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The cost implication of primary prevention in the HOPE 3 trial.
Lamy, A, Lonn, E, Tong, W, Swaminathan, B, Jung, H, Gafni, A, Bosch, J, Yusuf, S
European heart journal. Quality of care & clinical outcomes. 2019;(3):266-271
Abstract
AIMS: The Heart Outcomes Prevention Evaluation-3 (HOPE-3) found that rosuvastatin alone or with candesartan and hydrochlorothiazide (HCT) (in a subgroup with hypertension) significantly lowered cardiovascular events compared with placebo in 12 705 individuals from 21 countries at intermediate risk and without cardiovascular disease. We assessed the costs implications of implementation in primary prevention in countries at different economic levels. METHODS AND RESULTS Hospitalizations, procedures, study and non-study medications were documented. We applied country-specific costs to the healthcare resources consumed for each patient. We calculated the average cost per patient in US dollars for the duration of the study (5.6 years). Sensitivity analyses were also performed with cheapest equivalent substitutes. The combination of rosuvastatin with candesartan/HCT reduced total costs and was a cost-saving strategy in United States, Canada, Europe, and Australia. In contrast, the treatments were more expensive in developing countries even when cheapest equivalent substitutes were used. After adjustment for gross domestic product (GDP), the costs of cheapest equivalent substitutes in proportion to the health care costs were higher in developing countries in comparison to developed countries. CONCLUSION Rosuvastatin and candesartan/HCT in primary prevention is a cost-saving approach in developed countries, but not in developing countries as both drugs and their cheapest equivalent substitutes are relatively more expensive despite adjustment by GDP. Reductions in costs of these drugs in developing countries are essential to make statins and blood pressure lowering drugs affordable and ensure their use. CLINICAL TRIAL REGISTRATION HOPE-3 ClinicalTrials.gov number, NCT00468923.
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Does the Implantable Cardioverter-Defibrillator Benefit Vary With the Estimated Proportional Risk of Sudden Death in Heart Failure Patients?
Levy, WC, Li, Y, Reed, SD, Zile, MR, Shadman, R, Dardas, T, Whellan, DJ, Schulman, KA, Ellis, SJ, Neilson, M, et al
JACC. Clinical electrophysiology. 2017;(3):291-298
Abstract
BACKGROUND Prediction of which heart failure patients are most likely to die of sudden death vs. non-sudden death is an important factor in determining who will benefit the most from an ICD. OBJECTIVE We developed the Seattle Proportional Risk Model (SPRM) to estimate the proportion of total mortality due to sudden death. We prospectively validated the model in HF-ACTION and tested whether the ICD benefit varied with the SPRM. METHODS Among 2331 patients enrolled, 1947 patients were retained for analysis over a median follow-up of 2.5 years. The SPRM was calculated using age, gender, diabetes, BMI, SBP, EF, NYHA, sodium, creatinine, and digoxin use. RESULTS ICD use (ICD or CRT-D) was present prior to death in 1204 patients (62%). SPRM was predictive of sudden death vs. non-sudden death in those without an ICD (P=0.002). The hazard ratio representing ICD versus no ICD was 0.63 for all-cause mortality (P=0.0002). The ICD benefit varied with the SPRM for all-cause mortality (P=0.001), with a greater benefit in those with a higher conditional probability of sudden death. CONCLUSIONS In an ambulatory NYHA II-IV HF population and EF ≤35%, the SPRM was predictive of the proportional risk of sudden vs. non-sudden death. ICDs were associated with a decreased risk of all-cause mortality by 37% and the ICD benefit varied with the SPRM. The SPRM may have utility in risk stratifying patients for a primary prevention ICD.
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Design of lifestyle intervention trials to prevent excessive gestational weight gain in women with overweight or obesity.
Clifton, RG, Evans, M, Cahill, AG, Franks, PW, Gallagher, D, Phelan, S, Pomeroy, J, Redman, LM, Van Horn, L, ,
Obesity (Silver Spring, Md.). 2016;(2):305-13
Abstract
OBJECTIVE The Lifestyle Interventions for Expectant Moms (LIFE-Moms) Consortium is designed to determine, in pregnant women with overweight or obesity, whether various behavioral and lifestyle interventions reduce excessive gestational weight gain (GWG) and subsequent adverse maternal and neonatal outcomes and obesity in offspring. The design and planning process of the LIFE-Moms Consortium is described. METHODS The LIFE-Moms Consortium is a collaboration among seven clinical centers, a Research Coordinating Unit, and the NIH designed to support each clinical center's conduct of a separate trial of a unique intervention. Specific common measures, procedures, and eligibility criteria are consistent across the seven trials allowing data to be combined in exploratory analyses and/or compared readily. RESULTS Numerous committees and working groups were created to define common measures and outcomes during pregnancy and through 1 year postpartum, develop Consortium policies, and oversee progress of the trials. The primary outcome for the Consortium is excessive GWG. Secondary outcomes include maternal, neonatal, and infant anthropometric measures, physical activity, sleep, and complications of pregnancy and delivery. CONCLUSIONS A multi-center consortium of independent, lifestyle interventions with common measures and outcomes may enhance the ability to identify promising interventions for improving outcomes in pregnant women and their offspring.
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Novel Approaches in Primary Cardiovascular Disease Prevention: The HOPE-3 Trial Rationale, Design, and Participants' Baseline Characteristics.
Lonn, E, Bosch, J, Pogue, J, Avezum, A, Chazova, I, Dans, A, Diaz, R, Fodor, GJ, Held, C, Jansky, P, et al
The Canadian journal of cardiology. 2016;(3):311-8
Abstract
BACKGROUND Cholesterol and blood pressure (BP) can be effectively and safely lowered with statin drugs and BP-lowering drugs, reducing major cardiovascular (CV) events by 20%-30% within 5 years in high-risk individuals. However, there are limited data in lower-risk populations. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial is evaluating whether cholesterol lowering with a statin drug, BP lowering with low doses of 2 antihypertensive agents, and their combination safely reduce major CV events in individuals at intermediate risk who have had no previous vascular events and have average cholesterol and BP levels. METHODS A total of 12,705 women 65 years or older and men 55 years or older with at least 1 CV risk factor, no known CV disease, and without any clear indication or contraindication to the study drugs were randomized to rosuvastatin 10 mg/d or placebo and to candesartan/hydrochlorothiazide 16/12.5 mg/d or placebo (2 × 2 factorial design) and will be followed for a mean of 5.8 years. The coprimary study outcomes are the composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke and the composite of CV death, nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, heart failure, and arterial revascularization. RESULTS Participants were recruited from 21 countries in North America, South America, Europe, Asia, and Australia. Mean age at randomization was 66 years and 46% were women. CONCLUSIONS The HOPE-3 trial will provide new information on cholesterol and BP lowering in intermediate-risk populations with average cholesterol and BP levels and is expected to inform approaches to primary prevention worldwide (HOPE-3 ClinicalTrials.gov NCT00468923).
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The IDEFICS intervention trial to prevent childhood obesity: design and study methods.
Pigeot, I, Baranowski, T, De Henauw, S, , , ,
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2015;:4-15
Abstract
INTRODUCTION One of the major research dimensions of the Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS) study involved the development, implementation and evaluation of a setting-based community-oriented intervention programme for primary prevention of childhood obesity. In this supplement of Obesity Reviews, a compilation of key results of the IDEFICS intervention is packaged in a series of complementary papers. OBJECTIVE This paper describes the overall design and methods of the IDEFICS intervention in order to facilitate a comprehensive reading of the supplement. In addition, some 'best practice' examples are described. RESULTS The IDEFICS intervention trial was conducted to assess whether the IDEFICS intervention prevented obesity in young children aged 2 to 9.9 years. The study was a non-randomized, quasi-experimental trial with one intervention matched to one control region in each of eight participating countries. The intervention was designed following the intervention mapping framework, using a socio-ecological theoretical approach. The intervention was designed to address several key obesity-related behaviours in children, parents, schools and community actors; the primary outcome was the prevalence of overweight/obesity according to the IOTF criteria based on body mass index. The aim was to achieve a reduction of overweight/obesity prevalence in the intervention regions. The intervention was delivered in school and community settings over a 2-year period. Data were collected in the intervention and control cohort regions at baseline and 2 years later. CONCLUSION This paper offers an introductory framework for a comprehensive reading of this supplement on IDEFICS intervention key results.
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Mapisal Versus Urea Cream as Prophylaxis for Capecitabine-Associated Hand-Foot Syndrome: A Randomized Phase III Trial of the AIO Quality of Life Working Group.
Hofheinz, RD, Gencer, D, Schulz, H, Stahl, M, Hegewisch-Becker, S, Loeffler, LM, Kronawitter, U, Bolz, G, Potenberg, J, Tauchert, F, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2015;(22):2444-9
Abstract
PURPOSE Hand-foot syndrome (HFS) is a frequently occurring adverse event associated with anticancer drugs. This study compares a newly introduced ointment containing several antioxidants and exhibiting high radical protection factor, which has been available on the German market since 2011, with urea cream for prevention of HFS in patients treated with capecitabine. PATIENTS AND METHODS Patients with GI tumors or breast cancer treated with capecitabine were included in this randomized phase III study. The primary end point was prevention of HFS of any grade within 6 weeks of treatment as indicated by a standardized patient diary. The study had 80% power to show a 20% reduction of the incidence of HFS with the new ointment. Secondary end points included time to development of HFS greater than grade 1, evaluation of capecitabine dose intensity, and quality of life analyses. RESULTS A total of 152 patients were evaluable. In total, 47 of 152 patients experienced HFS (30.9%), 39.5% with the new ointment and 22.4% in the urea arm (stratified odds ratio, 2.37; P = .02). Time to HFS greater than grade 1 was comparable, but time to any-grade HFS was significantly longer in the urea group (P = .03). Capecitabine dose intensity, time under study, and percentage of days with correct administration of study medication were identical, as were adverse events except for HFS. Skin-related quality of life was significantly worse in the group treated with the new ointment at the end of study treatment. CONCLUSION This trial demonstrated that 10% urea cream was superior to the new ointment at preventing HFS over the first 6 weeks of treatment with capecitabine.
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Assessment of Life's Simple 7 in the primary care setting: the Stroke Prevention in Healthcare Delivery EnviRonmEnts (SPHERE) study.
Foraker, RE, Shoben, AB, Lopetegui, MA, Lai, AM, Payne, PR, Kelley, M, Roth, C, Tindle, H, Schreiner, A, Jackson, RD
Contemporary clinical trials. 2014;(2):182-9
Abstract
BACKGROUND Adverse health behaviors and factors predict increased coronary heart disease and stroke risk, and effective use of health information technology (HIT) to automate assessment of and intervention on these factors is needed. A comprehensive, automated cardiovascular health (CVH) assessment deployed in the primary care setting offers the potential to enhance prevention, facilitate patient-provider communication, and ultimately reduce cardiovascular (CV) disease risk. We describe the methods for a study to develop and test an automated CVH application for stroke prevention in older women. METHODS AND RESULTS The eligible study population for the Stroke Prevention in Healthcare Delivery EnviRonmEnts (SPHERE) study is approximately 1600 female patients aged 65 years and older and their primary care providers at The Ohio State University Wexner Medical Center. We will use an intervention design that will allow for a run-in period, comparison group data collection, a provider education period, and implementation of a best practice alert to prompt provider-patient interactions regarding CVH. Our primary outcome is a CVH score, comprising Life's Simple 7: smoking status, body mass index, blood pressure, cholesterol, fasting glucose, physical activity, and diet. The SPHERE application will generate visualizations of the CVH score within the electronic health record (EHR) during the patient-provider encounter. A key outcome of the study will be change in mean CVH score pre- and post-intervention. CONCLUSIONS The SPHERE application leverages the EHR and may improve health outcomes through HIT designed to empower clinicians to discuss CVH with their patients and enhance primary prevention efforts.
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Using prophylactic antioxidants to prevent noise-induced hearing damage in young adults: a protocol for a double-blind, randomized controlled trial.
Gilles, A, Ihtijarevic, B, Wouters, K, Van de Heyning, P
Trials. 2014;:110
Abstract
BACKGROUND During leisure activities young people are often exposed to excessive noise levels resulting in an increase of noise-induced symptoms such as hearing loss, tinnitus and hyperacusis. Noise-induced tinnitus is often perceived after loud music exposure and provides an important marker for overexposure as a temporary threshold shift that is often not experienced by the individual itself. As oxidative stress plays an important role in the pathogenesis of noise-induced hearing loss, the use of antioxidants to prevent hearing damage has recently become the subject of research. METHODS This study proposes a randomized, double-blind, placebo-controlled crossover trial to assess the effects of a prophylactic combination of N-acetylcysteine (600 mg) and magnesium (200 mg) prior to leisure noise exposure in young adults. The primary outcome measure is the tinnitus loudness scored by a visual analogue scale (VAS). Secondary outcome measures are the differences in audiological measurements for the antioxidant treatments compared to placebo intake. Audiological testing comprising of pure tone audiometry including frequencies up to 16 kHz, distortion product otoacoustic emissions, transient-evoked otoacoustic emissions and speech-in-noise testing will be performed prior to and within 7 hours after noise exposure. By use of a mixed effects statistical model, the effects of antioxidants compared to placebo intake will be assessed. DISCUSSION As adolescents and young adults often do not use hearing protection while being exposed to loud music, the use of preventive antioxidant intake may provide a useful and harmless way to prevent noise-induced hearing damage in this population. Furthermore, when exposed to hazardous noise levels the protection provided by hearing protectors might not be sufficient to prevent hearing damage and antioxidants may provide additive otoprotective effects. Previous research mainly focused on occupational noise exposure. The present study provides a protocol to assess the usefulness of antioxidants during leisure noise activities. TRIAL REGISTRATION The present protocol is registered at ClinicalTrials.gov: NCT01727492.
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Recruitment results among families contacted for an obesity prevention intervention: the Obesity Prevention Tailored for Health Study.
Ghai, NR, Reynolds, KD, Xiang, AH, Massie, K, Rosetti, S, Blanco, L, Martinez, MP, Quinn, VP
Trials. 2014;:463
Abstract
BACKGROUND Overweight and obesity are serious threats to health and increase healthcare utilization and costs. The Obesity Prevention Tailored for Health (OPT) study was designed to test the effectiveness of a family-based intervention targeting diet and physical activity. We describe the results of efforts to recruit parents and children enrolled in a large managed-care organization into the OPT study. METHODS Parents with 10- to 12-year-old children were randomly selected from the membership of Kaiser Permanente Southern California, a large integrated health plan, and contacted between June 2010 and November 2011. We describe recruitment outcomes and compare characteristics of parents and children who did and did not participate. Information was collected from calls with parents and through the administrative and electronic medical records of the health plan. RESULTS Of the 4,730 parents contacted, 16.1% expressed interest in participation (acceptors), 28.8% declined participation (refusers), 4.7% were ineligible, and, even after multiple attempts, we were unable to reach 50.4%. Slightly less than half of the acceptors (n = 361) were ultimately randomized to receive either the OPT program plus usual care or usual care alone (7.6% of all parents initially contacted). There were not any significant differences between acceptors who were or were not randomized. Overall, we found that acceptors were more likely to be female parents, have overweight/obese children, and higher utilization of outpatient visits by parents and children compared with refusers and those we were unable to reach. We found no differences in recruitment outcomes by body mass index or comorbidity score of the parents, level of physical activity of the parents and children, education of the parents, or household income. CONCLUSIONS Recruiting parents and children into an obesity prevention program in a healthcare setting proved to be challenging and resource-intensive. Barriers and incentives for participation in obesity prevention programs need to be identified and addressed. Concern for the weight of their children may motivate parents to participate in family-based lifestyle interventions; however, the healthcare setting may be more relevant to weight-related treatment than to primary prevention. TRIAL REGISTRATION NUMBER ISRCTN06248443, 30 January 2014.
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Quantifying cardiometabolic risk using modifiable non-self-reported risk factors.
Marino, M, Li, Y, Pencina, MJ, D'Agostino, RB, Berkman, LF, Buxton, OM
American journal of preventive medicine. 2014;(2):131-40
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Abstract
BACKGROUND Sensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance. PURPOSE To develop and validate a cumulative general cardiometabolic risk score that focuses on non-self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut-off points for risk categories. METHODS We prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14-year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender-specific Cox proportional hazards models were considered to evaluate the effects of non-self-reported modifiable risk factors (blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10-year general cardiometabolic risk score functions and evaluated its predictive performance in 2012-2013. RESULTS HbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit chi-square=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively). CONCLUSIONS This study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk on the basis of modifiable risk factors that can motivate an individual's commitment to prevention and intervention.