Yohalakshmi Chelladurai

Allergen-Specific Immunotherapy for Pediatric Asthma and Rhinoconjunctivitis: A Systematic Review

BACKGROUND AND OBJECTIVE: Subcutaneous immunotherapy (SCIT) is approved in the United States for the treatment of pediatric asthma and rhinitis; sublingual immunotherapy (SLIT) does not have regulatory approval but is used in clinical practice. The objective of this study was to systematically review the evidence regarding the efficacy and safety of SCIT and SLIT for the treatment of pediatric asthma and allergic rhinoconjunctivitis. METHODS: Two independent reviewers selected articles for inclusion, extracted data, and graded the strength of evidence for each clinical outcome. All studies were randomized controlled trials of children with allergic asthma or rhinoconjunctivitis treated with SCIT or an aqueous formulation of SLIT. Data sources were Medline, Embase, LILACS, CENTRAL, and the Cochrane Central Register of Controlled Trials through May 2012. RESULTS: In 13 trials, 920 children received SCIT or usual care; in 18 studies, 1583 children received SLIT or usual care. Three studies compared SCIT with SLIT head-to-head in 135 children. The strength of evidence is moderate that SCIT improves asthma and rhinitis symptoms and low that SCIT improves conjunctivitis symptoms and asthma medication scores. Strength of evidence is high that SLIT improves asthma symptoms and moderate that SLIT improves rhinitis and conjunctivitis symptoms and decreases medication usage. The evidence is low to support SCIT over SLIT for improving asthma or rhinitis symptoms or medication usage. Local reactions were frequent with SCIT and SLIT. There was 1 report of anaphylaxis with SCIT. CONCLUSIONS: Evidence supports the efficacy of both SCIT and SLIT for the treatment of asthma and rhinitis in children.

Comparative effectiveness of treatments for open-angle glaucoma: A systematic review for the U.S. preventive services task force

BACKGROUND Glaucoma is an acquired degeneration of the optic nerve and a leading cause of blindness worldwide. Medical and surgical treatments that decrease intraocular pressure may prevent visual impairment and blindness. PURPOSE To compare the effectiveness of medical, laser, and surgical treatments in adults with open-angle glaucoma with regard to decreasing intraocular pressure and preventing optic nerve damage, vision loss, and visual impairment. DATA SOURCES MEDLINE, CENTRAL, and an existing database for systematic reviews (through 2 March 2011); MEDLINE, EMBASE, LILACS, and CENTRAL for primary studies (through 30 July 2012). STUDY SELECTION English-language systematic reviews; randomized, controlled trials; and quasi-randomized, controlled trials for most outcomes and observational studies for quality of life and harms. DATA EXTRACTION Two investigators abstracted or checked information about study design, participants, and outcomes and assessed risk of bias and strength of evidence. DATA SYNTHESIS High-level evidence suggests that medical, laser, and surgical treatments decrease intraocular pressure and that medical treatment and trabeculectomy reduce the risk for optic nerve damage and visual field loss compared with no treatment. The direct effect of treatments on visual impairment and the comparative efficacy of different treatments are not clear. Harms of medical treatment are primarily local (ocular redness, irritation); surgical treatment carries a small risk for more serious complications. LIMITATION Heterogeneous outcome definitions and measurements among the included studies; exclusion of many treatment studies that did not stratify results by glaucoma type. CONCLUSION Medical and surgical treatments for open-angle glaucoma lower intraocular pressure and reduce the risk for optic nerve damage over the short to medium term. Which treatments best prevent visual disability and improve patient-reported outcomes is unclear.

The Effectiveness of Prophylactic Inferior Vena Cava Filters in Trauma Patients A Systematic Review and Meta-analysis

IMPORTANCE Trauma is known to be one of the strongest risk factors for pulmonary embolism (PE). Current guidelines recommend low-molecular-weight heparin therapy for prevention of PE, but trauma places some patients at risk of excess bleeding. Experts are divided on the role of prophylactic inferior vena cava (IVC) filters to prevent PE. OBJECTIVE To perform a systematic review and meta-analysis examining the comparative effectiveness of prophylactic IVC filters in trauma patients, particularly in preventing PE, fatal PE, and mortality. DATA SOURCES We searched the following databases for primary studies: MEDLINE, EMBASE, Scopus, CINAHL, International Pharmaceutical Abstracts, clinicaltrial.gov, and the Cochrane Library (all through July 31, 2012). We developed a search strategy using medical subject headings terms and text words of key articles that we identified a priori. We reviewed the references of all included articles, relevant review articles, and related systematic reviews to identify articles the database searches might have missed. STUDY SELECTION We reviewed titles followed by abstracts to identify randomized clinical trials or observational studies with comparison groups reporting on the effectiveness and/or safety of IVC filters for prevention of venous thromboembolism in trauma patients. DATA EXTRACTION AND SYNTHESIS Two investigators independently reviewed abstracts and abstracted data. For studies amenable to pooling with meta-analysis, we pooled using the random-effects model to analyze the relative risks. We graded the quantity, quality, and consistency of the evidence by adapting an evidence-grading scheme recommended by the Agency for Healthcare Research and Quality. RESULTS Eight controlled studies compared the effectiveness of no IVC filter vs IVC filter on PE, fatal PE, deep vein thrombosis, and/or mortality in trauma patients. Evidence showed a consistent reduction of PE (relative risk, 0.20 [95% CI, 0.06-0.70]; I(2)=0%) and fatal PE (0.09 [0.01-0.81]; I(2)=0%) with IVC filter placement, without any statistical heterogeneity. We found no significant difference in the incidence of deep vein thrombosis (relative risk, 1.76 [95% CI, 0.50-6.19]; P=.38; I(2)=56.8%) or mortality (0.70 [0.40-1.23]; I(2)=6.7%). The number needed to treat to prevent 1 additional PE with IVC filters is estimated to range from 109 (95% CI, 93-190) to 962 (819-2565), depending on the baseline PE risk. CONCLUSIONS AND RELEVANCE The strength of evidence is low but supports the association of IVC filter placement with a lower incidence of PE and fatal PE in trauma patients. Which patients experience benefit enough to outweigh the harms associated with IVC filter placement remains unclear. Additional well-designed observational or prospective cohort studies may be informative.

Interventions to Modify Health Care Provider Adherence to Asthma Guidelines: A Systematic Review

BACKGROUND AND OBJECTIVE: Health care provider adherence to asthma guidelines is poor. The objective of this study was to assess the effect of interventions to improve health care providers’ adherence to asthma guidelines on health care process and clinical outcomes. METHODS: Data sources included Medline, Embase, Cochrane CENTRAL Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Educational Resources Information Center, PsycINFO, and Research and Development Resource Base in Continuing Medical Education up to July 2012. Paired investigators independently assessed study eligibility. Investigators abstracted data sequentially and independently graded the evidence. RESULTS: Sixty-eight eligible studies were classified by intervention: decision support, organizational change, feedback and audit, clinical pharmacy support, education only, quality improvement/pay-for-performance, multicomponent, and information only. Half were randomized trials (n = 35). There was moderate evidence for increased prescriptions of controller medications for decision support, feedback and audit, and clinical pharmacy support and low-grade evidence for organizational change and multicomponent interventions. Moderate evidence supports the use of decision support and clinical pharmacy interventions to increase provision of patient self-education/asthma action plans. Moderate evidence supports use of decision support tools to reduce emergency department visits, and low-grade evidence suggests there is no benefit for this outcome with organizational change, education only, and quality improvement/pay-for-performance. CONCLUSIONS: Decision support tools, feedback and audit, and clinical pharmacy support were most likely to improve provider adherence to asthma guidelines, as measured through health care process outcomes. There is a need to evaluate health care provider-targeted interventions with standardized outcomes.

Pharmacologic and Mechanical Strategies for Preventing Venous Thromboembolism After Bariatric Surgery: A Systematic Review and Meta-analysis

We sought to assess the comparative effectiveness and safety of pharmacologic and mechanical strategies to prevent venous thromboembolism (VTE) in patients undergoing bariatric surgery. We searched (through August 2012) for primary studies that had at least 2 different interventions. Of 30,902 citations, we identified 8 studies of pharmacologic strategies and 5 studies of filter placement. No studies randomized patients to receive different interventions. One study suggested that low-molecular-weight heparin is more efficacious than unfractionated heparin in preventing VTE (0.25% vs 0.68%, P < .001), with no significant difference in bleeding. One study suggested that prolonged therapy (after discharge) with enoxaparin sodium may prevent VTE better than inpatient treatment only. There was insufficient evidence supporting the hypothesis that filters reduce the risk of pulmonary embolism, with a point estimate suggesting increased rates with filters (pooled relative risk [RR], 1.21 95% CI, 0.57-2.56). There was low-grade evidence that filters are associated with higher mortality (pooled RR, 4.30 95% CI, 1.60-11.54) and higher deep vein thrombosis rates (2.94 1.35-6.38). There was insufficient evidence to support that augmented subcutaneous enoxaparin doses (>40 mg daily or 30 mg twice daily) are more efficacious than standard dosing, with a trend toward increased bleeding. Of note, for both filters and augmented pharmacologic dosing strategies, patients at highest risk for VTE were more likely to receive more intensive interventions, limiting our ability to attribute outcomes to prophylactic strategies used.

Performance and Pain Tolerability of Current Diagnostic Allergy Skin Prick Test Devices

BACKGROUND Allergen skin prick testing remains an essential tool for diagnosing atopic disease and guiding treatment. Sensitivity needs to be defined for newly introduced devices. OBJECTIVE Our aim was to compare the performance of 10 current allergy skin prick test devices. METHODS Single- and multiheaded skin test devices (n = 10) were applied by a single operator in a prospective randomized manner. Histamine (1 and 6 mg/mL) and control diluent were introduced at 6 randomized locations onto the upper and lower arms of healthy subjects. Wheal and flare reactions were measured independently by 2 masked technicians. RESULTS Twenty-four subjects provided consent, and 768 skin tests were placed. Mean wheal diameter among devices differed from 3.0 mm (ComforTen; Hollister-Stier, Spokane, Wash) to 6.8 mm (UniTest PC; Lincoln Diagnostics, Decatur, Ill) using 1 mg/mL histamine (P < .001) and 4.8 mm (GREER Pick; Greer, Lenoir, NC) to 8.4 mm (Duotip-Test II; Lincoln Diagnostics, Decatur, Ill; and Sharp-Test; Panatrex, Placentia, Calif) using 6 mg/mL histamine (P < .001). The false-negative rates ranged from 0% to 45% with 1 mg/mL histamine. The analytical specificity was 100% for all devices tested. All devices were well tolerated, with average pain score of less than 4 on a 10-point visual analog scale. Pain scores were higher among women, but this did not reach statistical significance. The Multi-Test PC and the UniTest PC had the lowest pain scores compared with the other devices. CONCLUSIONS All 10 skin prick test devices displayed good analytical sensitivity and specificity; however, 3 mm cannot arbitrarily be used as a positive threshold. The use of histamine at 1 mg/mL is unacceptable for certain devices but may be preferable for the most sensitive devices. On average, there was no pain score difference between multiheaded and single-head devices.

Varenicline and cardiovascular adverse events: a perspective review

Smoking is a leading preventable cause of mortality and morbidity. Varenicline, a first-line smoking cessation aid, is used widely to achieve successful quit rates in smokers. A number of studies and systematic reviews have evaluated the safety profile of the drug. To date, three systematic reviews by Singh and colleagues, Prochaska and Hilton, and Ware and colleagues, published between 2011 and 2013, have evaluated serious cardiovascular adverse events with varenicline use. Even though all three reviews demonstrated that serious cardiovascular adverse events were nominally more frequent in varenicline-treated patients when compared with placebo, a significantly increased event rate was found only in the review by Singh and colleagues. The three reviews included similar trials but differed in the evaluation of outcomes and performance of summary statistic computation. Though the evidence from the two most recent systematic reviews demonstrated that risk of serious cardiovascular events might not be increased with varenicline use, the US Food and Drug Administration has advised prescription with caution combined with close monitoring and education of patients until more conclusive evidence is available. Results of these reviews cannot be generalized to patients with unstable cardiac conditions.

Effectiveness of subcutaneous versus sublingual immunotherapy for allergic rhinitis: current update

Purpose of reviewThe effectiveness of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in treatment of patients suffering from allergic rhinitis have been evaluated in a number of randomized controlled trials, systematic reviews and meta-analyses conducted over the past few decades. Currently, there is a growing interest in evaluating comparative effectiveness of SCIT versus SLIT to identify whether one form of immunotherapy is better than the other. In this current update, we discuss pertinent systematic reviews that have addressed this concern. Recent findingsThe four systematic reviews identified in this update are the only reviews of effectiveness of SCIT versus SLIT for allergic rhinitis available in the literature. Through direct and indirect comparisons, these four reviews demonstrate that SCIT is better than SLIT in reducing symptoms of allergic rhinitis and rescue medication use in adults and children. However, there was no difference between the two forms of immunotherapy in reducing combined symptom–medication scores and improving quality of life. With regard to safety, SLIT had fewer systemic reactions when compared with SCIT. SummaryThe evidence of effectiveness of SCIT versus SLIT was principally derived from indirect comparisons and meta-regression. Additional randomized controlled trials of head-to-head comparisons of SCIT versus SLIT are required to strengthen this evidence base. Future research should focus on development of standardized outcome assessment, allergen dosing, content, and treatment regimes.

Venous thromboembolism prophylaxis in patients with traumatic brain injury: a systematic review

Objective: There is considerable practice variation and clinical uncertainty about the choice of prophylaxis for preventing venous thromboembolism in patients with traumatic brain injury. We performed a systematic review to assess both the effectiveness and safety of pharmacologic and mechanical prophylaxis, and the optimal time to initiate pharmacologic prophylaxis in hospitalized patients with traumatic brain injury. Data sources and study selection: MEDLINE®, EMBASE®, SCOPUS, CINAHL, International Pharmaceutical Abstracts, clinicaltrial.gov, and the Cochrane Library were searched in July 2012 to identify randomized controlled trials and observational studies reporting on the effectiveness or safety of venous thromboembolism prevention in traumatic brain injury patients. Data extraction: Paired reviewers extracted detailed information from included articles on standardized forms and assessed the risk of bias in each article. Data synthesis: Twelve studies (2 randomized controlled trials and 10 cohort studies) evaluated the effectiveness and safety of venous thromboembolism prophylaxis in patients with traumatic brain injury. Five of the included studies assessed the optimal timing of initiation of pharmacological prophylaxis. Low grade evidence supports the effectiveness of enoxaparin over control in reducing deep vein thrombosis. Low grade evidence also supports the safety of unfractionated heparin over control in reducing mortality in patients with traumatic brain injury. Evidence was insufficient for remaining comparisons and outcomes including the optimal timing of initiation of pharmacoprophylaxis. Conclusion: There is some evidence that pharmacoprophylaxis improves deep vein thromboses and mortality outcomes in patients hospitalized with traumatic brain injury. Additional studies are required to strengthen this evidence base.

A systematic review of venous thromboembolism prophylaxis strategies in patients with renal insufficiency, obesity, or on antiplatelet agents

BACKGROUND There is uncertainty about optimal strategies for venous thromboembolism (VTE) prophylaxis among select populations such as patients with renal insufficiency, obesity, or patients taking antiplatelet drugs including aspirin. Their physiologies make prophylaxis particularly challenging. PURPOSE We performed a comparative effectiveness review of the literature on efficacy and safety of VTE prophylaxis in these populations. DATA SOURCES We searched MEDLINE, EMBASE, SCOPUS, CINAHL, International Pharmaceutical Abstracts, clinicaltrial.gov, and the Cochrane Library through August 2012. Eligible studies included controlled trials and observational studies. DATA EXTRACTION Two reviewers evaluated studies for eligibility, serially abstracted data, and independently evaluated the risk of bias and strength of evidence supporting interventions to prevent VTE in these populations. RESULTS After a review of 30,902 citations, we identified 9 controlled studies, 5 of which were trials, and the other 4 were observational studies. Five articles addressed prophylaxis of patients with renal insufficiency, 2 addressed obese patients, and 2 addressed patients on antiplatelet agents. No study tested prophylaxis in underweight patients or those with liver disease. The majority of observational studies had a high risk of bias. The strength of evidence ranged from low to insufficient regarding the comparative effectiveness and safety of VTE prophylaxis among these patients. CONCLUSION The current evidence is insufficient regarding optimal VTE prophylaxis for patients with renal insufficiency, obesity, or those who are on antiplatelet drugs including aspirin. High-quality studies are needed to inform clinicians about the best VTE prophylaxis for these patients.