Renee F Wilson

Systematic Review: Comparative Effectiveness and Safety of Oral Medications for Type 2 Diabetes Mellitus

The prevalence and morbidity associated with type 2 diabetes mellitus continue to increase in the United States and elsewhere (1, 2). Several studies of the treatment of type 2 diabetes suggest that improved glycemic control reduces microvascular risks (37). In contrast, the effects of treatment on macrovascular risk are more controversial (3, 4, 8, 9), and the comparative effects of oral diabetes agents on clinical outcomes are even less certain. As newer oral agents, such as thiazolidinediones and meglitinides, are increasingly marketed, clinicians and patients must decide whether they prefer these generally more costly medications over older agents, such as sulfonylureas and metformin. Systematic reviews and meta-analyses of oral diabetes agents have attempted to fill this gap (1019), but few have compared all agents with one another (18, 19). The few investigations that have compared all oral agents focused narrowly on individual outcomes, such as hemoglobin A1c level (18) or serum lipid levels (19). No systematic review has summarized all available head-to-head comparisons with regard to the full range of intermediate end points (including hemoglobin A1c level, lipid levels, and body weight) and other clinically important outcomes, such as adverse effects and macrovascular risks. Therefore, the Agency for Healthcare Research and Quality commissioned a systematic review to summarize the comparative benefits and harms of oral agents that are used to treat type 2 diabetes. Methods Data Sources and Selection We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to January 2006 for original articles. We also searched these databases until November 2005 for systematic reviews. We reviewed reference lists of related reviews and original data articles, hand-searched recent issues of 15 medical journals, invited experts to provide additional citations, reviewed selected medications from the U.S. Food and Drug Administration (FDA) Web site, and reviewed unpublished data from several pharmaceutical companies and public registries of clinical trials. Our search strategy for the bibliographic databases combined terms for type 2 diabetes and oral diabetes agents and was limited to English-language articles and studies in adults. The search for systematic reviews was similar but included terms for study design as well. We selected studies that included original data on adults with type 2 diabetes and assessed benefits or harms of FDA-approved oral diabetes agents that were available in the United States as of January 2006. To facilitate head-to-head comparisons of drug classes, we included drugs not on the U.S. market if members of their class were in use and had not been banned (voglibose, gliclazide, and glibenclamide). We also included studies of combinations of therapies that are commonly used, such as combinations of metformin, second-generation sulfonylureas, and thiazolidinediones. We excluded studies that evaluated combinations of 3 oral diabetes agents, and we also excluded first-generation sulfonylureas, because few clinicians prescribe these medications. We sought studies that reported on major clinical outcomes (for example, all-cause mortality, cardiovascular morbidity and mortality, and microvascular outcomes) or any of the following intermediate end points or adverse events: hemoglobin A1c level, body weight, systolic and diastolic blood pressure, high-density lipoprotein (HDL) cholesterol level, low-density lipoprotein (LDL) cholesterol level, triglyceride level, hypoglycemia, gastrointestinal problems, congestive heart failure, edema or hypervolemia, lactic acidosis, elevated aminotransferase levels, liver failure, anemia, leukopenia, thrombocytopenia, allergic reactions requiring hospitalization or causing death, and other serious adverse events. For intermediate end points, we included only randomized, controlled trials, which were abundant. For major clinical end points and adverse events, we considered observational studies as well as trials, because fewer randomized trials assessed these end points. We excluded studies that followed patients for less than 3 months (the conventional threshold for determining effects on hemoglobin A1c) or had fewer than 40 patients. Figure 1 shows the search and selection process, and the full technical report (available at effectivehealthcare.ahrq.gov/repFiles/OralFullReport.pdf) provides a more detailed description of the study methods (20). Figure 1. Study flow diagram. Data Extraction and Quality Assessment One investigator used standardized forms to abstract data about study samples, interventions, designs, and outcomes, and a second investigator confirmed the abstracted data. Two investigators independently applied the Jadad scale to assess some aspects of the quality of randomized trials (21). We considered observational studies and nonrandomized trials to provide weaker evidence than randomized trials, and we did not use a standardized scoring system to assess their quality (22). We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) working group definitions to grade the overall strength of the evidence as high, moderate, low, very low, or insufficient (23). Data Synthesis and Analysis We first performed a qualitative synthesis based on scientific rigor and type of end point. In general, we described the UKPDS (United Kingdom Prospective Diabetes Study) separately, because this large randomized, controlled trial differed from other trials in design, end points, and duration. When data were sufficient (that is, obtained from at least 2 randomized, controlled trials) and studies were relatively homogeneous in sample characteristics, study duration, and drug dose, we conducted meta-analyses for the following intermediate outcomes and adverse effects: hemoglobin A1c level, weight, systolic blood pressure, LDL cholesterol level, HDL cholesterol level, triglyceride level, and hypoglycemia. For trials with more than 1 dosing group, we chose the dose that was most comparable with other trials and most clinically relevant. We combined drugs into drug classes only when similar results were found across individual drugs. We could not perform formal meta-analyses for microvascular or macrovascular outcomes, mortality, and adverse events other than hypoglycemia because of methodological diversity among the trials or insufficient numbers of trials. We used a random-effects model with the DerSimonian and Laird formula to derive pooled estimates (posttreatment weighted mean differences for intermediate outcomes and posttreatment absolute risk differences for adverse events) (24). We tested for heterogeneity among the trials by using a chi-square test with set to 0.10 or less and an I 2 statistic greater than 50% (25). If heterogeneity was found, we conducted meta-regression analyses by using study-level characteristics of double-blinding, study duration, and dose ratio (calculated as the dose given in the study divided by the maximum approved dose of drug). The full report contains data on indirect comparisons, in which 2 interventions are compared through their relative effect against a common comparator (20). We tested for publication bias by using the tests of Begg and Mazumdar (26) and Egger and colleagues (27). All statistical analyses were done by using STATA Intercooled, version 8.0 (Stata, College Station, Texas). Role of the Funding Source The Agency for Healthcare Research and Quality suggested the initial questions and provided copyright release for this manuscript but did not participate in the literature search, data analysis, or interpretation of the results. Results Comparative Effectiveness of Oral Diabetes Agents in Reducing the Risk for Microvascular and Macrovascular Outcomes and Death We found no definitive evidence about the comparative effectiveness of oral diabetes agents on all-cause mortality, cardiovascular mortality or morbidity, peripheral arterial disease, neuropathy, retinopathy, or nephropathy (Table 1). For each head-to-head comparison on specific outcomes, the number of randomized trials (3 trials) and the absolute number of events were small (20). The few observational studies were limited in quantity, consistency, and adjustment for key confounders. Table 1. Evidence of the Comparative Effectiveness of Oral Diabetes Medications on Mortality, Microvascular and Macrovascular Outcomes, and Intermediate End Points Since our review, 2 high-profile comparative randomized trials with about 4 years of follow-up have been published, providing data on cardiovascular outcomes (28, 29). In ADOPT (A Diabetes Outcome Progression Trial) (28), the incidence of cardiovascular events was lower with glyburide than with rosiglitazone or metformin (1.8%, 3.4%, and 3.2%, respectively; P< 0.05). This effect was mainly driven by fewer congestive heart failure events and a lower rate of nonfatal myocardial infarction events in the glyburide group. Loss to follow-up was high (40%) and was disproportionate among the groups and therefore may account for some differences among groups. The interim analysis of the RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes) study reported that rosiglitazone plus metformin or a sulfonylurea compared with metformin plus a sulfonylurea had a hazard ratio of 1.08 (95% CI, 0.89 to 1.31) for the primary end point of hospitalization or death from cardiovascular disease (29). The hazard ratio was driven by more congestive heart failure in the rosiglitazone plus metformin or sulfonylurea group than in the control group of metformin plus sulfonylurea (absolute risk, 1.7% vs. 0.8%, respectively). In KaplanMeier curves, the risk for hospitalization or death from myocardial infarction was slightly lower in the control group than in the rosiglitazone group, but the difference was not statistically significant. A limitation of

Barriers to Recruiting Underrepresented Populations to Cancer Clinical Trials : A Systematic Review

Racial and ethnic minorities, older adults, rural residents, and individuals of low socioeconomic status are underrepresented among participants in cancer‐related trials. The authors conducted a systematic review to determine the barriers to participation of underrepresented populations in cancer‐related trials. Their search included English‐language publications that reported original data on the recruitment of underrepresented groups to cancer treatment or prevention trials between 1966 and December 2005 in multiple electronic databases. They also hand‐searched titles in 34 journals from January 2003 to December 2005 and they examined reference lists for eligible articles. Titles and abstracts were reviewed to identify relevant studies. Data on barriers to participation were synthesized both qualitatively and based on statistically significant associations with trial enrollment. Of 5257 studies that were cited, 65 studies were eligible for inclusion in the current analysis, including 46 studies on recruitment into cancer therapeutic trials, 15 studies on recruitment into prevention trials, and 4 studies on recruitment into both prevention and treatment trials. Numerous factors were reported as barriers to participation in cancer‐related trials. However, only 20 of the studies reported statistically significant associations between hypothesized barriers and enrollment. The available evidence had limitations in quality regarding representativeness, justification of study methods, the reliability and validity of data‐collection methods, potential for bias, and data analysis. The results indicated that underrepresented populations face numerous barriers to participation in cancer‐related trials. The current systematic review highlighting the literature on recruitment of underrepresented populations to cancer trials and may be used as the evidence base toward developing an agenda for etiologic and intervention research to reduce the disparities in participation in cancer‐related trials. Cancer 2008.

Cardiovascular Outcomes in Trials of Oral Diabetes Medications: A Systematic Review

BACKGROUND A wide variety of oral diabetes medications are currently available for the treatment of type 2 diabetes mellitus, but it is unclear how these agents compare with respect to long-term cardiovascular risk. Our objective was to systematically examine the peer-reviewed literature on the cardiovascular risk associated with oral agents (second-generation sulfonylureas, biguanides, thiazolidinediones, and meglitinides) for treating adults with type 2 diabetes. METHODS We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, from inception through January 19, 2006. Forty publications of controlled trials that reported information on cardiovascular events (primarily myocardial infarction and stroke) met our inclusion criteria. Using standardized protocols, 2 reviewers serially abstracted data from each article. Trials were first described qualitatively. For comparisons with 4 or more independent trials, results were pooled quantitatively using the Mantel-Haenszel method. Results are presented as odds ratios (ORs) and corresponding 95% confidence intervals (CIs). RESULTS Treatment with metformin hydrochloride was associated with a decreased risk of cardiovascular mortality (pooled OR, 0.74; 95% CI, 0.62-0.89) compared with any other oral diabetes agent or placebo; the results for cardiovascular morbidity and all-cause mortality were similar but not statistically significant. No other significant associations of oral diabetes agents with fatal or nonfatal cardiovascular disease or all-cause mortality were observed. When compared with any other agent or placebo, rosiglitazone was the only diabetes agent associated with an increased risk of cardiovascular morbidity or mortality, but this result was not statistically significant (OR, 1.68; 95% CI, 0.92-3.06). CONCLUSIONS Meta-analysis suggested that, compared with other oral diabetes agents and placebo, metformin was moderately protective and rosiglitazone possibly harmful, but lack of power prohibited firmer conclusions. Larger, long-term studies taken to hard end points and better reporting of cardiovascular events in short-term studies will be required to draw firm conclusions about major clinical benefits and risks related to oral diabetes agents.

Promoting a Culture of Safety as a Patient Safety Strategy: A Systematic Review

Developing a culture of safety is a core element of many efforts to improve patient safety and care quality. This systematic review identifies and assesses interventions used to promote safety culture or climate in acute care settings. The authors searched MEDLINE, CINAHL, PsycINFO, Cochrane, and EMBASE to identify relevant English-language studies published from January 2000 to October 2012. They selected studies that targeted health care workers practicing in inpatient settings and included data about change in patient safety culture or climate after a targeted intervention. Two raters independently screened 3679 abstracts (which yielded 33 eligible studies in 35 articles), extracted study data, and rated study quality and strength of evidence. Eight studies included executive walk rounds or interdisciplinary rounds; 8 evaluated multicomponent, unit-based interventions; and 20 included team training or communication initiatives. Twenty-nine studies reported some improvement in safety culture or patient outcomes, but measured outcomes were highly heterogeneous. Strength of evidence was low, and most studies were pre-post evaluations of low to moderate quality. Within these limits, evidence suggests that interventions can improve perceptions of safety culture and potentially reduce patient harm.

The Efficacy and Safety of Multivitamin and Mineral Supplement Use To Prevent Cancer and Chronic Disease in Adults: A Systematic Review for a National Institutes of Health State-of-the-Science Conference

Multivitamin and mineral supplements are the most commonly used dietary supplements in the United States (1). According to the National Health and Nutrition Examination Survey 19992000, 35% of adults reported recent use of multivitamin supplements (1). Most persons use multivitamin and mineral supplements to ensure adequate intake and to prevent or mitigate diseases. The commonly used over-the-counter multivitamin and mineral supplements contain at least 10 vitamins and 10 minerals. Many chronic diseases share common risk factors, including cigarette smoking, unhealthy diet, sedentary lifestyle, and obesity. Important underlying mechanisms for these factors to increase risk for disease include oxidative damage, inflammation, and 1-carbon metabolism (27). Numerous in vitro studies and animal studies have suggested favorable effects of several vitamins and minerals on these processes and on angiogenesis, immunity, cell differentiation, proliferation, and apoptosis (810). The U.S. Food and Nutrition Board has established tolerable upper intake levels for several nutrients. An upper intake level is defined as the highest level of daily nutrient intake that is likely to pose no risk for adverse effects to almost all persons in the general population (11). The strength of the evidence used to determine an upper intake level depends on data availability. Hence, an update of the data on adverse effects will help researchers to evaluate the appropriateness of upper intake levels. We performed a systematic review to synthesize the published literature on 1) the efficacy of multivitamin and mineral supplements and certain commonly used single vitamin or mineral supplements in the primary prevention of cancer and chronic disease in the general adult population and 2) the safety of multivitamin and mineral supplements and certain commonly used single vitamin or mineral supplements in the general population of adults and children (12). The review was done for a National Institutes of Health State-of-the-Science Statement for health care providers and the general public. This report is from the systematic review and focuses on 2 questions: What is the efficacy determined in randomized, controlled trials of multivitamin and mineral supplements (each at a dose less than the upper intake level) in the general adult population for the primary prevention of cancer and chronic diseases or conditions, and what is known about the safety of multivitamin and mineral supplement use in the general population of adults and children, on the basis of data from randomized, controlled trials and observational studies? Methods We defined multivitamin and mineral supplements as any supplements that contain 3 or more vitamins or minerals without herbs, hormones, or drugs. We defined the general population as community-dwelling persons who do not have special nutritional needs. (Examples of persons with special nutritional needs are those who are institutionalized, hospitalized, pregnant, or clinically deficient in nutrients.) A disease or condition was defined as chronic if it persists over an extended period, is not easily resolved, often cannot be cured by medication (although symptoms may be controlled or ameliorated with medication), frequently worsens over time, causes disability or impairment, and often requires ongoing medical care (13). The following chronic diseases were considered: breast cancer, colorectal cancer, lung cancer, prostate cancer, gastric cancer, or any other cancer (including colorectal polyps); myocardial infarction, stroke, hypertension, or other cardiovascular diseases; type 2 diabetes mellitus; Parkinson disease, cognitive decline, memory loss, or dementia; cataracts, macular degeneration, or hearing loss; osteoporosis, osteopenia, rheumatoid arthritis, or osteoarthritis; nonalcoholic steatohepatitis; chronic renal insufficiency or chronic nephrolithiasis; HIV infection, hepatitis C, or tuberculosis; and chronic obstructive pulmonary disease. We focused on primary prevention trials in adults because primary prevention is the main purpose of multivitamin supplement use in the general adult population (14). Primary prevention was defined as an action taken to prevent the development of a disease in persons who are well and do not have the disease in question (15). Using this definition, we included studies for prevention of chronic disease (for example, cardiovascular disease) in persons with risk factors (for example, type 2 diabetes mellitus or hypertension) for that disease. We also included studies for prevention of malignant disorders (such as colon cancer) in persons with selected precursors of disease (such as polyps). We did not include studies in persons with carcinoma in situ or similar malignant conditions. Literature Sources We searched the MEDLINE, EMBASE, and Cochrane databases, including Cochrane Reviews and the Cochrane Central Register of Controlled Trials, for articles published from 1966 through February 2006. Additional articles were identified by searching references in pertinent articles, querying experts, and hand-searching the tables of content of 15 relevant journals published from January 2005 through February 2006. Search Terms and Strategies We developed a core strategy for searching MEDLINE, accessed through PubMed, that was based on analysis of the Medical Subject Heading terms and text words of key articles identified a priori. This strategy formed the basis for the strategies developed for the other databases (see the complete evidence report for additional details) (12). Inclusion and Exclusion Criteria We focused on trials that ascertained clinical end points. Biomarker data were considered if data were presented in a way that permitted ascertainment of incident cases of chronic disease. Because users of multivitamin supplements were more likely than nonusers to be women, to be older, to have higher levels of education, to have a healthier lifestyle (more physical activities, more fruit and vegetable intake, and less likely to be smokers), and to more frequently use nonsteroidal anti-inflammatory drugs (1, 16), residual confounding would limit the internal validity of observational studies. Hence, for assessment of efficacy, we focused on data from randomized, controlled trials as the strongest source of evidence. However, for assessment of safety, we included data from randomized, controlled trials and observational studies in adults and children to minimize the risk for missing any potential safety concerns. An article was excluded if it was not written in English; presented no data in humans; included only pregnant women, infants, persons 18 years of age or younger (except if a study of persons 18 years of age presented data on the safety of multivitamin and mineral supplements), patients with chronic disease, patients receiving treatment for chronic disease, or persons living in long-term care facilities; studied only nutritional deficiency; did not address the use of supplements; did not address the use of supplements separately from dietary intake; did not cover any pertinent diseases; or was an editorial, commentary, or letter. Each article underwent title review, abstract review, and assessment of inclusion or exclusion by paired reviewers. Differences in opinion were resolved through consensus adjudication. Article review, organization, and tracking were performed by using Web-based SRS, version 3.0 (TrialStat! Corp., Ottawa, Ontario, Canada). Assessment of Study Quality Each eligible article was reviewed by paired reviewers who independently rated its quality according to 5 domains: the description of how study participants were representative of the source population (4 items), bias and confounding (12 items), descriptions of study supplements and supplementation (1 item), adherence to treatment and follow-up (7 items), and statistical analysis (6 items). Reviewers assigned a score of 0 (criterion not met), 1 (criterion partially met), or 2 (criterion fully met) to each item. The score for each quality domain was the proportion of the maximum score available in each domain. The overall quality score of a study was the average of the 5 scores for the 5 domains. The quality of each study in each domain was classified as good (score 80%), fair (score of 50% to 79%), or poor (score < 50%). For data on adverse effects, causality was evaluated with respect to temporal relationship, lack of alternative causes, doseresponse relationship, evidence of increased circulating levels of the nutrient under investigation, disappearance of adverse effects after cessation of supplement use, and response to rechallenge. Data Extraction Paired reviewers abstracted data on study design, participant characteristics, study supplements, and results. Data abstraction forms were completed by a primary reviewer and were verified for completeness and accuracy by a second reviewer. Evidence Grading We graded the quantity, quality, and consistency of the evidence on efficacy by adapting an evidence grading scheme recommended by the Grading of Recommendations Assessment, Development and Evaluation Working Group (17). The strength of evidence was classified into 1 of 4 categories: high (further research is very unlikely to change our confidence in the estimates of effects), moderate (further research is likely to greatly affect our confidence in the estimates of effects and may change the estimates), low (further research is very likely to greatly affect confidence in the estimates of effects and is likely to change the estimates), or very low (any estimate of effect is very uncertain). Role of the Funding Source This article is based on research conducted at the Johns Hopkins Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality (contract no. 290-02-0018), Rockville, Maryland, in response to a task order requested by the National Institutes of Health Office of M

Systematic review of community-based childhood obesity prevention studies

OBJECTIVE: This study systematically reviewed community-based childhood obesity prevention programs in the United States and high-income countries. METHODS: We searched Medline, Embase, PsychInfo, CINAHL, clinicaltrials.gov, and the Cochrane Library for relevant English-language studies. Studies were eligible if the intervention was primarily implemented in the community setting; had at least 1 year of follow-up after baseline; and compared results from an intervention to a comparison group. Two independent reviewers conducted title scans and abstract reviews and reviewed the full articles to assess eligibility. Each article received a double review for data abstraction. The second reviewer confirmed the first reviewer’s data abstraction for completeness and accuracy. RESULTS: Nine community-based studies were included; 5 randomized controlled trials and 4 non–randomized controlled trials. One study was conducted only in the community setting, 3 were conducted in the community and school setting, and 5 were conducted in the community setting in combination with at least 1 other setting such as the home. Desirable changes in BMI or BMI z-score were found in 4 of the 9 studies. Two studies reported significant improvements in behavioral outcomes (1 in physical activity and 1 in vegetable intake). CONCLUSIONS: The strength of evidence is moderate that a combined diet and physical activity intervention conducted in the community with a school component is more effective at preventing obesity or overweight. More research and consistent methods are needed to understand the comparative effectiveness of childhood obesity prevention programs in the community setting.

What childhood obesity prevention programmes work? A systematic review and meta-analysis

Previous reviews of childhood obesity prevention have focused largely on schools and findings have been inconsistent. Funded by the US Agency for Healthcare Research and Quality (AHRQ) and the National Institutes of Health, we systematically evaluated the effectiveness of childhood obesity prevention programmes conducted in high‐income countries and implemented in various settings. We searched MEDLINE®, Embase, PsycINFO, CINAHL®, ClinicalTrials.gov and the Cochrane Library from inception through 22 April 2013 for relevant studies, including randomized controlled trials, quasi‐experimental studies and natural experiments, targeting diet, physical activity or both, and conducted in children aged 2–18 in high‐income countries. Two reviewers independently abstracted the data. The strength of evidence (SOE) supporting interventions was graded for each study setting (e.g. home, school). Meta‐analyses were performed on studies judged sufficiently similar and appropriate to pool using random effect models. This paper reported our findings on various adiposity‐related outcomes. We identified 147 articles (139 intervention studies) of which 115 studies were primarily school based, although other settings could have been involved. Most were conducted in the United States and within the past decade. SOE was high for physical activity‐only interventions delivered in schools with home involvement or combined diet–physical activity interventions delivered in schools with both home and community components. SOE was moderate for school‐based interventions targeting either diet or physical activity, combined interventions delivered in schools with home or community components or combined interventions delivered in the community with a school component. SOE was low for combined interventions in childcare or home settings. Evidence was insufficient for other interventions. In conclusion, at least moderately strong evidence supports the effectiveness of school‐based interventions for preventing childhood obesity. More research is needed to evaluate programmes in other settings or of other design types, especially environmental, policy and consumer health informatics‐oriented interventions.

Hydroxyurea for sickle cell disease: a systematic review for efficacy and toxicity in children.

CONTEXT. Hydroxyurea is the only approved medication for the treatment of sickle cell disease in adults; there are no approved drugs for children. OBJECTIVE. Our goal was to synthesize the published literature on the efficacy, effectiveness, and toxicity of hydroxyurea in children with sickle cell disease. METHODS. Medline, Embase, TOXLine, and the Cumulative Index to Nursing and Allied Health Literature through June 2007 were used as data sources. We selected randomized trials, observational studies, and case reports (English language only) that evaluated the efficacy and toxicity of hydroxyurea in children with sickle cell disease. Two reviewers abstracted data sequentially on study design, patient characteristics, and outcomes and assessed study quality independently. RESULTS. We included 26 articles describing 1 randomized, controlled trial, 22 observational studies (11 with overlapping participants), and 3 case reports. Almost all study participants had sickle cell anemia. Fetal hemoglobin levels increased from 5%–10% to 15%–20% on hydroxyurea. Hemoglobin concentration increased modestly (∼1 g/L) but significantly across studies. The rate of hospitalization decreased in the single randomized, controlled trial and 5 observational studies by 56% to 87%, whereas the frequency of pain crisis decreased in 3 of 4 pediatric studies. New and recurrent neurologic events were decreased in 3 observational studies of hydroxyurea compared with historical controls. Common adverse events were reversible mild-to-moderate neutropenia, mild thrombocytopenia, severe anemia, rash or nail changes (10%), and headache (5%). Severe adverse events were rare and not clearly attributable to hydroxyurea. CONCLUSIONS. Hydroxyurea reduces hospitalization and increases total and fetal hemoglobin levels in children with severe sickle cell anemia. There was inadequate evidence to assess the efficacy of hydroxyurea in other groups. The small number of children in long-term studies limits conclusions about late toxicities.

Provider roles in the recruitment of underrepresented populations to cancer clinical trials

Providers play a vital role in the successful recruitment of underrepresented patients to cancer clinical trials because they often introduce the opportunity of clinical trials. The purpose of the current systematic review was to describe provider‐related factors influencing recruitment of underrepresented populations to cancer clinical trials.

A systematic review of home-based childhood obesity prevention studies

BACKGROUND AND OBJECTIVES: Childhood obesity is a global epidemic. Despite emerging research about the role of the family and home on obesity risk behaviors, the evidence base for the effectiveness of home-based interventions on obesity prevention remains uncertain. The objective was to systematically review the effectiveness of home-based interventions on weight, intermediate (eg, diet and physical activity [PA]), and clinical outcomes. METHODS: We searched Medline, Embase, PsychInfo, CINAHL, clinicaltrials.gov, and the Cochrane Library from inception through August 11, 2012. We included experimental and natural experimental studies with ≥1-year follow-up reporting weight-related outcomes and targeting children at home. Two independent reviewers screened studies and extracted data. We graded the strength of the evidence supporting interventions targeting diet, PA, or both for obesity prevention. RESULTS: We identified 6 studies; 3 tested combined interventions (diet and PA), 1 used diet intervention, 1 combined intervention with primary care and consumer health informatics components, and 1 combined intervention with school and community components. Select combined interventions had beneficial effects on fruit/vegetable intake and sedentary behaviors. However, none of the 6 studies reported a significant effect on weight outcomes. Overall, the strength of evidence is low that combined home-based interventions effectively prevent obesity. The evidence is insufficient for conclusions about home-based diet interventions or interventions implemented at home in association with other settings. CONCLUSIONS: The strength of evidence is low to support the effectiveness of home-based child obesity prevention programs. Additional research is needed to test interventions in the home setting, particularly those incorporating parenting strategies and addressing environmental influences.