Teruhiko Terasawa

Vitamin D With or Without Calcium Supplementation for Prevention of Cancer and Fractures: An Updated Meta-analysis for the U.S. Preventive Services Task Force

BACKGROUND Studies suggest that vitamin D supplementation may reduce cancer and fracture risks. PURPOSE To examine the benefits and harms of vitamin D with or without calcium supplementation on clinical outcomes of cancer and fractures in adults. DATA SOURCES English-language studies identified from MEDLINE and the Cochrane Central Register of Controlled Trials through July 2011. STUDY SELECTION Randomized, controlled trials (RCTs), prospective cohort studies, and nested case-control studies reporting incidence of or death from cancer and fracture outcomes. DATA EXTRACTION Multiple reviewers extracted details about participant characteristics, including baseline vitamin D status and use of supplements; details of statistical analyses, including adjustments for confounding; and methodological quality. Differences were resolved by consensus. DATA SYNTHESIS 19 RCTs (3 for cancer and 16 for fracture outcomes) and 28 observational studies (for cancer outcomes) were analyzed. Limited data from RCTs suggested that high-dose (1000 IU/d) vitamin D supplementation can reduce the risk for total cancer, and data from observational studies suggested that higher blood 25-hydroxyvitamin D (25-[OH]D) concentrations might be associated with increased risk for cancer. Mixed-effects dose-response meta-analyses showed that each 10-nmol/L increase in blood 25-(OH)D concentration was associated with a 6% (95% CI, 3% to 9%) reduced risk for colorectal cancer but no statistically significant dose-response relationships for prostate and breast cancer. Random-effects model meta-analysis showed that combined vitamin D and calcium supplementation reduced fracture risk (pooled relative risk, 0.88 [CI, 0.78 to 0.99]) in older adults, but the effects differed according to study setting: institution (relative risk, 0.71 [CI, 0.57 to 0.89]) versus community-dwelling (relative risk, 0.89 [CI, 0.76 to 1.04]). One RCT showed adverse outcomes associated with supplementation, including increased risk for renal and urinary tract stones. LIMITATIONS Most trial participants were older (aged≥65 years) postmenopausal women. Observational studies were heterogeneous and were limited by potential confounders. CONCLUSION Combined vitamin D and calcium supplementation can reduce fracture risk, but the effects may be smaller among community-dwelling older adults than among institutionalized elderly persons. Appropriate dose and dosing regimens, however, require further study. Evidence is not sufficiently robust to draw conclusions regarding the benefits or harms of vitamin D supplementation for the prevention of cancer. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Systematic Review: Computed Tomography and Ultrasonography To Detect Acute Appendicitis in Adults and Adolescents

Context Is computed tomography or ultrasonography better for diagnosing acute appendicitis? Contribution This meta-analysis summarized data from 22 prospective studies that compared results of computed tomography, ultrasonography, or both with surgical findings or clinical follow-up in patients with suspected appendicitis. Computed tomography findings (positive likelihood ratio, 13.3 [95% CI, 9.9 to 17.9]) increased the certainty of diagnosis more than did ultrasonography (positive likelihood ratio, 5.8 [CI, 3.5 to 9.5]). Cautions All studies had significant limitations that probably inflated estimates of diagnostic accuracy, such as inadequate blinding of the reference standard and pathologic verification of disease only in patients with positive test results. The Editors Acute appendicitis is one of the most common acute surgical conditions in the United States; 250000 appendectomies are performed each year (1). Although early clinical evaluation and surgical intervention are mandatory, conventional diagnostic approaches such as history taking, physical examination, and routine laboratory tests are not always accurate (2, 3). Therefore, imaging tests are commonly used to improve diagnostic accuracy (4). In addition, compared with inpatient observation and serial basic laboratory tests, appendiceal imaging may be relatively inexpensive (5). During the past decade, appendiceal computed tomography and graded compression ultrasonography (6) have gained widespread use (4). Appropriateness criteria prepared by the American College of Radiology recommended graded compression ultrasonography as a screening test for most patients with suspected appendicitis (7). These criteria also recommended that computed tomography be used only in patients who are obese; have a rigid, noncompressible abdomen; or are thought to have appendicitis complicated by abscess (7). Published review articles have also supported the initial use of ultrasonography and have advised that computed tomography be reserved for patients with inconclusive sonogram findings (4, 8). However, in a survey of practicing emergency radiologists, the selection of appendiceal imaging varied, and there was no consensus about the best imaging approach for patients with a typical or atypical presentation of appendicitis (9). Most published studies of appendiceal imaging have evaluated the diagnostic accuracy of a single method, either computed tomography or ultrasonography; only a few studies have directly compared the 2 tests (10-13). In addition, no recent systematic review or meta-analysis has critically appraised currently available data on appendiceal imaging. Although 1 meta-analysis on appendiceal ultrasonography was conducted in 1994 (14), most of the included studies evaluated both children and adults, and the meta-analysis did not explore methodologic quality. We conducted a meta-analysis of the diagnostic accuracy of appendiceal computed tomography and ultrasonography in adults and adolescents. We explored the following 2 questions: 1) What is the diagnostic accuracy of computed tomography and ultrasonography? 2) What are the strengths and limitations of the current literature? Methods Study Identification We searched MEDLINE and EMBASE for English- and nonEnglish-language literature published from January 1966 through December 2003. The detailed search strategy can be found in the Appendix. We also manually searched the reference lists of eligible studies, review articles, and textbooks and consulted with experts in diagnostic imaging. Study Selection Two of the authors reviewed the pertinent studies to determine eligibility. We included only studies that prospectively evaluated computed tomography or graded compression ultrasonography in adults and adolescents (patients 14 years of age) who had suspected appendicitis, followed by surgical and pathologic confirmation or clinical follow-up. We expanded the original inclusion criterion from age 18 years or older to age 14 years or older in March 2002 after performing the pilot MEDLINE search, when it became clear that many studies included both adolescents and adults. The 6 computed tomography studies and 4 ultrasonography studies identified by using the original criterion of 18 years of age or older were examined separately in a sensitivity analysis. Data Abstraction Two independent reviewers abstracted relevant data for English-language articles. For nonEnglish-language articles, data were abstracted by a single reviewer working with a physician who was a native speaker of the relevant language. Abstractors were not blinded to journals. On the basis of clinical presentation before the imaging test, we categorized studies into 2 groups: atypical, which referred to studies enrolling only patients with an atypical presentation for appendicitis, and suspected, which referred to studies enrolling patients with both typical and atypical presentations. For 1 computed tomography study (13), we abstracted the combined test results using 3 different computed tomography protocols because this was how the authors published the data. Inconsistencies between reviewers were resolved by discussion, and a third reviewer adjudicated unresolved disagreements. When we could not extract or appropriately analyze pertinent data from published articles, we contacted a corresponding author for clarification. Assessment of Study Quality and Applicability We assessed study quality and applicability by using the checklist prepared for the Cochrane Methods Group on Systematic Review of Screening and Diagnostic Tests (15). Since we included studies that had a combined reference standard of surgical and pathologic confirmation or medical follow-up, we also abstracted how each study obtained medical follow-up on patients who did not proceed to surgery. If there was no explicit description of how such patients were followed after leaving the emergency department, we considered the follow-up inadequate. Data Synthesis and Analysis For each study, we constructed a 2 2 contingency table consisting of true-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) results according to an imaging test and reference standard (surgery or clinical follow-up). We then calculated sensitivity as TP/(TP + FN), specificity as TN/(FP + TN), the likelihood ratio for a positive test result as (TP/[TP + FN])/(FP/[FP + TN]), and the likelihood ratio for a negative test result as (FN/[TP + FN])/(TN/[FP + TN]). We explored the heterogeneity of sensitivity and specificity between studies by comparing confidence intervals of individual study findings with the summary estimates, using forest plots (16). For likelihood ratios, we estimated the statistics Q and I2 as means of quantifying heterogeneity among studies, and we considered the studies heterogeneous if the I2 was more than 30% (17). The summary sensitivity and specificity were calculated as follows, respectively, regardless of heterogeneity: the sum of TPs/(TPs + FNs) and the sum of TNs/(FPs + TNs) (18). We calculated the summary likelihood ratio statistics using the MantelHaenszel fixed-effects model for computed tomography studies because there was no statistical evidence of heterogeneity (positive likelihood ratio: Q = 9.16 [P> 0.2], I2 = 0% [CI, 0% to 58%]; negative likelihood ratio: Q = 7.38 [P> 0.2], I2 = 0% [CI, 0% to 58%]) (19). We used the DerSimonianLaird random-effects model to combine the likelihood ratios for ultrasonography studies since statistical evidence of heterogeneity was suggested (positive likelihood ratio: Q = 86.33 [P< 0.001], I2 = 85% [CI, 76% to 90%]; negative likelihood ratio: Q = 52.75 [P< 0.001], I2 = 75% [CI, 59% to 85%]) (20). Sensitivity Analysis Three computed tomography studies (10, 21, 22) and 3 ultrasonography studies (10, 11, 23) reported nondiagnostic results of imaging tests, that is, cases in which interpreters could not judge whether test results were positive or negative. Nondiagnostic results, if any, were excluded from the calculation of statistics in the main analysis. In a sensitivity analysis, we estimated sensitivity and specificity considering the numbers of nondiagnostic studies as false-negative and false-positive results, respectively, to evaluate a worst-case scenario. Also, we performed preplanned subgroup analyses for studies of adult participants ( 18 years of age), studies with different patient presentations at enrollment (suspected vs. atypical), and studies that included a high percentage of women (>67%). Role of the Funding Sources The funding sources had no role in study design, conduct, data collection, data analysis, data interpretation, or reporting or in the decision to submit the manuscript for publication. Data Synthesis The MEDLINE search identified 316 potentially relevant articles (Figure 1). We excluded 199 studies by scanning the titles and abstracts. We then retrieved and reviewed 117 full reports for inclusion and excluded 97 studies: 80 studies because they enrolled patients younger than 14 years of age, 10 studies because they were retrospective, 5 studies because they were casecontrol studies or case series, and 2 studies for other reasons. Subsequently, the EMBASE search identified 81 potentially relevant articles, 63 of which were excluded after we scanned the titles and abstracts. We then retrieved and reviewed 18 full reports for inclusion and excluded 16 studies: 10 studies enrolling patients younger than 14 years of age, 3 retrospective studies, 1 case series, 1 review article, and 1 study from which pertinent data could not be obtained because it evaluated only the combined diagnostic accuracy of both computed tomography and preceding clinical examinations. Lists of the excluded articles can be found in the Appendix. Figure 1. Article selection process. Study Characteristics We identified 12 studies of computed tomography (10-13, 21, 22, 24-29) and 14 studies of ultrasonography (10-13, 23, 30

Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography for Interim Response Assessment of Advanced-Stage Hodgkin's Lymphoma and Diffuse Large B-Cell Lymphoma: A Systematic Review

PURPOSE To systematically review the prognostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) for interim response assessment of patients with untreated advanced-stage Hodgkins lymphoma (HL) or diffuse large B-cell lymphoma (DLBCL). METHODS MEDLINE, EMBASE, SCOPUS, and Biologic Abstracts were searched for relevant studies. Two assessors independently reviewed studies for inclusion and extracted data. Relevant unpublished data were requested from the investigators if unavailable from publications. A meta-analysis of the prognostic accuracy was performed. RESULTS Thirteen studies involving 360 advanced-stage HL patients and 311 DLBCL patients met our inclusion criteria. Advanced-stage HL studies included few unfavorable-risk patients. DLBCL studies were heterogeneous. FDG-PET had an overall sensitivity of 0.81 (95% CI, 0.72 to 0.89) and a specificity of 0.97 (95% CI, 0.94 to 0.99) for advanced-stage HL, and a sensitivity of 0.78 (95% CI, 0.64 to 0.87) and a specificity of 0.87 (95% CI, 0.75 to 0.93) for DLBCL. Meta-regression and subgroup analyses did not identify factors that affect prognostic accuracy. CONCLUSION For low- to intermediate-risk advanced-stage HL, FDG-PET performed after a few cycles of standard chemotherapy seems to be a reliable prognostic test to identify poor responders, warranting prospective studies to assess PET-based treatment strategies. For DLBCL, no reliable conclusions can be drawn due to heterogeneity. Interim PET remains an unproven test for routine clinical practice. Its use should be reserved for research settings where treatment regimens and imaging conditions are standardized.

Systematic Review: Anti-Epidermal Growth Factor Receptor Treatment Effect Modification by KRAS Mutations in Advanced Colorectal Cancer

BACKGROUND KRAS mutations have been extensively investigated as predictive biomarkers for treatment of advanced colorectal cancer with the anti-epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab. PURPOSE To summarize whether KRAS mutation status modifies effects of anti-EGFR-based treatments for patients with advanced colorectal cancer and whether KRAS status predicts clinical outcomes among such patients. DATA SOURCES MEDLINE and 2 curated genetics databases (through 24 March 2010) were searched for observational studies. MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects (through 1 September 2010) were searched for randomized, controlled trials. No search was restricted by language. STUDY SELECTION Three reviewers screened titles and abstracts to identify published studies assessing KRAS mutations as predictors of overall and progression-free survival or treatment failure for patients who received anti-EGFR-based therapy for metastatic colorectal cancer. DATA EXTRACTION Three investigators extracted data on population and study-design characteristics, including quality items, and on outcomes of interest. Random-effects meta-analyses were done on nonoverlapping studies. DATA SYNTHESIS In 4 reanalyses of randomized trials of anti-EGFR-based therapy versus best supportive care or cytotoxic chemotherapy, no significant benefit was found for overall or progression-free survival from anti-EGFR-based treatment among KRAS-positive patients (hazard ratio [HR], 1.0). However, evidence favors anti-EGFR therapy among KRAS wild-type patients; the relative HR across KRAS-positive and wild-type patients was 1.30 (95% CI, 0.95 to 1.78) for overall survival and 2.22 (CI, 1.74 to 2.84) for progression-free survival by random-effects meta-analysis. In 13 cohorts of patients who received anti-EGFR antibodies, the summary HR for overall survival was 1.79 (CI, 1.48 to 2.17), with better survival in wild-type patients. The corresponding HR for progression-free survival was 2.11 (CI, 1.74 to 2.55 [16 cohorts]). In random-effects bivariate meta-analysis of 22 studies, the summary sensitivity of KRAS mutations for predicting lack of response was 0.49 (CI, 0.43 to 0.55), and summary specificity was 0.93 (CI, 0.87 to 0.97). LIMITATIONS Limited evidence from randomized studies exists. Patient-level data are needed to assess modifiers of the mutation-by-treatment interaction. Publication bias could be a concern. CONCLUSION KRAS mutations are consistently associated with reduced overall and progression-free survival and increased treatment failure rates among patients with advanced colorectal cancer treated with anti-EGFR antibodies. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

18F-FDG PET for Posttherapy Assessment of Hodgkin's Disease and Aggressive Non-Hodgkin's Lymphoma: A Systematic Review

Although studies have shown that 18F-FDG PET, when used to assess the response of malignant lymphoma after treatment, has a strong ability to predict relapse, its diagnostic accuracy in clinical practice remains unclear. The aim of this study was to systematically review the diagnostic accuracy of 18F-FDG PET in detecting residual disease at the completion of first-line therapy of Hodgkins disease (HD) and aggressive non-Hodgkins lymphoma (NHL). Methods: We searched relevant articles from 1966 to July 2006 using MEDLINE, EMBASE, SCOPUS, Biological Abstracts, bibliographies, review articles, and textbooks without language restriction. One assessor (for non–English-language studies) or 2 assessors (for English-language studies) independently reviewed each article to abstract relevant study characteristics and results. Relevant individual patient data or subgroup data were provided by the investigators if they were unavailable from the publications. We estimated summary receiver operating characteristic curves and confidence regions for summary sensitivity and specificity. Results: Nineteen studies consisting of 474 HD and 254 aggressive NHL patients were included. These studies had heterogeneity and suboptimal methodologic quality and reporting. Reported ranges for the sensitivity and specificity of 18F-FDG PET in predicting disease relapse were 0.50–1.00 and 0.67–1.00, respectively, for HD and 0.33–0.77 and 0.82–1.00, respectively, for NHL. These estimates were similar when conventional imaging tests showed a residual mass. For HD studies, the summary receiver operating characteristic curves were similar irrespective of whether a residual mass was detected by conventional tests. Factors explaining the variability of diagnostic estimates were not identified. Conclusion: Although currently available evidence is still limited, 18F-FDG PET seems to have good diagnostic accuracy for assessing residual HD at the completion of first-line treatment. Clinical data on this use of 18F-FDG PET for aggressive NHL are more limited. Prospective studies with a more rigorous research design, conduct, and reporting would more reliably reveal the clinical diagnostic accuracy of this imaging modality.

Predictors of Atrial Fibrillation Recurrence After Radiofrequency Catheter Ablation: A Systematic Review

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.

Systematic Review: Comparative Effectiveness of Radiofrequency Catheter Ablation for Atrial Fibrillation

Context Is radiofrequency catheter ablation a better alternative than medical therapy for patients with atrial fibrillation? Contribution This systematic review found that radiofrequency ablation after a failed drug course maintained sinus rhythm more often than continuation of drug therapy alone. Some studies found that ablation improved quality of life but did not necessarily reduce stroke rates compared with medical therapy. Fewer than 5% of patients undergoing ablation reportedly experienced major adverse events, such as pulmonary-vein stenosis or cardiac tamponade. Caution Most available evidence was obtained in middle-age adults with preserved left ventricular function and involved follow-up periods of 1 year or less. The Editors Atrial fibrillation is the most common sustained arrhythmia in clinical practice (1). Its prevalence increases with age, from 0.1% in people younger than 55 years to more than 9% by 80 years of age (2). The heavy burden of atrial fibrillation on morbidity, mortality, and health care resources creates a pressing need for novel approaches to management. In some patients, adequate pharmacologic slowing of the ventricular response rate (a rate-control strategy) is sufficient to control symptoms. However, many patients remain symptomatic from the lack of organized atrial contraction and the persistent irregularity of the ventricular response in atrial fibrillation. In such patients, the appropriate treatment is restoration of normal sinus rhythm, achieved electrically or chemically (a rhythm-control strategy) (2). Overall, a rhythm-control strategy with antiarrhythmic drugs offered no survival advantage over a rate-control strategy in 1 large trial (3). An on-treatment analysis, however, suggested that sinus rhythm was associated with a considerable reduction in the risk for death, although antiarrhythmic drugs resulted in increased mortality (4). The benefits of maintaining sinus rhythm with antiarrhythmic drugs appeared to be offset by the serious adverse effects of the drugs. Radiofrequency catheter ablation is a promising approach that offers the benefits of maintaining sinus rhythm without the adverse effects of antiarrhythmic drugs. Catheter ablation for atrial fibrillation is based on the understanding that electrical activity emanating from the pulmonary veins frequently serves as a trigger for atrial fibrillation. In the late 1990s, Hassaguerre and colleagues (5) observed that elimination of local electrograms at these foci with radiofrequency energy reduced the risk for recurrence of atrial fibrillation. Currently, the foundation of most atrial fibrillation ablation procedures is to target and electrically isolate the pulmonary veins (6). This may be achieved by delivering lesions immediately outside the ostia of the pulmonary veins or along a wider area in the left atrium encircling the veins. Additional lesion sets have been used to ablate nonpulmonary vein triggers of atrial fibrillation and to target atrial areas thought to be responsible for maintaining atrial fibrillation (6). These linear lesions may be created in the posterior left atrium, the roof of the left atrium, the interatrial septum, and the isthmus formed between the mitral annulus and the pulmonary vein or left atrial appendage. The Agency for Healthcare Research and Quality commissioned this report to review the evidence for the clinical effects and safety of radiofrequency catheter ablation for the management of atrial fibrillation. At present, the Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation, put forth by the Heart Rhythm Society and endorsed by several professional organizations, states that the foundation of most atrial fibrillation ablation procedures is to target the pulmonary veins, pulmonary vein antra, or both (6). After discussion with a technical expert panel convened for this comparative effectiveness review and in accordance with the Heart Rhythm Societys consensus statement, we reviewed only studies that included the targeting of the pulmonary veins or pulmonary vein antra, with or without the addition of other strategies. Methods We developed and followed a standard protocol for all steps of the review. A technical report that describes our methods in detail, including the literature search strategies, results, and conclusions, is published elsewhere (7). Key Questions Key questions on the effectiveness of radiofrequency catheter ablation compared with other available treatments (for example, medical treatment or surgery) were refined with input from the technical expert panel. The panel advised us that 8-mmtip and irrigated-tip catheters are now the catheters of choice for radiofrequency ablation of atrial fibrillation in the United States. The conventional 4-mmtip catheter is rapidly being phased out of use for this indication. Thus, we limited our review to studies that used 8-mmtip or irrigated-tip catheters as a comparator. The following 3 key questions were formulated: 1. What is the effect of radiofrequency catheter ablation on short-term (6 to 12 months) and long-term (>12 months) rhythm control; rates of congestive heart failure; changes in the size of the left atrium and ventricle; rates of stroke; quality of life; avoiding anticoagulation; and readmissions for paroxysmal, persistent, and long-standing persistent (chronic) atrial fibrillation? 2. How does the effect of radiofrequency ablation on rhythm control differ among the various techniques used? 3. What are the short- and long-term complications and harms associated with radiofrequency ablation? Data Sources and Selection We searched MEDLINE and the Cochrane Central Register of Controlled Trials from 2000 to December 2008 for studies of adults with atrial fibrillation who underwent radiofrequency catheter ablation. We combined keywords and Medical Subject Heading terms for atrial fibrillation, pulmonary vein, radiofrequency ablation, and catheter ablation. We limited the search to English-language reports of primary studies in adults that were published in peer-reviewed journals. We did not include unpublished data. Six reviewers screened titles and abstracts to identify potentially relevant articles. They also examined the full-text articles of the potentially relevant abstracts for inclusion eligibility. We accepted longitudinal studies and excluded case series. We included randomized trials of any sample size. For pragmatic reasons, we restricted the sample sizes in nonrandomized studies. For nonrandomized comparative studies and casecontrol studies, we included only those with at least 10 patients per intervention group. Noncomparative prospective cohort studies had to have at least 50 patients receiving radiofrequency catheter ablation, and retrospective cohort studies must have had at least 100 patients. We included studies of adults (18 years of age) with paroxysmal, persistent, or permanent or chronic atrial fibrillation. We accepted the definitions of the various types of atrial fibrillation used by the study authors, using the terms permanent and chronic atrial fibrillation as reported in the individual studies, even though the definitions varied. Notably, the consensus statement on radiofrequency catheter ablation for the treatment of atrial fibrillation published by the Heart Rhythm Society in 2007 no longer used the term chronic, instead adopting the term long-standing persistent for continuous atrial fibrillation lasting more than 1 year (6). For a study to be included, at least 80% of the patients had to be treated with first-time radiofrequency ablation for atrial fibrillation. We excluded studies that were limited to patients with congenital heart disease, hypertrophic cardiomyopathy, or the WolffParkinsonWhite syndrome. The intervention of interest was catheter-directed radiofrequency ablation of the left atrium to prevent atrial fibrillation by using an 8-mmtip or irrigated-tip catheter. We included studies that compared 4-mmtip catheters to other catheters, but not studies that evaluated only 4-mmtip catheters. Radiofrequency ablation could be used as first- or second-line treatment (that is, before or after a course of antiarrhythmic drugs) and with or without concurrent antiarrhythmic drugs. We included studies of radiofrequency ablation strategies in which the explicit or intended goal was targeting of the pulmonary veins or pulmonary vein antra, with or without additional ablation. We did not evaluate cryoablation or microwave ablation. We included only studies that reported outcomes of interest at 6 months or more after the initial intervention or that reported adverse events at any time. Outcomes of interest included rhythm control, congestive heart failure, changes in the size of the left atrium or ventricle, stroke, quality-of-life measures, avoidance of anticoagulation, readmissions, and reinterventions for atrial fibrillation. We excluded arrhythmia outcomes that occurred during the blanking period, which is defined as a postprocedure period (typically between 1 and 3 months) during which an episode of atrial fibrillation was not considered a recurrence. Data Extraction and Quality Assessment Data from each study were extracted by 1 of 4 reviewers and were confirmed by a clinical cardiac electrophysiologist author. The extracted data included information on patient characteristics, ablation characteristics (for example, type of catheter tip, verification of electrical isolation, and ablation techniques), other interventions, outcomes, study design, and quality. For most outcomes, 6-month, 12-month, and last-reported-time-point data were included. All mortality and adverse event data were extracted. We used predefined criteria to grade study quality as good, fair, or poor. We also rated the strength of the overall body of evidence for each key question as high, moderate, low, or insufficient (Appendix Table). The quality assessment and strength of the overall bod

Diagnostic Accuracy of PET for Recurrent Glioma Diagnosis: A Meta-Analysis

These authors compared the diagnostic accuracy of PET with that of CT and MRI in the diagnosis of recurrent glioma in 26 previously published articles. PET studies with either FDG or carbon methionine were obtained once glioma recurrence was suspected on CT and/or MRI. Diagnostic accuracies were heterogeneous and studies did not compare PET with other imaging modalities. Despite these limitations, PET with both tracers appears to have a moderately good accuracy as an add-on test for diagnosing recurrent glioma. BACKGROUND AND PURPOSE: Studies have assessed PET by using various tracers to diagnose disease recurrence in patients with previously treated glioma; however, the accuracy of these methods, particularly compared with alternative imaging modalities, remains unclear. We conducted a meta-analysis to quantitatively synthesize the diagnostic accuracy of PET and compare it with alternative imaging modalities. MATERIALS AND METHODS: We searched PubMed and Scopus (until June 2011), bibliographies, and review articles. Two reviewers extracted study characteristics, validity items, and quantitative data on diagnostic accuracy. We performed meta-analysis when ≥5 studies were available. RESULTS: Twenty-six studies were eligible. Studies were heterogeneous in treatment strategies and diagnostic criteria of PET; recurrence was typically suspected by CT or MR imaging. The diagnostic accuracies of 18F-FDG (n = 16) and 11C-MET PET (n = 7) were heterogeneous across studies. 18F-FDG PET had a summary sensitivity of 0.77 (95% CI, 0.66–0.85) and specificity of 0.78 (95% CI, 0.54–0.91) for any glioma histology; 11C-methionine PET had a summary sensitivity of 0.70 (95% CI, 0.50–0.84) and specificity of 0.93 (95% CI, 0.44–1.0) for high-grade glioma. These estimates were stable in subgroup and sensitivity analyses. Data were limited on 18F-FET (n = 4), 18F-FLT (n = 2), and 18F-boronophenylalanine (n = 1). Few studies performed direct comparisons between different PET tracers or between PET and other imaging modalities. CONCLUSIONS: 18F-FDG and 11C-MET PET appear to have moderately good accuracy as add-on tests for diagnosing recurrent glioma suspected by CT or MR imaging. Studies comparing alternative tracers or PET versus other imaging modalities are scarce. Prospective studies performing head-to-head comparisons between alternative imaging modalities are needed.

Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Response Assessment Before High-Dose Chemotherapy for Lymphoma: A Systematic Review and Meta-Analysis

BACKGROUND We conducted a systematic review and meta-analysis to better define the prognostic ability of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) following salvage chemotherapy for relapsed or refractory Hodgkins lymphoma (HL) and aggressive non-Hodgkins lymphoma. METHODS We searched PubMed (from inception to January 31, 2010), bibliographies, and review articles without language restriction. Two assessors independently assessed study characteristics, quality, and results. We performed a meta-analysis to determine prognostic accuracy. RESULTS Twelve studies including 630 patients were eligible. The most commonly evaluated histologies were diffuse large B-cell lymphoma (n = 313) and HL (n = 187), which were typically treated with various salvage and high-dose chemotherapy regimens. Studies typically employed nonstandardized protocols and diagnostic criteria. The prognostic accuracy was heterogeneous across the included studies. (18)F-FDG PET had a summary sensitivity of 0.69 (95% confidence interval [CI], 0.56-0.81) and specificity of 0.81 (95% CI, 0.73-0.87). The summary estimates were stable in sensitivity analyses. In four studies that performed direct comparisons between PET and conventional restaging modalities, PET had a superior accuracy for predicting treatment outcomes. Subgroup and metaregression analyses did not identify any particular factor to explain the observed heterogeneity. CONCLUSION (18)F-FDG PET performed after salvage therapy appears to be an appropriate test to predict treatment failure in patients with refractory or relapsed lymphoma who receive high-dose chemotherapy. Some evidence suggests PET is superior to conventional restaging for this purpose. Given the methodological limitations in the primary studies, prospective studies with standardized methodologies are needed to confirm and refine these promising results.

Prediction of gastric cancer development by serum pepsinogen test and Helicobacter pylori seropositivity in Eastern Asians: a systematic review and meta-analysis.

Background To identify high-risk groups for gastric cancer in presumptively healthy populations, several studies have investigated the predictive ability of the pepsinogen test, H. Pylori antibodies, and a risk-prediction model based on these two tests. To investigate whether these tests accurately predict gastric cancer development, we conducted a systematic review and meta-analysis. Methods PubMed and other electronic databases were searched for cohort studies published in English or Japanese from January 1985 through December 2013. Six reviewers identified eligible studies, and at least two investigators extracted data on population and study-design characteristics, quality items, and outcomes of interest. Meta-analyses were performed on non-overlapping studies. Results Nine prospective cohorts from Eastern Asia reported in 12 publications, including 33,741 asymptomatic middle-aged participants of gastric cancer screening, were eligible. For discriminating between asymptomatic adults at high and low risk of gastric cancer, the pepsinogen test (summary hazard ratio [HR], 3.5; 95% confidence interval [CI], 2.7–4.7; I2 = 0%) and H. pylori antibodies (summary HR, 3.2; 95% CI, 2.0–5.2; I2 = 0%) were statistically significant predictors as standalone tests. Although the risk-prediction model was in general moderately accurate in separating asymptomatic adults into four risk groups (summary c-statistic, 0.71; 95% CI: 0.68–0.73; I2 = 7%), calibration seemed to be poor. The study validity was generally limited. Conclusions The serum pepsinogen test, H. pylori antibodies, and the four-risk-group model for predicting gastric cancer development seem to have the potential to stratify middle-aged presumptively healthy adults. Future research needs to focus on comparative studies to evaluate the impact of screening programs adopting these tests. Also, validation, preferably with model updating, is necessary to see whether the current model performance is transferable to different populations.