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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.
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Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Adulto , Humanos , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Fatores de Risco Cardiometabólico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes , Obesidade/complicações , Obesidade/tratamento farmacológico , Sobrepeso/complicações , Sobrepeso/tratamento farmacológicoRESUMO
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.
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Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Estado Pré-Diabético/tratamento farmacológico , Obesidade/complicações , Obesidade/tratamento farmacológico , Hipoglicemiantes/uso terapêuticoRESUMO
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.
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Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Humanos , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Obesidade/tratamento farmacológico , Peso Corporal , Redução de PesoRESUMO
AIMS: Among people with diabetes using insulin, severe hypoglycaemia (SH) can be a life-threatening complication, if untreated. The personal experiences during an SH event from the perspectives of people with diabetes and their caregivers are not well-characterized. This study assessed the perceptions of the event and the decision making processes of people with diabetes (T1D n = 36; T2D n = 24) and their caregivers during SH events. METHODS: In-depth one-on-one telephone interviews were conducted with dyads of people with diabetes and caregivers in the United States (n = 120). An initial synopsis and inductive codebook schema were used to analyse the data with two independent coders (kappa = 0.87-0.89). Themes were developed from the codes, and codes were re-mapped to the themes. RESULTS: Four themes were formed: (1) Caregivers scramble to do the right thing and support people with diabetes in treating SH; (2) Decision making capacity is impaired during an SH event, often a panicked time; (3) People learn to manage SH events through their own experiences and frequently make lifestyle changes to prevent and treat future events; and (4) Discussion with healthcare providers about SH, and particularly SH treatment, is limited. CONCLUSIONS: SH events are stressful and often evoke emotional reactions that can impair decision making. Thus, advance treatment planning of SH events needs to occur. Much of the knowledge about SH treatment derives from prior experience rather than healthcare provider guidance, suggesting a need for healthcare providers to initiate proactive discussions about SH treatment.
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Diabetes Mellitus , Hipoglicemia , Cuidadores , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêuticoRESUMO
BACKGROUND: The National Sleep Research Resource (NSRR) is a large-scale, openly shared, data repository of de-identified, highly curated clinical sleep data from multiple NIH-funded epidemiological studies. Although many data repositories allow users to browse their content, few support fine-grained, cross-cohort query and exploration at study-subject level. We introduce a cross-cohort query and exploration system, called X-search, to enable researchers to query patient cohort counts across a growing number of completed, NIH-funded studies in NSRR and explore the feasibility or likelihood of reusing the data for research studies. METHODS: X-search has been designed as a general framework with two loosely-coupled components: semantically annotated data repository and cross-cohort exploration engine. The semantically annotated data repository is comprised of a canonical data dictionary, data sources with a data dictionary, and mappings between each individual data dictionary and the canonical data dictionary. The cross-cohort exploration engine consists of five modules: query builder, graphical exploration, case-control exploration, query translation, and query execution. The canonical data dictionary serves as the unified metadata to drive the visual exploration interfaces and facilitate query translation through the mappings. RESULTS: X-search is publicly available at https://www.x-search.net/ with nine NSRR datasets consisting of over 26,000 unique subjects. The canonical data dictionary contains over 900 common data elements across the datasets. X-search has received over 1800 cross-cohort queries by users from 16 countries. CONCLUSIONS: X-search provides a powerful cross-cohort exploration interface for querying and exploring heterogeneous datasets in the NSRR data repository, so as to enable researchers to evaluate the feasibility of potential research studies and generate potential hypotheses using the NSRR data.
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Big Data , Mineração de Dados , Bases de Dados Factuais , Conjuntos de Dados como Assunto , Transtornos do Sono-Vigília , Sono , Estudos de Coortes , HumanosRESUMO
A small library of fluoroethoxy-1,4-diphenethyl piperidine and fluoroethoxy-1,4-diphenethyl piperazine derivatives were designed, synthesized and evaluated for their ability to inhibit [3H]dopamine (DA) uptake at the vesicular monoamine transporter-2 (VMAT2) and dopamine transporter (DAT), [3H]serotonin (5-HT) uptake at the serotonin transporter (SERT), and [3H]dofetilide binding at the human-ether-a-go-go-related gene (hERG) channel. The majority of the compounds exhibited potent inhibition of [3H]DA uptake at VMAT2, Ki changes in the nanomolar range (Kiâ¯=â¯0.014-0.073⯵M). Compound 15d exhibited the highest affinity (Kiâ¯=â¯0.014⯵M) at VMAT2, and had 160-, 5-, and 60-fold greater selectivity for VMAT2 vs. DAT, SERT and hERG, respectively. Compound 15b exhibited the greatest selectivity (>60-fold) for VMAT2 relative to all the other targets evaluated, and 15b had high affinity for VMAT2 (Kiâ¯=â¯0.073⯵M). Compound 15b was considered the lead compound from this analog series due to its high affinity and selectivity for VMAT2.
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Dopamina/metabolismo , Piperazinas/química , Piperidinas/química , Proteínas Vesiculares de Transporte de Monoamina/antagonistas & inibidores , Proteínas da Membrana Plasmática de Transporte de Dopamina/química , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Canal de Potássio ERG1/metabolismo , Humanos , Cinética , Piperazinas/metabolismo , Piperidinas/metabolismo , Ligação Proteica , Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/química , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Relação Estrutura-Atividade , Proteínas Vesiculares de Transporte de Monoamina/metabolismoRESUMO
OBJECTIVES: Normal aging results in cognitive decline and nutritional interventions have been suggested as potential approaches for mitigating these deficits. Here, we used rats to investigate the effects of short- and long-term dietary supplementation with the leucine metabolite ß-hydroxy-ß-methyl butyrate (HMB) on working memory and cognitive flexibility. METHODS: Beginning â¼12 months of age, male and female Long-Evans rats were given twice daily access to sipper tubes containing calcium HMB (450â mg/kg) or vehicle (285â mg/kg calcium lactate) in a sucrose solution (20% w/v). Supplementation continued for 1 or 7 months (middle- and old-age (OA) groups, respectively) before testing began. Working memory was assessed by requiring rats to respond on a previously sampled lever following various delays. Cognitive flexibility was assessed by training rats to earn food according to a visual strategy and then, once acquired, shifting to an egocentric response strategy. RESULTS: Treatment with HMB improved working memory performance in middle-age (MA) males and OA rats of both sexes. In the cognitive flexibility task, there was a significant age-dependent deficit in acquisition of the visual strategy that was not apparent in OA males treated with HMB. Furthermore, HMB ameliorated an apparent deficit in visual strategy acquisition in MA females. DISCUSSION: Together, these findings suggest that daily nutritional supplementation with HMB facilitates learning and improves working memory performance. As such, HMB supplementation may mitigate age-related cognitive deficits and may therefore be an effective tool to combat this undesirable feature of the aging process.
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Envelhecimento/efeitos dos fármacos , Cognição/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Valeratos/farmacologia , Animais , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Masculino , Ratos , Ratos Long-EvansRESUMO
AIMS: Continuous glucose monitoring (CGM) metrics can assist diabetes management. Consensus statements recommend > 70 % time in range (TIR) and ≤ 36 % glucose coefficient of variation (CV). However, how these targets perform in clinical practice is unknown. This retrospective, longitudinal cohort study analyzed relationships between TIR, CV, glycated hemoglobin (HbA1c), and hypoglycemia in a real-world setting. METHODS: Data of 542 adults with type 1 diabetes who used CGM (January 2014-July 2020) were analyzed. Associations between TIR and HbA1c at the same and subsequent visits, incidence rate ratios (IRRs) for hypoglycemia at different CVs, and number of hypoglycemic events at cross-sections of HbA1c and CV were estimated by regression. RESULTS: TIR was inversely related to HbA1c; for every 10 % increase in TIR, HbA1c was significantly reduced by 0.34 % (4 mmol/mol) and 0.20 % (2 mmol/mol) at the same and subsequent visits, respectively. Level 2 hypoglycemia was significantly reduced at CV < 30 %, 30-33 %, 33.1-36 %, and 36.1-40 %: adjusted IRRs vs CV ≥ 40.1 % of 0.14, 0.28, 0.32, and 0.50, respectively. Hypoglycemic events were reduced at lower CV across HbA1c levels and at higher HbA1c across CV levels. CONCLUSION: This study quantifies HbA1c improvements with increased TIR and hypoglycemia reductions with improved CV in clinical practice.
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Automonitorização da Glicemia , Glicemia , Diabetes Mellitus Tipo 1 , Hemoglobinas Glicadas , Hipoglicemia , Humanos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Masculino , Estudos Retrospectivos , Adulto , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Automonitorização da Glicemia/métodos , Hipoglicemia/sangue , Hipoglicemia/epidemiologia , Glicemia/análise , Glicemia/metabolismo , Pessoa de Meia-Idade , Estudos Longitudinais , Hipoglicemiantes/uso terapêutico , Monitoramento Contínuo da GlicoseRESUMO
Repeated exposure to psychostimulant drugs is associated with long-lasting changes in cognition, particularly in behavioral tasks that are sensitive to prefrontal cortex function. Adolescents may be especially vulnerable to these drug-induced cognitive changes because of the widespread adaptations in brain anatomy and function that are characteristic of normal development during this period. Here, we used a differential reinforcement of low rates of responding task in rats to determine if amphetamine (AMPH) exposure during adolescence would alter behavioral inhibition in adulthood. Between postnatal days (PND) 27 and 45, rats received every other day injections of saline or AMPH (3 mg/kg). At PND 125, rats were trained progressively through a series of four reinforcement schedules (DRL 5, 10, 15, and 30 s) that required them to withhold responding for the appropriate amount of time before a lever press was reinforced. Relative to controls, AMPH-treated rats displayed transient deficits in behavioral inhibition (i.e., decreases in efficiency ratio) that were only evident at DRL 5. In addition, they had increased responding during nonreinforced periods, which suggested increased perseveration and propensity to attribute incentive salience to reward-paired cues. Following challenge injections with AMPH (.25-1 mg/kg, i.p.), which were given 10 min before the start of DRL 30 test sessions, both groups exhibited dose-dependent decreases in efficiency. These results suggest that AMPH-induced alterations in incentive-motivation and perseveration are more robust and longer-lasting than its effects on impulse control.
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Anfetamina/farmacologia , Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Função Executiva/efeitos dos fármacos , Inibição Psicológica , Desempenho Psicomotor/efeitos dos fármacos , Fatores Etários , Anfetamina/administração & dosagem , Animais , Sinais (Psicologia) , Comportamento Impulsivo/psicologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Esquema de Reforço , RecompensaRESUMO
INTRODUCTION: Glycated hemoglobin A1c (HbA1c) is an important measure to assess glycemic control and predict diabetes complications. However, there is limited information on trends in HbA1c among people with diabetes (PwDs) who use insulin. The aim of this study was to describe trends in HbA1c among PwDs who use insulin by diabetes type and insulin regimen. METHODS: A retrospective analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES, 2009-2020). PwDs were classified into three cohorts: type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus using mealtime insulin (T2DM-MTI), and type 2 diabetes mellitus (T2DM) using basal-only insulin (T2DM basal-only). Trends in HbA1c over time were assessed using regression analysis after adjusting for age, gender, and race/ethnicity. RESULTS: Mean HbA1c values aggregated over 2009-2020 were 8.0% (T1DM), 8.6% (T2DM-MTI), and 8.6% (T2DM basal-only). The American Diabetes Association-recommended target of HbA1c of < 7% was achieved by 25.2% of people in the T1DM and T2DM-MTI groups each and by 12.3% of people in the T2DM basal-only group. Over time, an upward trend was observed in the percentage of people achieving HbA1c < 7% in the T2DM basal-only group. The percentage of PwDs achieving individualized HbA1c targets was 27.0%, 12.4%, and 16.1% for the T1DM, T2DM-MTI, and T2DM basal-only groups, respectively. CONCLUSIONS: Our study using NHANES data suggests that approximately 25% of PwDs achieve glycemic targets. This study highlights the need for improved therapies to better manage glycemic targets in PwDs.
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OBJECTIVE: Insulin pump use is increasing among people with type 2 diabetes (T2D), albeit at a slower rate compared to people with type 1 diabetes (T1D). Factors associated with insulin pump initiation among people with T2D in the real-world are understudied. METHODS: This retrospective, nested case-control study aimed to identify predictors of insulin pump initiation among people with T2D in the United States (US). Adults with T2D who were new to bolus insulin use were identified from the IBM MarketScan Commercial database (2015-2020). Candidate variables of pump initiation were entered into conditional logistic regression (CLR) and penalized CLR models. RESULTS: Of the 32,104 eligible adults with T2D, 726 insulin pump initiators were identified and matched to 2,904 non-pump initiators using incidence density sampling. Consistent predictors of insulin pump initiation across the base case, sensitivity, and post hoc analyses included continuous glucose monitor (CGM) use, visiting an endocrinologist, acute metabolic complications, higher count of HbA1c tests, lower age, and fewer diabetes-related medication classes. CONCLUSIONS: Many of these predictors could represent a clinical indication for treatment intensification, greater patient engagement in diabetes management, or proactive management by healthcare providers. Improved understanding of predictors for pump initiation may lead to more targeted efforts to improve access and acceptance of insulin pumps among persons with T2D.
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Diabetes Mellitus Tipo 2 , Adulto , Humanos , Estados Unidos/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemiantes/uso terapêutico , Estudos Retrospectivos , Estudos de Casos e Controles , Automonitorização da Glicemia , Insulina/uso terapêutico , Glicemia/metabolismo , Aprendizado de MáquinaRESUMO
Economic models in type 1 diabetes have relied on a change in haemoglobin A1c as the link between the blood glucose trajectory and long-term clinical outcomes, including microvascular and macrovascular disease. The landscape has changed in the past decade with the availability of regulatory approved, accurate and convenient continuous glucose monitoring devices and their ability to track patients' glucose levels over time. The data emerging from continuous glucose monitoring have enriched the clinical understanding of the disease and indirectly of patients' behaviour. This has triggered the development of new measures proposed to better define the quality of glycaemic control, beyond haemoglobin A1c. The objective of this paper is to review recent developments in clinical knowledge brought into focus with the application of continuous glucose monitoring devices, and to discuss potential approaches to incorporate the concepts into economic models in type 1 diabetes. Based on a targeted review and a series of multidisciplinary workshops, an influence diagram was developed that captures newer concepts (e.g. continuous glucose monitoring metrics) that can be integrated into economic models and illustrates their association with more established concepts. How the additional continuous glucose monitoring-based indicators of glycaemic control may contribute to economic modelling beyond haemoglobin A1c, and more accurately reflect the economic value of novel type 1 diabetes treatments, is discussed.
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Diabetes Mellitus Tipo 1 , Benchmarking , Glicemia , Automonitorização da Glicemia , Análise Custo-Benefício , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/análise , HumanosRESUMO
INTRODUCTION: Diabetes has been identified as a high-risk comorbidity for COVID-19 hospitalization. We evaluated additional risk factors for COVID-19 hospitalization and in-hospital mortality in a nationwide US database. METHODS: This retrospective study utilized the UnitedHealth Group Clinical Discovery Database (January 1, 2019-July 15, 2020) containing de-identified nationwide administrative claims, SARS-CoV-2 laboratory test results, and COVID-19 inpatient admissions data. Logistic regression was used to understand risk factors for hospitalization and in-hospital mortality among people with type 2 diabetes (T2D) and in the overall population. Robustness of associations was further confirmed by subgroup and sensitivity analyses in the T2D population. RESULTS: A total of 36,364 people were identified who were either SARS-CoV-2+ or hospitalized for COVID-19. T2D was associated with increased COVID-19-related hospitalization and mortality. Factors associated with increased hospitalization risk were largely consistent in the overall population and the T2D subgroup, including age, male sex, and these top five comorbidities: dementia, metastatic tumor, congestive heart failure, paraplegia, and metabolic disease. Biguanides (mainly metformin) were consistently associated with lower odds of hospitalization, whereas sulfonylureas and insulins were associated with greater odds of hospitalization among people with T2D. CONCLUSION: In this nationwide US analysis, T2D was identified as an independent risk factor for COVID-19 complications. Many factors conferred similar risk of hospitalization across both populations; however, particular diabetes medications may be markers for differential risk. The insights on comorbidities and medications may inform population health initiatives, including prevention efforts for high-risk patient populations such as those with T2D.
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OBJECTIVE: To test whether Medicaid expansion is associated with (a) a greater number of naloxone prescriptions dispensed and (b) a higher proportion of naloxone prescriptions paid by Medicaid. DATA SOURCES/STUDY SETTING: We used the IQVIA National Prescription Audit to obtain data on per state per quarter naloxone prescription dispensing for the period 2011-16. STUDY DESIGN: In this quasi-experimental design study, the impact of Medicaid expansion on naloxone prescription dispensing was examined using difference-in-difference estimation models. State-level covariates including pharmacy-based naloxone laws (standing/protocol orders and direct authority to dispense naloxone), third-party prescribing laws, opioid analgesic prescribing rates, opioid-involved overdose death rates, and population size were controlled for in the analysis. PRINCIPAL FINDINGS: Medicaid expansion was associated with 38 additional naloxone prescriptions dispensed per state per quarter compared to nonexpansion controls, on average (P = .030). Also, Medicaid expansion resulted in an average increase of 9.86 percent in the share of naloxone prescriptions paid by Medicaid per state per quarter (P < .001). CONCLUSIONS: Our study found that Medicaid expansion increased naloxone availability. This finding suggests that it will be important to consider naloxone access when making federal- and state-level decisions affecting Medicaid coverage.
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Analgésicos Opioides/economia , Analgésicos Opioides/uso terapêutico , Prescrições de Medicamentos/economia , Medicaid/legislação & jurisprudência , Naloxona/economia , Naloxona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Medicaid/economia , Medicaid/estatística & dados numéricos , Pessoa de Meia-Idade , Patient Protection and Affordable Care Act/economia , Patient Protection and Affordable Care Act/estatística & dados numéricos , Planos Governamentais de Saúde/legislação & jurisprudência , Planos Governamentais de Saúde/estatística & dados numéricos , Estados UnidosRESUMO
The availability of large healthcare datasets offers the opportunity for researchers to navigate the traditional clinical and translational science research stages in a nonlinear manner. In particular, data scientists can harness the power of large healthcare datasets to bridge from preclinical discoveries (T0) directly to assessing population-level health impact (T4). A successful bridge from T0 to T4 does not bypass the other stages entirely; rather, effective team science makes a direct progression from T0 to T4 impactful by incorporating the perspectives of researchers from every stage of the clinical and translational science research spectrum. In this exemplar, we demonstrate how effective team science overcame challenges and, ultimately, ensured success when a diverse team of researchers worked together, using healthcare big data to test population-level substance use disorder (SUD) hypotheses generated from preclinical rodent studies. This project, called Advancing Substance use disorder Knowledge using Big Data (ASK Big Data), highlights the critical roles that data science expertise and effective team science play in quickly translating preclinical research into public health impact.
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About 20% of individuals with attention deficit hyperactivity disorder are first diagnosed during adolescence. While preclinical experiments suggest that adolescent-onset exposure to attention deficit hyperactivity disorder medication is an important factor in the development of substance use disorder phenotypes in adulthood, the long-term impact of attention deficit hyperactivity disorder medication initiated during adolescence has been largely unexplored in humans. Our analysis of 11,624 adolescent enrollees with attention deficit hyperactivity disorder in the Truven database indicates that temporal medication features, rather than stationary features, are the most important factors on the health consequences related to substance use disorder and attention deficit hyperactivity disorder medication initiation during adolescence.
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Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Prescrições de Medicamentos , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Bases de Dados Factuais , Prescrições de Medicamentos/estatística & dados numéricos , HumanosRESUMO
Opioid overdose deaths have been on the rise in the United States since 1999. Naloxone is a competitive opioid antagonist that rapidly reverses opioid overdose. The implementation of naloxone access laws and development of naloxone formulations that can be administered by laypersons have coincided with changes in the landscape of naloxone availability in the United States. Using data from IQVIA's National Prescription Audit® we present the number of naloxone prescriptions dispensed quarterly from 2011 through the second quarter of 2017. The data demonstrate that nationwide naloxone dispensing increased nearly eight-fold from the fourth quarter of 2015 to the second quarter of 2017. Narcan® was the most commonly prescribed naloxone formulation as of the second quarter of 2017, accounting for 68% of prescriptions during that quarter followed by Evzio® (20%). There was considerable variability in the extent to which states experienced increases in naloxone dispensing, which may represent a general state-specific response to the opioid crisis, rather than direct association with opioid overdose death rates in a particular state. Although naloxone access laws continue to increase the amount of naloxone dispensed, cost remains a concern in terms of wide distribution of the life-saving medication.
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Overdose de Drogas/tratamento farmacológico , Overdose de Drogas/epidemiologia , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Prescrições de Medicamentos , Humanos , Estados Unidos/epidemiologiaRESUMO
Compared with adults, adolescent behavior is often characterized by reduced behavioral flexibility, increased sensitivity to reward, and increased likelihood to take risks. These traits, which have been hypothesized to confer heightened vulnerability to psychopathologies such as substance use disorders (SUDs), have been the focus of studies in laboratory animal models that seek to understand their neural underpinnings. However, rodent studies to date have typically used only males and have adopted standard methodological practices (e.g., weight loss inducing food restriction) that are likely to have a disparate impact on adolescents compared with adults. Here, we used adolescent and adult Sprague-Dawley rats of both sexes to study instrumental behavior tasks that assess behavioral flexibility (strategy shifting and reversal learning; Experiment 1), sensitivity to reward value (outcome devaluation; Experiment 2), and risky decision making (probability discounting; Experiment 3). In Experiment 1, we found that adolescents were faster to acquire reversal learning than adults but there were no differences in strategy shifting. In Experiments 2 and 3, adolescents and adults were equally sensitive to changes in reward value and exhibited similar reductions in preference for a large reward when reinforcement probability was decreased. However, adolescents responded more efficiently and earned reinforcers at a higher rate than their same-sex, adult counterparts. Together, these findings provide only limited support for the existence of an "adolescent-typical" phenotype in Sprague-Dawley rats and instead suggest that age differences in the expression of these behaviors may depend on conditions such as pubertal status and motivational state. (PsycINFO Database Record
Assuntos
Envelhecimento/psicologia , Tomada de Decisões/fisiologia , Reversão de Aprendizagem/fisiologia , Recompensa , Assunção de Riscos , Caracteres Sexuais , Envelhecimento/fisiologia , Animais , Condicionamento Operante/fisiologia , Feminino , Masculino , Ratos Sprague-Dawley , Maturidade SexualRESUMO
RATIONALE: Adolescence is a period of considerable development of brain and behavior and is the time during which most drug use is initiated. OBJECTIVE: Age-dependent differences in motivated behaviors may be one of the factors that contribute to heightened vulnerability to developing substance use disorders, so we sought to compare age differences in methamphetamine (METH) and saccharin seeking. METHODS: Beginning during adolescence or adulthood, male and female Sprague-Dawley rats were trained to self-administer 0.1% saccharin (via liquid dipper cup) or intravenous METH at one of three doses (0.02, 0.05, 0.08 mg/kg/inf) under increasing fixed ratio schedules of reinforcement. Subsequently, responding for METH (0.02, 0.05, 0.08, or 0.1 mg/kg/inf) under progressive ratio response requirements was assessed in rats that acquired METH self-administration at the highest dose (0.08 mg/kg/inf). RESULTS: We found that adult-onset rats acquired METH self-administration more readily and exhibited higher motivation compared to adolescent-onset rats, although there were no differences in METH intake during acquisition. Adult rats also acquired saccharin self-administration more readily, but in contrast to METH, there were age and sex differences in saccharin intake driven by high levels of responding in adult females. CONCLUSIONS: These findings challenge the prevailing notion that adolescents are hypersensitive to reward and instead raise questions about the potential role of methodological factors on which rodent studies often differ.
Assuntos
Estimulantes do Sistema Nervoso Central , Comportamento de Procura de Droga/fisiologia , Metanfetamina , Motivação/efeitos dos fármacos , Reforço Psicológico , Sacarina , Edulcorantes , Fatores Etários , Animais , Estimulantes do Sistema Nervoso Central/administração & dosagem , Feminino , Masculino , Metanfetamina/administração & dosagem , Ratos , Ratos Sprague-Dawley , Sacarina/administração & dosagem , Autoadministração/psicologia , Caracteres Sexuais , Edulcorantes/administração & dosagemRESUMO
About 20% of individuals with attention deficit hyperactivity disorder (ADHD) are first diagnosed during adolescence. While preclinical experiments suggest that adolescent-onset exposure to ADHD medication is an important factor in the development of substance use disorder (SUD) phenotypes in adulthood, the long-term impact of ADHD medication initiated during adolescence has been largely unexplored in humans. Our analysis of 11,624 adolescent ADHD patients in the Truven database indicates that temporal medication features are the important factors on the health consequences related to SUD and ADHD medication initiation during adolescence.