Determination of hair ketamine cut-off value from Hong Kong ketamine users by LC-MS/MS analysis.

Ketamine is one of the most frequent abused drugs in Hong Kong and South-East Asia, and the cases of ketamine abused have been reported worldwide. Hair has been commonly used as a specimen for the proof of chronic drug abused because of its non-invasiveness and long detection windows. The determinations of ketamine in hair with varieties of state-of-the-art instruments and detection methods have been developed in the past decade; however, the cut-off value for ketamine abuser has not been developed according to the international guidelines. The aim of this study is to propose a cut-off value for ketamine in hair by analyzing ketamine and its metabolite norketamine by LC-MS/MS method in a population of ketamine users in Hong Kong. The limit of detection (LOD) and limit of quantification (LOQ) for ketamine and norketamine were 20pg/mg and 100pg/mg, respectively. From 977 ketamine abusers, the cut-off value for ketamine in hair was proposed to be 400pg/mg of hair. This proposed cut-off value is the concentration of hair ketamine when over 90% of samples are being detected with the presence of norketamine, which is a proof of ketamine abuse. This value could be applied as a screening or occupational cut-off for reference.

A systematic review of approaches for engaging patients for research on rare diseases.

BACKGROUND: Patients with rare diseases have limited access to useful information to guide treatment decisions. Engagement of patients and other stakeholders in clinical research may help to ensure that research efforts in rare diseases address relevant clinical questions and patient-centered health outcomes. Rare disease organizations may provide an effective means to facilitate patient engagement in research. However, the effectiveness of patient-engagement approaches, particularly for the study of rare diseases, has not been well studied. OBJECTIVES: To synthesize evidence about engagement of patients and other stakeholders in research on rare diseases, including the role of rare disease organizations in facilitating patient-centered research. METHODS/RESEARCH DESIGN: A systematic review and gray literature search were guided by a technical expert panel composed of patient representatives, clinicians, and researchers. English-language studies that engaged patients or other stakeholders in research on rare diseases or evaluated engagement were included. Studies were assessed on how well key research questions were answered, based on the level of detail describing engagement activities and whether outcomes from engagement were assessed. RESULTS: Thirty-five studies were included, although many reported minimal information on engagement. Patients and other stakeholders were most commonly engaged to identify patient-centered research agendas, to select which study outcomes were important to patients, to provide input on study design, and to identify strategies for increasing enrollment in trials. Rare disease organizations mainly helped provide access to patients and communicated research opportunities and findings. They also helped promote collaborative networks and provided financial support for research infrastructures. Although authors reported benefits of engagement and identified changes to their research processes, no empirical assessments of engagement practices and their effectiveness were found. CONCLUSIONS: Researchers studying rare diseases can obtain patient input regarding which research questions and health outcomes to study; however, the most effective approaches to engagement have not been well defined.

A proposed approach may help systematic reviews retain needed expertise while minimizing bias from nonfinancial conflicts of interest.

OBJECTIVES: Groups such as the Institute of Medicine emphasize the importance of attention to financial conflicts of interest. Little guidance exists, however, on managing the risk of bias for systematic reviews from nonfinancial conflicts of interest. We sought to create practical guidance on ensuring adequate clinical or content expertise while maintaining independence of judgment on systematic review teams. STUDY DESIGN AND SETTING: Workgroup members built on existing guidance from international and domestic institutions on managing conflicts of interest. We then developed practical guidance in the form of an instrument for each potential source of conflict. RESULTS: We modified the Institute of Medicine's definition of conflict of interest to arrive at a definition specific to nonfinancial conflicts. We propose questions for funders and systematic review principal investigators to evaluate the risk of nonfinancial conflicts of interest. Once risks have been identified, options for managing conflicts include disclosure followed by no change in the systematic review team or activities, inclusion on the team along with other members with differing viewpoints to ensure diverse perspectives, exclusion from certain activities, and exclusion from the project entirely. CONCLUSION: The feasibility and utility of this approach to ensuring needed expertise on systematic reviews and minimizing bias from nonfinancial conflicts of interest must be investigated.

Opportunities and challenges in using studies without a control group in comparative effectiveness reviews.

When examining the evidence on therapeutic interventions to answer a comparative effectiveness research question, one should consider all studies that are informative on the interventions' causal effects. "Single group studies" evaluate outcomes longitudinally in cohorts of subjects who are managed with a single treatment strategy. Because these studies are "missing" a direct, concurrent comparison group, they are typically deemed non-informative on comparative effectiveness. However, in principle, single group studies can provide information on causal treatment effects by extrapolating expected outcomes in the "missing" untreated arm. Single group studies rely on before-after, implicit, or historical comparisons as a proxy for an ideal comparison group. The validity of these comparisons must be carefully examined on a case-by-case basis. While in many cases, researchers will disagree on whether such extrapolations are reasonable; circumstances exist where such studies are generally acceptable as a source of evidence. This article provides an overview of issues related to the interpretation of single group studies with a focus on the assumptions required to support their consideration in comparative effectiveness reviews. We discuss the various settings in which single group studies are employed, common research designs that systematic reviewers need to interpret, and challenges associated with using these designs to inform comparative effectiveness questions.

Self-measured blood pressure monitoring in the management of hypertension: a systematic review and meta-analysis.

BACKGROUND: Clinical guidelines recommend that adults with hypertension self-monitor their blood pressure (BP). PURPOSE: To summarize evidence about the effectiveness of self-measured blood pressure (SMBP) monitoring in adults with hypertension. DATA SOURCES: MEDLINE (inception to 8 February 2013) and Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (fourth quarter 2012). STUDY SELECTION: 52 prospective comparative studies of SMBP monitoring with or without additional support versus usual care or an alternative SMBP monitoring intervention in persons with hypertension. DATA EXTRACTION: Data on population, interventions, BP, other outcomes, and study method were extracted. Random-effects model meta-analyses were done. DATA SYNTHESIS: For SMBP monitoring alone versus usual care (26 comparisons), moderate-strength evidence supports a lower BP with SMBP monitoring at 6 months (summary net difference, -3.9 mm Hg and -2.4 mm Hg for systolic BP and diastolic BP) but not at 12 months. For SMBP monitoring plus additional support versus usual care (25 comparisons), high-strength evidence supports a lower BP with use of SMBP monitoring, ranging from -3.4 to -8.9 mm Hg for systolic BP and from -1.9 to -4.4 mm Hg for diastolic BP, at 12 months in good-quality studies. For SMBP monitoring plus additional support versus SMBP monitoring alone or with less intense additional support (13 comparisons), low-strength evidence fails to support a difference. Across all comparisons, evidence for clinical outcomes is insufficient. For other surrogate or intermediate outcomes, low-strength evidence fails to show differences. LIMITATION: Clinical heterogeneity in protocols for SMBP monitoring, additional support, BP targets, and management; follow-up of 1 year or less in most studies, with sparse clinical outcome data. CONCLUSION: Self-measured BP monitoring with or without additional support lowers BP compared with usual care, but the BP effect beyond 12 months and long-term benefits remain uncertain. Additional support enhances the BP-lowering effect. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

A Web-based archive of systematic review data.

Systematic reviews have become increasingly critical to informing healthcare policy; however, they remain a time-consuming and labor-intensive activity. The extraction of data from constituent studies comprises a significant portion of this effort, an activity which is often needlessly duplicated, such as when attempting to update a previously conducted review or in reviews of overlapping topics.In order to address these inefficiencies, and to improve the speed and quality of healthcare policy- and decision-making, we have initiated the development of the Systematic Review Data Repository, an open collaborative Web-based repository of systematic review data. As envisioned, this resource would serve as both a central archive and data extraction tool, shared among and freely accessible to organizations producing systematic reviews worldwide. A suite of easy-to-use software tools with a Web frontend would enable researchers to seamlessly search for and incorporate previously deposited data into their own reviews, as well as contribute their own.In developing this resource, we identified a number of technical and non-technical challenges, as well as devised a number of potential solutions, including proposals for systems and software tools to assure data quality, stratify and control user access effectively and flexibly accommodate all manner of study data, as well as means by which to govern and foster adoption of this new resource.Herein we provide an account of the rationale and development of the Systematic Review Data Repository thus far, as well as outline its future trajectory.

Auto-titrating versus fixed continuous positive airway pressure for the treatment of obstructive sleep apnea: a systematic review with meta-analyses.

BACKGROUND: Obstructive sleep apnea is a relatively common disorder that can lead to lost productivity and cardiovascular disease. The form of positive airway treatment that should be offered is unclear. METHODS: MEDLINE and the Cochrane Central Trials registry were searched for English language randomized controlled trials comparing auto-titrating positive airway pressure (APAP) with continuous positive airway pressure (CPAP) in adults with obstructive sleep apnea (inception through 9/2010). Six researchers extracted information on study design, potential bias, patient characteristics, interventions and outcomes. Data for each study were extracted by one reviewer and confirmed by another. Random effects model meta-analyses were performed for selected outcomes. RESULTS: Twenty-four randomized controlled trials met the inclusion criteria. In individual studies, APAP and fixed CPAP resulted in similar changes from baseline in the apnea-hypopnea index, most other sleep study measures and quality of life. By meta-analysis, APAP improved compliance by 11 minutes per night (95% CI, 3 to 19 minutes) and reduced sleepiness as measured by the Epworth Sleepiness Scale by 0.5 points (95% CI, 0.8 to 0.2 point reduction) compared with fixed CPAP. Fixed CPAP improved minimum oxygen saturation by 1.3% more than APAP (95% CI, 0.4 to 2.2%). Studies had relatively short follow-up and generally excluded patients with significant comorbidities. No study reported on objective clinical outcomes. CONCLUSIONS: Statistically significant differences were found but clinical importance is unclear. Because the treatment effects are similar between APAP and CPAP, the therapy of choice may depend on other factors such as patient preference, specific reasons for non-compliance and cost.

Electrocardiogram screening for disorders that cause sudden cardiac death in asymptomatic children: a meta-analysis.

BACKGROUND AND OBJECTIVES: Pediatric sudden cardiac death (SCD) occurs in an estimated 0.8 to 6.2 per 100 000 children annually. Screening for cardiac disorders causing SCD in asymptomatic children has public appeal because of its apparent potential to avert tragedy; however, performance of the electrocardiogram (ECG) as a screening tool is unknown. We estimated (1) phenotypic (ECG- or echocardiogram [ECHO]-based) prevalence of selected pediatric disorders associated with SCD, and (2) sensitivity, specificity, and predictive value of ECG, alone or with ECHO. METHODS: We systematically reviewed literature on hypertrophic cardiomyopathy (HCM), long QT syndrome (LQTS), and Wolff-Parkinson-White syndrome, the 3 most common disorders associated with SCD and detectable by ECG. RESULTS: We identified and screened 6954 abstracts, yielding 396 articles, and extracted data from 30. Summary phenotypic prevalences per 100 000 asymptomatic children were 45 (95% confidence interval [CI]: 10-79) for HCM, 7 (95% CI: 0-14) for LQTS, and 136 (95% CI: 55-218) for Wolff-Parkinson-White. The areas under the receiver operating characteristic curves for ECG were 0.91 for detecting HCM and 0.92 for LQTS. The negative predictive value of detecting either HCM or LQTS by using ECG was high; however, the positive predictive value varied by different sensitivity and specificity cut-points and the true prevalence of the conditions. CONCLUSIONS: Results provide an evidence base for evaluating pediatric screening for these disorders. ECG, alone or with ECHO, was a sensitive test for mass screening and negative predictive value was high, but positive predictive value and false-positive rates varied.

Active surveillance in men with localized prostate cancer: a systematic review.

BACKGROUND: Active surveillance (AS) and watchful waiting (WW) have been proposed as management strategies for low-risk, localized prostate cancer. PURPOSE: To systematically review strategies for observational management of prostate cancer (AS or WW), factors affecting their utilization, and comparative effectiveness of observational management versus immediate treatment with curative intent. DATA SOURCES: MEDLINE and Cochrane databases (from inception to August 2011). STUDY SELECTION: Screened abstracts and reviewed full-text publications to identify eligible studies. DATA EXTRACTION: One reviewer extracted data, and another verified quantitative data. Two independent reviewers rated study quality and strength of evidence for comparative effectiveness. DATA SYNTHESIS: Sixteen independent cohorts defined AS, 42 studies evaluated factors that affect the use of observational strategies, and 2 evidence reports and 22 recent studies reported comparisons of WW versus treatment with curative intent. The most common eligibility criteria for AS were tumor stage (all cohorts), Gleason score (12 cohorts), prostate-specific antigen (PSA) concentration (10 cohorts), and number of biopsy cores positive for cancer (8 cohorts). For monitoring, studies used combinations of periodic PSA testing (all cohorts), digital rectal examination (14 cohorts), and rebiopsy (14 cohorts). Predictors of receiving no active treatment included older age, comorbid conditions, lower Gleason score, tumor stage, PSA concentration, and favorable risk group. No published studies compared AS with immediate treatment with curative intent. Watchful waiting was generally less effective than treatment with curative intent; however, applicability to contemporary patients may be limited. LIMITATIONS: Active surveillance and WW often could not be differentiated in the reviewed studies. Published randomized trials have assessed only WW and did not enroll patients diagnosed by PSA screening. CONCLUSION: Evidence is insufficient to assess whether AS is an appropriate option for men with localized prostate cancer. A standard definition of AS that clearly distinguishes it from WW is needed to clarify scientific discourse. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Comparative evaluation of radiation treatments for clinically localized prostate cancer: an updated systematic review.

BACKGROUND: Radiation therapy is one of many treatment options for patients with prostate cancer. PURPOSE: To update findings on the clinical and biochemical outcomes of radiation therapies for localized prostate cancer. DATA SOURCES: MEDLINE (2007 through March 2011) and the Cochrane Central Register of Controlled Trials (2007 through March 2011). STUDY SELECTION: Published English-language comparative studies involving adults with localized prostate cancer who either had first-line radiation therapy or received no initial treatment. DATA EXTRACTION: 6 researchers extracted information on study design, potential bias, sample characteristics, interventions, and outcomes and rated the strength of overall evidence. Data for each study were extracted by 1 reviewer and confirmed by another. DATA SYNTHESIS: 75 studies (10 randomized, controlled trials [RCTs] and 65 nonrandomized studies) met the inclusion criteria. No RCTs compared radiation therapy with no treatment or no initial treatment. Among the 10 RCTs, 2 compared combinations of radiation therapies, 7 compared doses and fraction sizes of external-beam radiation therapy (EBRT), and 1 compared forms of low-dose rate radiation therapy. Heterogeneous outcomes were analyzed. Overall, moderate-strength evidence consistently showed that a higher EBRT dose was associated with increased rates of long-term biochemical control compared with lower EBRT dose. The body of evidence was rated as insufficient for all other comparisons. LIMITATIONS: Studies inconsistently defined and reported outcomes. Much of the available evidence comes from observational studies with treatment selection biases. CONCLUSION: A lack of high-quality comparative evidence precludes conclusions about the efficacy of radiation treatments compared with no treatments for localized prostate cancer. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

An evidence review of active surveillance in men with localized prostate cancer.

BACKGROUND: Radical prostatectomy and radiation therapy for prostate cancer have side effects and unclear survival benefits for early stage and low-risk disease. Prostate cancer often has an indolent natural history, making observational management strategies potentially appealing. PURPOSE: To systematically review the role of active surveillance for triggers to begin curative treatment in men with low-risk prostate cancer. Key Questions address changes in prostate cancer characteristics over time, definitions of active surveillance and other observational strategies, factors affecting the offer of, acceptance of, and adherence to active surveillance, the comparative effectiveness of active surveillance with curative treatments, and research gaps. DATA SOURCES: MEDLINE(®), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and existing systematic reviews, evidence reports, and economic evaluations. STUDY SELECTION: Randomized controlled trials and nonrandomized comparative studies of treatments, multivariable association studies, and studies of temporal trends in prostate cancer natural history. Only published, peer-reviewed, English-language articles were selected based on predetermined eligibility criteria. DATA EXTRACTION: A standardized protocol was used to extract details on design, diagnoses, interventions, predictive factors, outcomes, and study validity. DATA SYNTHESIS: In total, 80 studies provided information on epidemiologic trends; 56 on definitions of active surveillance; 42 on factors affecting the offer of, acceptance of, or adherence to observational management strategies; and 26 on comparative effectiveness. Increased diagnosis of early-stage prostate cancer due to prostate-specific antigen (PSA) testing, led to an increase in prostate cancer incidence from the mid-1980s to the mid-1990s. The prostate cancer-specific mortality rate decreased for all age groups from the early-1990s to 1999. Currently, patients are diagnosed with earlier stage and lower risk prostate cancers compared to the pre-PSA era. Over time, a lower proportion of men received observational management versus active treatment, even among those with low-risk disease. There was no standardized definition of active surveillance. Sixteen cohorts used different monitoring protocols, all with different combinations of periodic digital rectal examination, PSA testing, rebiopsy, and/or imaging findings. Predictors that a patient received no initial active treatment generally included older age, presence of comorbidities, lower Gleason score, lower tumor stage, lower diagnostic PSA, and lower disease progression risk group. No trial provided results comparing men with localized disease on active surveillance with surgery or radiation therapy. LIMITATIONS: Because of the nonstandardized usages of the terms "active surveillance" and "watchful waiting" and their intended and often mixed (both curative and palliative) treatment objectives, it was difficult to determine which study patients received active monitoring for triggers indicative of curative treatment and which observation for clinical symptoms indicative of palliative treatment. CONCLUSIONS: More men are being diagnosed with early stage prostate cancer. Whether active monitoring with a curative intent is an appropriate option for these men remains unclear. A standard, universally agreed-upon definition of active surveillance that clearly distinguishes it from watchful waiting and other observational management strategies is needed to help clarify scientific discourse on this topic. Ongoing clinical trials may provide information on the comparative effectiveness of active surveillance compared to immediate active treatment, but will require long term followup.

The vulnerable atherosclerotic plaque: scope of the literature.

The scope of recent literature on the concept of "vulnerable plaque" was reviewed by examining 463 abstracts of primary and review articles identified through MEDLINE (2003 to April 2010). Proposed definition criteria of vulnerable plaque included active inflammation, a thin cap with a large lipid core, endothelial denudation, fissured cap, severe stenosis, or combinations of these findings. In 242 primary studies, histopathology, biomarkers, and imaging of carotid and coronary artery plaques were evaluated for features suggestive of vulnerability. Notably, 89% of these studies were cross-sectional in design and were exclusively conducted in patients with known cardiovascular disease. None of the imaging studies documented whether the identified lesions were responsible for cardiovascular events. Cross-sectional design precludes evaluation of the predictive utility of biomarkers. Because vulnerable plaque is not an established medical diagnosis, no studies have been done that explicitly evaluate the treatment of vulnerable plaques. Few studies examined potential systemic treatments (for example, statins) to modify vulnerability features. Large prospective studies in patients with and without previous cardiovascular events during long follow-up are required to validate this concept.

Systematic review to support the development of nutrient reference intake values: challenges and solutions.

Workshops sponsored by the Institute of Medicine (IOM) and the World Health Organization suggested that incorporating systematic (evidence) reviews into the process of updating nutrient reference values would provide a comprehensive and distilled evidence document to decision makers and enhance the transparency of the decision-making process the IOM used in recommending the Dietary Reference Intake values (DRIs) for US and Canadian populations. At the request of the US and Canadian government sponsors of the ongoing review of the 1997 vitamin D and calcium DRI values, the Tufts Evidence-based Practice Center performed a systematic review for the current DRI Committee to use early in its deliberations. We described the approach used to include systematic review into the IOM process for updating nutrient reference values and highlighted major challenges encountered along with the solutions used. The challenges stemmed from the need to review and synthesize a large number of primary studies covering a broad range of outcomes. We resolved these challenges by 1) working with a technical expert panel to prioritize and select outcomes of interest, 2) developing methods to use existing systematic reviews and documenting the limitations by doing so, 3) translating results from studies not designed to address issues of interest by using a transparent process, and 4) establishing tailored quality-assessment tools to assist in decision making. The experiences described in this article can serve as a basis for future improvements in systematic reviews of nutrients and to better integrate systematic review into development of future nutrient reference values.

Predictors of atrial fibrillation recurrence after radiofrequency catheter ablation: a systematic review.

UNLABELLED: AF Recurrence After RFA: Systematic Review. INTRODUCTION: The relationship between success of radiofrequency ablation for atrial fibrillation (AF) and patient characteristics has not been systematically evaluated. METHODS AND RESULTS: We searched MEDLINE and Cochrane Central Trials Registry databases from 2000 through 2008 for studies reporting preprocedure predictors and AF recurrence after radiofrequency ablation. We extracted multivariable analyses and univariable data on predictors and AF recurrence. Eligible studies were highly heterogeneous, particularly regarding ablation technique and definition of AF recurrence. Among 25 studies with multivariable analyses, two-thirds to 90% of studies found that AF type, ejection fraction, left atrial diameter, structural heart disease, hypertension, and AF symptom duration did not predict AF recurrence (among patients with ejection fraction above 40% and left atrial diameter below about 55 mm). Studies found that gender and age were not predictors (in patients between 40 and 70 years old). Meta-analyses of univariable AF recurrence rates by AF type in 31 studies found that studies were statistically heterogeneous, but that nonparoxysmal AF predicted AF recurrence compared to paroxysmal AF (relative risk 1.59; 95% confidence interval 1.38-1.82; P < 0.001); meta-analyses of persistent or permanent versus paroxysmal AF yielded similar findings. CONCLUSION: Nonparoxysmal AF may be a clinically useful proxy for a combination of confounded variables, none of which alone is an independent predictor of AF recurrence. Evaluation of predictors was limited by exclusion of patients with severe heart disease or at the age extremes; thus, the evidence may not be as applicable to these populations.

A summary of the Agency for Healthcare Research and Quality's evidence report on breastfeeding in developed countries.

OBJECTIVES: This article summarizes the Agency for Healthcare Research and Quality's evidence report on the effects of breastfeeding on term infant and maternal health outcomes in developed countries. EVIDENCE REPORT DATA SOURCES: Medline, CINAHL, Cochrane Library, bibliographies of selected reviews, and suggestions from domain experts were surveyed. Searches were limited to English-language publications. EVIDENCE REPORT REVIEW METHODS: Eligible comparisons examined the association between differential exposure to breastfeeding and health outcomes. We assessed 15 infant and six maternal outcomes. For four outcomes, we also updated previously published systematic reviews. For the rest of the outcomes, we either summarized previous systematic reviews or conducted new systematic reviews; randomized and non-randomized comparative trials, prospective cohorts, and case-control studies were included. Adjusted estimates were extracted from non-experimental designs. The studies were graded for methodological quality. We did not draw conclusions from poor quality studies. EVIDENCE REPORT RESULTS: We screened over 9,000 abstracts. Thirty-two primary studies on term infant health outcomes, 43 primary studies on maternal health outcomes, and 28 systematic reviews or meta-analyses that covered approximately 400 individual studies were included in this review. A history of breastfeeding was associated with a reduction in the risk of acute otitis media, nonspecific gastroenteritis, severe lower respiratory tract infections, atopic dermatitis, asthma (young children), obesity, type 1 and 2 diabetes, childhood leukemia, and sudden infant death syndrome. There was no relationship between breastfeeding in term infants and cognitive performance. There were insufficient good quality data to address the relationship between breastfeeding and cardiovascular diseases and infant mortality. For maternal outcomes, a history of lactation was associated with a reduced risk of type 2 diabetes, breast, and ovarian cancer. Early cessation of breastfeeding or no breastfeeding was associated with an increased risk of maternal postpartum depression. There was no relationship between a history of lactation and the risk of osteoporosis. The effect of breastfeeding in mothers on return-to-prepregnancy weight was negligible, and the effect of breastfeeding on postpartum weight loss was unclear. EVIDENCE REPORT CONCLUSIONS: A history of breastfeeding is associated with a reduced risk of many diseases in infants and mothers. Future research would benefit from clearer selection criteria, definitions of breastfeeding exposure, and adjustment for potential confounders. Matched designs such as sibling analysis may provide a method to control for hereditary and household factors that are important in certain outcomes.

Systematic review of screening for bilirubin encephalopathy in neonates.

CONTEXT: Severe neonatal hyperbilirubinemia is associated with chronic bilirubin encephalopathy (kernicterus). OBJECTIVE: To systematically review the effectiveness of specific screening modalities to prevent neonatal bilirubin encephalopathy. METHODS: We identified studies through Medline searches, perusing reference lists and by consulting with US Preventive Services Task Force lead experts. We included English-language publications evaluating the effects of screening for bilirubin encephalopathy using early total serum bilirubin (TSB), transcutaneous bilirubin (TcB) measurements, or risk scores. Severe hyperbilirubinemia was used as a surrogate for possible chronic bilirubin encephalopathy, because no studies directly evaluated the latter as an outcome. We calculated the sensitivity and specificity of early TSB, TcB measurements, or risk scores in detecting hyperbilirubinemia. RESULTS: Ten publications (11 studies) were eligible. Seven (2 prospective) studies evaluated the ability of risk factors (n = 3), early TSB (n = 3), TcB (n = 2), or combinations of risk factors and early TSB (n = 1) to predict hyperbilirubinemia (typically TSB > 95th hour-specific percentile 24 hours to 30 days postpartum). Screening had good ability to detect hyperbilirubinemia: reported area-under-the-curve values ranged between 0.69 and 0.84, and reported sensitivities and specificities suggested similar diagnostic ability. Indirect evidence from 3 descriptive uncontrolled studies suggests favorable associations between initiation of screening and decrease in hyperbilirubinemia rates, and rates of treatment or readmissions for hyperbilirubinemia compared with the baseline of no screening. No study assessed harms of screening. CONCLUSIONS: Effects of screening on the rates of bilirubin encephalopathy are unknown. Although screening can predict hyperbilirubinemia, there is no robust evidence to suggest that screening is associated with favorable clinical outcomes.

Systematic review: charged-particle radiation therapy for cancer.

BACKGROUND: Radiation therapy with charged particles can potentially deliver maximum doses while minimizing irradiation of surrounding tissues, and it may be more effective or less harmful than other forms of radiation therapy. PURPOSE: To review evidence about the benefits and harms of charged-particle radiation therapy for patients with cancer. DATA SOURCES: MEDLINE (inception to 11 July 2009) was searched for publications in English, German, French, Italian, and Japanese. Web sites of manufacturers, treatment centers, and professional organizations were searched for relevant information. STUDY SELECTION: Four reviewers identified studies of any design that described clinical outcomes or adverse events in 10 or more patients with cancer treated with charged-particle radiation therapy. DATA EXTRACTION: The 4 reviewers extracted study, patient, and treatment characteristics; clinical outcomes; and adverse events for nonoverlapping sets of articles. A fifth reviewer verified data on comparative studies. DATA SYNTHESIS: Currently, 7 centers in the United States have facilities for particle (proton)-beam irradiation, and at least 4 are under construction, each costing between $100 and $225 million. In 243 eligible articles, charged-particle radiation therapy was used alone or in combination with other interventions for common (for example, lung, prostate, or breast) or uncommon (for example, skull-base tumors or uveal melanomas) types of cancer. Of 243 articles, 185 were single-group retrospective studies. Eight randomized and 9 nonrandomized clinical trials compared treatments with or without charged particles. No comparative study reported statistically significant or important differences in overall or cancer-specific survival or in total serious adverse events. LIMITATION: Few studies directly compared treatments with or without particle irradiation. CONCLUSION: Evidence on the comparative effectiveness and safety of charged-particle radiation therapy in cancer is needed to assess the benefits, risks, and costs of treatment alternatives.

Systematic review: comparative effectiveness of radiofrequency catheter ablation for atrial fibrillation.

BACKGROUND: Atrial fibrillation is the most common sustained arrhythmia. Medical treatment often fails to control symptoms. PURPOSE: To compare the benefits and harms of radiofrequency catheter ablation and medical therapy in adults with atrial fibrillation. DATA SOURCES: MEDLINE and the Cochrane Central Register of Controlled Trials (2000 to December 2008) were searched for English-language reports of studies in adults. STUDY SELECTION: 6 independent reviewers screened abstracts to identify longitudinal studies of adults with atrial fibrillation who underwent radiofrequency catheter ablation. Studies reported arrhythmia or other cardiovascular outcomes at least 6 months after ablation or any adverse events. DATA EXTRACTION: Data were extracted by 1 of 4 reviewers and were verified by a cardiac electrophysiologist. Study quality and overall strength of evidence for each question were rated by 2 independent reviewers; disagreements were resolved by consensus. DATA SYNTHESIS: 108 studies met eligibility criteria. Moderate strength of evidence (3 trials; n = 30 to 198) showed that radiofrequency ablation after a failed drug course was more likely than continuation of drug therapy alone to lead to maintained sinus rhythm. Low strength of evidence (4 trials [n = 30 to 137] and 1 retrospective study [n = 1171]) suggested that radiofrequency ablation improved quality of life, promoted avoidance of anticoagulation, and decreased readmission rates compared with medical treatment. Major adverse events occurred in fewer than 5% of patients in most of 84 studies. LIMITATIONS: Study follow-up was generally 12 months or less. Large heterogeneity of applied techniques and reporting of outcomes precluded many definitive conclusions. Reporting of adverse events was poor. Publication and selective reporting biases could not be ruled out. Studies with small samples and studies reported in a language other than English were excluded. CONCLUSION: Radiofrequency catheter ablation is effective for up to 12 months of rhythm control when used as a second-line therapy for atrial fibrillation in relatively young patients with near-intact cardiac function. Longer studies that use primary end points of stroke and mortality are needed.

Systematic review: association of low-density lipoprotein subfractions with cardiovascular outcomes.

BACKGROUND: Measures of low-density lipoprotein (LDL) subfractions have been proposed as an independent risk factor for cardiovascular disease. PURPOSE: To review published studies that reported relationships between LDL subfractions and cardiovascular outcomes. DATA SOURCES: MEDLINE (1950 to 5 January 2009), CAB Abstracts (1973 to 30 June 2008), and Cochrane Central Register of Controlled Trials (2nd quarter of 2008), limited to English-language studies. STUDY SELECTION: 3 reviewers selected longitudinal studies with 10 or more participants that reported an association between LDL subfractions and incidence or severity of cardiovascular disease and in which plasma samples were collected before outcome determination. DATA EXTRACTION: Data were extracted from 24 studies. The 10 studies that used analytical methods available for clinical use (all of which used nuclear magnetic resonance) had full data extraction, including quality assessment (good, fair, or poor). All studies were extracted by 1 researcher and verified by another. DATA SYNTHESIS: All 24 studies, and the subset of 10 nuclear magnetic resonance studies, were heterogeneous in terms of the specific tests analyzed, analytical methods used, participants investigated, and outcomes measured. Higher LDL particle number was consistently associated with increased risk for cardiovascular disease, independent of other lipid measurements. Other LDL subfractions were generally not associated with cardiovascular disease after adjustment for cholesterol concentrations. No study evaluated the incremental value of LDL subfractions beyond traditional cardiovascular risk factors or their test performance. LIMITATION: Publication bias was a possibility. CONCLUSION: Higher LDL particle number has been associated with cardiovascular disease incidence, but studies have not determined whether any measures of LDL subfractions add incremental benefit to traditional risk factor assessment. Routine use of clinically available LDL subfraction tests to estimate cardiovascular disease risk is premature.

Predictors of clinical outcomes following fundoplication for gastroesophageal reflux disease remain insufficiently defined: a systematic review.

OBJECTIVES: Surgical treatment is a therapeutic option for patients with gastroesophageal reflux disease (GERD). It is unclear which patient characteristics influence postoperative success. The purpose of this paper was to review the literature on prognostic factors for patients with GERD treated with fundoplication. METHODS: We searched Medline and the Cochrane Library Central for studies from 1966 through July 2007. We identified additional studies by reviewing bibliographies of retrieved articles and by consulting experts. We included English language studies that evaluated factors potentially affecting the outcomes after surgical treatments in patients with GERD. We recorded baseline patient characteristics associated with treatment efficacy, details on the study design, comparators, and definitions of outcomes. RESULTS: We assessed 6,318 abstracts; 53 cohorts and 10 case-control studies met our inclusion criteria. Age, body mass index, sex, esophagitis grade, and dysmotility were generally not associated with treatment outcomes. There were no consistent associations between preoperative response to acid suppression medications, baseline symptoms, baseline acid exposure, degree of lower esophageal sphincter competence, or position of reflux and surgical outcomes. Certain psychological factors might be associated with worse treatment outcomes. CONCLUSIONS: Although several preoperative predictors of surgical outcomes have been described, the quality and consistency of the data were mixed and the strength of the associations remains unclear. Additional studies with improved methodological designs are needed to better define which patient characteristics are associated with surgical outcomes following fundoplication.