Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT-1 post hoc analysis.

AIM: To assess the effect of tirzepatide on long-term risk of atherosclerotic cardiovascular disease (ASCVD) among people with obesity or overweight without diabetes from SURMOUNT-1. MATERIALS AND METHODS: SURMOUNT-1, a phase 3 trial, evaluated the efficacy and safety of tirzepatide in adults with body mass index ≥30 or ≥27 kg/m2 and at least one weight-related complication, excluding diabetes. Participants were randomly assigned to tirzepatide (5/10/15 mg) or placebo. Changes from baseline in cardiometabolic variables were assessed. The predicted 10-year ASCVD risk scores were calculated (American College of Cardiology/American Heart Association risk engine) at baseline, week 24, and week 72 in SURMOUNT-1 participants without a history of ASCVD. Percent change in risk scores from baseline to weeks 24 and 72 was compared between tirzepatide and placebo using mixed model for repeated measures analysis. Analyses were also conducted in participants with intermediate to high risk at baseline. RESULTS: Tirzepatide-treated groups demonstrated reductions in cardiometabolic variables over 72 weeks. In participants without a history of ASCVD (N = 2461), the baseline median risk score was low and did not differ across groups (1.5%-1.6%). Relative change in risk from baseline to week 72 was greater for tirzepatide (-23.5% to -16.4%) than placebo (12.7%; P < 0.001). Relative change among participants with intermediate-to-high baseline risk was significantly greater for tirzepatide (P < 0.05). Intermediate-to-high-risk participants demonstrated similar relative change but greater absolute risk reduction compared to the overall population. CONCLUSION: Tirzepatide treatment significantly reduced the 10-year predicted risk of ASCVD versus placebo in patients with obesity or overweight without diabetes.

Low Rates of Colorectal Cancer Screening in First-Degree Relatives of Our Patients: Are We Failing Them?

BACKGROUND: Guidelines recommend screening those with a family history of early-onset colorectal cancer at age 40 years or 10 years before the age of their relative's diagnosis. Currently, there is no literature reporting the screening rate in these individuals, and no protocols are in place to identify and target this population for screening awareness. OBJECTIVE: This study aimed to assess adherence to current screening guidelines among first-degree relatives of patients with early-onset colorectal cancer. DESIGN: Retrospective and qualitative study involving a telephone survey where patients were asked about relative's screening status and barriers to screening. SETTINGS: Two community-based institutions between January 2018 and December 2021. PATIENTS: Individuals diagnosed with early-onset colorectal cancer who had undergone surgery at our institutions. MAIN OUTCOME MEASURES: Rate of screening in first-degree relatives of our patients with early-onset colorectal cancer. Other factors measured included demographics, clinicopathologic characteristics, and screening barriers. RESULTS: Thirty-six patients were identified. The survey response rate was 66.6% (n = 24). A total of 88 first-degree relatives who met the screening criteria resulted in 67.1% of patients (n = 59) having a known screening status. Of the 59 patients with known screening status, only 44% (n = 26) had undergone screening. Patients of Black race, having stage III/IV disease, having Medicare/Medicaid insurance, and living within Baltimore City County were more likely to have family members with unknown or no screening. Lack of insurance coverage was the most common barrier, which was noted in 12.5% of patients (n = 3), whereas 54.1% of patients (n = 13) reported no barriers to screening. LIMITATIONS: Retrospective design. CONCLUSIONS: Most first-degree relatives of patients diagnosed with early-onset colorectal cancer do not undergo colorectal cancer screening. This could be attributed to the lack of protocols that could guarantee these individuals are informed of their elevated risk and the different options available for screening. Furthermore, our study suggests that racial and socioeconomic disparities exist among high-risk patients who should pursue screening. See Video Abstract . BAJAS TASAS DE DETECCIN DEL CNCER COLORRECTAL EN LOS FAMILIARES DE PRIMER GRADO DE NUESTROS PACIENTES LES ESTAMOS FALLANDO: ANTECEDENTES:Las directrices recomiendan realizar pruebas de detección a las personas con antecedentes familiares de cáncer colorrectal de aparición temprana a los 40 años o 10 años antes de la edad del diagnóstico de su familiar. Actualmente, no hay literatura que informe la tasa de detección en estos individuos y no existen protocolos para identificar y dirigirse a esta población para concientizar sobre la detección.OBJETIVO:Evaluar el cumplimiento de las pautas de detección actuales entre los FDR de pacientes con cáncer colorrectal de aparición temprana.DISEÑO:Estudio retrospectivo y cualitativo que incluyó una encuesta telefónica en la que se preguntó a los pacientes sobre el estado de detección de sus familiares y las barreras para la detección.AJUSTES:Dos instituciones comunitarias entre enero de 2018 y diciembre de 2021.PACIENTES:Personas diagnosticadas con cáncer colorrectal de inicio temprano que habían sido intervenidas quirúrgicamente en nuestras instituciones.PRINCIPALES MEDIDAS DE RESULTADO:Tasa de detección en familiares de primer grado de nuestros pacientes con cáncer colorrectal de aparición temprana. Otros factores medidos incluyeron datos demográficos, características clínico-patológicas y barreras de detección.RESULTADOS:Se identificaron treinta y seis pacientes. La tasa de respuesta a la encuesta fue del 66,6% (n = 24). Resultaron un total de 88 familiares de primer grado que cumplieron con los criterios para la detección, y el 67,1% (n = 59) tenía un estado de detección conocido. De los 59 con estado de detección conocido, se informó que solo el 44% (n = 26) se había sometido a pruebas de detección. Los pacientes de raza afroamericana, enfermedad en etapa III/IV, Medicare/Medicaid y que vivían dentro del condado de la ciudad de Baltimore tenían más probabilidades de tener familiares con pruebas de detección desconocidas o sin ellas. La falta de cobertura de seguro fue la barrera más común observada por el 12,5% (n = 3); mientras que el 54,1% (n = 13) no informó ninguna barrera para el cribado.LIMITACIONES:Diseño retrospectivo.CONCLUSIONES:La mayoría de los familiares de primer grado de pacientes diagnosticados con cáncer colorrectal de aparición temprana no se someten a pruebas de detección de cáncer colorrectal. Esto podría atribuirse a la falta de protocolos que garanticen que estas personas estén informadas sobre su elevado riesgo y las diferentes opciones disponibles para el cribado. Además, nuestro estudio sugiere que existen disparidades raciales y socioeconómicas entre los pacientes de alto riesgo que deberían someterse a pruebas de detección. (Traducción-Dr. Francisco M. Abarca-Rendon).

Metabolomics-derived biomarkers for biosafety assessment of Gd-based nanoparticle magnetic resonance imaging contrast agents.

With the rapid development of nanotechnology and biomedicine, numerous gadolinium (Gd)-based nanoparticle MRI contrast agents have been widely investigated. Due to the unique physicochemical properties of nanoparticles and the complexity of biological systems, the biosafety of Gd-based nanoparticle MRI contrast agents has been paid more and more attention. Herein, for the first time, we employed an ultra-high performance liquid chromatography-electrospray ionization quadrupole time-of-flight/mass spectrometry (UPLC-ESI-QTOF/MS)-based metabolomics approach to investigate the potential toxicity of Gd-based nanoparticle MRI contrast agents. In this work, NaGdF4 and PEG-NaGdF4 nanoparticles were successfully constructed and selected as the representative Gd-based nanoparticle MRI contrast agents for the metabolomics analysis. Based on the results of metabolomics, more metabolic biomarkers and pathways were identified in the NaGdF4 group than those in the PEG-NaGdF4 group. Careful analysis of these metabolic biomarkers and pathways suggested that NaGdF4 nanoparticles induced disturbance of pyrimidine and purine metabolism, inflammatory response, and kidney injury to a certain extent compared with PEG-NaGdF4 nanoparticles. These results indicated that Gd-based nanoparticle contrast agents modified with PEG had better biosafety. Additionally, it was demonstrated that the discovery of characteristic metabolomics biomarkers induced by nanoparticles would provide a new approach for biosafety assessment and stimulate the development of nanomedicine.

Weight-Reduction Preferences Among OBSERVE Study Participants With Obesity or Overweight: Opportunities for Shared Decision-Making.

OBJECTIVE: Limited recent evidence exists regarding weight-reduction preferences among people with obesity in the United States (US). We assessed preferred magnitudes of weight reduction among adults with obesity and how these preferences differ by participant characteristics. METHODS: The Perceptions, Barriers, and Opportunities for Anti-obesity Medications in Obesity Care: A Survey of Patients, Providers and Employers was a cross-sectional study assessing perceptions of obesity and anti-obesity medications among people with obesity, healthcare providers, and employers in the US. Adults with obesity and overweight with obesity-related complications self-reported current weight and weight they associated with 5 preferences ("dream," "goal," "happy," "acceptable," and "disappointed.") Preferred percent weight reductions for each preference were calculated. Multivariable regression analyses were performed identifying associations between weight-reduction preferences and participant characteristics. RESULTS: The study included 1007 participants (women: 63.6%; White: 41.0%; Black or African American: 28.9%; Asian: 6.5%; Hispanic: 15.3%; and median body mass index (BMI): 34.2 kg/m2). Median preferred percent weight reductions were dream = 23.5%; goal = 16.7%; happy = 14.6%; acceptable = 10.3%; and disappointed = 4.8%. Women reported higher preferred weight reductions than men. Preferred weight reductions among Black/African American participants were lower than White participants. Regression analyses indicated significant associations, with higher preferred magnitudes of weight reduction within females, higher weight self-stigma, and BMI class in Hispanic participants compared to White. CONCLUSION: In this large, real-world study, preferred magnitudes of weight reduction exceeded outcomes typically achieved with established nonsurgical obesity treatments but may be attained with bariatric procedures and newer and emerging anti-obesity medications. Respecting patients' preferences for treatment goals with obesity management could help support shared decision-making. Evaluating for an individual's contributors to weight preferences, such as weight self-stigma, can further benefit holistic obesity care.

Biological effects of diesel exhaust inhalation. III cardiovascular function.

OBJECTIVE: Inhalation of diesel exhaust (DE) has been shown to be an occupational hazard in the transportation, mining, and gas and oil industries. DE also contributes to air pollution, and therefore, is a health hazard to the general public. Because of its effects on human health, changes have been made to diesel engines to reduce both the amounts of particulate matter and volatile fumes they generate. The goal of the current study was to examine the effects of inhalation of diesel exhaust. MATERIALS AND METHODS: The study presented here specifically examines the effects of exposure to 0.2 and 1.0 mg/m3 DE or filtered air (6h/d for 4 d) on measures of peripheral and cardio-vascular function, and biomarkers of heart and kidney dysfunction in male rats. A Tier 2 engine used in oil and gas fracking operations was used to generate the diesel exhaust. RESULTS: Exposure to 0.2 mg/m3 DE resulted in an increase in blood pressure 1d following the last exposure, and increases in dobutamine-induced cardiac output and stroke volume 1 and 27d after exposure. Changes in peripheral vascular responses to norepinephrine and acetylcholine were minimal as were changes in transcript expression in the heart and kidney. Exposure to 1.0 mg/m3 DE did not result in major changes in blood pressure, measures of cardiac function, peripheral vascular function or transcript expression. DISCUSSION AND CONCLUSIONS: Based on the results of this study, we suggest that exposure to DE generated by a Tier 2 compliant diesel engine generates acute effects on biomarkers indicative of cardiovascular dysfunction. Recovery occurs quickly with most measures of vascular/cardiovascular function returning to baseline levels by 7d following exposure.

General versus central adiposity as risk factors for cardiovascular-related outcomes in a high-risk population with type 2 diabetes: a post hoc analysis of the REWIND trial.

BACKGROUND: In clinical practice, anthropometric measures other than BMI are rarely assessed yet may be more predictive of cardiovascular (CV) risk. We analyzed the placebo group of the REWIND CV Outcomes Trial to compare several anthropometric measures as baseline risk factors for cardiovascular disease (CVD)-related outcomes in participants with type 2 diabetes (T2D). METHODS: Data from the REWIND trial placebo group (N = 4952) were analyzed. All participants had T2D, age ≥ 50 years, had either a previous CV event or CV risk factors, and a BMI of ≥ 23 kg/m2. Cox proportional hazard models were used to investigate if BMI, waist-to-hip ratio (WHR), and waist circumference (WC) were significant risk factors for major adverse CV events (MACE)-3, CVD-related mortality, all-cause mortality, and heart failure (HF) requiring hospitalization. Models were adjusted for age, sex, and additional baseline factors selected by LASSO method. Results are presented for one standard deviation increase of the respective anthropometric factor. RESULTS: Participants in the placebo group experienced 663 MACE-3 events, 346 CVD-related deaths, 592 all-cause deaths, and 226 events of HF requiring hospitalization during the median follow-up of 5.4 years. WHR and WC, but not BMI, were identified as independent risk factors of MACE-3 (hazard ratio [HR] for WHR: 1.11 [95% CI 1.03 to 1.21]; p = 0.009; HR for WC: 1.12 [95% CI 1.02 to 1.22]; p = 0.012). WC adjusted for hip circumference (HC) showed the strongest association with MACE-3 compared to WHR, WC, or BMI unadjusted for each other (HR: 1.26 [95% CI 1.09 to 1.46]; p = 0.002). Results for CVD-related mortality and all-cause mortality were similar. WC and BMI were risk factors for HF requiring hospitalization, but not WHR or WC adjusted for HC (HR for WC: 1.34 [95% CI 1.16 to 1.54]; p < 0.001; HR for BMI: 1.33 [95% CI 1.17 to 1.50]; p < 0.001). No significant interaction with sex was observed. CONCLUSIONS: In this post hoc analysis of the REWIND placebo group, WHR, WC and/or WC adjusted for HC were risk factors for MACE-3, CVD-related mortality, and all-cause mortality; while BMI was only a risk factor for HF requiring hospitalization. These findings indicate the need for anthropometric measures that consider body fat distribution when assessing CV risk.

Tirzepatide reduces the predicted risk of developing type 2 diabetes in people with obesity or overweight: Post hoc analysis of the SURMOUNT-1 trial.

AIM: We assessed the impact of tirzepatide on 10-year predicted risk of developing type 2 diabetes (T2D) among participants in the SURMOUNT-1 trial. MATERIALS AND METHODS: In this post hoc analysis of SURMOUNT-1, the Cardiometabolic Disease Staging risk engine was used to calculate the 10-year predicted risk of T2D at baseline, week 24 and week 72 among participants randomized to receive 5, 10, or 15 mg tirzepatide or placebo. Mean changes in risk scores from baseline to weeks 24 and 72 were compared between tirzepatide and placebo groups. Subgroup analyses were conducted based on participants' glycaemic status and body mass index at baseline. RESULTS: Mean baseline T2D predicted risk scores did not differ between tirzepatide and placebo groups (range: 22.9%-24.3%). At week 72, mean absolute T2D predicted risk score reductions were significantly greater in tirzepatide groups (5 mg, 12.4%; 10 mg, 14.4%; 15 mg, 14.7%) versus placebo (0.7%). At week 72, median relative predicted risk reductions following tirzepatide treatment ranged from 60.3% to 69.0%. For participants with and without prediabetes, risk reductions were significantly greater in tirzepatide groups versus placebo. At week 72, participants with prediabetes (range: 16.0%-20.3%) had greater mean risk score reductions from baseline versus those without prediabetes (range: 10.1%-11.3%). Across body mass index subgroups, mean reductions from baseline were significantly greater in tirzepatide groups versus placebo. CONCLUSION: Tirzepatide treatment significantly reduced the 10-year predicted risk of developing T2D compared with placebo in participants with obesity or overweight, regardless of baseline glycaemic status.

Tirzepatide 10 and 15 mg compared with semaglutide 2.4 mg for the treatment of obesity: An indirect treatment comparison.

AIM: To compare the efficacy of tirzepatide 10 and 15 mg with semaglutide 2.4 mg using an indirect treatment comparison. MATERIALS AND METHODS: Using SURMOUNT-1 and STEP 1 trial data, mean percentage change in body weight from baseline and odds ratio (OR) of achieving 5% or greater weight loss were compared between tirzepatide 10 and 15 mg at week 72 and semaglutide 2.4 mg at week 68 using matching-adjusted indirect comparison of the efficacy estimand. Sensitivity analyses were completed using different methods, including the Bucher method, also using different estimands and/or time points. RESULTS: Greater reductions in percentage change in body weight were observed with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg (tirzepatide 10 mg mean difference: -4.67% [95% CI -5.91%, -3.43%]; tirzepatide 15 mg mean difference: -5.92% [95% CI -7.16%, -4.68%]; both P < .001). Similarly, more participants achieved 5% or greater weight loss with tirzepatide 10 mg (OR 2.61 [95% CI 1.48, 4.57]; P < .001) and 15 mg (OR 2.75 [95% CI 1.57, 4.81]; P < .001) compared with semaglutide 2.4 mg. All sensitivity analyses were consistent, except for an OR of achieving 5% or greater weight loss with tirzepatide 10 mg using the Bucher method to analyse the treatment regimen estimand (P = .074). CONCLUSIONS: Currently there are no direct comparisons of tirzepatide and semaglutide for weight management. Using the matching-adjusted indirect treatment comparison method to compare the efficacy of tirzepatide and semaglutide for chronic weight management, this analysis showed greater weight loss with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg.

Survival processing advantage demonstrated with virtual reality-based survival environment: A promising tool for survival processing research.

Many studies have been conducted to demonstrate the survival processing advantage (SPA) as an evolutionary-oriented memory effect. But few studies were conducted to demonstrate this effect in real-life or simulated survival environments. This study tested whether the SPA could be replicated in a survival virtual reality environment (VRE). In Experiment 1, the SPAs were measured in VREs (survival grasslands, survival battlefield, nonsurvival moving) in which Experiment 1A used the standard long instructions and Experiment 1B used the modified short instructions. In Experiment 2, the SPAs were measured again with the scenarios corresponding to the VREs used in Experiment 1A. All experiments demonstrated typical SPAs, suggesting that the survival VRE is a reliable tool in designing and delivering a survival situation. The potential problems of applying survival VRE to survival processing research are discussed at the end.

Biological effects of crude oil vapor. IV. Cardiovascular effects.

Workers in the oil and gas extraction industry are at risk of inhaling volatile organic compounds. Epidemiological studies suggest oil vapor inhalation may affect cardiovascular health. Thus, in this hazard identification study we investigated the effects of inhalation of crude oil vapor (COV) on cardiovascular function. Male rats were exposed to air or COV (300 ppm) for 6 h (acute), or 6 h/day × 4 d/wk. × 4 wk. (sub-chronic). The effects of COV inhalation were assessed 1, 28, and 90 d post-exposure. Acute exposure to COV resulted in reductions in mean arterial and diastolic blood pressures 1 and 28 d after exposure, changes in nitrate-nitrite and H2O2 levels, and in the expression of transcripts and proteins that regulate inflammation, vascular remodeling, and the synthesis of nitric oxide (NO) in the heart and kidneys. The sub-chronic exposure resulted in a reduced sensitivity to α1-adrenoreceptor-mediated vasoconstriction in vitro 28 d post-exposure, and a reduction in oxidative stress in the heart. Sub-chronic COV exposure led to alterations in the expression of NO synthases and anti-oxidant enzymes, which regulate inflammation and oxidative stress in the heart and kidneys. There seems to be a balance between changes in the expression of transcripts associated with the generation of reactive oxygen species (ROS) and antioxidant enzymes. The ability of antioxidant enzymes to reduce or inhibit the effects of ROS may allow the cardiovascular system to adapt to acute COV exposures. However, sub-chronic exposures may result in longer-lasting negative health consequences on the cardiovascular system.

Health care utilization and costs of systemic lupus erythematosus in the United States: A systematic review.

OBJECTIVES: To evaluate health care utilization and costs for patients with systemic lupus erythematosus (SLE) by disease severity. METHODS: We searched PubMed and Embase from January 2000 to June 2020 for observational studies examining health care utilization and costs associated with SLE among adults in the United States. Two independent reviewers reviewed the selected full-text articles to determine the final set of included studies. Costs were converted to 2020 US $. RESULTS: We screened 9224 articles, of which 51 were included. Mean emergency department visits were 0.3-3.5 per year, and mean hospitalizations were 0.1-2.4 per year (mean length of stay 0.4-13.0 days). Patients averaged 10-26 physician visits/year. Mean annual direct total costs were $17,258-$63,022 per patient and were greater for patients with moderate or severe disease ($19,099-$82,391) compared with mild disease ($12,242-$29,233). Mean annual direct costs were larger from commercial claims ($24,585-$63,022) than public payers (Medicare and Medicaid: $18,302-$27,142). CONCLUSIONS: SLE remains a significant driver of health care utilization and costs. Patients with moderate to severe SLE use more health care services and incur greater direct and indirect costs than those with mild disease.

Previously unrecognized risk factors for severe hypoglycaemia requiring emergency medical care in insulin-treated type 2 diabetes: Results from a real-world nested case-control study.

AIM: Several risk factors for severe hypoglycaemia (SH) are associated with insulin-treated diabetes. This study explored potential risk factors in adults with insulin-treated type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: In this case-control study, adults with T2DM initiating insulin were identified in the IQVIA PharMetrics® Plus database. The index date was the date of the first SH event (cases). Using incidence-density sampling, controls were selected from those who had been exposed 'at risk' of SH for the same amount of time as each case. After exact-matching on the well-established factors, previously unreported risk factors were evaluated through conditional logistic regression. RESULTS: In 3153 case-control pairs, pregnancy [odds ratios (OR) = 3.20, p = .0003], alcohol abuse (OR = 2.43, p < .0001), short-/rapid-acting insulin (OR = 2.22/1.47, p < .0001), cancer (OR = 1.87, p < .0001), dementia/Alzheimer's disease (OR = 1.73, p = .0175), peripheral vascular disease (OR = 1.59, p < .0001), antipsychotics (OR = 1.59; p = .0059), anxiolytics (OR = 1.51, p = .0012), paralysis/hemiplegia/paraplegia (OR = 1.51, p = .0416), hepatitis (OR = 1.50, p = .0303), congestive heart failure (OR = 1.47, p = .0002), adrenergic-corticosteroid combinations (OR = 1.45, p = .0165), ß-adrenoceptor agonists (OR = 1.40, p = .0225), opioids (OR = 1.38, p < .0001), corticosteroids (OR = 1.35, p = .0159), cardiac arrhythmia (OR = 1.29. p = .0065), smoking (OR = 1.28, p = .005), Charlson Comorbidity Index score 2 (OR = 1.28, p = .0026), 3 (OR = 1.41, p = .0016) or ≥4 (OR = 1.57, p = .0002), liver/gallbladder/pancreatic disease (OR = 1.26, p = .0182) and hypertension (OR = 1.19, p = .0164) were independently associated with SH. CONCLUSIONS: Although all people with insulin-treated diabetes are at risk of SH, these results have identified some previously unrecognized risk factors and sub-groups of insulin-treated adults with T2DM at greater risk. Scrutiny of current therapies and comorbidities are advised as well as additional glucose monitoring and education, when identifying and managing SH in vulnerable populations.

Caffeine intake from coffee and tea and invasive breast cancer incidence among postmenopausal women in the Women's Health Initiative.

Research findings remain inconsistent whether caffeine consumption is associated with invasive breast cancer. We aimed to examine the association between caffeine intake from coffee and tea and incident invasive breast cancer among postmenopausal women. We included 79 871 participants in the Women's Health Initiative Observational Study in the current analysis. Incident invasive breast cancers were identified through September 30, 2015. Caffeine intake (mg/day) from caffeinated and decaffeinated coffee and tea was estimated based on self-reported frequency (cups/day) and average caffeine amount in each beverage. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses were conducted to explore whether associations of caffeine intake from coffee and tea with invasive breast cancer were different by age, race and ethnicity, smoking status, body mass index, history of hormone therapy use, alcohol intake and subtypes of breast cancer. During a median follow-up of 16.0 years, 4719 incident invasive breast cancers were identified. No significant association was found between caffeine intake from coffee and tea and invasive breast cancer incidence after adjusting for demographic, lifestyle and reproductive factors: HRs (95% CIs) for increasing quartiles of caffeine intake compared to the lowest were 1.03 (0.94, 1.12), 1.04 (0.95, 1.13) and 1.03 (0.94, 1.13), respectively (P-for-trend = .54). No significant associations of coffee and tea intake (cups/day) with overall breast cancer risk were found. Our findings are consistent with others showing no clear association of caffeine consumption with invasive breast cancer among postmenopausal women.

Antiobesity Medication Use Among Overweight and Obese Adults in the United States: 2015-2018.

OBJECTIVE: To estimate the utilization of U.S. Food and Drug Administration- approved prescription antiobesity medications (AOMs) and to identify factors associated with AOM use in the United States. METHODS: Respondents aged ≥18 years meeting AOM eligibility criteria in the 2015-2016 and 2017-2018 National Health and Nutrition Examination Survey and the 2016 Medical Expenditure Panel Survey were included in the study. AOM eligibility was defined as having a body mass index (BMI) of ≥30 kg/m2 or having a BMI between 27 and 29.9 kg/m2 and at least 1 obesity-related comorbidity. Demographic, socioeconomic, and clinical characteristics, economic outcomes, and health-related quality of life were summarized and compared between AOM users and nonusers. Multivariable logistic regression was used to identify factors that were associated with AOM use. RESULTS: Only 0.80% of eligible adults reported using AOMs in the past 30 days in 2015-2016 and 2017-2018 National Health and Nutrition Examination Survey. A greater proportion of current AOM users previously tried dietary changes compared with nonusers. They also reported an average weight loss of 3.1 kg over the previous year compared with a 1.5-kg gain among the nonusers. The total health care costs trended higher among AOM users, driven mostly by higher outpatient service costs. A BMI of ≥30 kg/m2, depression, dyslipidemia, and infertility predicted AOM use, whereas Medicare and being at risk of sleep apnea were associated with lower odds of AOM use. CONCLUSION: Despite the availability of newer AOMs and their inclusion in medical treatment guidelines, the utilization of AOMs remains low. This may reflect under-prescribing of and/or restricted patient access to approved evidence-based pharmacotherapy for obesity.

Exploitation of HPLC Analytical Method for Simultaneous Determination of Six Principal Unsaturated Fatty Acids in Oviductus Ranae Based on Quantitative Analysis of Multi-Components by Single-Marker (QAMS).

As one of the featured products in northeast China, Oviductus Ranae has been widely used as a nutritious food, which contains a variety of bioactive unsaturated fatty acids (UFAs). It is necessary to establish a scientific and reliable determination method of UFA contents in Oviductus Ranae. In this work, six principal UFAs in Oviductus Ranae, namely eicosapentaenoic acid (EPA), linolenic acid (ALA), docosahexaenoic acid (DHA), arachidonic acid (ARA), linoleic acid (LA) and oleic acid (OA), were identified using UPLC-MS/MS. The UFAs identified in Oviductus Ranae were further separated based on the optimized RP-HPLC conditions. Quantitative analysis of multi-components by single-marker (QAMS) method was implemented in content determination of EPA, ALA, DHA, ARA and OA, where LA was used as the internal standard. The experiments based on Taguchi design verified the robustness of the QAMS method on different HPLC instruments and chromatographic columns. The QAMS and external standard method (ESM) were used to calculate the UFA content of 15 batches of Oviductus Ranae samples from different regions. The relative error (r < 0.73%) and cosine coefficient showed that the two methods obtained similar contents, and the method validations met the requirements. The results showed that QAMS can comprehensively and effectively control the quality of UFAs in Oviductus Ranae which provides new ideas and solutions for studying the active components in Oviductus Ranae.

Antioxidant Activity Evaluation of Oviductus Ranae Protein Hydrolyzed by Different Proteases.

As nutrition and a health tonic for both medicine and food, the protein content of Oviductus Ranae is more than 40%, making it an ideal source to produce antioxidant peptides. This work evaluated the effects of six different proteases (pepsin, trypsin, papain, flavourzyme, neutral protease and alcalase) on the antioxidant activity of Oviductus Ranae protein, and analyzed the relationship between the hydrolysis time, the degree of hydrolysis (DH) and the antioxidant activity of the enzymatic hydrolysates. The results showed that the antioxidant activity of Oviductus Ranae protein was significantly improved and the optimal hydrolysis time was maintained between 3-4 h under the action of different proteases. Among them, the protein hydrolysate which was hydrolyzed by pepsin for 180 min had the strongest comprehensive antioxidant activity and was most suitable for the production of antioxidant peptides. At this time, the DH, the DPPH radical scavenging activity, the absorbance value of reducing power determination and the hydroxyl radical scavenging activity corresponding to the enzymatic hydrolysate were 13.32 ± 0.24%, 70.63 ± 1.53%, 0.376 ± 0.009 and 31.96 ± 0.78%, respectively. Correlation analysis showed that there was a significant positive correlation between the hydrolysis time, the DH and the antioxidant activity of the enzymatic hydrolysates, further indicating that the hydrolysates of Oviductus Ranae protein had great antioxidant potential. The traditional anti-aging efficacy of Oviductus Ranae is closely related to the scavenging of reactive oxygen species, and its hydrolysates have better antioxidant capacity, which also provides support for further development of its traditional anti-aging efficacy.

Biological effects of inhaled hydraulic fracturing sand dust. VI. Cardiovascular effects.

Hydraulic fracturing is used to access oil and natural gas reserves. This process involves the high-pressure injection of fluid to fracture shale. Fracking fluid contains approximately 95% water, chemicals and 4.5% fracking sand. Workers may be exposed to fracking sand dust (FSD) during the manipulation of the sand, and negative health consequences could occur if FSD is inhaled. In the absence of any information about its potential toxicity, a comprehensive rat animal model study (see Fedan et al., 2020) was designed to investigate the bioactivities of several FSDs in comparison to MIN-U-SIL® 5, a respirable α-quartz reference dust used in previous animal models of silicosis, in several organ systems. The goal of this study was to assess the effects of inhalation of one FSD, i.e., FSD 8, on factors and tissues that affect cardiovascular function. Male rats were exposed to 10 or 30 mg/m3 FSD (6 h/d for 4 d) by whole body inhalation, with measurements made 1, 7 or 27 d post-exposure. One day following exposure to 10 mg/m3 FSD the sensitivity to phenylephrine-induced vasoconstriction in tail arteries in vitro was increased. FSD exposure at both doses resulted in decreases in heart rate (HR), HR variability, and blood pressure in vivo. FSD induced changes in hydrogen peroxide concentrations and transcript levels for pro-inflammatory factors in heart tissues. In kidney, expression of proteins indicative of injury and remodeling was reduced after FSD exposure. When analyzed using regression analysis, changes in proteins involved in repair and remodeling were correlated. Thus, it appears that inhalation of FSD does have some prolonged effects on cardiovascular, and, possibly, renal function. The findings also provide information regarding potential mechanisms that may lead to these changes, and biomarkers that could be examined to monitor physiological changes that could be indicative of impending cardiovascular dysfunction.

Defining and Assessing Geriatric Risk Factors and Associated Health Care Utilization Among Older Adults Using Claims and Electronic Health Records.

BACKGROUND: Using electronic health records (EHRs), in addition to claims, to systematically identify patients with factors associated with adverse outcomes (geriatric risk) among older adults can prove beneficial for population health management and clinical service delivery. OBJECTIVE: To define and compare geriatric risk factors derivable from claims, structured EHRs, and unstructured EHRs, and estimate the relationship between geriatric risk factors and health care utilization. RESEARCH DESIGN: We performed a retrospective cohort study of patients enrolled in a Medicare Advantage plan from 2011 to 2013 using both administrative claims and EHRs. We defined 10 individual geriatric risk factors and a summary geriatric risk index based on diagnosed conditions and pattern matching techniques applied to EHR free text. The prevalence of geriatric risk factors was estimated using claims, structured EHRs, and structured and unstructured EHRs combined. The association of geriatric risk index with any occurrence of hospitalizations, emergency department visits, and nursing home visits were estimated using logistic regression adjusted for demographic and comorbidity covariates. RESULTS: The prevalence of geriatric risk factors increased after adding unstructured EHR data to structured EHRs, compared with those derived from structured EHRs alone and claims alone. On the basis of claims, structured EHRs, and structured and unstructured EHRs combined, 12.9%, 15.0%, and 24.6% of the patients had 1 geriatric risk factor, respectively; 3.9%, 4.2%, and 15.8% had ≥2 geriatric risk factors, respectively. Statistically significant association between geriatric risk index and health care utilization was found independent of demographic and comorbidity covariates. For example, based on claims, estimated odds ratios for having 1 and ≥2 geriatric risk factors in year 1 were 1.49 (P<0.001) and 2.62 (P<0.001) in predicting any occurrence of hospitalizations in year 1, and 1.32 (P<0.001) and 1.34 (P=0.003) in predicting any occurrence of hospitalizations in year 2. CONCLUSIONS: The results demonstrate the feasibility and potential of using EHRs and claims for collecting new types of geriatric risk information that could augment the more commonly collected disease information to identify and move upstream the management of high-risk cases among older patients.

Huntingtin differentially regulates the axonal transport of a sub-set of Rab-containing vesicles in vivo.

Loss of huntingtin (HTT), the Huntington's disease (HD) protein, was previously shown to cause axonal transport defects. Within axons, HTT can associate with kinesin-1 and dynein motors either directly or via accessory proteins for bi-directional movement. However, the composition of the vesicle-motor complex that contains HTT during axonal transport is unknown. Here we analyze the in vivo movement of 16 Rab GTPases within Drosophila larval axons and show that HTT differentially influences the movement of a particular sub-set of these Rab-containing vesicles. While reduction of HTT perturbed the bi-directional motility of Rab3 and Rab19-containing vesicles, only the retrograde motility of Rab7-containing vesicles was disrupted with reduction of HTT. Interestingly, reduction of HTT stimulated the anterograde motility of Rab2-containing vesicles. Simultaneous dual-view imaging revealed that HTT and Rab2, 7 or 19 move together during axonal transport. Collectively, our findings indicate that HTT likely influences the motility of different Rab-containing vesicles and Rab-mediated functions. These findings have important implications for our understanding of the complex role HTT plays within neurons normally, which when disrupted may lead to neuronal death and disease.

Evaluating the Impact of Prescription Fill Rates on Risk Stratification Model Performance.

BACKGROUND: Risk adjustment models are traditionally derived from administrative claims. Prescription fill rates-extracted by comparing electronic health record prescriptions and pharmacy claims fills-represent a novel measure of medication adherence and may improve the performance of risk adjustment models. OBJECTIVE: We evaluated the impact of prescription fill rates on claims-based risk adjustment models in predicting both concurrent and prospective costs and utilization. METHODS: We conducted a retrospective cohort study of 43,097 primary care patients from HealthPartners network between 2011 and 2012. Diagnosis and/or pharmacy claims of 2011 were used to build 3 base models using the Johns Hopkins ACG system, in addition to demographics. Model performances were compared before and after adding 3 types of prescription fill rates: primary 0-7 days, primary 0-30 days, and overall. Overall fill rates utilized all ordered prescriptions from electronic health record while primary fill rates excluded refill orders. RESULTS: The overall, primary 0-7, and 0-30 days fill rates were 72.30%, 59.82%, and 67.33%. The fill rates were similar between sexes but varied across different medication classifications, whereas the youngest had the highest rate. Adding fill rates modestly improved the performance of all models in explaining medical costs (improving concurrent R by 1.15% to 2.07%), followed by total costs (0.58% to 1.43%), and pharmacy costs (0.07% to 0.65%). The impact was greater for concurrent costs compared with prospective costs. Base models without diagnosis information showed the highest improvement using prescription fill rates. CONCLUSIONS: Prescription fill rates can modestly enhance claims-based risk prediction models; however, population-level improvements in predicting utilization are limited.