WITHDRAWN: Oral sumatriptan for acute migraine.

BACKGROUND: Migraine is a common neurovascular disorder characterized by recurrent episodes of disabling headache, autonomic nervous system dysfunction, and, in some patients, neurological aura symptoms. Sumatriptan is one of a class of selective serotonin 5-hydroxytryptamine (5-HT1B/1D) agonists (triptans) thought to relieve migraine attacks by several mechanisms, including cranial vasoconstriction and peripheral and central neural inhibition. OBJECTIVES: To describe and assess the evidence from randomized controlled trials (RCTs) concerning the efficacy and tolerability of oral sumatriptan for the treatment of a single acute attack of migraine in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 4, 2001), MEDLINE (1966 through November 2001), and reference lists of articles and books. SELECTION CRITERIA: We included double-blind RCTs comparing oral sumatriptan (100 mg, 50 mg, 25 mg) with placebo, no intervention, other drug treatments, behavioral therapy, or physical therapy for the treatment of an acute attack of migraine in adults. Trials comparing different doses of sumatriptan or dosing regimens were also included. Outcomes considered were: 2-hour pain-free response, headache relief/headache intensity, and functional disability; headache recurrence; and adverse events. DATA COLLECTION AND ANALYSIS: Data were abstracted by one reviewer and over-read by the other. The two reviewers independently assessed trial quality. Information on adverse events was collected from trial reports. MAIN RESULTS: Twenty-five trials involving 16,200 participants were included. Methodological quality was generally good. Sixteen trials were placebo comparisons and showed that sumatriptan in doses of 100 mg (14 trials), 50 mg (five trials), and 25 mg (three trials) provided significantly better pain-free response (100 mg and 25 mg only), headache relief, and relief of disability at 2 hours. Numbers-needed-to-treat (NNTs) for pain-free response at 2 hours were 5.1 (3.9 to 7.1) for the 100-mg dose (n = 2221) and 7.5 (2.7 to 142) for the 25-mg dose (n = 131); there was no significant difference between the 50-mg dose and placebo for this outcome (n = 127). For headache relief at 2 hours, NNTs were 3.4 (3.0 to 4.0), 3.2 (2.4 to 5.1), and 3.4 (2.3 to 6.6) for sumatriptan 100 mg (n = 2940), 50 mg (n = 420), and 25 mg (n = 226), respectively. Precise estimates of the efficacy of the 50- and 25-mg doses relative to the 100-mg dose could not be obtained.Adverse events were more common with sumatriptan 100 mg than with placebo (risk difference [RD] = 0.14 [0.09 to 0.20]; number-needed-to-harm [NNH] = 7.1 [5.0 to 11.1]; n = 3172). RDs for the 50- and 25-mg vs. placebo comparisons were not statistically significant. AUTHORS' CONCLUSIONS: Oral sumatriptan has been shown to be an effective drug for the treatment of a single acute attack of migraine. It is well tolerated, though minor adverse events were not uncommon in the included trials. Other triptans were generally similar in efficacy and adverse events. Among non-triptan drugs, ergotamine + caffeine was significantly less effective than sumatriptan, and other drugs have been insufficiently studied to draw firm conclusions.

Updated report on comparative effectiveness of ACE inhibitors, ARBs, and direct renin inhibitors for patients with essential hypertension: much more data, little new information.

OBJECTIVES: A 2007 systematic review compared angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in patients with hypertension. Direct renin inhibitors (DRIs) have since been introduced, and significant new research has been published. We sought to update and expand the 2007 review. DATA SOURCES: We searched MEDLINE and EMBASE (through December 2010) and selected other sources for relevant English-language trials. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We included studies that directly compared ACE inhibitors, ARBs, and/or DRIs in at least 20 total adults with essential hypertension; had at least 12 weeks of follow-up; and reported at least one outcome of interest. Ninety-seven (97) studies (36 new since 2007) directly comparing ACE inhibitors versus ARBs and three studies directly comparing DRIs to ACE inhibitor inhibitors or ARBs were included. STUDY APPRAISAL AND SYNTHESIS METHODS: A standard protocol was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality; and summarize the evidence. RESULTS: In spite of substantial new evidence, none of the conclusions from the 2007 review changed. The level of evidence remains high for equivalence between ACE inhibitors and ARBs for blood pressure lowering and use as single antihypertensive agents, as well as for superiority of ARBs for short-term adverse events (primarily cough). However, the new evidence was insufficient on long-term cardiovascular outcomes, quality of life, progression of renal disease, medication adherence or persistence, rates of angioedema, and differences in key patient subgroups. LIMITATIONS: Included studies were limited by follow-up duration, protocol heterogeneity, and infrequent reporting on patient subgroups. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Evidence does not support a meaningful difference between ACE inhibitors and ARBs for any outcome except medication side effects. Few, if any, of the questions that were not answered in the 2007 report have been addressed by the 36 new studies. Future research in this area should consider areas of uncertainty and be prioritized accordingly.

Percutaneous heart valve replacement for aortic stenosis: state of the evidence.

Surgical aortic valve replacement (SAVR) is the only treatment known to improve symptoms and survival in patients with severe, symptomatic aortic stenosis. Perioperative mortality, however, is high among many patients for whom SAVR may be indicated. Percutaneous heart valve replacement (PHVR) is an emerging, catheter-based technology that allows for implantation of a prosthetic valve without open heart surgery. This review describes the available literature on PHVR for aortic stenosis, which comprised 84 published reports representing 76 distinct studies and 2375 unique patients. Successful implantation was achieved in 94% of patients; 30-day survival was 89%. Differences between patients undergoing PHVR and those typically selected for SAVR make full interpretation of these results difficult. A large, multicenter, randomized, controlled trial comparing PHVR with SAVR or medical management was recently completed, with initial results expected in September 2010. Pending publication of findings from that trial, the available evidence is inadequate to determine the most appropriate clinical role of PHVR or the specific patient populations for whom it might eventually be indicated.

Systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension.

BACKGROUND: The relative effectiveness of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) for lowering blood pressure is unknown. PURPOSE: To compare the benefits and harms of ACE inhibitors versus ARBs for treating essential hypertension in adults. DATA SOURCES: MEDLINE (1966 to May 2006), the Cochrane Central Register of Controlled Trials (Issue 2, 2006), and selected reference lists were searched for relevant English-language trials. The MEDLINE search was updated to August 2007 to identify head-to-head trials that reported blood pressure outcomes and major cardiovascular events. STUDY SELECTION: 61 clinical studies that directly compared ACE inhibitors versus ARBs in adult patients with essential hypertension, reported an outcome of interest, lasted at least 12 weeks, and included at least 20 patients. DATA EXTRACTION: A standardized protocol with predefined criteria was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality and applicability; and assess the strength of the body of evidence for key outcomes. DATA SYNTHESIS: ACE inhibitors and ARBs had similar long-term effects on blood pressure (50 studies; strength of evidence, high). No consistent differential effects were observed for other outcomes (few studies reported long-term outcomes), including death, cardiovascular events, quality of life, rate of single antihypertensive agent use, lipid levels, progression to diabetes, left ventricular mass or function, and kidney disease. Consistent fair- to good-quality evidence showed that ACE inhibitors were associated with a greater risk for cough. There were fewer withdrawals due to adverse events and greater persistence with therapy for ARBs than for ACE inhibitors, although this evidence was not definitive. Patient subgroups for whom ACE inhibitors or ARBs were more effective, associated with fewer adverse events, or better tolerated were not identified. LIMITATIONS: Few studies involved a representative sample treated in a typical clinical setting over a long duration, treatment protocols had marked heterogeneity, and substantive amounts of data about important outcomes and patient subgroups were missing. CONCLUSION: Available evidence shows that ACE inhibitors and ARBs have similar effects on blood pressure control, and that ACE inhibitors have higher rates of cough than ARBs. Data regarding other outcomes are limited.

Review of evidence for genetic testing for CYP450 polymorphisms in management of patients with nonpsychotic depression with selective serotonin reuptake inhibitors.

PURPOSE: Cytochrome P450 (CYP450) enzymes metabolize selective serotonin reuptake inhibitor (SSRI) drugs used in treatment of depression. Variants in these genes may impact treatment efficacy and tolerability. The purpose of this study was 2-fold: to systematically review the literature for evidence supporting CYP450 genotyping to guide SSRI treatment for major depression, and, where evidence is inadequate, to suggest future research. METHODS: We searched MEDLINE(R) and other databases for studies addressing five key questions suggested by the Evaluation of Genomic Applications in Practice and Prevention Working Group. Eligibility criteria were defined, and studies were reviewed independently by paired researchers. A conceptual model was developed to guide future research. RESULTS: Review of 1200 abstracts led to the final inclusion of 37 articles. The evidence indicates relatively high analytic sensitivity and specificity of tests detecting a subset of polymorphisms of CYP2D6, 2C19, 2C8, 2C9, and 1A1. We found marginal evidence regarding a clinical association between CYP450 variants and SSRI metabolism, efficacy, and tolerability in the treatment of depression. CONCLUSIONS: Current evidence does not support the use of CYP450 genotyping to guide SSRI treatment of patients with depression. Studies are proposed that will effectively guide decision-making in the area of CYP450 testing in depression, and genetic testing more generally.

Testing for cytochrome P450 polymorphisms in adults with non-psychotic depression treated with selective serotonin reuptake inhibitors (SSRIs).

OBJECTIVES: To determine if testing for cytochrome P450 (CYP450) polymorphisms in adults entering selective serotonin reuptake inhibitor (SSRI) treatment for non-psychotic depression leads to improvement in outcomes, or if testing results are useful in medical, personal, or public health decisionmaking. DATA SOURCES: We searched MEDLINE, the Cochrane Database of Abstracts of Reviews of Effects, PsychInfo, HealthSTAR, and CINAHL, and reviewed the reference lists of included articles and relevant review articles and meta-analyses for eligible studies. We also included documents from the U.S. Food and Drug Administration (FDA) that could be publicly accessed. REVIEW METHODS: We developed an analytic framework and identified key questions to guide the review process. Project-specific inclusion/exclusion criteria were also developed and were used by paired researchers independently to review both abstracts and full-text articles; both researchers were required to agree on inclusion status at the full-text stage. Abstractors evaluated each included article for factors affecting internal and external validity. RESULTS: A review of 1,200 abstracts led to the final inclusion of 37 articles. The evidence indicates the existence of tests with high sensitivity and specificity for detecting only a few of the more common known polymorphisms of 2D6, 2C19, 2C8, 2C9, and 1A1. There is mixed evidence regarding the association between CYP450 genotypes and SSRI metabolism, efficacy, and tolerability in the treatment of depression, mainly from a series of heterogeneous studies in small samples. There are no data regarding: (a) if testing for CYP450 polymorphisms in adults entering SSRI treatment for non-psychotic depression leads to improvement in outcomes versus not testing, or if testing results are useful in medical, personal, or public health decisionmaking; (b) if CYP450 testing influences depression management decisions by patients and providers in ways that could improve or worsen outcomes; or (c) if there are direct or indirect harms associated with testing for CYP450 polymorphisms or with subsequent management options. CONCLUSIONS: There is a paucity of good-quality data addressing the questions of whether testing for CYP450 polymorphisms in adults entering SSRI treatment for non-psychotic depression leads to improvement in outcomes, or whether testing results are useful in medical, personal, or public health decisionmaking.

Quality measures for the use of adjuvant chemotherapy and radiation therapy in patients with colorectal cancer: a systematic review.

BACKGROUND: Chemotherapy (CT) and radiation therapy (RT) are essential components of adjuvant (preoperative or postoperative) therapy for many patients with colorectal cancer (CRC); however, quality measures (QMs) of these critical aspects of CRC treatment have not been characterized well. Therefore, the authors conducted a systematic review of the literature to determine the available QMs for adjuvant CT and RT in patients with CRC and rated their usefulness for assessing the delivery of quality care. METHODS: The MEDLINE and Cochrane data bases were searched for all publications that contained potential/actual QMs pertaining to adjuvant therapy for CRC. Identified QMs were rated by using criteria developed by the National Quality Forum. RESULTS: Thirty-two articles met the established inclusion/exclusion criteria. Those 32 articles contained 12 potential or actual QMs, 6 of which had major flaws that limited their applicability. The most useful QMs identified were 1) the percentage of patients with AJCC Stage III colon cancer who received postoperative CT and 2) the percentage of patients with Stage II or III rectal cancer who received chemoradiotherapy. CONCLUSIONS: To the authors' knowledge, very few QMs pertaining to adjuvant CT or RT for CRC have been published to date, and only half of those measures were rated as useful, acceptable, and valid in the current literature review. Future research should focus on refining existing QMs and on developing new QMs that target important leverage points with respect to the provision of adjuvant therapy for patients with CRC.

Genomic tests for ovarian cancer detection and management.

OBJECTIVES: To assess the evidence that the use of genomic tests for ovarian cancer screening, diagnosis, and treatment leads to improved outcomes. DATA SOURCES: PubMed and reference lists of recent reviews. REVIEW METHODS: We evaluated tests for: (a) single gene products; (b) genetic variations affecting risk of ovarian cancer; (c) gene expression; and (d) proteomics. For tests covered in recent evidence reports (cancer antigen 125 [CA-125] and breast cancer genes 1 and 2 [BRCA1/2]), we added studies published subsequent to the reports. We sought evidence on: (a) the analytic performance of tests in clinical laboratories; (b) the sensitivity and specificity of tests in different patient populations; (c) the clinical impact of testing in asymptomatic women, women with suspected ovarian cancer, and women with diagnosed ovarian cancer; (d) the harms of genomic testing; and (e) the impact of direct-to-consumer and direct-to-physician advertising on appropriate use of tests. We also constructed a computer simulation model to test the impact of different assumptions about ovarian cancer natural history on the relative effectiveness of different strategies. RESULTS: There are reasonable data on the clinical laboratory performance of most radioimmunoassays, but the majority of the data on other genomic tests comes from research laboratories. Genomic test sensitivity/specificity estimates are limited by small sample sizes, spectrum bias, and unrealistically large prevalences of ovarian cancer; in particular, estimates of positive predictive values derived from most of the studies are substantially higher than would be expected in most screening or diagnostic settings. We found no evidence relevant to the question of the impact of genomic tests on health outcomes in asymptomatic women. Although there is a relatively large literature on the association of test results and various clinical outcomes, the clinical utility of changing management based on these results has not been evaluated. We found no evidence that genomic tests for ovarian cancer have unique harms beyond those common to other tests for genetic susceptibility or other tests used in screening, diagnosis, and management of ovarian cancer. Studies of a direct-to-consumer campaign for BRCA1/2 testing suggest increased utilization, but the effect on "appropriateness" was unclear. Model simulations suggest that annual screening, even with a highly sensitive test, will not reduce ovarian cancer mortality by more than 50 percent; frequent screening has a very low positive predictive value, even with a highly specific test. CONCLUSIONS: Although research remains promising, adaptation of genomic tests into clinical practice must await appropriately designed and powered studies in relevant clinical settings.

Cancer care quality measures: diagnosis and treatment of colorectal cancer.

OBJECTIVES: To identify measures that are currently available to assess the quality of care provided to patients with colorectal cancer (CRC), and to assess the extent to which these measures have been developed and tested. DATA SOURCES: Published and unpublished measures identified through a computerized search of English-language citations in MEDLINE (1966-January 2005), the Cochrane Database of Systematic Reviews, and the National Guideline Clearinghouse; through review of reference lists contained in seed articles, all included articles, and relevant review articles; and through searches of the grey literature (institutional or government reports, professional society documents, research papers, and other literature, in print or electronic format, not controlled by commercial publishing interests). Sources for grey literature included professional organization websites and the Internet. REVIEW METHODS: Measures were selected by reviewers according to standardized criteria relating to each question, and were then rated according to their importance and usability, scientific acceptability, and extent of testing; each domain was rated from 1 (poor) to 5 (ideal). RESULTS: We identified a number of well-developed and well-tested CRC-related quality-of-care measures, both general process-of-care measures (on a broader scale) and technical measures (pertaining to specific details of a procedure). At least some process measures are available for diagnostic imaging, staging, surgical therapy, adjuvant chemotherapy, adjuvant radiation therapy, and colonoscopic surveillance. Various technical measures were identified for quality of colonoscopy (e.g., cecal intubation rate, complications) and staging (adequate lymph node retrieval and evaluation). These technical measures were guideline-based and well developed, but less well tested, and the linkage between them and patient outcomes, although intuitive, was not always explicitly provided. For some elements of the care pathway, such as operative reports and chemotherapy reports, no technical measures were found. CONCLUSIONS: Some general process measures have a stronger evidence base than others. Those based on guidelines have the strongest evidence base; those derived from basic first principles supported by some research findings are relatively weaker, but are often sufficient for the task at hand. A consistent source of tension is the distinction between the clinically derived fine-tuning of the definition of a quality measure and the limitations of available data sources (which often do not contain sufficient information to act on such distinctions). Although some excellent technical measures were found, the overall development of technical measures seems less advanced than that of the general process measures.

Management of adnexal mass.

OBJECTIVES: To assess diagnostic strategies for distinguishing benign from malignant adnexal masses. DATA SOURCES: MEDLINE(R) and reference lists of recent reviews; discharge data from the Nationwide Inpatient Sample. REVIEW METHODS: The major diagnostic methods evaluated were bimanual pelvic examination, ultrasound (morphology and Doppler velocimetry), MRI, CT, FDG-PET, CA-125, and scoring systems that incorporated multiple clinical, laboratory, and radiologic findings. Meta-analysis using a random-effects model was used to estimate pooled sensitivity and specificity for discriminating benign from malignant. We reviewed evidence for followup strategies for masses considered benign, and for adverse outcomes of diagnostic surgery. We also reviewed published models of the natural history of ovarian cancer and compared the impact of assumptions about natural history on outcomes. RESULTS: The majority of studies did not describe whether patients presented with asymptomatic masses detected through screening or with symptoms. Prevalence of malignant masses in a U.S. postmenopausal screening population was approximately 0.1 percent, while benign masses were found in 0.8 to 1.8 percent of women. Pooled (a) sensitivity and (b) specificity were: bimanual exam (a) 0.45, (b) 0.90; ultrasound morphology scores (a) 0.86 to 0.91, (b) 0.68 to 0.83; Doppler resistive index (a) 0.72, (b) 0.90; pulsatility index (a) 0.80, (b) 0.73; maximum systolic velocity (a) 0.74, (b) 0.81; presence of vessels (a) 0.88, (b) 0.78; combined morphology and Doppler (a) 0.86, (b) 0.91; MRI (a) 0.91, (b) 0.88; CT (a) 0.90, (b) 0.75; FDG-PET (a) 0.67, (b) 0.79; and CA-125 (a) 0.78, (b) 0.78. Both sensitivity and specificity of CA-125 were better in postmenopausal than in premenopausal women. In modeled outcomes, combinations of imaging and CA-125 were both more sensitive and more specific than either alone. Performance of scoring systems in validation studies was consistently worse than in development studies; the highest demonstrated specificity observed was 0.91, with a concurrent sensitivity of 0.74. Evidence on followup strategies was sparse, although one large study provided good evidence for safely following unilocular cysts less than 10 cm in diameter. Overall complication rates in studies of surgically managed adnexal masses were low, but important clinical information was not reported. CONCLUSIONS: All diagnostic modalities showed trade-offs between sensitivity and specificity, but the available literature does not provide sufficient detail on relevant characteristics of study populations to allow confident estimation of the results of alternative diagnostic strategies. Although modeling studies may prove useful in evaluating diagnostic algorithms, further work is needed to explore the implications of uncertainty about the natural history of ovarian cancer.

Behavioral headache treatment: history, review of the empirical literature, and methodological critique.

Theoretical developments and burgeoning research on stress and illness in the mid-20th century yielded the foundations necessary to conceptualize headache as a psychophysiological disorder and eventually to develop and apply contemporary behavioral headache treatments. Over the past three decades, these behavioral headache treatments (relaxation training, biofeedback, cognitive-behavioral therapy, and stress-management training) have amassed a sizeable evidence base. Meta-analytic reviews of the literature consistently have shown behavioral interventions to yield 35% to 55% improvements in migraine and tension-type headache and that these outcomes are significantly superior to control conditions. The strength of the evidence has lead many professional practice organizations to recommend use of behavioral headache treatments alongside pharmacologic treatments for primary headache. The present overview was prepared as a companion article to and intended to provide a background for the Guidelines for Trials of Behavioral Treatments for Recurrent Headache also published within this journal supplement. This article begins with a synopsis of key historical developments leading to our current conceptualization of migraine and tension-type headache as psychophysiological disorders amenable to behavioral intervention. The evolution of the behavioral headache literature is discussed, exemplified by publication trends in the journal Headache. Leading empirically-based behavioral headache interventions are described, and meta-analytic reviews examining the migraine and tension-type headache literatures are summarized, compared, and contrasted. A critique of the methodological quality of the clinical trials literature is presented, highlighting the strengths and weaknesses in relation to recruitment and selection of patients, sample size and statistical power, the use of a credible control, and the reproducibility of the study interventions in clinical practice.

Methodological issues in systematic reviews of headache trials: adapting historical diagnostic classifications and outcome measures to present-day standards.

Recent efforts to make headache diagnostic classification and clinical trial methodology more consistent provide valuable advice to trialists generating new evidence on effectiveness of treatments for headache; however, interpreting older trials that do not conform to new standards remains problematic. Systematic reviewers seeking to utilize historical data can adapt currently recommended diagnostic classification and clinical trial methodological approaches to interpret all available data relative to current standards. In evaluating study populations, systematic reviewers can: (i) use available data to attempt to map study populations to diagnoses in the new International Classification of Headache Disorders; and (ii) stratify analyses based on the extent to which study populations are precisely specified. In evaluating outcome measures, systematic reviewers can: (i) summarize prevention studies using headache frequency, incorporating headache index in a stratified analysis if headache frequency is not available; (ii) summarize acute treatment studies using pain-free response as reported in directly measured headache improvement or headache severity outcomes; and (iii) avoid analysis of recurrence or relapse data not conforming to the sustained pain-free response definition.

Colorectal cancer screening and treatment: review of outcomes research.

BACKGROUND: Colorectal cancer is the second leading cause of cancer deaths in the United States each year. Screening is effective in reducing colorectal cancer mortality; however, compliance with screening is poor, and factors associated with its compliance are poorly understood. The outcomes of treatment of colorectal cancer (surgery, radiation therapy, and chemotherapy) may have profound effects on quality of life (QOL). Furthermore, colorectal cancer screening and treatment may be expensive, and the costs are important from a policy perspective. This review examines patient-centered outcomes research related to colorectal cancer screening and treatment and outlines the work that has been done in several areas, including patient preferences, QOL, and economic analysis. METHODS: The literature on the health outcomes associated with colorectal cancer screening and treatment was reviewed. A MEDLINE search of English language articles published from January 1, 1990 through February 2001, was conducted and was supplemented by a review of references of obtained articles. Criteria for study inclusion were identified a priori. A standardized data abstraction form was developed. Summary statistical analyses were performed on the results. RESULTS: Six hundred eighty-six articles were selected for review. In total, 530 articles were excluded because they either did not include patient-centered outcomes, were duplicate articles, or could not be obtained. There were 156 articles included in the analysis; 67 addressed screening, 18 examined surveillance of high-risk groups, 22 concerned treatment of local disease, 10 examined treatment of local and metastatic disease, and 19 considered treatment of metastatic disease only. One study examined end-of-life care. In 19 studies, the phase of care was unspecified. CONCLUSIONS: Standardized, disease-specific QOL instruments should be applied in clinical trials so that the results may be compared across different types of interventions. Valid and reliable methods that accurately capture patient preferences regarding screening and treatment should be developed.