Rose Relevo

Screening for hepatocellular carcinoma in chronic liver disease: a systematic review.

Hepatocellular carcinoma (HCC) incidence and mortality have increased internationally over the past 4 decades (1, 2), with localized tumors accounting for most of the increase (3). The rationale for screening is that imaging tests, such as ultrasonography, may identify patients with early-stage HCC (4), and several potential options exist for treating patients with early-stage HCC, including liver transplantation, radiofrequency ablation, and liver resection (5). Several professional societies currently recommend HCC screening using imaging studies and tumor markers, primarily in patients at higher risk for HCC due to chronic hepatitis B or cirrhosis (57). However, recommendations for HCC screening remain controversial, in part because of concerns over the quality and paucity of existing evidence and because concerns about overdiagnosis and patient harms have been raised in other cancer screening programs (812). We conducted a systematic review of the published literature to better understand the incremental benefits and harms of routine HCC screening compared with clinical diagnosis. Methods This manuscript is part of a larger report commissioned by the Veterans Health Administration (13). A protocol describing the review plan was posted to a public Web site before the study was initiated (14). The analytic framework that guided this review was developed in collaboration with a panel of technical experts and is provided in Figure 1 of Supplement 1. Supplement 1. Figures Data Sources and Searches We searched MEDLINE, PsycINFO, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from database inception to June 2013. We updated the MEDLINE, PsycINFO, and ClinicalTrials.gov searches in April 2014. The detailed search strategy is provided in Supplement 2. We obtained additional articles from systematic reviews, reference lists of pertinent studies, reviews, and editorials and by consulting technical advisors. Supplement 2. Search Strategy Study Selection Detailed inclusion and exclusion criteria are provided in Supplement 3. We included English-language, controlled clinical trials and observational studies that assessed the effects of screening on HCC-specific and all-cause mortality in adult populations. We used the term screening to include any surveillance or screening program in which specific tests (ultrasonography, computed tomography, magnetic resonance imaging, or -fetoprotein measurement) were performed explicitly to detect HCC in asymptomatic patients. Studies had to include a comparison group of patients who did not have routine screening. We excluded observational studies that did not consider important confounding factors, such as age, sex, and liver disease severity. Because we anticipated few clinical trials comparing screening versus no screening, we also included trials comparing frequencies of screening. We included studies of any population with chronic liver disease with or without cirrhosis but excluded studies of patients with prior HCC. We also searched for systematic reviews and primary studies that focused on potential harms of HCC screening. Supplement 3. Inclusion/Exclusion Criteria Seven investigators reviewed the titles and abstracts of citations identified from literature searches. If at least 1 reviewer indicated that a citation may be relevant, a second reviewer screened the citation for concordance. Two reviewers independently assessed the full-text articles for inclusion using the eligibility criteria in Supplement 3. Disagreements were resolved through consensus. Data Extraction and Quality Assessment From each study, we abstracted study design, objectives, setting, population characteristics (including sex, age, race or ethnicity, and liver disease cause and severity), patient eligibility and exclusion criteria, number of patients, years of enrollment, method and frequency of screening, adjusted and unadjusted mortality, and adverse events. A second author checked each entry for accuracy. Two reviewers independently assessed the quality of each trial by using a tool developed by the Cochrane Collaboration (15). We resolved disagreements through discussion. Each trial was given an overall summary assessment of low, high, or unclear risk of bias. Two reviewers graded the strength of evidence for outcomes by using published criteria that consider the consistency, coherence, directness, and applicability of a body of evidence as well as the internal validity of individual studies (16). We adapted existing tools to assess the quality of observational studies (1719). We do not report an overall summary assessment for observational studies because there are no validated criteria for doing so. Data Synthesis and Analysis We qualitatively synthesized the evidence on the benefits and harms of HCC screening. Clinical heterogeneity and the small number of trials precluded a meta-analysis of the findings. Role of the Funding Source The U.S. Department of Veterans Affairs Quality Enhancement Research Initiative supported this review but had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Results The electronic and manual searches yielded 13801 total citations, from which we identified 286 potentially relevant full-text articles. Twenty-two primary studies contained primary data relevant to the efficacy of HCC screening and met our inclusion criteria (Figure). Figure. Summary of evidence search and selection. RCT = randomized, controlled trial. Effects of Screening on Mortality Two trials and 18 observational studies provided very-low-strength evidence from which to draw conclusions about the mortality effects of HCC screening compared with no screening. The trials had substantial methodological flaws that threatened their internal validity, and their findings have limited applicability beyond the patient population with hepatitis B. The observational studies, most of which included patients with cirrhosis and hepatitis B, hepatitis C, or alcoholic liver disease, showed that screening detects patients with earlier-stage disease, who more frequently receive curative therapy. However, it is impossible to say whether the longer survival in patients with screen-detected disease was a true effect of screening or reflects lead- and length-time biases inherent to all observational studies, as well as selection biases that were common in many of the studies. Randomized, Controlled Trials Two community-based trials compared the effects on mortality of screening versus no screening (20, 21). Both were conducted in China in areas with high prevalence of HCC, and most participants had hepatitis B with or without cirrhosis (Table 1 of Supplement 4). One cluster randomized trial recruited screening group participants (n= 9757) from 1993 to 1995 and offered them serum -fetoprotein testing and ultrasonography every 6 months. Participants in the control group (n= 9443) were not made aware of the study nor actively followed. Death from HCC occurred less frequently in the screening group (83.2 vs. 131.5 per 100000 person-years; rate ratio, 0.63 [95% CI, 0.41 to 0.98]). Supplement 4. Tables However, the trial had several serious methodological limitations that gave it a high risk of bias (Table 2 of Supplement 4). One major concern is whether patients in both groups had the same risk for HCC. There is no information about randomization technique or allocation concealment and very little information about the baseline characteristics of the 2 groups, which is especially important in cluster randomized trials. Another concern is that weak methods used to ascertain the outcome measuredeath from HCCcould have introduced bias. If deaths were underreported in the control group, results could have been biased toward the null. On the other hand, if outcome adjudicators were not blinded, more deaths in the control group could have been misclassified as HCC-related, especially because the symptoms that define stage III HCC (cachexia, jaundice, and ascites) overlap substantially with symptoms of end-stage liver disease and no data were provided about liver disease severity in either group. Selective reporting and analysis of favorable outcomes were other concerns. Although the authors reported that vital status was available for all patients, overall mortality was not reported and there was no statistical adjustment for the effects of clustering. Finally, the study is less applicable to patients in the United States, in whom cirrhosis and thus HCC are usually secondary to hepatitis C, and the results probably have limited applicability to contemporary practice, in which the threshold for imaging for symptoms may be lower and the number of patients with incidentally discovered HCC on imaging is higher. The second trial used patient-level randomization stratified by township to assign patients with hepatitis B from 1989 to 1992 to the screening intervention (n= 3712), which consisted of serial -fetoprotein tests followed by ultrasonography for high -fetoprotein values, or the usual care group (n= 1869) (21). The population-based cancer registry used active case-finding techniques, and mortality was ascertained through the cancer registry and a population-based vital status registry. Cancer staging and cause of death were assessed by personnel blinded to intervention status. Only 28.8% of screening group participants completed all scheduled testing, but all participants completed at least 1 screening test. Fewer patients had stage III HCC in the screening group (19.8% vs. 41.0%; P value not reported). Hepatocellular carcinoma mortality was similar in both groups (1138 vs. 1114 per 100000 person-years; P= 0.86), as was all-cause mortality (1843 vs. 1788 per 100000 person-years; P value not s

The Effects of Pay-for-Performance Programs on Health, Health Care Use, and Processes of Care: A Systematic Review

Pay-for-performance (P4P) programs provide financial rewards or penalties to individual health care providers, groups of providers, or institutions according to their performance on measures of quality. In theory, if properly targeted and designed, P4P programs would help drive the behavior of providers and health care systems to improve the quality of care delivered, reduce unnecessary use of expensive health care services, and improve patient health outcomes (1). The idea is particularly relevant in the United States, where serious and broad gaps in health care quality have been tied in part to the long-standing fee-for-service system, which may provide incentives for service volume rather than quality (2). Despite their intuitive appeal, the promise of P4P programs in improving outcomes has not been empirically realized in past studies (36). The most recent systematic review examining the effectiveness of P4P programs in the United States found mixed evidence that P4P was associated with modest improvements in process-of-care outcomes but had little effect on patient outcomes (7). However, the literature has grown considerably since this review (which searched through 2012), and other countries, such as the United Kingdom, have gained considerable experience with large P4P initiatives that may provide information relevant to the United States. The purpose of the current review is to update and expand the prior systematic review in order to summarize current understanding of the effects of P4P programs targeted at physicians, groups, and institutions on process-of-care and patient outcomes in ambulatory and outpatient settings in and outside the United States. Methods This review was conducted according to a protocol that was developed using established reporting standards and posted to a public Web site (8) before the study was initiated (Appendix 1 of the Supplement). We used an analytic framework based on work by Damberg and colleagues (7) (Appendix 2 of the Supplement). Supplement. Supplemental Materials Data Sources and Searches We searched the following databases for studies that evaluated P4P programs: PubMed (1 June 2007 to 6 October 2016), MEDLINE, PsycINFO, CINAHL, Business Economics and Theory, Business Source Elite, Scopus, Faculty of 1000, and Gartner Research (1 June 2007 to 29 February 2016). We also performed targeted Google and PubMed searches aimed at well-known P4P demonstrations. We obtained additional articles from reference lists of pertinent studies, reviews, editorials, and expert recommendations. The search strategies are detailed in Appendix 3 of the Supplement. Study Selection Investigators reviewed titles and abstracts identified from literature searches. Two investigators independently assessed each potentially relevant article for inclusion using preestablished criteria (Appendices 4 and 5 of the Supplement). We included English-language studies of adult patients that evaluated ambulatory care or hospital-based P4P programs targeting health care providers at the individual, group, managerial, or institutional level and that reported any process-of-care, utilization, health, or intermediate health (clinical measures, such as a laboratory value or blood pressure) outcome. We included studies from other countries that have health systems similar to portions of the U.S. health care system. Studies examining only patient-targeted financial incentives, as well as payment models other than direct P4P, such as managed care, capitation, bundled payments, and accountable care organizations, were excluded. We also excluded studies that were not conducted in hospital or ambulatory settings, such as studies in long-term care facilities or nursing homes. We included clinical or cluster randomized, controlled trials (RCTs) of any size. We used a best-evidence approach, which is a method of specifying minimum inclusion criteria for nonrandomized studies (9). Inclusion of observational studies was limited to those with a comparison group, interrupted time series (ITS) studies, or large (n> 10000) cross-sectional or uncontrolled beforeafter studies. We excluded smaller uncontrolled studies because we had identified a large number of potentially relevant studies during a preliminary search and because the smaller uncontrolled studies were less likely to provide broadly applicable information given their limited scope and inherent methodological deficiencies. Data Extraction and Quality Assessment One investigator abstracted data elements from each included study, which were reviewed for accuracy by at least 1 additional investigator. We abstracted information on study design, sample size, country, program description, incentive structure (size and timing), target of the incentive, comparator, and outcomes (grouped as health, intermediate health, process-of-care, and utilization measures). Appendices 6 and 7 of the Supplement report these data. We classified studies according to 4 broad groupings: RCTs, ITS studies, controlled beforeafter studies, and uncontrolled beforeafter studies. Two investigators independently assessed study quality using the Newcastle-Ottawa Scale (10) for observational studies and the Cochrane Risk-of-Bias tool (11) for RCTs (Appendix 8 of the Supplement). Disagreements were resolved by consensus. Data Synthesis and Analysis We qualitatively synthesized the results of ambulatory and hospital studies separately and report process-of-care and patient outcomes for each setting. We synthesized results for specific P4P programs whenever possible. The review team evaluated the strength of the evidence according to guidance from the Agency for Healthcare Research and Quality (12). We did not perform meta-analysis because of the marked clinical heterogeneity across studies and the large number of observational studies. Role of the Funding Source The U.S. Department of Veterans Affairs Quality Enhancement Research Initiative supported this review but had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Results Search Results We reviewed 3418 titles and abstracts, identified 586 potentially eligible full-text articles, and ultimately included 69 studies (Figure). Fifty-eight studies were in ambulatory settings (Table 1 and Appendix 6 of the Supplement), 11 were in hospital settings (Table 2 and Appendix 7 of the Supplement), 52 reported process-of-care outcomes, and 38 assessed patient outcomes. The studies examined a wide range of P4P programs with varying incentive structures, goals, and contexts. The programs also differed in their purposes and targets, but the largest number of studies focused on managing chronic conditions in the primary care setting. Studies were conducted in a wide range of countries, including the United Kingdom (27 studies), the United States (17 studies), Taiwan (13 studies), France (3 studies), the Netherlands (3 studies), Canada (3 studies), Australia (1 study), South Korea (1 study), and Italy (1 study). There were 2 RCTs and 67 observational studies (10 ITS studies, 37 controlled beforeafter studies, and 20 large uncontrolled beforeafter studies). Figure. Literature flow diagram. P4P= pay-for-performance. * The current systematic review updates and expands on the review by Damberg and colleagues (7). Table 1. Findings From Studies of Ambulatory-Based Pay-for-Performance Programs Table 2. Findings From Studies of Hospital-Based Pay-for-Performance Programs A large number of studies evaluated different aspects of 2 large-scale national programs: the United Kingdoms Quality and Outcomes Framework (QOF) (24 studies) and Taiwans diabetes mellitus (DM-P4P) program (9 studies). The QOF is a nationwide program that began in 2004. It incentivizes primary care practices to achieve quality indicators that support clinical care and public health goals. Incentive payments can comprise up to approximately 30% of total income. Practices are aided by integrated health information technology that delivers automated prompts and decision support (36, 83). Taiwans DM-P4P program, implemented in 2001, allows physicians to voluntarily enroll in the program, and they in turn are given freedom to choose which patients to enroll (51). From 2001 to 2006, incentives targeted process-of-care outcomes, which were augmented with intermediate health outcome measures after 2006. Ambulatory CareBased Programs Process-of-Care Outcomes We found 9 studies from the United States evaluating the effects of P4P on process-of-care outcomes (14, 1620, 2224). Most of these studies examined outcomes over 4 years and had an average follow-up of 2.5 years; very few studies reported longer-term data. One RCT found that individual incentives increased appropriate response to high blood pressure but not use of guideline-recommended antihypertensive medication (14). Of the 6 studies that reported positive results (16, 18, 19, 2224), 1 did not have a control group (24), and selection bias was a serious concern in 3 others because of the way the control group was chosen (18, 22, 23). Two methodologically sound controlled beforeafter studies found no improvements in processes of care (17, 20). In general, there was evidence across 17 studies in the United Kingdom (2631, 33, 3638, 4147) that the QOF was associated with improvements in process-of-care measures, although the evidence was mixed among the more methodologically rigorous studies. There were 6 ITS studies. One showed substantial improvements in the prescription of long-acting reversible contraceptives (26), and another showed modest improvement in the initiation of diabetes medications (27). Another study found increased rates of depression screening and diagnoses, but antidepressant prescribing remained unchanged (31). In the other 3 studies, improvements had begun well bef

Finding evidence for comparing medical interventions: AHRQ and the Effective Health Care Program.

OBJECTIVE This article discusses search methodology to identify evidence for comparative effectiveness reviews (CERs) as practiced by the Effective Health Care program. STUDY DESIGN AND SETTING Review. RESULTS Search methods described attempt to overcome the bias inherent in the publication and distribution of clinical evidence. Bibliographic databases and search strategies are discussed with special emphasis on searching for observational studies and harms data. Other techniques described include the use of key articles, citation tracking, hand searching, and personal communications. Strategies for locating gray literature, such as clinical trial protocols and regulatory information, are described. Search reporting and other practical matters are also discussed. CONCLUSION Better reporting and further research on search strategies is needed to develop additional evidence-based recommendations.

So many options, where do we start? An overview of the care transitions literature.

BACKGROUND Health systems are faced with a large array of transitional care interventions and patient populations to whom such activities might apply. PURPOSE To summarize the health and utilization effects of transitional care interventions, and to identify common themes about intervention types, patient populations, or settings that modify these effects. DATA SOURCES PubMed and Cochrane Database of Systematic Reviews (January 1950-May 2014), reference lists, and technical advisors. STUDY SELECTION Systematic reviews of transitional care interventions that reported hospital readmission as an outcome. DATA EXTRACTION We extracted transitional care procedures, patient populations, settings, readmissions, and health outcomes. We identified commonalities and compiled a narrative synthesis of emerging themes. DATA SYNTHESIS Among 10 reviews of mixed patient populations, there was consistent evidence that enhanced discharge planning and hospital-at-home interventions reduced readmissions. Among 7 reviews in specific patient populations, transitional care interventions reduced readmission in patients with congestive heart failure and general medical populations. In general, interventions that reduced readmission addressed multiple aspects of the care transition, extended beyond hospital stay, and had the flexibility to accommodate individual patient needs. There was insufficient evidence on how caregiver involvement, transition to sites other than home, staffing, patient selection practices, or care settings modified intervention effects. CONCLUSIONS Successful interventions are comprehensive, extend beyond hospital stay, and have the flexibility to respond to individual patient needs. The strength of evidence should be considered low because of heterogeneity in the interventions studied, patient populations, clinical settings, and implementation strategies.

Implementation Processes and Pay for Performance in Healthcare: A Systematic Review

Over the last decade, various pay-for-performance (P4P) programs have been implemented to improve quality in health systems, including the VHA. P4P programs are complex, and their effects may vary by design, context, and other implementation processes. We conducted a systematic review and key informant (KI) interviews to better understand the implementation factors that modify the effectiveness of P4P. We searched PubMed, PsycINFO, and CINAHL through April 2014, and reviewed reference lists. We included trials and observational studies of P4P implementation. Two investigators abstracted data and assessed study quality. We interviewed P4P researchers to gain further insight. Among 1363 titles and abstracts, we selected 509 for full-text review, and included 41 primary studies. Of these 41 studies, 33 examined P4P programs in ambulatory settings, 7 targeted hospitals, and 1 study applied to nursing homes. Related to implementation, 13 studies examined program design, 8 examined implementation processes, 6 the outer setting, 18 the inner setting, and 5 provider characteristics. Results suggest the importance of considering underlying payment models and using statistically stringent methods of composite measure development, and ensuring that high-quality care will be maintained after incentive removal. We found no conclusive evidence that provider or practice characteristics relate to P4P effectiveness. Interviews with 14 KIs supported limited evidence that effective P4P program measures should be aligned with organizational goals, that incentive structures should be carefully considered, and that factors such as a strong infrastructure and public reporting may have a large influence. There is limited evidence from which to draw firm conclusions related to P4P implementation. Findings from studies and KI interviews suggest that P4P programs should undergo regular evaluation and should target areas of poor performance. Additionally, measures and incentives should align with organizational priorities, and programs should allow for changes over time in response to data and provider input.BackgroundOver the last decade, various pay-for-performance (P4P) programs have been implemented to improve quality in health systems, including the VHA. P4P programs are complex, and their effects may vary by design, context, and other implementation processes. We conducted a systematic review and key informant (KI) interviews to better understand the implementation factors that modify the effectiveness of P4P.MethodsWe searched PubMed, PsycINFO, and CINAHL through April 2014, and reviewed reference lists. We included trials and observational studies of P4P implementation. Two investigators abstracted data and assessed study quality. We interviewed P4P researchers to gain further insight.ResultsAmong 1363 titles and abstracts, we selected 509 for full-text review, and included 41 primary studies. Of these 41 studies, 33 examined P4P programs in ambulatory settings, 7 targeted hospitals, and 1 study applied to nursing homes. Related to implementation, 13 studies examined program design, 8 examined implementation processes, 6 the outer setting, 18 the inner setting, and 5 provider characteristics. Results suggest the importance of considering underlying payment models and using statistically stringent methods of composite measure development, and ensuring that high-quality care will be maintained after incentive removal. We found no conclusive evidence that provider or practice characteristics relate to P4P effectiveness. Interviews with 14 KIs supported limited evidence that effective P4P program measures should be aligned with organizational goals, that incentive structures should be carefully considered, and that factors such as a strong infrastructure and public reporting may have a large influence.DiscussionThere is limited evidence from which to draw firm conclusions related to P4P implementation. Findings from studies and KI interviews suggest that P4P programs should undergo regular evaluation and should target areas of poor performance. Additionally, measures and incentives should align with organizational priorities, and programs should allow for changes over time in response to data and provider input.

Twelve recommendations for integrating existing systematic reviews into new reviews: EPC guidance

OBJECTIVES As time and cost constraints in the conduct of systematic reviews increase, the need to consider the use of existing systematic reviews also increases. We developed guidance on the integration of systematic reviews into new reviews. METHODS A workgroup of methodologists from Evidence-based Practice Centers developed consensus-based recommendations. Discussions were informed by a literature scan and by interviews with organizations that conduct systematic reviews. RESULTS Twelve recommendations were developed addressing selecting reviews, assessing risk of bias, qualitative and quantitative synthesis, and summarizing and assessing body of evidence. CONCLUSIONS We provide preliminary guidance for an efficient and unbiased approach to integrating existing systematic reviews with primary studies in a new review.

Chapter 4: Effective Search Strategies for Systematic Reviews of Medical Tests

ABSTRACTThis article discusses techniques that are appropriate when developing search strategies for systematic reviews of medical tests. This includes general advice for searching for systematic reviews and issues specific to systematic reviews of medical tests. Diagnostic search filters are currently not sufficiently developed for use when searching for systematic reviews. Instead, authors should construct a highly sensitive search strategy that uses both controlled vocabulary and text words. A comprehensive search should include multiple databases and sources of grey literature. A list of subject-specific databases is included in this article.