Understanding the impact of five major determinants of health (genetics, biology, behavior, psychology, society/environment) on type 2 diabetes in U.S. Hispanic/Latino families: Mil Familias - a cohort study.

BACKGROUND: In the United States (U.S.), the prevalence of both diagnosed and undiagnosed type 2 diabetes (T2D) is nearly twice as high among Mexican-origin Hispanic/Latino adults compared to non-Hispanic Whites. Rates of diabetes-related complications, e.g., acute stroke and end-stage renal disease, are also higher among Hispanic/Latino adults compared to their non-Hispanic/Latino White counterparts. Beyond genetic and biological factors, it is now recognized that sociocultural influences are also important factors in determining risk for T2D and the associated complications. These influences include ethnicity, acculturation, residence, education, and economic status. The primary objective of this study is to determine the influence of the 5 major determinants of human health (genetics, biology, behavior, psychology, society/environment) on the burden of T2D for Latino families. To achieve this objective, Mil Familias (www.milfamilias.sansum.org/) is establishing an observational cohort of 1000 Latino families, with at least one family member living with T2D. METHODS: Specially trained, bilingual Latino/a community health workers (Especialistas) recruit participant families and conduct research activities. Each individual family member will contribute data annually on over 100 different variables relating to their genetics, biology, psychology, behavior, and society/environment, creating a Latino-focused biobank ("Living Information Bank"). This observational cohort study is cross-sectional and longitudinal. Participants are divided into 4 groups: adults age ≥ 18 years with and without T2D, and children age ≥ 7 and < 18 years with and without T2D. Study activities take place through encounters between families and their Especialista. Encounters include screening/enrollment, informed consent, health promotion assessment, laboratory tests, questionnaires, physical activity monitoring, and reflection. DISCUSSION: By creating and providing the framework for the Cohort Establishment study, we intend to inform new approaches regarding equity and excellence in diabetes research and care. We will examine the complex set of factors that contribute to the burden of diabetes in Latino families and assess if cardio-metabolic disease risks go beyond the traditional biological and genetic factors. Breaking the code on the interplay of cardio-metabolic risk factors may help not only this fast growing segment of the U.S. population, but also other high-risk populations. TRIAL REGISTRATION: Study retrospectively registered at ClinicalTrials.gov (NCT03830840), 2/5/2019 (enrollment began 2/1/2019).

Treatment patterns in patients with type 2 diabetes mellitus treated with glucagon-like peptide-1 receptor agonists: Higher adherence and persistence with dulaglutide compared with once-weekly exenatide and liraglutide.

AIMS: To compare adherence (proportion of days covered [PDC]), persistence, and treatment patterns among patients with type 2 diabetes mellitus (T2DM) newly initiating glucagon-like peptide-1 receptor agonists (GLP-1RAs). More specifically, the main objectives were to compare dulaglutide vs exenatide once weekly and dulaglutide vs liraglutide. METHODS: Patients with T2DM newly initiating dulaglutide, albiglutide, exenatide once weekly, exenatide twice daily and liraglutide between November 2014 and April 2015 were hierarchically selected from Truven Health's MarketScan Research Databases. Propensity score matching was used to account for selection bias. Adherence to and persistence with the index GLP-1RA, and switching and augmentation patterns were assessed during the 6-month post-index period. RESULTS: Mean adherence for the matched cohorts was significantly higher for dulaglutide than for exenatide once weekly (0.72 vs 0.61; P < .0001) and liraglutide (0.71 vs 0.67; P < .0001). The percentage of patients achieving PDC ≥ 0.80 was significantly higher for dulaglutide compared with exenatide once weekly (54.2% vs 37.9%; P < .0001) and liraglutide (53.5% vs 44.3%; P < .0001). The mean (standard deviation) days on treatment for all matched patients was significantly higher for patients in the dulaglutide cohort compared with those in the exenatide once-weekly (148.4 [55.4] vs 123.6 [61.6]; P < .0001) and liraglutide cohorts (146.0 [56.9] vs 137.4 [60.1]; P < .0001). A significantly lower proportion of patients on dulaglutide discontinued treatment compared with those on exenatide once weekly (26.2% vs 48.4%; P < .0001) and those on liraglutide (28.0% vs 35.6%; P < .0001). CONCLUSIONS: Dulaglutide initiators had significantly higher adherence, were more persistent, and had lower discontinuation rates compared with initiators of exenatide once weekly or liraglutide during the 6-month follow-up period.

Comprehensive review of factors implicated in the heterogeneity of response in depression.

BACKGROUND: Heterogeneity in overall response and outcomes to pharmacological treatment has been reported in several depression studies but with few sources that integrate these results. The goal of this study was to review the literature and attempt to identify nongenetic factors potentially predictive of overall response to depression treatments. METHODS: A comprehensive review of the literature from the last 10 years was performed using three key databases (PubMed, EMBASE, and Cochrane). All relevant studies that met the inclusion criteria were selected and scored for their levels of evidence using the NICE scoring method. A subjective assessment of the strength of evidence for each factor was performed using predefined criteria. RESULTS: Our broad search yielded 76 articles relevant to treatment heterogeneity. Sociodemographic factors, disease characteristics, and comorbidities were the most heavily researched areas. Some of the factors associated with more favorable overall response include being married, other social support, and low levels of baseline depressive symptoms. Evidence relating to baseline disease severity as a factor predictive of antidepressant response was particularly convincing among the factors reviewed. The presence of comorbid anxiety and pain contributed to worse antidepressant treatment outcomes. CONCLUSIONS: Several factors either predictive of or associated with overall response to antidepressant treatment have been identified. Inclusion of factors predictive of response in the design of future trials may help tailor treatments to depression patients presenting to the average clinical practice, resulting in improved outcomes.

Healthcare utilization and costs of children with attention deficit/hyperactivity disorder initiating atomoxetine versus extended-release guanfacine.

OBJECTIVES: To compare 1-year direct healthcare costs and utilization among children and adolescents initiating non-stimulant medications atomoxetine (ATX) or extended-release guanfacine (GXR). METHODS: In this retrospective, observational cohort study, children and adolescents aged 6-17 years with attention deficit/hyperactivity disorder (ADHD) who had ≥1 prescription claim for ATX or GXR between December 31, 2009 and January 1, 2011 were identified in the MarketScan Commercial or Multi-State Medicaid claims databases. The first claim was set as the index. Patients with no claims for other ADHD medications that overlapped with the days' supply for the index therapy during the post-period were classified as initiating monotherapy. All-cause and ADHD-related utilization and costs (2011 US$) and treatment patterns (adherence and persistence) were evaluated during the 12 months following index. Propensity score adjustment accounted for differences in patient characteristics, and bootstrapping was used for comparisons. RESULTS: A total of 13,239 children and adolescents with ADHD met the study criteria (4,411 ATX initiators and 8,828 GXR initiators). There were 2,699 ATX monotherapy patients. In propensity-score-adjusted analyses, mean all-cause total costs were significantly less for monotherapy ATX initiators than for GXR initiators ($7,553 vs $10,639; difference = -$3,086, p < .0001), as were mean ADHD-related total costs ($3,213 vs $4,544; difference = -$1,330, p < .0001). Monotherapy ATX initiators had significantly fewer all-cause and ADHD-related total medical visits and ∼22 days shorter persistence to index therapy (p < .0001). Results were similar for secondary analyses comparing all ATX with all GXR initiators, regardless of monotherapy or combination regimen, and comparing only monotherapy initiators. CONCLUSIONS: Children and adolescents with ADHD who initiated ATX monotherapy incurred lower all-cause and ADHD-related total healthcare costs than patients who initiated GXR. This was due in part to less healthcare resource utilization and slightly shorter persistence for ATX patients. These findings may aid decision-making and inform future studies, but must be tempered due to inherent observational research limitations.

Factors associated with stroke, myocardial infarction, ischemic heart disease, unstable angina, or mortality in patients from real world clinical practice with newly-diagnosed type 2 diabetes and early glycemic control.

OBJECTIVES: The objective of this study was to identify factors associated with stroke, myocardial infarction (MI), all-cause mortality, or a diagnosis of ischemic heart disease (IHD) or unstable angina (UA), among patients newly-diagnosed with type 2 diabetes (T2DM) with no recent history of cardiovascular (CV) events who rapidly achieve and maintain HbA1c ≤8.0%. METHODS: Data were obtained from the Clinical Practice Research Datalink (CPRD) from January 1990 to December 2012. A nested case-control design was used with Cox proportional hazards analysis. Cases were identified by the first occurrence of stroke, MI, IHD, UA, or death within 5 years after HbA1c ≤ 8.0% was first reached (index date) following T2DM diagnosis. Controls were selected using a risk-set sampling approach and were matched 4:1 to cases using index date, exposure time, age, gender, and HbA1c at index date. RESULTS: A total of 11,426 T2DM patients met the inclusion criteria for cases. Of these, 5,261 experienced a CV event. Stroke was the most frequent CV event (40%), followed by IHD (29%), MI (22%), and UA (9%). Mean HbA1c ≥7.0% over the length of exposure (vs 6.5 to <7.0%) was associated with an increased risk of stroke, MI, and IHD. The use of anti-platelet medications at baseline was also associated with increased risk of stroke (HR = 1.82 [CI = 1.60-2.06]), MI (HR = 1.67 [CI = 1.38-2.03]), and IHD (HR = 1.85 [CI = 1.57-2.17]). Mean HbA1c < 6.0% was associated with increased risk of stroke (HR = 1.29 [CI = 1.02-1.63]) and IHD (HR = 1.65 [CI = 1.25-2.19]). Use of nitrate medications at baseline was associated with increased risk of MI (HR = 2.83 [CI = 2.24-3.57]), IHD (HR = 4.32 [CI = 3.57-5.22]), and UA (HR = 10.38 [CI = 7.67-14.03]). CONCLUSIONS: Early and sustained HbA1c control between 6.5 and <7.0% appears to be an important modifiable factor that helps reduce CV risk in patients with newly-diagnosed T2DM in real-world clinical practice.

Real-World Dosing Patterns of Atomoxetine in Adults with Attention-Deficit/Hyperactivity Disorder.

AIMS: The aim was to investigate the dosing patterns of atomoxetine monotherapy in adult patients with attention-deficit/hyperactivity disorder (ADHD) in a retrospective analysis. METHODS: Adult (≥ 18 years) patients with ADHD newly initiated on atomoxetine with ≥ 1 outpatient pharmacy claim for atomoxetine between January 2006 and December 2011 were selected from the Truven Health MarketScan(®) Commercial database. After a 30-day titration period, dosing patterns of atomoxetine monotherapy were analyzed in the 12 months following initiation. In addition, patient demographic and clinical characteristics were compared to identify characteristics associated with suboptimal versus recommended dosing. RESULTS: Of the 12,412 adult patients with ADHD newly initiated on atomoxetine, 4548 (36.6%) were suboptimally dosed, whereas 3323 (26.7%) were treated at recommended dose. Overall, study patients were treated at a mean (standard deviation [SD]) dose of 68.5 (44.9) mg/day. The suboptimal dosing cohort included significantly more females (54% vs. 44%, P < 0.001) and had fewer patients with pre-index use of other ADHD medications (17% vs. 20%, P < 0.001) compared with the recommended dosing cohort. CONCLUSIONS: Adult patients with ADHD receiving atomoxetine therapy in a real-world setting are often dosed suboptimally. Increasing the awareness on optimal dosing strategy among clinicians and patients is warranted to maximize the therapeutic benefits of atomoxetine among adult patients with ADHD.

Heterogeneity of response to biologic treatment: perspective for psoriasis.

Psoriasis treatment responses are affected by patient characteristics. However, the literature does not contain reviews of factors that affect the response to biologic therapies. We therefore performed a comprehensive literature search to identify papers describing demographic, lifestyle, and clinical factors associated with response to biologic drug therapy in psoriatic patients. We found that age, gender, ethnicity, alcohol consumption, smoking, geographic location, age at diagnosis, duration and severity of psoriasis, and baseline C-reactive protein levels did not consistently affect response to biologic psoriasis therapy. However, increased body mass index (BMI) appears to adversely affect responses. It might therefore be valuable to include BMI as a stratification variable in future studies of psoriasis therapies and to consider a patient's weight or BMI when selecting a systemic psoriasis treatment.

Review of treatment response in rheumatoid arthritis: assessment of heterogeneity.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, systemic, progressive, inflammatory disorder. The primary goals of treatment in RA are to reduce the signs and symptoms of disease, prevent progression of joint damage and improve patients' physical function. Patients with different sociodemographic characteristics, varying degrees of severity of illness, and comorbidities tend to exhibit differential response to treatment. The purpose of this review was to identify a broad set of factors that are associated with and/or predictive of RA treatment response and determine those that warrant further research. RESEARCH DESIGN AND METHODS: A comprehensive review of the literature from the last 10 years was performed using three key databases (PubMed, EMBASE, and Cochrane). All relevant articles that met the inclusion/exclusion criteria were selected and scored for their levels of evidence using the National Institute of Clinical Excellence (NICE) scoring method. Data on study design, interventions and treatment outcomes were abstracted using a structured abstraction table. RESULTS: A total of 30 articles were included in the review and data abstraction. Besides gender, baseline clinical variables such as C-reactive protein level, erythrocyte sedimentation rate, measures of disease activity, and Health Assessment Questionnaire scores (based on five patient-centered dimensions) were consistently associated with treatment response over time. CONCLUSIONS: This comprehensive literature review identified several factors associated with treatment response which might be valuable to include as relevant measures in future studies of RA treatment. Inclusion of these factors, particularly those in the clinical and sociodemographic domains, in the design of future trials will further the understanding that ultimately may help clinicians deliver targeted treatment to community practice RA patients, thus resulting in improved patient outcomes.

The role of translational bioinformatics in drug discovery.

The application of translational approaches (e.g. from bed to bench and back) is gaining momentum in the pharmaceutical industry. By utilizing the rapidly increasing volume of data at all phases of drug discovery, translational bioinformatics is poised to address some of the key challenges faced by the industry. Indeed, computational analysis of clinical data and patient records has informed decision-making in multiple aspects of drug discovery and development. Here, we review key examples of translational bioinformatics approaches to emphasize its potential to enhance the quality of drug discovery pipelines, reduce attrition rates and, ultimately, lead to more effective treatments.

Dinorfinas: una nueva familia de opioides endógenos / Dinorphin: a new family of endogenous opioids

Se caracterizan las tres familias de opioides endógenos conocidas: endorfinas, encefalinas y dinorfinas. Se mencionan a sus substancias precursoras. Se analiza la bibliografía a partir de 1975, en que el grupo de Goldstein identificó a la primera dinorfina, y se refieren las implicaciones que las dinorfinas pueden tener sobre analgesia, vasodilatación, vasoconstricción, sistema endócrino, tono muscular, parálisis y movimientos anormales musculares, marcha y estación ortostática así como respuesta inmune, probable influencia sobre crecimiento o involución de tumores, acción protectora cerebral en embolismo experimental en gatos, influencia sobre hambre y sed

Nalbufina-naloxona antagonistas del fentanyl en anestesia pediátrica / Nalbuphine-naloxone fentanyl antagonists in pediatric anesthesia

De Castro y Nalda emplearon la nalbufina desde hace aproximadamente una década como antagonista del fentanyl durante la anestesia analgésica, estos autores han asociado antimorfínicos agonistas (pentazocina-naloxona) para antagonizar la depresión respiratoria de los morfinomiméticos. García, propuso la asociación de un antagonista agonista (nalbufina) y un antagonista agonista (naloxona) en adultos. Basados en este antecedente científico analizamos esta asociación revirtiendo los efectos del fentanyl en niños. Se cóncluye que la asociación nalbufina-naloxona revierte la depresión respiratoria del fentanyl en dosis promedio de 1.91 + ou - 0.62mcg/kg de naloxona más 75.35 + ou - 14.97mcg/kg de nalbufina. La repercusión de esta asociación sobre la frecuencia cardiaca y la tensión arterial sistólica fue mínima o nula, ya que las diferencias de sus promedios analizados a través de la prueba t no fueron significativos. El estado físico post-anestésico evaluado bajo el índice de Aldrete fue en promedio por arriba de los 9 puntos. La asociación nalbufina-naloxona es un elemento útil para el tratamiento de la depresión respiratoria secundaria a morfinosímiles. Esta reversión es de buena calidad desde el punto de vista hemodinámico y mantiene un estado físico post-anestésico satisfactorio

Fentanyl fraccionado y lidocaína en perfusión en anestesia pediátrica / Fractionated fentanyl and perfusion lidocaine in pediatric anesthesia

Se llevó a cabo un estudio clínico, para analizar lidocaína en perfusión; y dosis fraccionadas de citrato de fentanyl, con el objeto de proporcionar un estado anestésico óptimo en 50 pacientes pediátricos intervenidos quirúrgicamente. Se comprobó el efecto potencializador de la lidocaína en asociación con fentanyl. Los resultados fueron procesados estadísticamente, mostrando estabilidad cardiocirculatoria, en base a la respuesta clínica y resultados estadísticos, obteniéndose a anestesia satisfactoria

Asociación de nalbufina-enfluorano en anestesia para paciente pediátrico / Association of nalbuphine-enflurane in anesthesia for pediatric patients

El clorhidrato de nalbufina es un derivado sintético de la morfina, que tiene un poder analgésico útil en anestesiología y con poca influencia depresiva respiratoria. Cuando se asocia a enfluorano, permite disminuir el consumo de este anestésico inhalatorio. Por estas razones, se asociaron estos dos medicamentos para proporcionar un estado anestésico en niños que fueron sometidos a cirugía. Los resultados finales fueron confrontados con otros referidos en la bibliografía

Empleo de clorhidrato de lidocaina durante la intubación endotraqueal de neonatos / Use of lidocaine chlohydrate during endotracheal intubation newborn infants

El propósito de este estudio fue determinar el efecto de la lidocaína IV para la intubación en el recién nacido. Se administró lidocaína 5 mg/Kg. intravenosa, despúes de inducción bajo mascarilla con mezcla de 02-Halotano. Se monitorizaron frecuencia cardiaca, tensión arterial, temperatura y ECG y las condiciones para intubar fueron evaluadas según la escala de Fahey. Se observó estabilidad hemodinámica después de la administración de lidocaína y 76% de los pacientes fueron intubados según el grado 0 de la escala de Fahey. No hubo depresión miocárdica ni signos de toxicidad del sistema nervioso central. Se concluye que la lidocaína administrada por vía IV es un medicamento útil en la intubación para paciente recién nacido

Dosis preparatoria del vecuronio para relajación muscular útil en intubación endotraqueal / Vecuronium priming dose for useful muscle relaxation in endotracheal intubation

Se analizó en el bromuro de vecuronio el fenómeno farmacológico, que en ingles se denomina "Priming Principle" y en español podría llamarse "Principio de Preparación o Cebamiento", en pacientes que fueron anestesiados para instituir tratamiento quirúrgico por diferentes padecimientos oncológicos. Se formaron dos grupos: El grupo "A" o problema, que estuvo constituido por 20 pacientes a los cuales se administró diazepam 5 mg y cinco minutos antes de la intubación de tráquea se aplicó una primera dosis de vecuronio de 15 mcgrs por Kg de peso, la cual supuestamente prepara a la placa neuromuscular y no es paralizante. Se observaron: suficiencia respiratoria, visión borrosa, dificultad, para la deglutación, incapacidad para sacar la lengua y para abrir los ojos. Cuatro minutos después se administró tiopental 5 mg. por Kg. de peso y una segunda dosis de vecuronio, a razón de 50 mcgrs. por Kg. Un minuto después se intentó de la tráquea. En el grupo "B" o control constituido por 15 pacientes, se administraron 5 mg. de diazepam, se anotaron las observaciones antes mencionadas y después de 4 minutos, se aplicó tiopental 5 mcgrs por Kg. de peso y una dosis única de vecuronio de 65 mcgrs. por Kg. de peso. Un minuto después se intentó intubación de tráquea. Las condiciones de relajación muscular fueron buenas en el 100% de los casos del grupo "A" y sólo en el 53.33% del grupo "B" (p<0.05). La respuesta de la placa neuromuscular al estímulo mioeléctrico al minuto de haber aplicado la segunda dosis en el grupo "A" y la dosis única en el grupo "B" mostró lo siguiente: Al tren de cuatro, el 100% de los pacientes del grupo "B", respondieron con 4 contracciones, mientras que en el grupo "A" de 9 pacientes a los que se monitorizó la placa neuromuscular, 2 pacientes no tuvieron contracciones, tres pacientes presentaron una, un paciente presentó tres contracciones y tres pacientes manifestaron cuatro. Respecto al efecto Wedensky en los pacientes que respondieron con 4 contracciones al tren de cuatro, ninguno del grupo "B" lo presentó, en tanto que del grupo "A", de tres pacientes dos sí lo manifestaron. Al analizar la PPT se encontró que 15 pacientes del grupo "B" y tres del grupo "A" que respondieron con 4 contracciones al tren de cuatro, sí la presentaron

Estudio comparativo de la conducta farmacológica de dos bloqueadores neuromusculares, en niños anestesiados sanos e insuficientes renales / Comparative study of the pharmacological effect of 2 neuromuscular agents, in anesthetized health children and patients with renal failure

El empleo de bloqueadores neuromusculares en niños con insuficiencia renal crónica es un asunto aún no resuelto al íntegro. El presente reporte informa de los resultados obtenidos en cuatro grupos de niños anestesiados y en los cuales se empleo bromuro de vecuronio y besilato de atracurio, dos fueron subgrupos de niños sin daño renal y dos subgrupos de pacientes con insuficiencia renal crónica. El tiempo de latencia de ambos fármacos y bajo las circunstancias clínicas descritas fue más en niños con insuficiencia renal a los cuales se les administró vecuronio (X:1.40 min), en tanto que el tiempo más prolongado fue para niños sin daño renal a los que se administró vecuronio (X=2.50 min). El tiempo de acción más corto fue para atracurio en niños sin daño renal (X=23 min) y el tiempo más prolongado fue para vecuronio en niños sin daño renal (X=36 min). Diferencia con significación estadística (p<0.05). Las condiciones de intubación fueron semejantes en todos los grupos (p>0.05). La presión arterial y la frecuencia cardiaca no tuvieron cambio significativos estadísticamente

Estudio comparativo entre el atracurium y el pancuronio en niños anestesiados / Comparative study between atracurion and pancuroniun in chidren under anesthesia

Se realizó un estudio prospectivo en el cual se analizó comparativamente la conducta clínica de dos bloqueadores neuromusculares no depolarizantes (pancuronio y atracurium), en un grupo de 62 niños sometidos a cirugía programada, bajo anestesia analgésica a base de fentanyl. Se observó su influencia sobre la frecuencia cardiaca, tensión arterial y presión ocular, a una dosis de 80 mcgrs. de pancuronio y 600 mcgr. de atracurium, ambos por Kg. de peso. Se analizó el tiempo de latencia y de acción, así como la presencia de efectos indeseables. Las cifras basales de frecuencia cardiaca y tensión arterial con ambos relajantes musculares no sufrieron cambios con significación estadística en el periodo inductivo. Durante el transanestésico hubo decremento significativo de la frecuencia cardiaca y tensión arterial en el grupo al que se le administró atracurium, posiblemente debido a la influencia del fentanyl y al término del tiempo de acción del bloqueador neuromuscular. Se observó también que la presión ocular no sufrió cambios significativos en el grupo del pancuronio, sin embargo el grupo de atracurium incrementó discretamente la presión ocular