Veronica Yank

Systematic Review: Benefits and Harms of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications

BACKGROUND Recombinant factor VIIa (rFVIIa), a hemostatic agent approved for hemophilia, is increasingly used for off-label indications. PURPOSE To evaluate the benefits and harms of rFVIIa use for 5 off-label, in-hospital indications: intracranial hemorrhage, cardiac surgery, trauma, liver transplantation, and prostatectomy. DATA SOURCES Ten databases (including PubMed, EMBASE, and the Cochrane Library) queried from inception through December 2010. Articles published in English were analyzed. STUDY SELECTION Two reviewers independently screened titles and abstracts to identify clinical use of rFVIIa for the selected indications and identified all randomized, controlled trials (RCTs) and observational studies for full-text review. DATA EXTRACTION Two reviewers independently assessed study characteristics and rated study quality and indication-wide strength of evidence. DATA SYNTHESIS 16 RCTs, 26 comparative observational studies, and 22 noncomparative observational studies met inclusion criteria. Identified comparators were limited to placebo (RCTs) or usual care (observational studies). For intracranial hemorrhage, mortality was not improved with rFVIIa use across a range of doses. Arterial thromboembolism was increased with medium-dose rFVIIa use (risk difference [RD], 0.03 [95% CI, 0.01 to 0.06]) and high-dose rFVIIa use (RD, 0.06 [CI, 0.01 to 0.11]). For adult cardiac surgery, there was no mortality difference, but there was an increased risk for thromboembolism (RD, 0.05 [CI, 0.01 to 0.10]) with rFVIIa. For body trauma, there were no differences in mortality or thromboembolism, but there was a reduced risk for the acute respiratory distress syndrome (RD, -0.05 [CI, -0.02 to -0.08]). Mortality was higher in observational studies than in RCTs. LIMITATIONS The amount and strength of evidence were low for most outcomes and indications. Publication bias could not be excluded. CONCLUSION Limited available evidence for 5 off-label indications suggests no mortality reduction with rFVIIa use. For some indications, it increases thromboembolism.

Financial ties and concordance between results and conclusions in meta-analyses: retrospective cohort study

Objective To determine whether financial ties to one drug company are associated with favourable results or conclusions in meta-analyses on antihypertensive drugs. Design Retrospective cohort study. Setting Meta-analyses published up to December 2004 that were not duplicates and evaluated the effects of antihypertensive drugs compared with any comparator on clinical end points in adults. Financial ties were categorised as one drug company compared with all others. Main outcome measures The main outcomes were the results and conclusions of meta-analyses, with both outcomes separately categorised as being favourable or not favourable towards the study drug. We also collected data on characteristics of meta-analyses that the literature suggested might be associated with favourable results or conclusions. Results 124 meta-analyses were included in the study, 49 (40%) of which had financial ties to one drug company. On univariate logistic regression analyses, meta-analyses of better methodological quality were more likely to have favourable results (odds ratio 1.16, 95% confidence interval 1.07 to 1.27). Although financial ties to one drug company were not associated with favourable results, such ties constituted the only characteristic significantly associated with favourable conclusions (4.09, 1.30 to 12.83). When controlling for other characteristics of meta-analyses in multiple logistic regression analyses, meta-analyses that had financial ties to one drug company remained more likely to report favourable conclusions (5.11, 1.54 to 16.92). Conclusion Meta-analyses on antihypertensive drugs and with financial ties to one drug company are not associated with favourable results but are associated with favourable conclusions.

Translating the Diabetes Prevention Program Lifestyle Intervention for Weight Loss Into Primary Care A Randomized Trial

BACKGROUND The Diabetes Prevention Program (DPP) lifestyle intervention reduced the incidence of type 2 diabetes mellitus (DM) among high-risk adults by 58%, with weight loss as the dominant predictor. However, it has not been adequately translated into primary care. METHODS We evaluated 2 adapted DPP lifestyle interventions among overweight or obese adults who were recruited from 1 primary care clinic and had pre-DM and/or metabolic syndrome. Participants were randomized to (1) a coach-led group intervention (n = 79), (2) a self-directed DVD intervention (n = 81), or (3) usual care (n = 81). During a 3-month intensive intervention phase, the DPP-based behavioral weight-loss curriculum was delivered by lifestyle coach-led small groups or home-based DVD. During the maintenance phase, participants in both interventions received lifestyle change coaching and support remotely-through secure email within an electronic health record system and the American Heart Association Heart360 website for weight and physical activity goal setting and self-monitoring. The primary outcome was change in body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) from baseline to 15 months. RESULTS At baseline, participants had a mean (SD) age of 52.9 (10.6) years and a mean BMI of 32.0 (5.4); 47% were female; 78%, non-Hispanic white; and 17%, Asian/Pacific Islander. At month 15, the mean ± SE change in BMI from baseline was -2.2 ± 0.3 in the coach-led group vs -0.9 ± 0.3 in the usual care group (P < .001) and -1.6 ± 0.3 in the self-directed group vs usual care (P = .02). The percentages of participants who achieved the 7% DPP-based weight-loss goal were 37.0% (P = .003) and 35.9% (P = .004) in the coach-led and self-directed groups, respectively, vs 14.4% in the usual care group. Both interventions also achieved greater net improvements in waist circumference and fasting plasma glucose level. CONCLUSION Proven effective in a primary care setting, the 2 DPP-based lifestyle interventions are readily scalable and exportable with potential for substantial clinical and public health impact. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00842426.

Disclosure of Researcher Contributions: A Study of Original Research Articles in The Lancet

In response to a proposal suggesting that researcher contributions to published papers be specified, The Lancet began disclosing these contributions at the end of original articles. This study of t...Vision without action is a daydream. Action without vision is a nightmare. -Derived from The Analects of Confucius All over the world, physicians are treating patients who carry Helicobacter pylori in an attempt to eradicate the organism. The discovery of H. pylori (1) and its relationship with peptic ulcer disease and gastric cancer (2) has led to a new era. In a relatively short time, the field of gastric microbiology has moved from obscurity to a central stage in medical practice. In this editorial I review the fundamental associations between H. pylori and human health and disease. The issues of how best to diagnose the presence of the organism and how best to eliminate it must follow from the larger question: In whom is elimination of H. pylori beneficial? Consensus Issues In the past 15 years, much has been learned about H. pylori (2). We know that once H. pylori is acquired, colonization continues for life unless the organism is eliminated by antimicrobial treatment or by the usually late-in-life development of atrophic gastritis. We also know that essentially everyone who carries the organism in the gastric mucous layer has evidence of tissue reaction (termed chronic active gastritis), yet most colonized persons remain asymptomatic for life. In the absence of treatment, the presence of H. pylori can be determined with a high degree of confidence by endoscopy (with culture, histologic examination, or urease testing of gastric biopsy specimens), by serologic testing, or by urea breath tests. After successful treatment, specific antibody levels decrease so slowly that serologic testing cannot be used to document success for at least 6 months. We know that colonization with H. pylori is associated with an increased risk for developing peptic ulcer disease, noncardia gastric adenocarcinomas, and gastric mucosa-associated lymphoid type (MALT) B-cell lymphomas (2, 3). We know that in most patients, elimination of H. pylori changes the natural history of peptic ulcer disease and of gastric MALT lymphomas (2). It is now recommended that patients with ulcer disease be treated to eliminate H. pylori because the benefits seem to substantially outweigh the risks and costs. However, patients with ulcers represent only a small subset of all those who carry H. pylori. Emerging Issues Increasing microbiological and epidemiologic evidence indicates that H. pylori was once more common, perhaps nearly universal in humans, than it is in our postmodern society (4). Clearly, H. pylori has been disappearing as industrialization has proceeded (5), reflecting changes in living conditions. Its decline has probably been accelerated by the widespread use of antibiotics in recent decades and by the now-concerted efforts by physicians to remove it from large numbers of people. If H. pylori once was so common, as it remains in most developing countries, and its presence generally benign, could colonization have benefits as well as costs to humans? Helicobacter pylori strains are highly diverse, and emerging evidence suggests that the type of strain with which an individual patient is colonized affects risk for disease. In western countries, carriage of cagA +, vacA s1, or iceA 1 strains is associated with an increased risk for duodenal ulceration, atrophic gastritis, and noncardia gastric adenocarcinomas (6-8). However, because strains differ among geographic regions, it has not been possible to generalize about virulence genotypes on a global basis (9). This is particularly germane to the United States, where our ancestors brought their H. pylori with them from their European, African, Asian, and American origins. The relation between bacterial and host genotypes and clinical outcomes is one of the most dynamic areas in current H. pylori investigation. As H. pylori has been disappearing, peptic ulcer disease and noncardia gastric cancers have predictably been decreasing. However, maladies such as gastroesophageal reflux disease, Barrett esophagus, and adenocarcinomas of the lower esophagus and gastric cardia have been dramatically and progressively increasing. In white men in the United States, adenocarcinoma has surpassed squamous cell carcinomas as the main type of esophageal tumor, and among gastric tumors, cancers at the cardia have become nearly as frequent as those located more distally. Are these phenomena in any way related to the disappearance of H. pylori? This is a critical area for investigation, but preliminary studies already suggest that the presence of H. pylori may protect against these diseases (10-13), especially cagA + strains; in a seeming paradox, these strains are those most highly associated with risk for lower gastric diseases (7). If these findings are confirmed, as I believe they will be, then the clinical evaluation of H. pylori will become increasingly complex. By eliminating H. pylori to reduce risk in one group of diseases, could we be increasing risk for others? Such ideas suggest another possibility: Might H. pylori have other beneficial features, not readily apparent today, the loss of which might subject humans to unknown perils? A protective role of H. pylori against orally ingested pathogens is attractive, and experimental support for that hypothesis is emerging (14). An important question is whether we should refer to our interaction with H. pylori as colonization or as infection. Infection indicates a relation that is harmful to the host. Colonization is a broader term that indicates a persistent interaction without qualifying whether or not it is harmful. Favoring the concept of infection for H. pylori is the presence of a tissue response, and the fact that the organisms presence increases risk for disease. However, studies in germ-free animals show that their colonic lamina propria is nearly devoid of cells until their usual colonic bacteria are restored; the lamina propria then fills with immune and phagocytic cells, a phenomenon that we consider the normal response. I believe it likely that the tissue response to H. pylori in the stomach represents a parallel process, but one that we are calling chronic active gastritis. Viridans streptococci and Bacteroides species are persistent colonizers of humans that occasionally cause disease (endocarditis and peritonitis, respectively), but for the most part, our interactions with them are favorable to us. The interactions of H. pylori and humans have many parallels with those for these organisms. The presence of H. pylori increases risk for some diseases (such as peptic ulcer disease) but seems to decrease risk for other diseases (such as esophageal diseases). For these reasons, the broader term, colonization, appears most appropriate for describing the fundamental interaction of H. pylori and humans. Clinical Dilemmas Treatment to eradicate H. pylori is improving. Current optimal therapies involve three or four medications, usually including two antibiotics (such as amoxicillin, metronidazole, tetracycline, or clarithromycin), acid inhibitors (such as proton-pump inhibitors or H2-blockers), or bismuth salts (15). With use of such combined regimens for 7 to 10 days, it seems possible to have eradication rates better than 90%. However, rigorously conducted studies have shown that the results in the United States are 10% to 20% lower than those in Europe. In addition, no head-to-head trials have been done to define optimal therapy. Resistance to macrolides (such as clarithromycin) and nitroimidazoles (such as metronidazole) substantially worsens therapeutic efficacy, and rates of such resistance are increasing (16). A more important question is, Which persons who are colonized with H. pylori should be treated? Many studies show that there is little, if any, relation between eradication of H. pylori and substantial (greater than placebo effect) improvement in symptoms of nonulcer dyspepsia (17). Even studies with the most positive results show short-term benefit in only a small fraction of patients with nonulcer dyspepsia (18), and no methods are available to prospectively distinguish such patients from the others. Nevertheless, around the world, physicians are treating patients with nonulcer dyspepsia in an attempt to eradicate H. pylori. Whether they are doing more good or causing more harm will, in part, turn on the relation between H. pylori and esophageal diseases. In certain persons, colonization with H. pylori contributes to the development of chronic atrophic gastritis, which may lead to the intestinal type of noncardia gastric cancer. An important question is whether early intervention can interdict this phenomenon. A treatment trial in Japan of patients who had early removal of gastric tumors showed that with H. pylori eradication, the likelihood of developing a subsequent gastric cancer was reduced (19). Although these data are preliminary, they suggest that in some patients, prophylactic eradication of H. pylori could decrease risk for noncardia gastric cancer. An important challenge will be to define the patients for whom the benefits exceed the costs and risks and to develop simple screening assays to identify these patients in the general population. Challenges Investigations of the relation of H. pylori to disease were begun by practitioners who focused on clinical symptoms and clinically defined outcomes. These approaches have had much benefit, especially among persons with ulcer disease. Yet analyses of clinical data often have undefined biases, and, until recently, the field lacked a viable paradigm of the biological associations between H. pylori and humans. In the absence of a paradigm, viewpoints are short-term and immediate results are favored. Yet for maximizing human health, a way of understanding our interactions with H. pylori that addresses both short- and long-term consequences is needed. The foundation of such a model must be ecological and be rooted in understanding the selective forces that have governed our relations

Off-label use of recombinant factor VIIa in U.S. hospitals: analysis of hospital records.

BACKGROUND Recombinant factor VIIa (rFVIIa) is approved for treatment of bleeding in patients who have hemophilia with inhibitors but has been applied to a wide range of off-label indications. OBJECTIVE To estimate patterns of off-label rFVIIa use in U.S. hospitals. DESIGN Retrospective database analysis. SETTING Data were extracted from the Premier Perspectives database (Premier, Charlotte, North Carolina), which contains discharge records from a sample of academic and nonacademic U.S. hospitals. PATIENTS 12 644 hospitalizations for patients who received rFVIIa during a hospital stay. MEASUREMENTS Hospital diagnoses and patient dispositions from 1 January 2000 to 31 December 2008. Statistical weights for each hospital were used to provide national estimates of rFVIIa use. RESULTS From 2000 to 2008, off-label use of rFVIIa in hospitals increased more than 140-fold, such that in 2008, 97% (95% CI, 96% to 98%) of 18 311 in-hospital uses were off-label. In contrast, in-hospital use for hemophilia increased less than 4-fold and accounted for 2.7% (CI, 1.9% to 3.5%) of use in 2008. Adult and pediatric cardiovascular surgery (29% [CI, 21% to 33%]), body and brain trauma (29% [CI, 19% to 38%]), and intracranial hemorrhage (11% [CI, 7.7% to 14%]) were the most common indications for rFVIIa use. Across all indications, in-hospital mortality was 27% (CI, 19% to 34%) and 43% (CI, 26% to 59%) of patients were discharged to home. LIMITATION Accuracy and completeness of the discharge diagnoses and patient medication records in the database sample cannot be verified. CONCLUSION Off-label use of rFVIIa in the hospital setting far exceeds use for approved indications. These patterns raise concern about the application of rFVIIa to conditions for which strong supporting evidence is lacking.

Association of Objectively Measured Physical Activity With Cardiovascular Risk in Mobility‐limited Older Adults

Background Data are sparse regarding the impacts of habitual physical activity (PA) and sedentary behavior on cardiovascular (CV) risk in older adults with mobility limitations. Methods and Results This study examined the baseline, cross‐sectional association between CV risk and objectively measured PA among participants in the Lifestyle Interventions and Independence for Elders (LIFE) study. The relationship between accelerometry measures and predicted 10‐year Hard Coronary Heart Disease (HCHD) risk was modeled by using linear regression, stratified according to CVD history. Participants (n=1170, 79±5 years) spent 642±111 min/day in sedentary behavior (ie, <100 accelerometry counts/min). They also spent 138±43 min/day engaging in PA registering 100 to 499 accelerometry counts/min and 54±37 min/day engaging in PA ≥500 counts/min. Each minute per day spent being sedentary was associated with increased HCHD risk among both those with (0.04%, 95% CI 0.02% to 0.05%) and those without (0.03%, 95% CI 0.02% to 0.03%) CVD. The time spent engaging in activities 100 to 499 as well as ≥500 counts/min was associated with decreased risk among both those with and without CVD (P<0.05). The mean number of counts per minute of daily PA was not significantly associated with HCHD risk in any model (P>0.05). However, a significant interaction was observed between sex and count frequency (P=0.036) for those without CVD, as counts per minute was related to HCHD risk in women (β=−0.94, −1.48 to −0.41; P<0.001) but not in men (β=−0.14, −0.59 to 0.88; P=0.704). Conclusions Daily time spent being sedentary is positively associated with predicted 10‐year HCHD risk among mobility‐limited older adults. Duration, but not intensity (ie, mean counts/min), of daily PA is inversely associated with HCHD risk score in this population—although the association for intensity may be sex specific among persons without CVD. Clinical Trial Registration URL: www.clinicaltrials.gov Unique identifier: NCT01072500

Two-year weight-loss maintenance in primary care-based Diabetes Prevention Program lifestyle interventions.

Objective:To investigate whether the effects on weight loss and cardiometabolic risk factor reduction of two technology-mediated lifestyle interventions for 15 months in a primary care-based translation trial sustained at 24 months (that is, 9 months after the end of intervention).Design:This study analyzed data from an extended follow-up of participants in the original ‘E-LITE’ (Evaluation of Lifestyle Interventions to Treat Elevated Cardiometabolic Risk in Primary Care)-randomized controlled trial, which demonstrated the effectiveness of two adapted Diabetes Prevention Program (DPP) lifestyle interventions compared with usual primary care.Subjects:E-LITE randomized 241 overweight or obese participants with pre-diabetes and/or metabolic syndrome to receive usual care alone (n=81) or usual care plus a coach-led (n=79) or self-directed intervention (n=81). The interventions provided coach-led group behavioral weight-loss treatment or a take-home, self-directed DVD using the same 12-week curriculum, followed by 12 additional months of technology-mediated coach contact and self-monitoring support. Participants received no further intervention after month 15. A blinded assessor conducted 24-month visits by following the measurement protocols of the original trial. Measurements include weight and cardiometabolic risk factors (waist circumference, fasting plasma glucose, resting blood pressure, triglycerides, high- and low-density lipoprotein cholesterol, total cholesterol and triglyceride to high-density lipoprotein cholesterol ratio).Results:At month 24, mean±s.e. changes in body mass index (trial primary outcome) and weight (kg) from baseline were –1.9±0.3 (P=0.001) and –5.4±0.9 (P<0.001) in the coach-led intervention, and –1.6±0.3 (P=0.03) and –4.5±0.9 (P=0.001) in the self-directed intervention, compared with –0.9±0.3 and 2.4±0.9 in the usual care group. In addition, both interventions led to a greater percentage of participants maintaining ⩾7% weight loss and sustained improvements in waist circumference and fasting plasma glucose levels than usual care.Conclusion:This study shows sustained benefits of the two primary care-based, technology-mediated DPP lifestyle interventions. The findings warrant replication in long-term studies involving diverse populations.

Randomized Trial of Personal Genomics for Preventive Cardiology Design and Challenges

Background Genome-wide association studies (GWAS) have identified more than 1500 disease-associated single nucleotide polymorphisms (SNPs), including many related to atherosclerotic cardiovascular disease (CVD). Associations have been found for most traditional risk factors (TRFs), including lipids,1,2 blood pressure/hypertension,3,4 weight/body mass index,5,6 smoking behavior,7 and diabetes.8–13 GWAS have also identified susceptibility variants for coronary heart disease (CHD). The first and, so far, strongest of these signals was found in the 9p21.3 locus, where common variants in this region increase the relative risk of CVD by 15% to 30% per risk allele in most race/ethnic groups.13–20 Subsequent largescale GWAS meta-analyses and replication studies in largely white/European populations have led to the reliable identification of an additional 26 loci conferring susceptibility to CHD,2,20–23 all with substantially lower effects sizes compared with the 9p21 locus. Many of these CVD susceptibility loci appear to be conferring risk independent of TRFs and thus cannot currently be assessed by surrogate clinical measures (Table 1). Among the 27 independent loci identified in the most recent large meta-analyses of CVD, 21 were reported not to be associated with any of the TRFs.20,21 Several studies have explored whether initial CVD-related genetic markers can improve risk prediction over standard models restricted to TRFs using a genetic risk score (GRS) constructed on the basis of the number of risk alleles inherited.24–26 Results to date have been mixed. Although all have shown that a GRS is strongly associated with the outcome of interest independent of TRFs, none were able to demonstrate a significant improvement in the c-statistic. Two of the 3 studies showed some modest improvement in newly defined discrimination indices, including the integrated discrimination index, the net reclassification index, and the clinical net reclassification index (net reclassification index in the intermediate-risk subjects). Thus, the use of these markers has not yet been shown to convincingly outperform models that include TRFs and family history alone. One important reason for the failure of these markers to demonstrate clinically meaningful improvement of risk prediction relates to the small proportion of the genetic variance explained by these markers, a phenomenon commonly referred to as the heritability gap. The basis for this heritability gap is the focus of intense investigation. Despite this gap, it is still possible that knowledge of genetic risk may improve patient outcomes through means other than enhanced risk reclassification. For instance, genetic testing may improve patient adherence and CVD risk factor reduction for Mendelian disorders related to CHD, such as familial hypercholesterolemia.27 This effect may be owing to an increase in patient motivation (eg, people who recognize and accept their high risk are more encouraged to reduce it); however, no clinical trial to date has demonstrated that newly discovered genetic markers improve risk factor profiles by improving adherence to prescribed therapy for complex (garden variety) CVD. Here, we describe the design of an ongoing randomized trial to investigate whether CVD risk factor profiles can be improved by providing participants with knowledge related to their inherited risk of CVD in addition to information on their risk related to measured TRFs. We also discuss some of the challenges that arise in the design and conduct of such a trial and how they were addressed.

Baseline reach and adoption characteristics in a randomized controlled trial of two weight loss interventions translated into primary care: A structured report of real-world applicability

BACKGROUND Although the Diabetes Prevention Program (DPP) lifestyle intervention reduced type 2 diabetes incidence by 58% among high-risk adults at academic centers, it requires translation into typical primary care settings. Using baseline data from the Evaluation of Lifestyle Interventions to Treat Elevated Cardiometabolic Risk in Primary Care (E-LITE) randomized controlled trial, we evaluated the potential of its two DPP-based interventions to reach their target populations and be adopted into routine use. METHODS Overweight/obese adults with increased cardiometabolic risk enrolled from one primary care clinic. Using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) model, we assessed reach with data on patient identification, participation, and representativeness, and adoption with data on intervention feasibility and potential for organizational diffusion. RESULTS The target population was identified by searching electronic health records. Contact was attempted for 2391 patients who completed initial screening by phone (56% uptake) or online (44%). Most (88%) of those screened ineligible were not within the target population; 12% were excluded because of research requirements. Conservatively estimated participation rate was 44%. Participants (n=241) included 54% men and had a mean (SD) age of 52.9 years (10.6) and body mass index of 32 kg/m(2) (5.4). Regarding adoption, all clinic physicians agreed to participate. The feasibility of intervention implementation and dissemination was enhanced by leveraging existing intervention, training, and primary care resources. CONCLUSIONS E-LITEs lifestyle interventions had fair-to-good potential for primary care reach and adoption. Our trial evidence and structured reporting may inform real-world implementation of translational trials by health networks, physicians, and payers.

The Effectiveness of Two Community-Based Weight Loss Strategies among Obese, Low-Income US Latinos

BACKGROUND Latino immigrants have high rates of obesity and face barriers to weight loss. OBJECTIVE To evaluate the effectiveness of a case-management (CM) intervention with and without community health workers (CHWs) for weight loss. DESIGN This was a 2-year, randomized controlled trial comparing two interventions with each other and with usual care (UC). PARTICIPANTS/SETTING Eligible participants included Latinos with a body mass index of 30 to 60 and one or more heart disease risk factors. The 207 participants recruited during 2009-2010 had a mean age of 47 years and were mostly women (77%). At 24 months, 86% of the sample was assessed. INTERVENTION The CM+CHW (n=82) and CM (n=84) interventions were compared with each other and with UC (n=41). Both included an intensive 12-month phase followed by 12 months of maintenance. The CM+CHW group received home visits. MAIN OUTCOME MEASURES Weight change at 24 months. STATISTICAL ANALYSES Generalized estimating equations using intent-to-treat. RESULTS At 6 months, mean weight loss in the CM+CHW arm was -2.1 kg (95% CI -2.8 to -1.3) or -2% of baseline weight (95% CI -1% to -2%) compared with -1.6 kg (95% CI -2.4 to -0.7; % weight change, -2%, -1%, and -3%) in CM and -0.9 kg (95% CI -1.8 to 0.1; % weight change, -1%, 0%, and -2%) in UC. By 12 and 24 months, differences narrowed and CM+CHW was no longer statistically distinct. Men achieved greater weight loss than women in all groups at each time point (P<0.05). At 6 months, men in the CM+CHW arm lost more weight (-4.4 kg; 95% CI -6.0 to -2.7) compared with UC (-0.4 kg; 95% CI -2.4 to 1.5), but by 12 and 24 months differences were not significant. CONCLUSIONS This study demonstrated that incorporation of CHWs may help promote initial weight loss, especially among men, but not weight maintenance. Additional strategies to address social and environmental influences may be needed for Latino immigrant populations.