Makalapua Motu'apuaka

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

Factors associated with mild traumatic brain injury in veterans and military personnel: a systematic review.

A history of mild traumatic brain injury (mTBI) is common among military members who served in Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND). We completed a systematic review to describe the cognitive, mental health, physical health, functional, social, and cost consequences of mTBI in Veteran and military personnel. Of 2668 reviewed abstracts, the 31 included studies provided very low strength evidence for the questions of interest. Cognitive, physical, and mental health symptoms were commonly reported by Veterans/military members with a history of mTBI. On average, these symptoms were not significantly more common in those with a history of mTBI than in those without, although a lack of significant mean differences does not preclude the possibility that some individuals could experience substantial effects related to mTBI history. Evidence of potential risk or protective factors moderating mTBI outcomes was unclear. Although the overall strength of evidence is very low due to methodological limitations of included studies, our findings are consistent with civilian studies. Appropriate re-integration services are needed to address common comorbid conditions, such as treatment for post-traumatic stress disorder, substance use disorders, headaches, and other difficulties that Veterans and members of the military may experience after deployment regardless of mTBI history. (JINS, 2014, 20, 1-13).

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.

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.

Fit for purpose: perspectives on rapid reviews from end-user interviews

BackgroundThere is increasing demand for rapid reviews and timely evidence synthesis. The goal of this project was to understand end-user perspectives on the utility and limitations of rapid products including evidence inventories, rapid responses, and rapid reviews.MethodsInterviews were conducted with key informants representing: guideline developers (n = 3), health care providers/health system organizations (n = 3), research funders (n = 1), and payers/health insurers (n = 1). We elicited perspectives on important characteristics of systematic reviews, acceptable methods to streamline reviews, and uses of rapid products. We analyzed content of the interview transcripts and identified themes and subthemes.ResultsKey informants identified the following as critical features of evidence reviews: (1) originating from a reliable source (i.e., conducted by experienced reviewers from an established research organization), (2) addressing clinically relevant questions, and (3) trusted relationship between the user and producer. Key informants expressed strong preference for the following review methods and characteristics: use of evidence tables, quality rating of studies, assessments of total evidence quality/strength, and use of summary tables for results and conclusions. Most acceptable trade-offs to increase efficiencies were limiting the literature search (e.g., limiting search dates or language) and performing single screening of citations and full texts for relevance. Key informants perceived rapid products (particularly evidence inventories and rapid responses) as useful interim products to inform downstream investigation (e.g., whether to proceed with a full review or guideline, direction for future research). Most key informants indicated that evidence analysis/synthesis and quality/strength of evidence assessments were important for decision-making. They reported that rapid reviews in particular were useful for guideline development on narrow topics, policy decisions when a quick turn-around is needed, decision-making for practicing clinicians in nuanced clinical settings, and decisions about coverage by payers/health insurers. Rapid reviews may be more relevant within specific clinical settings or health systems; whereas, broad/national guidelines often need a traditional systematic review.ConclusionsKey informants interviewed in our study indicated that evidence inventories, rapid responses, and rapid reviews have utility in specific decisions and contexts. They indicated that the credibility of the review producer, relevance of key questions, and close working relationship between the end-user and producer are critical for any rapid product. Our findings are limited by the sample size which may have been too small to reach saturation for the themes described.

Defining the benefits and challenges of stakeholder engagement in systematic reviews

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Comparative Effectiveness Research 2015:5 13–19 Comparative Effectiveness Research Dovepress