Showing papers by "Ralph B. D'Agostino published in 2020"

Physical distancing interventions and incidence of coronavirus disease 2019: natural experiment in 149 countries.

Abstract: Objective To evaluate the association between physical distancing interventions and incidence of coronavirus disease 2019 (covid-19) globally. Design Natural experiment using interrupted time series analysis, with results synthesised using meta-analysis. Setting 149 countries or regions, with data on daily reported cases of covid-19 from the European Centre for Disease Prevention and Control and data on the physical distancing policies from the Oxford covid-19 Government Response Tracker. Participants Individual countries or regions that implemented one of the five physical distancing interventions (closures of schools, workplaces, and public transport, restrictions on mass gatherings and public events, and restrictions on movement (lockdowns)) between 1 January and 30 May 2020. Main outcome measure Incidence rate ratios (IRRs) of covid-19 before and after implementation of physical distancing interventions, estimated using data to 30 May 2020 or 30 days post-intervention, whichever occurred first. IRRs were synthesised across countries using random effects meta-analysis. Results On average, implementation of any physical distancing intervention was associated with an overall reduction in covid-19 incidence of 13% (IRR 0.87, 95% confidence interval 0.85 to 0.89; n=149 countries). Closure of public transport was not associated with any additional reduction in covid-19 incidence when the other four physical distancing interventions were in place (pooled IRR with and without public transport closure was 0.85, 0.82 to 0.88; n=72, and 0.87, 0.84 to 0.91; n=32, respectively). Data from 11 countries also suggested similar overall effectiveness (pooled IRR 0.85, 0.81 to 0.89) when school closures, workplace closures, and restrictions on mass gatherings were in place. In terms of sequence of interventions, earlier implementation of lockdown was associated with a larger reduction in covid-19 incidence (pooled IRR 0.86, 0.84 to 0.89; n=105) compared with a delayed implementation of lockdown after other physical distancing interventions were in place (pooled IRR 0.90, 0.87 to 0.94; n=41). Conclusions Physical distancing interventions were associated with reductions in the incidence of covid-19 globally. No evidence was found of an additional effect of public transport closure when the other four physical distancing measures were in place. Earlier implementation of lockdown was associated with a larger reduction in the incidence of covid-19. These findings might support policy decisions as countries prepare to impose or lift physical distancing measures in current or future epidemic waves.

Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia

Abstract: This meta-analysis of 24 phase 2 and phase 3 trials summarizes important data about the efficacy and safety of PCSK9 inhibitors in adults with hypercholesterolemia. PCSK9 antibodies produced profou...

The Predictive Approaches to Treatment effect Heterogeneity (PATH) Statement

Abstract: Heterogeneity of treatment effect (HTE) refers to the nonrandom variation in the magnitude or direction of a treatment effect across levels of a covariate, as measured on a selected scale, against a clinical outcome. In randomized controlled trials (RCTs), HTE is typically examined through a subgroup analysis that contrasts effects in groups of patients defined "1 variable at a time" (for example, male vs. female or old vs. young). The authors of this statement present guidance on an alternative approach to HTE analysis, "predictive HTE analysis." The goal of predictive HTE analysis is to provide patient-centered estimates of outcome risks with versus without the intervention, taking into account all relevant patient attributes simultaneously. The PATH (Predictive Approaches to Treatment effect Heterogeneity) Statement was developed using a multidisciplinary technical expert panel, targeted literature reviews, simulations to characterize potential problems with predictive approaches, and a deliberative process engaging the expert panel. The authors distinguish 2 categories of predictive HTE approaches: a "risk-modeling" approach, wherein a multivariable model predicts the risk for an outcome and is applied to disaggregate patients within RCTs to define risk-based variation in benefit, and an "effect-modeling" approach, wherein a model is developed on RCT data by incorporating a term for treatment assignment and interactions between treatment and baseline covariates. Both approaches can be used to predict differential absolute treatment effects, the most relevant scale for clinical decision making. The authors developed 4 sets of guidance: criteria to determine when risk-modeling approaches are likely to identify clinically important HTE, methodological aspects of risk-modeling methods, considerations for translation to clinical practice, and considerations and caveats in the use of effect-modeling approaches. The PATH Statement, together with its explanation and elaboration document, may guide future analyses and reporting of RCTs.

Inhibitors of the Renin-Angiotensin-Aldosterone System and Covid-19.

Abstract: RAAS Inhibitors and Covid-19 The editors comment on three Journal articles that provide observational data about whether ACE inhibitors and ARBs are harmful in the context of the Covid-19 epidemic....

The Predictive Approaches to Treatment effect Heterogeneity (PATH) Statement: Explanation and Elaboration

Abstract: The PATH (Predictive Approaches to Treatment effect Heterogeneity) Statement was developed to promote the conduct of, and provide guidance for, predictive analyses of heterogeneity of treatment effects (HTE) in clinical trials. The goal of predictive HTE analysis is to provide patient-centered estimates of outcome risk with versus without the intervention, taking into account all relevant patient attributes simultaneously, to support more personalized clinical decision making than can be made on the basis of only an overall average treatment effect. The authors distinguished 2 categories of predictive HTE approaches (a "risk-modeling" and an "effect-modeling" approach) and developed 4 sets of guidance statements: criteria to determine when risk-modeling approaches are likely to identify clinically meaningful HTE, methodological aspects of risk-modeling methods, considerations for translation to clinical practice, and considerations and caveats in the use of effect-modeling approaches. They discuss limitations of these methods and enumerate research priorities for advancing methods designed to generate more personalized evidence. This explanation and elaboration document describes the intent and rationale of each recommendation and discusses related analytic considerations, caveats, and reservations.

Establishing the Link Between Lean Mass and Grip Strength Cut Points With Mobility Disability and Other Health Outcomes: Proceedings of the Sarcopenia Definition and Outcomes Consortium Conference.

Abstract: BACKGROUND Lack of consensus on how to diagnose sarcopenia has limited the ability to diagnose this condition and hindered drug development. The Sarcopenia Definitions and Outcomes Consortium (SDOC) was formed to develop evidence-based diagnostic cut points for lean mass and/or muscle strength that identify people at increased risk of mobility disability. We describe here the proceedings of a meeting of SDOC and other experts to discuss strategic considerations in the development of evidence-based sarcopenia definition. METHODS Presentations and panel discussions reviewed the usefulness of sarcopenia as a biomarker, the analytical approach used by SDOC to establish cut points, and preliminary findings, and provided strategic direction to develop an evidence-based definition of sarcopenia. RESULTS The SDOC assembled data from eight epidemiological cohorts consisting of 18,831 participants, clinical populations from 10 randomized trials and observational studies, and 2 nationally representative cohorts. In preliminary assessments, grip strength or grip strength divided by body mass index was identified as discriminators of risk for mobility disability (walking speed <0.8 m/s), whereas dual-energy X-ray absorptiometry-derived lean mass measures were not good discriminators of mobility disability. Candidate definitions based on grip strength variables were associated with increased risk of mortality, falls, mobility disability, and instrumental activities of daily living disability. The prevalence of low grip strength increased with age. The attendees recommended the establishment of an International Expert Panel to review a series of position statements on sarcopenia definition that are informed by the findings of the SDOC analyses and synthesis of literature. CONCLUSIONS International consensus on an evidence-based definition of sarcopenia is needed. Grip strength-absolute or adjusted for body mass index-is an important discriminator of mobility disability and other endpoints. Additional research is needed to develop a predictive risk model that takes into account sarcopenia components as well as age, sex, race, and comorbidities.

Prediction Models — Development, Evaluation, and Clinical Application

Abstract: Prediction Models Prediction models’ newfound importance and the emergence of model development based on machine learning raise questions about how to ensure their safety and efficacy, given their ...

Effects of Weather on Coronavirus Pandemic.

Abstract: The novel coronavirus (SARS-CoV-2) has spread globally and has been declared a pandemic by the World Health Organization. While influenza virus shows seasonality, it is unknown if COVID-19 has any weather-related affect. In this work, we analyze the patterns in local weather of all the regions affected by COVID-19 globally. Our results indicate that approximately 85% of the COVID-19 reported cases until 1 May 2020, making approximately 3 million reported cases (out of approximately 29 million tests performed) have occurred in regions with temperature between 3 and 17 °C and absolute humidity between 1 and 9 g/m3. Similarly, hot and humid regions outside these ranges have only reported around 15% or approximately 0.5 million cases (out of approximately 7 million tests performed). This suggests that weather might be playing a role in COVID-19 spread across the world. However, this role could be limited in US and European cities (above 45 N), as mean temperature and absolute humidity levels do not reach these ranges even during the peak summer months. For hot and humid countries, most of them have already been experiencing temperatures >35 °C and absolute humidity >9 g/m3 since the beginning of March, and therefore the effect of weather, however little it is, has already been accounted for in the COVID-19 spread in those regions, and they must take strict social distancing measures to stop the further spread of COVID-19. Our analysis showed that the effect of weather may have only resulted in comparatively slower spread of COVID-19, but not halted it. We found that cases in warm and humid countries have consistently increased, accounting for approximately 500,000 cases in regions with absolute humidity >9 g/m3, therefore effective public health interventions must be implemented to stop the spread of COVID-19. This also means that 'summer' would not alone stop the spread of COVID-19 in any part of the world.

Randomized Pragmatic Trial of Stroke Transitional Care: The COMPASS Study.

Abstract: Background The objectives of this study were to develop and test in real-world clinical practice the effectiveness of a comprehensive postacute stroke transitional care (TC) management program. Methods and Results The COMPASS study (Comprehensive Post-Acute Stroke Services) was a pragmatic cluster-randomized trial where the hospital was the unit of randomization. The intervention (COMPASS-TC) was initiated at 20 hospitals, and 20 hospitals provided their usual care. Hospital staff enrolled 6024 adult stroke and transient ischemic attack patients discharged home between 2016 and 2018. COMPASS-TC was patient-centered and assessed social and functional determinates of health to inform individualized care plans. Ninety-day outcomes were evaluated by blinded telephone interviewers. The primary outcome was functional status (Stroke Impact Scale-16); secondary outcomes were mortality, disability, medication adherence, depression, cognition, self-rated health, fatigue, care satisfaction, home blood pressure monitoring, and falls. The primary analysis was intention to treat. Of intervention hospitals, 58% had uninterrupted intervention delivery. Thirty-five percent of patients at intervention hospitals attended a COMPASS clinic visit. The primary outcome was measured for 59% of patients and was not significantly influenced by the intervention. Mean Stroke Impact Scale-16 (±SD) was 80.6±21.1 in TC versus 79.9±21.4 in usual care. Home blood pressure monitoring was self-reported by 72% of intervention patients versus 64% of usual care patients (adjusted odds ratio, 1.43 [95% CI, 1.21-1.70]). No other secondary outcomes differed. Conclusions Although designed according to the best available evidence with input from various stakeholders and consistent with Centers for Medicare and Medicaid Services TC policies, the COMPASS model of TC was not consistently incorporated into real-world health care. We found no significant effect of the intervention on functional status at 90 days post-discharge. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02588664.

Radiomics of Coronary Artery Calcium in the Framingham Heart Study.

Abstract: A radiomics-based score that incorporates complex properties of coronary artery calcium may constitute an imaging biomarker to identify individuals at risk for composite endpoint of major adverse c...

A systematic review and meta-analysis of randomized controlled trials for the reduction of surgical site infection in closed incision management versus standard of care dressings over closed vascular groin incisions.

Abstract: ObjectiveSurgical site infection after groin incision is a common complication and a financial burden to patients and healthcare systems. Closed incision negative pressure therapy (ciNPT) has been ...

Periodic Oscillations in Daily Reported Infections and Deaths for Coronavirus Disease 2019.

Abstract: This cross-sectional study investigates oscillatory patterns in daily reported infections and deaths for coronavirus disease 2019.

Simultaneous Left Ventricular Volume and Strain Changes During Chemotherapy Associate With 2‐Year Postchemotherapy Measures of Left Ventricular Ejection Fraction

Abstract: Background Although changes in left ventricular end‐systolic volume (LVESV), left ventricular end‐diastolic volume, and global circumferential strain occur during cancer treatment, the relationship...

Progression to hypertension in youth and young adults with type 1 or type 2 diabetes: The SEARCH for Diabetes in Youth Study

Abstract: Central obesity may contribute to the development of hypertension in youths with diabetes. The SEARCH for Diabetes in Youth Study followed 1518 youths with type 1 diabetes (T1D) and 177 with type 2 diabetes (T2D) diagnosed when <20 years of age for incident hypertension. Incident hypertension was defined as blood pressure ≥95th percentile (or ≥130/80 mm Hg) or reporting antihypertensive therapy among those without hypertension at baseline. Poisson regression models were stratified by diabetes type and included demographic and clinical factors, clinical site, and waist-to-height ratio (WHtR). Youths with T2D were more likely to develop hypertension than those with T1D (35.6% vs 14.8%, P < .0001). For each 0.01 unit of annual increase in WHtR, adjusted relative risk for hypertension was 1.53 (95% CI 1.36-1.73) and 1.20 (95% CI 1.00-1.43) for youths with T1D and T2D, respectively. Effective strategies targeted toward reducing central obesity may reduce hypertension among youths with diabetes.

Phase I trial of convection-enhanced delivery of IL13RA2 and EPHA2 receptor targeted cytotoxins in dogs with spontaneous intracranial gliomas.

Abstract: Wake Forest University Translational Sciences Institute, National Cancer Institute [R01CA139099, R01CA74145, P01CA207206]; Comprehensive Cancer Center of Wake Forest University Brain Tumor Center of Excellence; Hearn Fund for Brain Tumor Research; Pratto Fund for Brain Tumor Research; Dallas Ray Swing Brain Tumor Fund

Attenuating hypoxia driven malignant behavior in glioblastoma with a novel hypoxia-inducible factor 2 alpha inhibitor

Abstract: Hypoxia inducible factor (HIFs) signaling contributes to malignant cell behavior in glioblastoma (GBM). We investigated a novel HIF2α inhibitor, PT2385, both in vitro, with low-passage patient-derived cell lines, and in vivo, using orthotopic models of glioblastoma. We focused on analysis of HIF2α expression in situ, cell survival/proliferation, and survival in brain tumor-bearing mice treated with PT2385 alone and in combination with standard of care chemoradiotherapy. HIF2α expression increased with glioma grade, with over half of GBM specimens HIF2α positive. Staining clustered in perivascular and perinecrotic tumor regions. Cellular phenotype including proliferation, viability, migration/invasion, and also gene expression were not altered after PT2385 treatment. In the animal model, PT2385 single-agent treatment did improve median overall survival compared to placebo (p = 0.04, n = 21) without a bioluminescence correlate (t = 0.67, p = 0.52). No difference in animal survival was seen in combination treatment with radiation (RT)/temozolomide (TMZ)/PT2385 (p = 0.44, n = 10) or mean tumor bioluminescence (t 1.13, p = 0.32). We conclude that HIF2α is a reasonable novel therapeutic target as expressed in the majority of glioblastomas in our cohort. PT2385 as a single-agent was efficacious in vivo, however, an increase in animal survival was not seen with PT2385 in combination with RT/TMZ. Further study for targeting HIF2α as a therapeutic approach in GBM is warranted.

Statistical inference for decision curve analysis, with applications to cataract diagnosis.

Abstract: Statistical learning methods are widely used in medical literature for the purpose of diagnosis or prediction. Conventional accuracy assessment via sensitivity, specificity, and ROC curves does not fully account for clinical utility of a specific model. Decision curve analysis (DCA) becomes a novel complement as it incorporates a clinical judgment of the relative value of benefits (treating a true positive case) and harms (treating a false positive case) associated with prediction models. The preference of a patient or a policy-maker is formulated statistically as the underlying threshold probability, above which the patient would choose to be treated. Net benefit is then calculated for possible threshold probability, which places benefits and harms on the same scale. We consider the inference problems for DCA in this paper. Interval estimation procedure and inference methodology are provided after we derive the relevant asymptotic properties. Our formulation can accommodate the classification problems with multiple categories. We carry out numerical studies to assess the performance of the proposed methods. An eye disease dataset is analyzed to illustrate our proposals.

The FDA and the Importance of Trust.

Abstract: The FDA and the Importance of Trust Under enormous pressure to help patients with Covid-19, clinicians rely on the transparency of the scientific process and on the careful judgment of regulators w...

Baseline 10-Year Cardiovascular Risk Scores Predict Cognitive Function in Older Persons, and Particularly Women, Living With Human Immunodeficiency Virus Infection.

Abstract: Background Cardiovascular disease (CVD) and associated comorbidities increase the risk of cognitive impairment in persons living with human immunodeficiency virus (PLWH). Given the potential composite effect of multiple cardiovascular risk factors on cognition, we examined the ability of the Atherosclerotic Cardiovascular Disease (ASCVD) risk score and the Framingham Heart Study Global CVD risk score (FRS) to predict future cognitive function in older PLWH. Methods We constructed linear regression models evaluating the association between baseline 10-year cardiovascular risk scores and cognitive function (measured by a summary z-score, the NPZ-4) at a year 4 follow-up visit. Results Among 988 participants (mean age, 52 years; 20% women), mean 10-year ASCVD risk score at entry into the cohort was 6.8% (standard deviation [SD], 7.1%) and FRS was 13.1% (SD, 10.7%). In models adjusted only for cognitive function at entry, the ASCVD risk score significantly predicted year 4 NPZ-4 in the entire cohort and after stratification by sex (for every 1% higher ASCVD risk, year 4 NPZ-4 was lower by 0.84 [SD, 0.28] overall, P = .003; lower by 2.17 [SD, 0.67] in women, P = .001; lower by 0.78 [SD, 0.32] in men, P = .016). A similar relationship was observed between FRS and year 4 NPZ-4. In multivariable models, higher 10-year ASCVD risk and FRS predicted lower NPZ-4 in women. Conclusions Baseline 10-year ASCVD risk and FRS predicted future cognitive function in older PLWH with well-controlled infection. Cardiovascular risk scores may help to identify PLWH, especially women, who are at risk for worse cognition over time.

Multireceptor targeting of glioblastoma.

Abstract: Background Treatment for glioblastoma (GBM) remains an unmet need in medicine. Novel therapies that address GBM complexity and heterogeneity in particular are warranted. To this end, we target 4 tumor-associated receptors at a time that span virtually all of the GBM microenvironment including bulk tumor cells, infiltrating tumor cells, neovasculature, and tumor-infiltrating cells with one pharmaceutical agent delivering a cytotoxic load. Methods We engineered multivalent ligand-based vector proteins termed QUAD with an ability to bind to 4 of the following GBM-associated receptors: IL-13RA2, EphA2, EphA3, and EphB2. We conjugated QUAD with a modified bacterial toxin PE38QQR and tested it in vitro and in vivo. Results The QUAD variants preserved functional characteristics of the respective ligands for the 4 receptors. The QUAD 3.0 variant conjugate was highly cytotoxic to GBM cells, but it was nontoxic in mice, and the conjugate exhibited strong antitumor effect in a dog with spontaneous GBM. Conclusion The QUAD addresses, to a large extent, the issues of intra- and intertumoral heterogeneity and, at the same time, it targets several pathophysiologically important tumor compartments in GBM through multiple receptors overexpressed in tumors allowing for what we call "molecular resection." QUAD-based targeted agents warrant further pre- and clinical development.

Myocardial Extracellular and Cardiomyocyte Volume Expand After Doxorubicin Treatment Similar to Adjuvant Breast Cancer Therapy.

Abstract: Increased left ventricular (LV) myocardial extracellular volume fraction (ECVF) measured by cardiac magnetic resonance (CMR) is now a recognized consequence of anthracycline chemotherapy ([1][1],[2][2]). It remains unknown, however, whether elevated ECVF may be attributable to an expansion of the LV

The association of low‐density lipoprotein cholesterol with elevated arterial stiffness in adolescents and young adults with type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth study

Abstract: Aim Our aim was to explore the relationship of Low-Density Lipoprotein Cholesterol (LDL-C) with subclinical cardiovascular disease (CVD) in youth with T1D and T2D. We hypothesized the association of LDL-C with elevated arterial stiffness (AS) would be partially accounted by the co-occurrence of other CVD factors. Method We included 1376 youth with T1D and 157 with T2D from the SEARCH study. CVD risk factors including LDL-C, waist to height ratio (WHtR), mean arterial pressure (MAP), HbA1c, albumin to creatinine ratio (ACR), and insulin sensitivity (IS) score were measured at both visits. At follow up, elevated carotid-femoral AS was defined as levels above 6.8 m/s. Multivariable logistic regression evaluated the odds of elevated AS as a function of the average CVD risk factors. Results At follow up, age was 18.0 ± 4.1 and 21.6 ± 3.5 years and duration of diabetes was 7.8 ± 1.9 and 7.7 ± 1.9 years in T1D and T2D, respectively. Elevated AS was found in 8.4% of T1D and 49.0% of T2D participants. Each SD increase in LDL-C was associated with 1.28 increased odds (95% CI 1.05-1.54, P = .013) of elevated AS in youth with T1D. The association was similar but not statistically significant in T2D. WHtR, IS, and MAP were associated with elevated AS in both groups. Adjustment for WHtR or IS attenuated to non-significance the relationship between LDL-C and AS in T1D. Conclusions Obesity and insulin resistance attenuate the association of high LDL-C with AS suggesting they partially account for the adverse effects of LDL-C on cardiovascular health in youth with T1D.

Transcriptomic Features of T Cell-Barren Tumors Are Conserved Across Diverse Tumor Types.

Abstract: Background: Understanding how tumors subvert immune destruction is essential to the development of cancer immunotherapies. New evidence suggests that tumors limit anti-tumor immunity by exploiting transcriptional programs that regulate intratumoral trafficking and accumulation of effector cells. Here, we investigated the gene expression profiles that distinguish immunologically "cold" and "hot" tumors across diverse tumor types. Methods: RNAseq profiles of tumors (n = 8,920) representing 23 solid tumor types were analyzed using immune gene signatures that quantify CD8+ T cell abundance. Genes and pathways associated with a low CD8+ T cell infiltration profile (CD8-Low) were identified by correlation, differential expression, and statistical ranking methods. Gene subsets were evaluated in immunotherapy treatment cohorts and functionally characterized in cell lines and mouse tumor models. Results: Among different cancer types, we observed highly significant overlap of genes enriched in CD8-Low tumors, which included known immunomodulatory genes (e.g., BMP7, CMTM4, KDM5B, RCOR2) and exhibited significant associations with Wnt signaling, neurogenesis, cell-cell junctions, lipid biosynthesis, epidermal development, and cancer-testis antigens. Analysis of mutually exclusive gene clusters demonstrated that different transcriptional programs may converge on the T cell-cold phenotype as well as predict for response and survival of patients to Nivo treatment. Furthermore, we confirmed that a top-ranking candidate belonging to the TGF-β superfamily, BMP7, negatively regulates CD8+ T cell abundance in immunocompetent murine tumor models, with and without anti-PD-L1 treatment. Conclusions: This study presents the first evidence that solid tumors of diverse anatomical origin acquire conserved transcriptional alterations that may be operative in the T cell-cold state. Our findings demonstrate the potential clinical utility of CD8-Low tumor-associated genes for predicting patient immunotherapy outcomes and point to novel mechanisms with potential for broad therapeutic exploitation.

β2-adrenoreceptor Signaling Increases Therapy Resistance in Prostate Cancer by Upregulating MCL1

Abstract: There is accumulating evidence that continuous activation of the sympathetic nervous system due to psychosocial stress increases resistance to therapy and accelerates tumor growth via β2-adrenoreceptor signaling (ADRB2). However, the effector mechanisms appear to be specific to tumor type. Here we show that activation of ADRB2 by epinephrine, increased in response to immobilization stress, delays the loss of MCL1 apoptosis regulator (MCL1) protein expression induced by cytotoxic drugs in prostate cancer cells; and thus, increases resistance of prostate cancer xenografts to cytotoxic therapies. The effect of epinephrine on MCL1 protein depended on protein kinase A (PKA) activity, but was independent from androgen receptor expression. Furthermore, elevated blood epinephrine levels correlated positively with an increased MCL1 protein expression in human prostate biopsies. In summary, we demonstrate that stress triggers an androgen-independent antiapoptotic signaling via the ADRB2/PKA/MCL1 pathway in prostate cancer cells. IMPLICATIONS: Presented results justify clinical studies of ADRB2 blockers as therapeutics and of MCL1 protein expression as potential biomarker predicting efficacy of apoptosis-targeting drugs in prostate cancer.

Dietary strategies to manage diabetes and glycemic control in youth and young adults with youth-onset type 1 and type 2 diabetes: The SEARCH for diabetes in youth study.

Abstract: AIMS Examine associations of dietary strategies used to manage diabetes over time with hemoglobin A1c in youth-onset type 1 or type 2 diabetes. METHODS The SEARCH for Diabetes in Youth observational study assessed dietary strategies used by 1814 participants with diabetes (n = 1558 type 1, n = 256 type 2) at two to three research visits over 5.5 years (range 1.7-12.2). Participants reported often, sometimes, or never using 10 different dietary strategies, and use over time was categorized into five mutually exclusive groups: often using across visits; started using at later visits; sometimes using across visits; stopped using at later visits; or never using across visits. General multivariable linear models evaluated most recent A1c by use category for each strategy. RESULTS In type 1 diabetes, A1c was lower among those who starting tracking calories (-0.4%, Tukey P < .05), often counted carbs (-0.8%, Tukey P < .001), or sometimes chose low glycemic index foods (-0.5%, Tukey P = .02) vs those with less use, while participants who never drank more milk had the lowest A1c (-0.5%, Tukey P = .04). In type 2 diabetes, A1c was lower among those who often limited high fat foods (-2.0%, Tukey P = .02) or started counting carbohydrates (-1.7%, Tukey P = .07) than those who did so less. CONCLUSIONS For several dietary strategies, more frequent use over time was related to lower A1c in youth-onset type 1 and type 2 diabetes, suggesting these strategies can likely support diabetes management for this population. Investigation into factors predicting receipt of advice for specific strategies and corresponding impact on intake might be considered.

Cardiovascular Outcomes in Relation to Antihypertensive Medication Use in Women with and Without Cancer: Results from the Women's Health Initiative.

Abstract: Background Recent clinical trials have evaluated angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), and beta blockers (BBs) in relation to cardiotoxicity in patients with cancer, typically defined by ejection fraction declines. However, these trials have not examined long-term, hard clinical endpoints. Within a prospective study, we examined the risk of heart failure (HF) and coronary heart disease (CHD) events in relation to use of commonly used antihypertensive medications, including ACEis/ARBs, BBs, calcium channel blockers (CCB), and diuretics, comparing women with and without cancer. Materials and methods In a cohort of 56,997 Women's Health Initiative study participants free of cardiovascular disease who received antihypertensive treatment, we used multivariable-adjusted Cox regression models to calculate the hazard ratios (HRs) of developing CHD, HF, and a composite outcome of cardiac events (combining CHD and HF) in relation to use of ACEis/ARBs, CCBs, or diuretics versus BBs, separately in women with and without cancer. Results Whereas there was no difference in risk of cardiac events comparing ACEi/ARB with BB use among cancer-free women (HR = 0.99 [0.88-1.12]), among cancer survivors ACEi/ARB users were at a 2.24-fold risk of total cardiac events (1.18-4.24); p-interaction = .06). When investigated in relation to CHD only, an increased risk was similarly observed in ACEi/ARB versus BB use for cancer survivors (HR = 1.87 [0.88-3.95]) but not in cancer-free women (HR = 0.91 [0.79-1.06]; p-interaction = .04). A similar pattern was also seen in relation to HF but did not reach statistical significance (p-interaction = .23). Conclusion These results from this observational study suggest differing risks of cardiac events in relation to antihypertensive medications depending on history of cancer. Although these results require replication before becoming actionable in a clinical setting, they suggest the need for more rigorous examination of the effect of antihypertensive choice on long-term cardiac outcomes in cancer survivors. Implications for practice Although additional research is needed to replicate these findings, these data from a large, nationally representative sample of postmenopausal women indicate that beta blockers are favorable to angiotensin-converting enzyme inhibitors in reducing the risk of cardiac events among cancer survivors. This differs from the patterns observed in a noncancer cohort, which largely mirrors what is found in the randomized clinical trials in the general population.

Mid-Cancer Left Ventricular Function Measures Predict Long-Term Post-Cancer Left Ventricular Ejection Fraction.

Abstract: This study was a secondary analysis of previously published results from a National Institutes of Health–funded cohort (R01CA167821) of patients scheduled to receive potentially cardiotoxic chemotherapy ([1][1]). We sought to determine the utility of mid-cancer treatment assessments of left