The Look AHEAD Trial: Translating Lessons Learned Into Clinical Practice and Further Study.
Ontology highlight
ABSTRACT:
SUBMITTER: Salvia MG
PROVIDER: S-EPMC5556585 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
Publications
The Look AHEAD Trial: Translating Lessons Learned Into Clinical Practice and Further Study.
Diabetes spectrum : a publication of the American Diabetes Association 20170801 3
<b>IN BRIEF</b> Although the Look AHEAD (Action for Health in Diabetes) trial, which spanned more than 8 years, did not find significant differences in cardiovascular morbidity and mortality between study groups, it did demonstrate significant differences in weight loss and maintenance. Using lessons learned from the Look AHEAD protocol, clinicians can help people with type 2 diabetes lose weight, improve glucose management, increase physical activity, alter eating patterns, and support long-ter ...[more]
Similar Datasets
Project description:IntroductionDuring the past 2 decades, basic research deciphering the underlying mechanisms of nociception and chronic pain was thought to finally step beyond opioids and nonsteroidals and provide patients with new analgesics. But apart from calcitonin gene-related peptide antagonists, nothing arrived in hands of clinicians.ObjectivesTo present existing evidence of 3 representative target molecules in the development of novel pain treatment that, so far, did not result in approved drugs.MethodsThis Clinical Update aligns with the 2022 IASP Global Year Translating Pain Knowledge into Practice and selectively reviews best available evidence and practice.ResultsWe highlight 3 targets: a ion channel, a neuronal growth factor, and a neuropeptide to explore why these drug targets have been dropped in clinical phase II-III trials. Antibodies to nerve growth factor had very good effects in musculoskeletal pain but resulted into more patients requiring joint replacements. Blockers of NaV1.7 were often not effective enough-at least if patients were not stratified. Blockers of neurokinin receptor were similarly not successful enough. In general, failure was most often to the result of a lack of effect and to a lesser extend because of unexpected severe side effects. However, all studies and trials lead to an enormous move in the scientific community to better preclinical models and testing as well as revised methods to molecularly phenotype and stratify patients.ConclusionAll stakeholders in the process can help in the future: better preclinical studies, phenotyping and stratifying patients, and participation in clinical trials to move the discovery of analgesics forward.
| S-EPMC10624476 | biostudies-literature
Project description:Despite the increasing popularity of translation research, few studies have described the process and challenges involved in implementing a translation study. The main objective was to determine whether a multi-component group behavioral intervention could be successfully translated from an academic setting into the community health system of federally qualified health centers (FQHCs) funded by the Health Resources and Services Administration (HRSA) in Miami, NY, and NJ. Key challenges and "lessons learned" from the dissemination and implementation process for the SMART/EST (Stress Management And Relaxation Training/Emotional Supportive Therapy) Women's Project (SWP) III in low-resource primary care settings are described. The Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) model served as the theoretical framework for the translation of the study. This study outlines several essential factors related to Glasgow's RE-AIM model that need to be considered in order to accomplish successful translation of evidence-based interventions from traditional academia to "real-world" community health center settings.
| S-EPMC4444700 | biostudies-other
Project description:Genome-wide association studies have provided new insights into the genetic factors that contribute to the development of obesity. We hypothesized that these genetic markers would also predict magnitude of weight loss and weight regain after initial weight loss.Established obesity risk alleles available on the Illumina CARe iSelect (IBC) chip were characterized in 3899 overweight or obese participants with type 2 diabetes from the Look AHEAD (Action for Health in Diabetes), a randomized trial to determine the effects of intensive lifestyle intervention (ILI) and diabetes support and education (DSE) on cardiovascular morbidity and mortality. Primary analyses examined the interaction between 13 obesity risk polymorphisms in eight genes and randomized treatment arm in predicting weight change at year 1, and weight regain at year 4 among individuals who lost 3% or more of their baseline weight by year 1.No single-nucleotide polymorphisms (SNPs) were significantly associated with magnitude of weight loss or interacted with treatment arm at year 1. However, fat mass and obesity associated gene (FTO) rs3751812 predicted weight regain within DSE (1.56?kg per risk allele, P=0.005), but not ILI (P=0.761), resulting in SNP × treatment arm interaction (P=0.009). In a partial replication of prior research, the obesity risk (G) allele at BDNF rs6265 was associated with greater weight regain across treatment arms (0.773?kg per risk allele), although results were of borderline statistical significance (P=0.051).Variations in the FTO and BDNF loci may contribute risk of weight regain after weight loss.
| S-EPMC3750057 | biostudies-literature
Project description:ObjectivesImplementing new programs to support precision medicine in clinical settings is a complex endeavor. We describe challenges and potential solutions based on the Indiana GENomics Implementation: an Opportunity for the Underserved (INGenious) program at Eskenazi Health-one of six sites supported by the Implementing GeNomics In pracTicE network grant of the National Institutes of Health/National Human Genome Research Institute. INGenious is an implementation of a panel of genomic tests.MethodsWe conducted a descriptive case study of the implementation of this pharmacogenomics program, which has a wide scope (14 genes, 27 medications) and a diverse population (patients who often have multiple chronic illnesses, in a large urban safety-net hospital and its outpatient clinics).ChallengesWe placed the clinical pharmacogenomics implementation challenges into six categories: patient education and engagement in care decision making; clinician education and changes in standards of care; integration of technology into electronic health record systems; translational and implementation sciences in real-world clinical environments; regulatory and reimbursement considerations, and challenges in measuring outcomes. A cross-cutting theme was the need for careful attention to workflow. Our clinical setting, a safety-net health care system, presented some distinctive challenges. Patients often had multiple chronic illnesses and sometimes were taking more than one pharmacogenomics-relevant medication. Reaching patients for recruitment or follow-up was another challenge.ConclusionsNew, large-scale endeavors in health care are challenging. A description of the challenges that we encountered and the approaches that we adopted to address them may provide insights for those who implement and study innovations in other health care systems.
| S-EPMC7543044 | biostudies-literature
Project description:The Look AHEAD trial was a multi-center, randomized controlled trial, to determine whether weight loss reduces cardiovascular morbidity and mortality in overweight individuals with type 2 diabetes. The objective of this study was to evaluate the incidence of severe hypoglycemia in patients enrolled in Look AHEAD. Research Design and Methods 5,145 subjects were randomized to diabetes support and education (DSE) or intensive lifestyle intervention (ILI). Instances of severe hypoglycemia were recorded. Regression analysis was used to compare the development of severe hypoglycemia between groups.Over the entire study, the severe hypoglycemia rate was not different between ILI and DSE groups (0.49 ILI, 0.51 DSE/100 person-years, rate ratio=1.12, p=0.41), but was greater in ILI during year 1 (p=0.008 for year by intervention interaction). During follow-up, severe hypoglycemia risk was higher with insulin, sulfonylurea or glitinide use at baseline (p<0.0001). The intervention effect differed by post-randomization insulin use (ILI to DSE HR=1.45 in insulin users versus HR=0.71 in non-users, p=0.009). Insulin use reduced by 3% in ILI in year 1. Compared to DSE, ILI participants in the lower 50% of weight loss in year 1 had similar percent insulin use and incident hypoglycemia, but ILI participants in the upper 50% of weight loss had lower percent insulin use and incident hypoglycemia.Reduction in insulin is necessary during intensive weight loss to avoid episodes of hypoglycemia. Although limited by self-reported evaluation of hypoglycemia, greater weight loss in ILI during year 1 was associated with reduced insulin use and lower rates of hypoglycemia later in the trial.
| S-EPMC4912885 | biostudies-literature
Project description:Malignant brain tumors, including glioblastoma, represent some of the most difficult to treat of solid tumors. Nevertheless, recent progress in immunotherapy, across a broad range of tumor types, provides hope that immunological approaches will have the potential to improve outcomes for patients with brain tumors. Chimeric antigen receptors (CAR) T cells, a promising immunotherapeutic modality, utilizes the tumor targeting specificity of any antibody or receptor ligand to redirect the cytolytic potency of T cells. The remarkable clinical response rates of CD19-targeted CAR T cells and early clinical experiences in glioblastoma demonstrating safety and evidence for disease modifying activity support the potential of further advancements ultimately providing clinical benefit for patients. The brain, however, is an immune specialized organ presenting unique and specific challenges to immune-based therapies. Remaining barriers to be overcome for achieving effective CAR T cell therapy in the central nervous system (CNS) include tumor antigenic heterogeneity, an immune-suppressive microenvironment, unique properties of the CNS that limit T cell entry, and risks of immune-based toxicities in this highly sensitive organ. This review will summarize preclinical and clinical data for CAR T cell immunotherapy in glioblastoma and other malignant brain tumors, including present obstacles to advancement.
| S-EPMC6771592 | biostudies-literature
Project description:PURPOSE:This paper describes the approach used to develop the Adolescent Family Life Program (AFLP) Positive Youth Development (PYD) Model within the structure of an existing state government-run program. DESCRIPTION:The California Department of Public Health, Maternal, Child and Adolescent Health (CDPH/MCAH) Division undertook an innovative approach to develop a program model to help expectant and parenting youth build resilience. CDPH/MCAH started by assessing existing program efforts and theory to develop and test new strategies in the field, structure a program model, and build toward broader expansion and sustainability. CDPH/MCAH engaged local organizations from across the state, their staff and enrolled youth, experts, and evaluators in an iterative program development process to standardize an effective model that could be replicated and evaluated. ASSESSMENT:Key lessons for program developers and administrators are to ensure adequate staffing with diverse expertise related to the topic and content to support the multiple components of program development and implementation, evaluation, and training; identify the guiding theory and framework early and link them with clearly articulated core components to ensure the final model reflects the intended purpose and is structured to support implementation; engage implementation staff on the ground and focus early and often on processes for supporting people through change. CONCLUSION:The lessons learned can guide others working with existing programs to develop standardized program models or translate new science and theory into practice.
| S-EPMC7497358 | biostudies-literature
Project description:To identify challenges and solutions to the efficient conduct of a multisite, practice-based randomized controlled trial to improve nurses' adherence to personal protective equipment use in ambulatory oncology settings.The Drug Exposure Feedback and Education for Nurses' Safety (DEFENS) study is a clustered, randomized, controlled trial. Participating sites are randomized to Web-based feedback on hazardous drug exposures in the sites plus tailored messages to address barriers versus a control intervention of a Web-based continuing education video.The study principal investigator, the study coordinator, and two site leaders identified challenges to study implementation and potential solutions, plus potential methods to prevent logistical challenges in future studies.Noteworthy challenges included variation in human subjects' protection policies, grants and contracts budgeting, infrastructure for nursing-led research, and information technology variation. Successful strategies included scheduled Web conferences, site-based study champions, site visits by the principal investigator, and centrally based document preparation. Strategies to improve efficiency in future studies include early and continued engagement with contract personnel in sites, and proposed changes to the common rule concerning human subjects. The DEFENS study successfully recruited 393 nurses across 12 sites. To date, 369 have completed surveys and 174 nurses have viewed educational materials.Multisite studies of nursing personnel are rare and challenging to the existing infrastructure. These barriers can be overcome with strong engagement and planning.Leadership engagement, onsite staff support, and continuous communication can facilitate successful recruitment to a workplace-based randomized, controlled behavioral trial.
| S-EPMC5334367 | biostudies-other
Project description:BACKGROUND:Pragmatic randomized clinical trials are essential to determine the effectiveness of interventions in "real-world" clinical practice. These trials frequently use a cluster-randomized methodology, with randomization at the site level. Despite policymakers' increased interest in supporting pragmatic randomized clinical trials, no studies to date have reported on the unique recruitment challenges faced by cluster-randomized pragmatic trials. We investigated key challenges and successful strategies for hospital recruitment in the Comprehensive Post-Acute Stroke Services (COMPASS) study. METHODS:The COMPASS study is designed to compare the effectiveness of the COMPASS model versus usual care in improving functional outcomes, reducing the numbers of hospital readmissions, and reducing caregiver strain for patients discharged home after stroke or transient ischemic attack. This model integrates early supported discharge planning with transitional care management, including nurse-led follow-up phone calls after 2, 30, and 60 days and an in-person clinic visit at 7-14 days involving a functional assessment and neurological examination. We present descriptive statistics of the characteristics of successfully recruited hospitals compared with all eligible hospitals, reasons for non-participation, and effective recruitment strategies. RESULTS:We successfully recruited 41 (43%) of 95 eligible North Carolina hospitals. Leading, non-exclusive reasons for non-participation included: insufficient staff or financial resources (n?=?33, 61%), lack of health system support (n?=?16, 30%), and lack of support of individual decision-makers (n?=?11, 20%). Successful recruitment strategies included: building and nurturing relationships, engaging team members and community partners with a diverse skill mix, identifying gatekeepers, finding mutually beneficial solutions, having a central institutional review board, sharing published pilot data, and integrating contracts and review board administrators. CONCLUSIONS:Although we incorporated strategies based on the best available evidence at the outset of the study, hospital recruitment required three times as much time and considerably more staff than anticipated. To reach our goal, we tailored strategies to individuals, hospitals, and health systems. Successful recruitment of a sufficient number and representative mix of hospitals requires considerable preparation, planning, and flexibility. Strategies presented here may assist future trial organizers in implementing cluster-randomized pragmatic trials. TRIAL REGISTRATION:Clinicaltrials.gov, NCT02588664 . Registered on 23 October 2015.
| S-EPMC5787294 | biostudies-literature
Project description:OBJECTIVES:Numerous studies have found elevated depressive symptoms among individuals with Type 2 diabetes, yet the mechanisms remain unclear. We examined whether genetic loci previously associated with depressive symptoms predict depressive symptoms among overweight/obese individuals with Type 2 diabetes or change in depressive symptoms during behavioral weight loss. METHODS:The Illumina CARe iSelect (IBC) chip and Cardiometabochip were characterized in 2118 overweight or obese participants with Type 2 diabetes from Look AHEAD (Action for Health in Diabetes), a randomized trial to determine the effects of intensive life-style intervention and diabetes support and education on cardiovascular morbidity and mortality. Primary analyses focused on baseline Beck Depression Inventory (BDI) scores and depressive symptom change at 1 year. RESULTS:Of eight single nucleotide polymorphisms (SNPs) in six loci, three a priori SNPs in two loci (chromosome 5: rs60271; LBR: rs2230419, rs1011319) were associated with baseline BDI scores, but in the opposite direction of prior research. In joint analysis of 90,003 IBC and Cardiometabochip SNPs, rs1543654 in the region of KCNE1 predicted change in BDI scores at Year 1 in diabetes support and education (? = -1.05, standard error [SE] = 0.21, p = 6.9 × 10(-7)) at the level of chip-wide significance, while also showing a nominal association with baseline BDI (? = 0.35, SE = 0.16, p = .026). Adjustment for antidepressant medication and/or limiting analyses to non-Hispanic white individuals did not meaningfully alter results. CONCLUSIONS:Previously reported genetic associations with depressive symptoms did not replicate in this cohort of overweight/obese individuals with Type 2 diabetes. We identified KCNE1 as a potential novel locus associated with depressive symptoms.
| S-EPMC4643359 | biostudies-literature