were not involved in training activities for 1 or more months before testing and were able to complete a progressive resistance exercise test to determine peak oxygen consumption (Vo₂peak).InterventionsNot applicable.Main Outcome MeasurePercentile ranking (poor<20%; fair; 20%–40%; average, 40%–60%; good, 60%–80%; excellent, 80%–100%) used to establish reference values.ResultsReference cardiorespiratory fitness values based on functional classification as paraplegic or tetraplegic were established (paraplegic: median, 16.0mL·kg⁻¹·min⁻¹; range, 1.4–35.2mL·kg⁻¹·min⁻¹; tetraplegic: median, 8.8mL·kg⁻¹·min⁻¹; range, 1.5–21.5mL·kg⁻¹·min⁻¹) for untrained men and women. For the primary outcome measure (Vo₂peak), persons with paraplegia had significantly higher values than did persons with tetraplegia (P<.001). Although men had higher values than did women, these differences did not reach significance (P=.256). Regression analysis revealed that motor level of injury was associated with 22.3% of the variability in Vo₂peak (P<.001), and an additional 8.7% was associated with body mass index (P<.001). No other measure accounted for additional significant variability.ConclusionsEstablished reference fitness values will allow investigators/clinicians to stratify the relative fitness of subjects/patients from the general SCI population. Key determinants are motor level of injury and body habitus, yet most variability in aerobic capacity is not associated with standard measures of SCI status or demographic characteristics.     

Brain Machine Interface and Limb Reanimation Technologies: Restoring Function After Spinal Cord Injury Through Development of a Bypass System

Functional restoration of limb movement after traumatic spinal cord injury (SCI) remains the ultimate goal in SCI treatment and directs the focus of current research strategies. To date, most investigations in the treatment of SCI focus on repairing the injury site. Although offering some promise, these efforts have met with significant roadblocks because treatment measures that are successful in animal trials do not yield similar results in human trials. In contrast to biologic therapies, there are now emerging neural interface technologies, such as brain machine interface (BMI) and limb reanimation through electrical stimulators, to create a bypass around the site of the SCI. The BMI systems analyze brain signals to allow control of devices that are used to assist SCI patients. Such devices may include a computer, robotic arm, or exoskeleton. Limb reanimation technologies, which include functional electrical stimulation, epidural stimulation, and intraspinal microstimulation systems, activate neuronal pathways below the level of the SCI. We present a concise review of recent advances in the BMI and limb reanimation technologies that provides the foundation for the development of a bypass system to improve functional outcome after traumatic SCI. We also discuss challenges to the practical implementation of such a bypass system in both these developing fields.     

Health Care Resource Utilization and Medical Costs of Spinal Cord Injury With Neuropathic Pain in a Commercially Insured Population in the United States

ObjectiveTo evaluate health care resource use, costs, and cost drivers among patients with neuropathic pain (NeP) after spinal cord injury (SCI) in a commercially insured population.DesignRetrospective longitudinal cohort study comparing SCI patients with and without NeP.SettingTruven Health MarketScan commercial claims database from 2005 through 2012.ParticipantsCommercially insured SCI patients with NeP (n=3524) propensity score matched to SCI patients without NeP (n=3524).InterventionsNot applicable.Main Outcomes MeasuresHealth care resource utilization and expenditures for the 12 months after NeP onset (index event; identified through International Classification of Diseases, 9th Revision, Clinical Modification diagnosis 338.0x or use of NeP-specific antiepileptic drugs or NeP-specific antidepressants) in patients with SCI compared with matched patients without NeP.ResultsUtilization over 12 months postindex among patients with SCI-associated NeP was higher than among SCI-only patients for inpatient admissions (27.4% vs 22.1%), emergency department visits (36.7% vs 26.4%), and office visits per patient (mean ± SD: 13.0±9.5 vs 9.5±8.3); all P values were <.001. All-cause expenditures showed adjusted incremental costs of $22,545 (95% confidence interval, $19,010–$26,168) per patient with SCI-associated NeP during the 12-month postindex period.ConclusionsPatients with evidence of NeP secondary to SCI have significantly higher health care utilization and total costs compared with SCI patients without evidence of NeP. Factors contributing to NeP in patients with SCI need to be clinically assessed to determine the optimal approach for treating these individuals.     

Comparative Effectiveness of Telaprevir-Based Triple Therapy in Patients With Chronic Hepatitis C

ObjectiveTo examine the effectiveness and tolerability of triple therapy with pegylated interferon (p-IFN), ribavirin (RBV), and telaprevir in patients with chronic hepatitis C receiving treatment in an academic practice setting and in a more clinically diverse population compared with patients receiving treatment in phase 3 trials.Patients and MethodsA prospective database of all patients with viral hepatitis undergoing antiviral therapy from January 1, 2006, to July 1, 2012, was queried to identify treatment-naive and -experienced patients with chronic hepatitis C receiving dual and triple therapies. On-treatment response categories included rapid virologic response, extended rapid virologic response, early virologic response, and sustained virologic response. These patients were compared with matched controls, namely, patients who underwent dual therapy with p-IFN and RBV. Matching was performed for age, cirrhosis status, and prior treatment.ResultsThere were 55 patients who received triple therapy and met the eligibility criteria, consisting of treatment-naive (n=35) and -experienced patients (n=20: those with relapse, 9; those with nonresponse, 9; and those who terminated the treatment early, 2). Rapid virologic response was achieved in 41% of the patients, extended rapid virologic response in 41%, and early virologic response in 75%. Sustained virologic response was observed in 51% (18/35) of treatment-naive patients, 67% (6/9) of the patients with prior nonresponse, and 56% (5/9) of those with prior relapse. Corresponding results after dual therapy were 37% (23/62), 11% (2/18), and 27% (3/11), respectively. The mean decrease in the hemoglobin level at weeks 4, 8, and 24 of triple therapy was 2.8, 3.8, and 3.2 mg/dL compared with 2.4, 2.6, and 2.4 mg/dL with dual therapy (to convert mg/dL to mmol/L, multiply values by 0.0259).ConclusionTelaprevir-based triple therapy in clinical practice is considerably more effective than dual therapy with p-IFN and RBV despite the significant degree of anemia that complicated therapy, requiring RBV dose reduction and erythropoietin support.     

Drug-Induced Liver Injury

Drug hepatoxicity can be nonidiosyncratic (predictable), as in the case of acetaminophen, or idiosyncratic (unpredictable). This review article focuses primarily on idiosyncratic drug-induced liver injury (DILI). New epidemiologic data suggest that approximately 20 new cases of DILI per 100,000 persons occur each year. Idiosyncratic DILI accounts for 11% of the cases of acute liver failure in the United States. Risk factors for DILI include medication dose, drug lipophilicity, and extent of hepatic metabolism. There is mixed evidence to support the role of host factors such as age, sex, and chronic liver disease in the development of DILI. For specific drugs, a genetic predisposition appears to be a risk factor for DILI. Suspected cases of idiosyncratic DILI should be categorized as hepatitic, cholestatic, or mixed on the basis of the degree/ratio of abnormalities in the alanine aminotransferase and alkaline phosphatase. A careful evaluation for other causes of liver disease should be performed, though a liver biopsy is rarely needed. There is evidence that some patients with DILI may actually have hepatitis E and this diagnosis should be considered. Amoxicillin/clavulanate isoniazid, and nonsteroidal anti-inflammatory drugs are among the most common causes of DILI. Drug discontinuation or dechallenge should lead to an improvement in liver biochemistries in most patients, though a bilirubin value of more than 3 g/dL is associated with mortality of at least 10%. New biomarkers for DILI using proteomics and micro RNA appear promising but require further study. New studies on drugs with potential for causing DILI are reviewed herein, including tumor necrosis factor-alpha antagonists, fluoroquinolones, tyrosine kinase inhibitors, statins, and supplements. PubMed was used with search terms of drug induced liver injury OR DILI with filter settings of “English language” and “humans” and custom date range of “January 1, 2000.” The authors also manually searched bibliographies from key references and included seminal references before the year 2000.     

Cellular Therapy for Liver Disease

Regenerative medicine is energizing and empowering basic science and has the potential to dramatically transform health care in the future. Given the remarkable intrinsic regenerative properties of the liver, as well as widespread adoption of regenerative strategies for liver disease (eg, liver transplant, partial hepatectomy, living donor transplant), hepatology has always been at the forefront of clinical regenerative medicine. However, an expanding pool of patients awaiting liver transplant, a limited pool of donor organs, and finite applicability of the current surgical approaches have created a need for more refined and widely available regenerative medicine strategies. Although cell-based therapies have been used extensively for hematologic malignant diseases and other conditions, the potential application of cellular therapy for acute and chronic liver diseases has only more recently been explored. New understanding of the mechanisms of liver regeneration and repair, including activation of local stem/progenitor cells and contributions from circulating bone marrow–derived stem cells, provide the theoretical underpinnings for the rational use of cell-based therapies in clinical trials. In this review, we dissect the scientific rationale for various modalities of cell therapy for liver diseases being explored in animal models and review those tested in human clinical trials. We also attempt to clarify some of the important ongoing questions that need to be addressed in order to bring these powerful therapies to clinical translation. Discussions will cover transplant of hepatocytes and liver stem/progenitor cells as well as infusion or stimulation of bone marrow–derived stem cells. We also highlight tremendous scientific advances on the horizon, including the potential use of induced pluripotent stem cells and their derivatives as individualized regenerative therapy for liver disease.     

Biobank Participants' Preferences for Disclosure of Genetic Research Results: Perspectives From the OurGenes,OurHealth, OurCommunity Project

ObjectiveTo assess biobank participants' preferences for disclosure of genetic research results.Patients and MethodsWe conducted a cross-sectional survey of participants in the OurGenes, OurHealth, OurCommunity biobank. Respondents were surveyed about preferences for disclosure, importance of disclosure, communication of results with practitioners, and sharing of results after respondents' death. Multivariate regression analysis was used to assess independent sociodemographic and clinical predictors of disclosure preferences. Data collection occurred from June 6, 2011, to June 25, 2012.ResultsAmong 1154 biobank participants, 555 (48%) responded. Most thought that research result disclosure was important (90%). Preference for disclosure varied, depending on availability of disease treatment (90% vs 64%, P<.001), high vs low disease risk (79% vs 66%, P<.001), and serious vs mild disease (83% vs 68%, P<.001). More than half of respondents (57%) preferred disclosure even when there is uncertainty about the results' meaning, and 87% preferred disclosure if the disease is highly heritable. Older age was positively associated with interest in disclosure, whereas female sex, nonwhite race, diabetes mellitus, and depression and/or anxiety were negatively associated with disclosure. More than half of respondents (52%) would want their results returned to their nearest biological relative after death.ConclusionsOurGenes biobank participants report strong preferences for disclosure of research results, and most would designate a relative to receive results after death. Participant preferences for serious vs mild disease, high vs low disease risk, and availability of disease treatment differed significantly. Future research should consider family members' preferences for receiving research results from enrolled research participants.     

Recovery Over 6 Months of Medical Decision-Making Capacity After Traumatic Brain Injury

ObjectiveTo investigate recovery of medical decision-making capacity (MDC) over 6 months in persons with traumatic brain injury (TBI) stratified by injury severity.DesignLongitudinal study comparing controls and patients with TBI 1 month after injury (t1) and 6 months after injury (t2).SettingInpatient TBI rehabilitation unit and outpatient neurology department.ParticipantsParticipants (N=151) consisted of control subjects (n=60) and patients with TBI (n=91) stratified by injury severity: mild TBI (mTBI; n=27), complicated mild TBI (cmTBI; n=20), and moderate/severe TBI (msevTBI; n=44).InterventionsNot applicable.Main Outcome MeasuresWe used the Capacity to Consent to Treatment Instrument to evaluate MDC performance on 5 consent standards (expressing choice, reasonable choice, appreciation, reasoning, and understanding). We also assigned capacity impairment ratings on the consent standards to each participant with TBI using cut scores referenced to control performance.ResultsControl performance was stable across time on the consent standards. Patients with mTBI and cmTBI performed below controls on the understanding standard at t1 but not t2. Patients with msevTBI performed below controls on appreciation, reasoning, and understanding at t1, and on appreciation and understanding at t2, but showed substantial improvement over time.ConclusionsRegardless of injury severity, all groups with TBI demonstrated baseline impairment of MDC with subsequent partial or full recovery of MDC over a 6-month period. However, a sizeable proportion of individual patients with TBI in each group continued to demonstrate capacity compromise at 6 months postinjury. Clinically, this finding suggests that individuals with TBI, regardless of injury severity, need continued monitoring regarding MDC for at least 6 months after injury.     

Breakthroughs in Cell Therapy for Heart Disease: Focus on Cardiosphere-Derived Cells

The clinical reality of cell therapy for heart disease dates back to the 1990s, when autologous skeletal myoblasts were first transplanted into failing hearts during open-chest surgery. Since then, the focus has shifted to bone marrow–derived cells and, more recently, cells extracted from the heart itself. Although progress has been nonlinear and often disheartening, the field has nevertheless made remarkable progress. Six major breakthroughs are notable: (1) the establishment of safety with intracoronary delivery; (2) the finding that therapeutic regeneration is possible; (3) the increase in allogeneic cell therapy; (4) the effect of increasing mechanistic insights; (5) glimmers of clinical efficacy; and (6) the progression to phase 2 and 3 studies. This article individually reviews these landmark developments in detail and concludes that the field has reached a new phase of maturity where the prospect of clinical impact is increasingly imminent.     

Safety and Efficacy of Extracorporeal Shock Wave Myocardial Revascularization Therapy for Refractory Angina Pectoris

ObjectiveTo assess the safety and efficacy of extracorporeal shockwave myocardial revascularization (ESMR) therapy in treating patients with refractory angina pectoris.Patients and MethodsA single-arm multicenter prospective trial to assess safety and efficacy of the ESMR therapy in patients with refractory angina (class III/IV angina) was performed. Screening exercise treadmill tests and pharmacological single-photon emission computed tomography (SPECT) were performed for all patients to assess exercise capacity and ischemic burden. Patients were treated with 9 sessions of ESMR to ischemic areas over 9 weeks. Efficacy end points were exercise capacity by using treadmill test as well as ischemic burden on pharmacological SPECT at 4 months after the last ESMR treatment. Safety measures included electrocardiography, echocardiography, troponin, creatine kinase, and brain natriuretic peptide testing, and pain questionnaires.ResultsFifteen patients with medically refractory angina and no revascularization options were enrolled. There was a statistically significant mean increase of 122.3±156.9 seconds (38% increase compared with baseline; P=.01) in exercise treadmill time from baseline (319.8±157.2 seconds) to last follow-up after the ESMR treatment (422.1±183.3 seconds). There was no improvement in the summed stress perfusion scores after pharmacologically induced stress SPECT at 4 months after the last ESMR treatment in comparison to that at screening; however, SPECT summed stress score revealed that untreated areas had greater progression in ischemic burden vs treated areas (3.69±6.2 vs 0.31±4.5; P=.03). There was no significant change in the mean summed echo score from baseline to posttreatment (0.4±5.1; P=.70). The ESMR therapy was performed safely without any adverse events in electrocardiography, echocardiography, troponins, creatine kinase, or brain natriuretic peptide. Pain during the ESMR treatment was minimal (a score of 0.5±1.2 to 1.1±1.2 out of 10).ConclusionIn this multicenter feasibility study, ESMR seems to be a safe and efficacious treatment for patients with refractory angina pectoris. However, larger sham-controlled trials will be required to confirm these findings.     

Treatment Discontinuations With New Oral Agents for Long-term Anticoagulation: Insights From a Meta-analysis of 18 Randomized Trials Including 101,801 Patients

ObjectiveTo systematically examine discontinuation rates with new US Food and Drug Administration–approved oral anticoagulants (NOACs) in patients with various indications for long-term anticoagulation.Patients and MethodsPoor adherence to medications is considered a potential and frequent cause of treatment failure. We searched the PubMed, Cochrane Central Register of Controlled Trials, EMBASE, EBSCO, Web of Science, and CINAHL databases for articles published from January 1, 2001, through September 15, 2013. The following Medical Subject Heading terms and/or keywords were used for our database searches: rivaroxaban, dabigatran, apixaban, new oral anticoagulants, oral thrombin inhibitors, and oral factor Xa inhibitors. Articles in English that focused on randomized controlled trials (RCTs) comparing NOACs (apixaban, dabigatran, and rivaroxaban) with conventional therapy or placebo were abstracted. Independent extraction of relevant data was performed by 2 authors. The primary end point of interest was discontinuation due to all causes. Other end points of interest were discontinuation due to adverse events, consent withdrawal, and nonadherence.ResultsEighteen RCTs including a total of 101,801 patients were included for analysis. Total study drug discontinuation rates were not statistically different with NOACs in comparison to pharmacologically active comparators for treatment of venous thromboembolism/pulmonary embolism (risk ratio [RR], 0.91; 95% CI, 0.74-1.13; P=.40) and for NOACs in comparison to warfarin and aspirin for prevention of stroke in patients with atrial fibrillation (RR, 1.01; 95% CI, 0.87-1.17; P=.92). In contrast, in acute coronary syndromes, total study drug discontinuation with NOACs was significantly higher than with placebo (RR, 1.40; 95% CI, 1.07-1.83; P=.01). Overall discontinuations were comparable to those with active comparators.ConclusionStudy drug discontinuations with NOACs were not significantly different from those with conventional drugs in treatment of venous thromboembolism/pulmonary embolism and prevention of stroke in patients with atrial fibrillation but were worse in acute coronary syndromes as noted in evidence from contemporary RCTs.     

Chronic Cough: An Update

Cough persisting beyond 8 weeks (ie, chronic cough) is one of the most common reasons for an outpatient visit. A protracted cough can negatively affect one’s quality of life by causing anxiety, physical discomfort, social isolation, and personal embarrassment. Herein, the anatomy and physiology of the cough reflex are reviewed. Upper airway cough syndrome, asthma, eosinophilic bronchitis, and gastroesophageal reflux disease account for most chronic cough after excluding smoking, angiotensin-converting enzyme inhibitor use, and chronic bronchitis. Many patients have more than one reason for chronic cough. Treating the underlying cause(s) resolves cough in most instances. There are some coughs that seem refractory despite an extensive work-up. The possibility of a hypersensitive cough reflex response has been proposed to explain these cases. Several clinical algorithms to evaluate chronic cough are presented.     

Prehospital Use of Inhaled Corticosteroids and Point Prevalence of Pneumonia at the Time of Hospital Admission: Secondary Analysis of a Multicenter Cohort Study

ObjectiveTo address clinical concern regarding the use of inhaled corticosteroids (ICSs) and the risk for pneumonia, particularly among patients with chronic obstructive pulmonary disease (COPD) and asthma.Patients and MethodsA multicentered prospective cohort of patients admitted to the hospital from March 1, 2009, through August 31, 2009, with pneumonia or another risk factor for acute respiratory distress syndrome was analyzed to determine the risk for pneumonia requiring hospitalization among patients taking ICSs. The adjusted risk (odds ratio [OR]) for developing pneumonia because of ICSs was determined in a multiple logistic regression model.ResultsOf the 5584 patients in the cohort, 495 (9%) were taking ICSs and 1234 (22%) had pneumonia requiring hospitalization. In univariate analyses, pneumonia occurred in 222 (45%) of the patients on ICSs vs 1012 (20%) in those who were not (OR, 3.28; 95% CI, 2.71-3.96; P<.001). After adjusting in the logistic regression model, prehospital ICS use was not significantly associated with pneumonia in the whole cohort (OR, 1.20; 95% CI, 0.93-1.53; P=.162), among the subset of 589 patients with COPD (OR, 1.40; 95% CI, 0.95-2.09; P=.093), among the 440 patients with asthma (OR, 1.07; 95% CI, 0.61-1.87; P=.81), nor among the remaining 4629 patients without COPD or asthma (OR, 1.32; 95% CI, 0.88-1.97; P=.179).ConclusionWhen adjusted for multiple confounding variables, ICS use was not substantially associated with an increased risk for pneumonia requiring admission in our cohort.     

Endovascular Therapy for Acute Ischemic Stroke: A Systematic Review and Meta-analysis

ObjectiveTo consolidate the evidence from randomized trials for the use of endovascular therapy (ET) in patients with acute ischemic stroke.MethodsWe searched major databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus) from their inception to February 12, 2013, for randomized trials evaluating the efficacy of ET compared with standard of care for acute ischemic stroke. Pooled absolute and relative risk estimates were synthesized by using a random-effects model. Heterogeneity was assessed by using Q statistic and I² statistic. Subset analysis was performed for patients with severe stroke (National Institutes of Health Stroke Scale score ≥20). The study was conducted from January 15, 2013 to April 30, 2013.ResultsOf the 1252 retrieved articles, 5 randomized trials enrolling 1197 patients with acute ischemic stroke were included. Seven hundred eleven patients received ET, and 486 received intravenous (IV) tissue plasminogen activator. There was no significant improvement in any of the outcomes in patients receiving ET compared with those receiving IV thrombolysis. On subgroup analysis, ET was found to have better outcomes in patients with severe stroke (National Institutes of Health Stroke Scale score ≥20), showing a dose-response gradient and improving excellent, good, and fair outcomes by an additional 4%, 7%, and 13%, respectively, compared with IV thrombolysis.ConclusionOverall, ET is not superior to IV thrombolysis for acute ischemic strokes (level B recommendation). However, ET showed promise and improved outcomes in patients with severe strokes, but the evidence is limited due to sample size. There is a need for further trials evaluating the role of ET in this high-risk group.     

Association of Coronary Artery Calcium and Coronary Heart Disease Events in Young and Elderly Participants in the Multi-Ethnic Study of Atherosclerosis: A Secondary Analysis of a Prospective,Population-Based Cohort

ObjectiveTo evaluate the association of coronary artery calcium (CAC) and coronary heart disease (CHD) events among young and elderly individuals.Participants and MethodsThis is a secondary analysis of data from a prospective, multiethnic, population-based cohort study designed to study subclinical atherosclerosis. A total of 6809 persons 45 through 84 years old without known cardiovascular disease at baseline were enrolled from July 2000 through September 2002. All participants had CAC scoring performed and were followed up for a median of 8.5 years. The main outcome measures studied were CHD events, defined as myocardial infarction, definite angina or probable angina followed by revascularization, resuscitated cardiac arrest, or death attributable to CHD.ResultsComparing individuals with a CAC score of 0 with those with a CAC score greater than 100, there was an increased incidence of CHD events from 1 to 21 per 1000 person-years and 2 to 23 per 1000 person-years in the 45- through 54-year-old and 75- through 84-year-old groups, respectively. Compared with a CAC score of 0, CAC scores of 1 through 100 and greater than 100 impart an increased multivariable-adjusted CHD event risk in the 45- through 54-year-old and 75- through 84-year-old groups (hazard ratio [HR], 2.3; 95% CI, 0.9-5.8; for those 45-54 years old with CAC scores of 1-100; HR, 12.4; 95% CI, 5.1-30.0; for those 45-54 years old with CAC scores >100: HR, 5.4; 95% CI, 1.2-23.8; for those 75-84 years old with CAC scores of 1-100; and HR, 12.1; 95% CI, 2.9-50.2; for those 75-84 years old with CAC scores >100).ConclusionIncreased CAC imparts an increased CHD risk in younger and elderly individuals. CAC is highly predictive of CHD event risk across all age groups, suggesting that once CAC is known chronologic age has less importance. The utility of CAC scoring as a risk-stratification tool extends to both younger and elderly patients.