[Clinical outcomes, health-related quality of life, and cost-effectiveness of a 6-month community- based lifestyle program for adults at increased cardiovascular risk in lower Austria]. / Klinische Ergebnisse, gesundheitsbezogene Lebensqualität und Kosten-Effektivität eines 6-monatigen Programms zur Lebensstilmodifikation bei Personen mit erhöhtem kardioväskularen Risiko in Niederösterreich.

AIM: To investigate lifestyle intervention effects and cost-effectiveness of a structured 6-month exercise and nutrition program for individuals at high risk for cardiovascular disease. METHODS: Uncontrolled before and after study with assessments at baseline and six months. Adults without existing cardiovascular disease (CVD) but at increased CVD risk were eligible. The analysis was done by intention-to-treat (last-observation-carried-forward). Incremental cost-effectiveness analysis was performed. Main outcome measures were changes in cardiovascular risk-factors (blood pressure, weight, body-mass index, serum lipids, blood glucose, smoking cessation, and exercise) and health-related quality of life. RESULTS: A total of 356 adults (70.5% female; mean age 48.9 years; mean body mass index 32.4; drop-out 10.4%) participated. At 6 months significant favorable effects were observed in several cardiovascular risk outcomes, exercise behaviour and health related quality of life. At an average incremental cost per life year saved for the ITT-population of 22.474 the program can be considered cost-effective.

Comparative benefits and harms of second-generation antidepressants for treating major depressive disorder: an updated meta-analysis.

BACKGROUND: Second-generation antidepressants dominate the management of major depressive disorder (MDD), but evidence on the comparative benefits and harms of these agents is contradictory. PURPOSE: To compare the benefits and harms of second-generation antidepressants for treating MDD in adults. DATA SOURCES: English-language studies from PubMed, Embase, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to August 2011 and reference lists of pertinent review articles and gray literature. STUDY SELECTION: 2 independent reviewers identified randomized trials of at least 6 weeks' duration to evaluate efficacy and observational studies with at least 1000 participants to assess harm. DATA EXTRACTION: Reviewers abstracted data about study design and conduct, participants, and interventions and outcomes and rated study quality. A senior reviewer checked and confirmed extracted data and quality ratings. DATA SYNTHESIS: Meta-analyses and mixed-treatment comparisons of response to treatment and weighted mean differences were conducted on specific scales to rate depression. On the basis of 234 studies, no clinically relevant differences in efficacy or effectiveness were detected for the treatment of acute, continuation, and maintenance phases of MDD. No differences in efficacy were seen in patients with accompanying symptoms or in subgroups based on age, sex, ethnicity, or comorbid conditions. Individual drugs differed in onset of action, adverse events, and some measures of health-related quality of life. LIMITATIONS: Most trials were conducted in highly selected populations. Publication bias might affect the estimates of some comparisons. Mixed-treatment comparisons cannot conclusively exclude differences in efficacy. Evidence within subgroups was limited. CONCLUSION: Current evidence does not warrant recommending a particular second-generation antidepressant on the basis of differences in efficacy. Differences in onset of action and adverse events may be considered when choosing a medication. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

The impact of inclusion criteria in health economic assessments.

The debate surrounding whether the findings of efficacy studies are applicable to real-world treatment situations is ongoing. The issue of lack of applicability due to a lack of clinical heterogeneity could be addressed by employing less restrictive inclusion criteria. Given that health economic assessments based on cost-effectiveness measures are required by many governments and insurance providers, the impact of this choice may be far reaching. The objective of this article was to explore the use of a pilot study to examine the impact of inclusion criteria on cost-effectiveness results and clinical heterogeneity. A health economic assessment was conducted using QRISK®2 and simulation modelling of different population groups within the pilot study in Lower Austria. Patients were referred by their family physicians to 'Active Prevention' (Vorsorge Aktiv), a community-based lifestyle intervention focused on exercise and nutritional programmes. Cardiovascular risk factors were recorded before and after the intervention and translated to cardiovascular events. As expected, enforcing restrictive inclusion criteria produced stronger and more irrefutable computations - in the expected number of events, the number of deaths, the incremental cost per life-year saved and in the 95% confidence interval. These findings provide insight into the issues surrounding clinical heterogeneity and the need for restrictive inclusion criteria. This is not a full health economic assessment of the intervention. While inclusion criteria provide stronger results by limiting populations to those who would benefit the most, they must be enforced, both within and outside the clinical trial setting. Enforcement has costs, both monetary and arising from unintended negative consequences of enforcement mechanisms. All these considerations will affect the results realized by the payer organization. A pilot study can reveal whether an intervention may be cost effective 'enough' without restrictive inclusion criteria and can enable researchers to search for population subgroups in which the intervention remains cost effective. When the pilot study does not indicate sufficiently strong cost-effectiveness results, the broader trade-offs between clinical heterogeneity and the strength of the submission package to the reimbursement agency can be discussed by all parties. Payer concerns about the ability to generalize the results beyond the clinical trial can also be discussed at this time. Applicability then depends on the ability to enforce inclusion criteria similar to those used in the trials in the real world.

Outcomes and costs of community health worker interventions: a systematic review.

OBJECTIVES: We conducted a systematic review on outcomes and costs of community health worker (CHW) interventions. CHWs are increasingly expected to improve health outcomes cost-effectively for the underserved. RESEARCH DESIGN: We searched Medline, Cochrane Collaboration resources, and the Cumulative Index to Nursing and Allied Health Literature for studies conducted in the United States and published in English from 1980 through November 2008. We dually reviewed abstracts, full-text articles, data abstractions, quality ratings, and strength of evidence grades and resolved disagreements by consensus. RESULTS: We included 53 studies on outcomes of CHW interventions and 6 on cost or cost-effectiveness. For outcomes, limited evidence (5 studies) suggests that CHW interventions can improve participant knowledge compared with alternative approaches or no intervention. We found mixed evidence for participant behavior change (22 studies) and health outcomes (27 studies). Some studies suggested that CHW interventions can result in greater improvements in participant behavior and health outcomes compared with various alternatives, but other studies suggested that CHW interventions provide no statistically different benefits than alternatives. We found low or moderate strength of evidence suggesting that CHWs can increase appropriate health care utilization for some interventions (30 studies). Six studies with economic information yielded insufficient data to evaluate the cost-effectiveness of CHW interventions relative to other interventions. CONCLUSIONS: CHWs can improve outcomes for underserved populations for some health conditions. The effectiveness of CHWs in many health care areas requires further research that addresses the methodologic limitations of prior studies and that contributes to translating research into practice.

The effect of study sponsorship on a systematically evaluated body of evidence of head-to-head trials was modest: secondary analysis of a systematic review.

OBJECTIVE: The objective of this study was to determine the effect of industry bias in a systematically reviewed body of evidence of head-to-head trials. STUDY DESIGN AND SETTING: We limited our analysis to published head-to-head randomized controlled trials of selective serotonin reuptake inhibitors (SSRIs) identified in a comparative effectiveness review. Two reviewers independently determined the status of funding for each trial. We classified drugs into one of two groups: (1) drugs associated with the funding source and (2) drugs not associated with the funding source. To determine the effect of any underlying industry bias, we conducted relative-benefit meta-analyses comparing the response rates of drugs when associated with the funding source with response rates of the same drugs when not associated with the funding source. RESULTS: Thirteen out of 20 studies (65%) numerically favored drugs associated with the funding source over drugs used as controls. The pooled response rates of SSRIs, when associated with the funding source, are significantly greater than those of the same SSRIs when not associated with the sponsor (relative benefit=1.07; 95% confidence interval=1.02-1.11). The difference, however, is likely to be not of clinical importance. CONCLUSIONS: The effect of industry bias in comparative effectiveness reviews might play a lesser role than in systematic reviews of placebo-controlled trials.

A systematic review of outcomes of maternal weight gain according to the Institute of Medicine recommendations: birthweight, fetal growth, and postpartum weight retention.

This systematic review focuses on outcomes of gestational weight gain, specifically birthweight, fetal growth, and postpartum weight retention, for singleton pregnancies with respect to the 1990 Institute of Medicine weight gain recommendations. A total of 35 studies met the inclusion criteria and were reviewed. There was strong evidence to support associations between excessive gestational weight gain and increased birthweight and fetal growth (large for gestational age) as well as inadequate gestational weight gain and decreased birthweight and fetal growth (small for gestational age). There was moderate evidence to support the association between excessive gestational weight gain and postpartum weight retention. Clear clinical recommendations based on this review are challenging because of several limitations in the literature. Improvements in future research include the use of consistent definitions of gestational weight gain and outcomes of interest, assessment of confounders, and better collection of weight and weight gain data.

Inadequate reporting of trials compromises the applicability of systematic reviews.

BACKGROUND: Uncertainty about the applicability of controlled trial findings is an increasing concern for clinicians and policy decision makers. This study aimed to determine whether information reported in studies included in systematic reviews was adequate enough to assess their applicability. METHODS: We used the databases of four recently conducted systematic reviews on the comparative efficacy and safety of second-generation antidepressants, inhaled corticosteroids, Alzheimer's drugs, and targeted immune modulators. We developed and pilot-tested a questionnaire to assess the adequacy of reporting with respect to seven previously validated criteria of study design that distinguish explanatory from pragmatic studies. For each of the 137 included studies, two reviewers independently assessed the adequacy of reporting. RESULTS: Overall, only 12 percent of the included studies provided sufficient information to reliably distinguish explanatory from pragmatic studies. The areas with the greatest lack of reporting were the setting of the study, methods of adverse event assessment, and sample size considerations to determine a minimally important difference from a patient perspective. CONCLUSIONS: Substantial shortcomings in reporting exist in aspects of study design important to determine whether a study is applicable to specific populations of interest.

Outcomes of community health worker interventions.

OBJECTIVES: To conduct a systematic review of the evidence on characteristics of community health workers (CHWs) and CHW interventions, outcomes of such interventions, costs and cost-effectiveness of CHW interventions, and characteristics of CHW training. DATA SOURCES: We searched MEDLINE, Cochrane Collaboration resources, and the Cumulative Index to Nursing and Allied Health Literature for studies published in English from 1980 through November 2008. REVIEW METHODS: We used standard Evidence-based Practice Center methods of dual review of abstracts, full-text articles, abstractions, quality ratings, and strength of evidence grades. We resolved disagreements by consensus. RESULTS: We included 53 studies on characteristics and outcomes of CHW interventions, 6 on cost-effectiveness, and 9 on training. CHWs interacted with participants in a broad array of locations, using a spectrum of materials at varying levels of intensity. We classified 8 studies as low intensity, 18 as moderate intensity, and 27 as high intensity, based on the type and duration of interaction. Regarding outcomes, limited evidence (five studies) suggests that CHW interventions can improve participant knowledge when compared with alternative approaches such as no intervention, media, mail, or usual care plus pamphlets. We found mixed evidence for CHW effectiveness on participant behavior change (22 studies) and health outcomes (27 studies): some studies suggested that CHW interventions can result in greater improvements in participant behavior and health outcomes when compared with various alternatives, but other studies suggested that CHW interventions provide no statistically different benefits than alternatives. Low or moderate strength of evidence suggests that CHWs can increase appropriate health care utilization for some interventions (30 studies). The literature showed mixed results of effectiveness when analyzed by clinical context: CHW interventions had the greatest effectiveness relative to alternatives for some disease prevention, asthma management, cervical cancer screening, and mammography screening outcomes. CHW interventions were not significantly different from alternatives for clinical breast examination, breast self-examination, colorectal cancer screening, chronic disease management, or most maternal and child health interventions. Six studies with economic and cost information yielded insufficient data to evaluate the cost-effectiveness of CHW interventions relative to other community health interventions. Limited evidence described characteristics of CHW training; no studies examined the impact of CHW training on health outcomes. CONCLUSIONS: CHWs can serve as a means of improving outcomes for underserved populations for some health conditions. The effectiveness of CHWs in numerous areas requires further research that addresses the methodological limitations of prior studies and that contributes to translating research into practice.

Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians.

BACKGROUND: Second-generation antidepressants dominate the management of major depressive disorder, dysthymia, and subsyndromal depression. Evidence on the comparative benefits and harms is still accruing. PURPOSE: To compare the benefits and harms of second-generation antidepressants (bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine) for the treatment of depressive disorders in adults. DATA SOURCES: MEDLINE, EMBASE, PsychLit, Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts from 1980 to April 2007, limited to English-language articles. Reference lists of pertinent review articles were manually searched and the Center for Drug Evaluation and Research database was explored to identify unpublished research. STUDY SELECTION: Abstracts and full-text articles were independently reviewed by 2 persons. Six previous good- or fair-quality systematic reviews or meta-analyses were included, as were 155 good- or fair-quality double-blind, placebo-controlled, or head-to-head randomized, controlled trials of at least 6 weeks' duration. For harms, 35 observational studies with at least 100 participants and follow-up of at least 12 weeks were also included. DATA EXTRACTION: Using a standard protocol, investigators abstracted data on study design and quality-related details, funding, settings, patients, and outcomes. DATA SYNTHESIS: If data were sufficient, meta-analyses of head-to-head trials were conducted to determine the relative benefit of response to treatment and the weighted mean differences on specific depression rating scales. If sufficient evidence was not available, adjusted indirect comparisons were conducted by using meta-regressions and network meta-analyses. Second-generation antidepressants did not substantially differ in efficacy or effectiveness for the treatment of major depressive disorder on the basis of 203 studies; however, the incidence of specific adverse events and the onset of action differed. The evidence is insufficient to draw conclusions about the comparative efficacy, effectiveness, or harms of these agents for the treatment of dysthymia and subsyndromal depression. LIMITATION: Adjusted indirect comparisons have methodological limitations and cannot conclusively rule out differences in efficacy. CONCLUSION: Current evidence does not warrant the choice of one second-generation antidepressant over another on the basis of differences in efficacy and effectiveness. Other differences with respect to onset of action and adverse events may be relevant for the choice of a medication.

Meta-analysis of major depressive disorder relapse and recurrence with second-generation antidepressants.

OBJECTIVE: This meta-analysis reviewed data on the efficacy and effectiveness of second-generation antidepressants for preventing major depression relapse and recurrence during continuation and maintenance phases of treatment, respectively. METHODS: MEDLINE, EMBASE, and PsycINFO, the Cochrane Library, and International Pharmaceutical Abstracts were searched for the period of January 1980 through April 2007 for reviews, randomized controlled trials, meta-analyses, and observational studies on the topic. Two persons independently reviewed abstracts and full-text articles using a structured data abstraction form to ensure consistency in appraisal and data extraction. RESULTS: Four comparative trials and 23 placebo-controlled trials that addressed relapse or recurrence prevention were included. Results of comparative trials have not demonstrated statistically significant differences between duloxetine and paroxetine, fluoxetine and sertraline, fluvoxamine and sertraline, and trazodone and venlafaxine. Pooled data for the class of second-generation antidepressants compared with placebo suggested a relatively large effect size that persists over time. For preventing both relapse and recurrence, the number of patients needed to treat is five (95% confidence interval of 4 to 6). Differences in the length of open-label treatment before randomization, drug type, and trial duration did not affect pooled estimates of relapse rates. Across all trials, 7% of patients randomly assigned to receive active treatment and 5% of patients randomly assigned to receive a placebo discontinued treatment because of adverse events. CONCLUSIONS: This review demonstrates the overall benefits of continuation- and maintenance-phase treatment of major depression with second-generation antidepressants and emphasizes the need for additional studies of comparative differences among drugs.

Comparative risk for harms of second-generation antidepressants : a systematic review and meta-analysis.

BACKGROUND: Evidence indicates that only minor differences in efficacy exist among second-generation antidepressants for the treatment of major depressive disorder (MDD). However, a comprehensive assessment of both benefits and harms is crucial to evaluate the net benefit. OBJECTIVE: To review systematically the comparative harms of second-generation antidepressants for the treatment of MDD in adults by including both experimental and observational evidence. DATA SOURCES: We searched MEDLINE, EMBASE, PsychLit, The Cochrane Library and the International Pharmaceutical Abstracts from 1980 to April 2007. We manually searched reference lists of pertinent review articles and explored the Center for Drug Evaluation and Research database to identify unpublished research. STUDY SELECTION: Eligible study designs were trials and observational studies comparing one drug of interest with another. DATA EXTRACTION: Two persons independently reviewed abstracts and full-text articles. One investigator extracted relevant data. A senior reviewer checked data for completeness and accuracy. DATA SYNTHESIS: We included 104 experimental and observational studies. If data were sufficient, we conducted meta-analyses of randomized controlled trials on the relative risk of specific adverse events. Findings indicate that the spectrum of adverse events is similar. The frequency of specific adverse events, however, differed across drugs. Venlafaxine was associated with a significantly higher rate of nausea and vomiting than selective serotonin reuptake inhibitors. Compared with other drugs, paroxetine frequently led to more sexual adverse effects and bupropion to fewer such effects; mirtazapine and paroxetine was associated with more weight gain and sertraline with a higher rate of diarrhoea. Overall, however, these differences did not lead to different discontinuation rates. The evidence is insufficient to draw conclusions about rare but severe adverse events. CONCLUSIONS: Adverse event profiles are similar among second-generation antidepressants. However, different frequencies of specific adverse events might be clinically relevant and influence the choice of a treatment.

Outcomes of maternal weight gain.

OBJECTIVES: The RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center (RTI-UNC EPC) systematically reviewed evidence on outcomes of gestational weight gain and their confounders and effect modifiers, outcomes of weight gain within or outside the 1990 Institute of Medicine (IOM) guidelines, risks and benefits of weight gain recommendations, and anthropometric measures of weight gain. DATA SOURCES: We searched MEDLINE Cochrane Collaboration resources, Cumulative Index to Nursing & Allied Health Literature, and Embase. REVIEW METHODS: We included studies published in English from 1990 through October 2007. We excluded studies with low sample size (based on study design: case series <100 subjects and cohorts <40 subjects). RESULTS: Overall, strong evidence supported an association between gestational weight gains and the following outcomes: preterm birth, total birthweight, low birthweight (<2,500 g), macrosomia, large-for-gestational-age (LGA) infants, and small-for-gestational-age (SGA) infants; moderate evidence supported an association for cesarean delivery and intermediate-term weight retention (3 months to 3 years postpartum). The studies reviewed provided strong evidence for the independent association of pregravid weight status and outcomes, moderate evidence for age and parity, and weak evidence for race. Regarding outcomes of weight gain within or outside 1990 IOM guidelines, moderate to strong evidence suggests an association between weight gain below IOM recommendations and preterm birth, low birthweight, SGA birthweights, and failure to initiate breastfeeding, and strong evidence for the association between weight gain above IOM recommendations and high birthweight, macrosomia, and LGA birthweights. Moderate evidence supports an association between weight gain above IOM guidelines and cesarean delivery and postpartum weight retention in the short, intermediate, and long term. Included research is inadequate for objective assessments of the range of harms and benefits of providing all women, irrespective of age, race or ethnicity, or pregravid body mass index (BMI), with the same recommendation for weight gain in pregnancy. CONCLUSIONS: Gestational weight gain is associated with some infant and maternal outcomes. One weight gain recommendation for all women is not supported by the evidence identified in this review. To understand fully the impact of gestational weight gain on short- and long-term outcomes for women and their offspring will require that researchers use consistent definitions of weight gain during pregnancy, better address confounders in their analyses, improve study designs and statistical models, and conduct studies with longer followup.

Treating the physical symptoms of depression with second-generation antidepressants: a systematic review and metaanalysis.

BACKGROUND: Approximately two-thirds of patients with depression experience physical pain symptoms. Coexisting pain complicates the treatment of depression and is associated with worse depression outcomes. OBJECTIVE: The authors reviewed the effect of newer antidepressants on pain in patients with depression. METHOD: The authors searched systematically for trials of second-generation antidepressants that enrolled depression patients and reported pain outcomes, pooling changes on the pain visual-analog scale (VAS), using random-effects models. RESULTS: Eight trials were eligible. Pooled analysis of head-to-head trials showed no difference in VAS between duloxetine and paroxetine. Both drugs were superior to placebo. CONCLUSION: The authors found insufficient evidence to support the choice of one second-generation antidepressant over another in patients with pain accompanying depression.

Systematic review: comparative effectiveness and harms of disease-modifying medications for rheumatoid arthritis.

BACKGROUND: The comparative effectiveness of rheumatoid arthritis therapies is uncertain. PURPOSE: To compare the benefits and harms of disease-modifying antirheumatic drugs (DMARDs) for adults with rheumatoid arthritis. DATA SOURCES: Records limited to the English language and studies of adults were identified by using MEDLINE, EMBASE, The Cochrane Library, and International Pharmaceutical Abstracts from 1980 to September 2007. STUDY SELECTION: Two persons independently selected relevant head-to-head trials and prospective cohort studies with at least 100 participants and 12-week follow-up and relevant good- or fair-quality meta-analyses that compared benefits or harms of 11 drug therapies. For harms, they included retrospective cohort studies. DATA EXTRACTION: Information on study design, interventions, outcomes, and quality were extracted according to a standard protocol. DATA SYNTHESIS: Head-to-head trials (n = 23), mostly examining synthetic DMARDs, showed no clinically important differences in efficacy among synthetic DMARDs (limited to methotrexate, leflunomide, and sulfasalazine) or among anti-tumor necrosis factor drugs (adalimumab, etanercept, and infliximab). Monotherapy with anti-tumor necrosis factor drugs resulted in better radiographic outcomes than did methotrexate but no important differences in clinical outcomes (for example, 20%, 50%, or 70% improvement according to American College of Rheumatology response criteria). Various combinations of biological DMARDs plus methotrexate improved clinical response rates and functional outcomes more than monotherapy with either methotrexate or biological DMARDs. In patients whose monotherapy failed, combination therapy with synthetic DMARDs improved response rates. Numbers and types of short-term adverse events were similar for biological and synthetic DMARDs. The evidence was insufficient to draw conclusions about differences for rare but serious adverse events for biological DMARDs. LIMITATION: Most studies were short-term efficacy trials conducted in selected populations with few comorbid conditions. CONCLUSION: Limited available comparative evidence does not support one monotherapy over another for adults with rheumatoid arthritis. Although combination therapy is more effective for patients whose monotherapy fails, the evidence is insufficient to draw firm conclusions about whether one combination or treatment strategy is better than another or is the best treatment for early rheumatoid arthritis.

Biologics for the treatment of juvenile idiopathic arthritis: a systematic review and critical analysis of the evidence.

Biologics are an important therapeutic option for treating patients with juvenile idiopathic arthritis (JIA). In adults, they are associated with rare but severe adverse events such as serious infections and malignancies. We reviewed systematically the evidence on the efficacy and safety of biologics for the treatment of JIA. We searched electronic databases up to August 2006. We limited evidence to prospective studies for efficacy but included retrospective observational evidence for safety. Outcomes of interest were clinical response, radiographic progression, quality of life, and adverse events. One randomized controlled trial (RCT) and 11 uncontrolled prospective studies provided data on efficacy; three additional studies assessed safety. The only RCT and six uncontrolled trials support the general efficacy of etanercept for the treatment of JIA. Internal and external validity of these studies are limited. The evidence on other biologic agents such as adalimumab, abatacept, anakinra, infliximab, rituximab, and tocilizumab is sparse or entirely missing. Because of the lack of sound long-term safety data, evidence is insufficient to draw firm conclusions about the balance of risks and benefits of any biologic agent for the treatment of JIA. Clinicians have to be aware of the lack of evidence supporting a long-term net benefit when considering biologics for patients with JIA.

Management of uterine fibroids: an update of the evidence.

OBJECTIVES: The RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center (RTI-UNC EPC) systematically updated evidence on the management of uterine fibroids, specifically incidence and prevalence of fibroids, treatment outcomes, comparisons of treatment, modifiers of outcomes, and costs. DATA SOURCES: We searched MEDLINE(R), Cochrane Collaboration resources, and Embase. REVIEW METHODS: We included studies published in English from February 2000 through August 2006. We excluded studies with low sample size (based on study design, cases series < 100 and cohorts < 40) or lack of relevance to uterine fibroids. Of 107 included studies, 3 were good quality, 56 fair, and 48 poor. RESULTS: The cumulative incidence by age 50 is 70 percent to 80 percent; black women are more likely to get fibroids at younger ages. Appearance of new fibroids and growth of existing fibroids after treatment are poorly studied. Trials of preoperative medical management indicate that treatment reduces fibroid volume but do not provide sufficient evidence of improvement in important operative outcomes. When women are treated for reasons other than symptom relief, such as when pregnancy is desired, weak evidence supports treating submucous fibroids via hysteroscopy. No well-conducted trials in U.S. populations directly compared treatment options, including the option of expectant management, or followed women to determine whether the intervention met their treatment objectives. Common procedures such as hysterectomy and myomectomy, including choice among types of myomectomy, still cannot be meaningfully compared. Studies comparing uterine artery embolization (UAE) with other procedures reported procedure time and length of stay favoring UAE, but inconsistency of the direction of effect for complications and absence of key information on longer-term outcomes suggest that this evidence base is inadequate to comment on the relative risks and benefits of UAE versus hysterectomy or myomectomy. Costs of fibroid treatment, despite shorter average lengths of stay, are rising. CONCLUSIONS: The dearth of high-quality evidence supporting the effectiveness of most interventions for uterine fibroids is remarkable, given how common this problem is. The current state of the literature does not permit definitive conclusions about benefit, harm, or relative costs to help guide women's choices. Significant research gaps include well-conducted trials in U.S. populations that directly compare interventions on short- and, especially, long-term outcomes, studies on therapeutics for medical management, and information on treatment decisions for women who desire a pregnancy.

The comparative efficacy and safety of biologics for the treatment of rheumatoid arthritis: a systematic review and metaanalysis.

OBJECTIVE: Biologics are an important therapeutic option for treating patients with rheumatoid arthritis (RA). However, they are associated with rare but severe adverse events such as serious infections, lymphoma, or chronic heart failure. In addition, dosing regimens and routes of administration differ substantially among biologics. In a systematic review, we assessed the comparative efficacy and safety of biologic agents for RA. METHODS: We searched electronic databases up to May 2006. We limited evidence to controlled trials for efficacy but included observational evidence for safety. Outcomes of interest were clinical response, radiographic progression, and quality of life. Given the paucity of head-to-head evidence, we conducted adjusted, indirect comparisons of placebo-controlled trials. RESULTS: Twenty-six controlled trials provided efficacy data; 18 additional studies assessed safety. The only evidence directly comparing 2 biologic agents was a nonrandomized, open-label trial that found no differences in effectiveness and safety between etanercept and infliximab. Adjusted indirect comparisons indicate no significant differences in efficacy between anti-tumor necrosis factor (TNF) drugs. However, anti-TNF drugs appear to be more efficacious than anakinra, although not all comparisons reached statistical significance. Because of the lack of sound longterm safety data, evidence is insufficient to draw firm conclusions about the comparative safety of biologics. CONCLUSION: Anti-TNF drugs appear to be more efficacious than anakinra but do not differ significantly among each other. Clinical considerations such as comorbidities, route of administration, dosing regimens, and specific side effect profiles may guide the choice of an anti-TNF drug.

The economic impact of uterine fibroids in the United States: a summary of published estimates.

OBJECTIVE: To present a summary of published estimates of the economic burden of uterine fibroids in the United States and identify areas for additional research. METHODS: A search of three electronic databases, MEDLINE, EMBASE, and Current Contents, was conducted, along with a review of information on the Internet and abstraction of economic data. RESULTS: Only 10 papers and 1 Internet document met our inclusion criteria and were used to abstract data. Cost estimates for surgically invasive treatments of uterine fibroids included hysterectomy (USD 5,012-7,934), myomectomy (USD 5,425-11,839), and uterine artery embolization (UAE) (USD 5,425-7,645) (2004 USD). One cost-effectiveness study estimated lower costs and higher quality-adjusted life years with UAE compared with hysterectomy. A second study estimated potential savings of USD 4.2 million in hospital charges in the United States if higher rates of vaginal (vs. abdominal) hysterectomy would be achieved after pretreatment with gonadotropin hormone-releasing hormone (GnRH) agonists compared to without pretreatment with GnRH agonists (80% vs. 13%). There were no estimates of the total direct and indirect economic burden of uterine fibroids. Neither estimates of the costs for the ambulatory care of fibroids nor studies estimating the indirect costs associated with the management of fibroids and their symptoms were found. CONCLUSIONS: This summary of published U.S. economic estimates shows that despite the high prevalence of fibroids and their impact on clinical practice and women's lives, there is very little published information on their economic impact apart from data showing standard treatments for uterine fibroids are invasive and expensive. Reduction in the need for and cost of invasive procedures by the increased usage of noninvasive treatments could potentially achieve significant national cost savings, but further clinical and economic studies are needed.

An economic review of compliance with medication therapy in the treatment of schizophrenia.

OBJECTIVES: The authors examined published economic evaluations of schizophrenia and antipsychotic therapies to determine the role of compliance with medication therapy in the economic cost of schizophrenia. METHODS: The authors reviewed studies published from 1995 to 2002 that evaluated compliance with treatment for schizophrenia. Literature searches were conducted for that period by using MEDLINE, EMBASE, and Current Contents. The primary search terms were "schizophrenia," "compliance," "relapse," and "economic costs." RESULTS AND CONCLUSIONS: A definitive relationship exists between compliance and the economic costs of schizophrenia. Lower rates of compliance lead to higher costs of treating schizophrenia. However, the full implications are difficult to surmise from the literature because of inadequacies in the reporting of compliance rates and outcomes of treatment over time. The authors suggest collection of data on longer-term clinical outcomes as a means to improve future economic evaluations of schizophrenia treatments.