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We report that two widely-used drugs for erectile dysfunction, tadalafil and vardenafil, trigger bone gain in mice through a combination of anabolic and antiresorptive actions on the skeleton. Both drugs were found to enhance osteoblastic bone formation in vivo using a unique gene footprint and to inhibit osteoclast formation. The target enzyme, phosphodiesterase 5A (PDE5A), was found to be expressed in mouse and human bone as well as in specific brain regions, namely the locus coeruleus, raphe pallidus, and paraventricular nucleus of the hypothalamus. Localization of PDE5A in sympathetic neurons was confirmed by coimmunolabeling with dopamine ß-hydroxylase, as well as by retrograde bone-brain tracing using a sympathetic nerve-specific pseudorabies virus, PRV152. Both drugs elicited an antianabolic sympathetic imprint in osteoblasts, but with net bone gain. Unlike in humans, in whom vardenafil is more potent than tadalafil, the relative potencies were reversed with respect to their osteoprotective actions in mice. Structural modeling revealed a higher binding energy of tadalafil to mouse PDE5A compared with vardenafil, due to steric clashes of vardenafil with a single methionine residue at position 806 in mouse PDE5A. Collectively, our findings suggest that a balance between peripheral and central actions of PDE5A inhibitors on bone formation together with their antiresorptive actions specify the osteoprotective action of PDE5A blockade.
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Disfunción Eréctil/tratamiento farmacológico , Osteogénesis/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/farmacología , Envejecimiento/fisiología , Animales , Densidad Ósea/efectos de los fármacos , Densidad Ósea/fisiología , Huesos/citología , Huesos/efectos de los fármacos , Huesos/metabolismo , Encéfalo/citología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Diferenciación Celular/efectos de los fármacos , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/química , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/metabolismo , Reposicionamiento de Medicamentos , Disfunción Eréctil/complicaciones , Humanos , Masculino , Ratones , Persona de Mediana Edad , Modelos Animales , Modelos Moleculares , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Osteoblastos/efectos de los fármacos , Osteoblastos/fisiología , Osteoclastos/efectos de los fármacos , Osteoclastos/fisiología , Osteoporosis/complicaciones , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/prevención & control , Inhibidores de Fosfodiesterasa 5/química , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Cultivo Primario de Células , Tadalafilo/química , Tadalafilo/farmacología , Tadalafilo/uso terapéutico , Diclorhidrato de Vardenafil/química , Diclorhidrato de Vardenafil/farmacología , Diclorhidrato de Vardenafil/uso terapéuticoRESUMEN
INTRODUCTION: Understanding trends and associated factors in internet-based health care communication (IBHC) among cancer survivors is important for meeting patient needs because their reliance on telehealth is growing. We aimed to examine IBHC use among cancer survivors in the US. METHODS: We identified adult cancer survivors aged 18 to 64 (n = 8,029) and 65 or older (n = 11,087) from the National Health Interview Survey in 2011-2018. We calculated temporal trends of self-reported IBHC in the previous year (filled a prescription, scheduled a medical appointment, or communicated with a health care provider) and used multivariable logistic models to identify associated factors. RESULTS: Approximately 84% of survivors had been diagnosed 2 years or more before the survey. IBHC prevalence increased among cancer survivors aged 18 to 64, from 19.3% to 40.2%, and among those aged 65 or older, from 11.4% to 22.6%, from 2011 to 2018 (P for trend <.001). Among both age groups, lower educational attainment, lack of usual source of care, and current smoking were associated with less IBHC, whereas residing in the South or West, having 1 or more chronic conditions, and drinking any alcohol were associated with higher IBHC (all P < .05). Factors associated with less IBHC also included being non-Hispanic Black or Hispanic, lacking private insurance, and being 11 or more years postdiagnosis among survivors aged 18 to 64; among survivors aged 65 or older, factors were being an older age, not married, and non-US born (all P < .05). CONCLUSION: IBHC among cancer survivors is common and increasing, with differences across sociodemographic and behavioral characteristics. As health care delivery continues adopting IBHC and other advanced telehealth techniques, disparities need to be addressed to ensure equitable access to care for all cancer survivors.
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Supervivientes de Cáncer , Neoplasias , Telemedicina , Adulto , Anciano , Comunicación , Humanos , Internet , Neoplasias/epidemiología , SobrevivientesRESUMEN
The SGLT2 inhibitor empagliflozin reduced cardiovascular mortality by 38% and heart failure (HF) hospitalizations by 35% in diabetic patients. We have recently demonstrated the efficacy of empagliflozin in ameliorating HF and improving cardiac function in a non-diabetic porcine model of HF mediated via a switch in myocardial metabolism that enhances cardiac energetics. Therefore, we hypothesized that the cardiac benefits of empagliflozin can also be extended to non-diabetic HF patients. The EMPA-TROPISM clinical trial is a randomized, double-blind, parallel group, placebo-controlled, trial comparing the efficacy of and safety of empagliflozin in non-diabetic HF patients. Eighty patients with stable HF for over 3 months, LVEF < 50%, and New York Heart Association functional class II to IV symptoms will be randomized to empagliflozin 10 mg for 6 months or placebo. All patients will undergo cardiac magnetic resonance (CMR), cardiopulmonary exercise test (CPET), 6-min walk test, and quality of life questionnaires. The primary outcome is the change in left ventricular end-diastolic volume measured by CMR. Secondary end-points include change in peak VO2 (CPET); change in LV mass, in LVEF, in myocardial mechanics (strains), in left atrium volumes, in RV function and volumes, in interstitial myocardial fibrosis, and in epicardial adipose tissue (CMR); change in the distance in the 6-min walk test; and changes in quality of life (Kansas Cardiomyopathy questionnaire [KCCQ-12] and the 36-Item Short Form Survey [SF-36]). Safety issues (e.g., hypoglycemia, urinary infections, ketoacidosis, ) will also be monitored. In summary, EMPA-TROPISM clinical trial will determine whether the SGLT2 inhibitor empagliflozin improves cardiac function and heart failure parameters in non-diabetic HF patients (EMPA-TROPISM [ATRU-4]: Are the "cardiac benefits" of Empagliflozin independent of its hypoglycemic activity; NCT 03485222).
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Compuestos de Bencidrilo/uso terapéutico , Fármacos Cardiovasculares/uso terapéutico , Glucósidos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Compuestos de Bencidrilo/efectos adversos , Fármacos Cardiovasculares/efectos adversos , Método Doble Ciego , Tolerancia al Ejercicio/efectos de los fármacos , Glucósidos/efectos adversos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Imagen por Resonancia Magnética , Ciudad de Nueva York , Estudios Prospectivos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la Función , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Función Ventricular Izquierda/efectos de los fármacos , Función Ventricular Derecha/efectos de los fármacos , Prueba de PasoRESUMEN
OBJECTIVE: Glargine and detemir insulin are the two most commonly prescribed basal insulin analogues for the ambulatory and inpatient management of diabetes. The efficacy and safety of basal insulin analogues in the hospital setting has not been established. METHODS: This observational study compared differences in glycemic control and outcomes in non-intensive care unit patients with blood glucose (BG) >140 mg/dL who were treated with glargine or detemir, between January 1, 2012, and September 30, 2015, in two academic centers. RESULTS: Among 6,245 medical and surgical patients with hyperglycemia, 5,749 received one or more doses of glargine, and 496 patients received detemir during the hospital stay. There were no differences in the mean daily BG (glargine, 182 ± 46 mg/dL vs. detemir, 180 ± 44 mg/dL; P = .70). There were no differences in mortality, hospital complications, or re-admissions between groups (all, P>.05). After adjusting for potential confounders, there was no statistically significant difference in hypoglycemia rates between treatment groups. Patients treated with detemir required higher total daily basal insulin doses (0.27 ± 0.16 units/kg/day vs. 0.22 ± 0.15 units/kg/day; P<.001). Glargine-treated patients had statistically longer length of stay; however, this difference may not be clinically relevant (6.8 ± 7.4 days vs. 6.0 ± 6.3 days; P<.001). CONCLUSION: Our study indicates that treatment with glargine and detemir results in similar inpatient glycemic control in general medicine and surgery patients. Detemir treatment was associated with higher daily basal insulin dose and number of injections. A prospective randomized study is needed to confirm these findings. ABBREVIATIONS: BG = blood glucose BMI = body mass index CI = confidence interval eGFR = estimated glomerular filtration rate HbA1c = glycated hemoglobin ICD-9 = International Classification of Diseases, ninth revision ICU = intensive care unit IQR = interquartile range LOS = length-of-stay OR = odd ratio.
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Diabetes Mellitus/tratamiento farmacológico , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina Detemir/uso terapéutico , Insulina Glargina/uso terapéutico , Anciano , Glucemia/análisis , Diabetes Mellitus/sangre , Femenino , Humanos , Hiperglucemia/sangre , Pacientes Internos , Tiempo de Internación , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Posttransplantation diabetes (PTDM) is a common occurrence after solid-organ transplantation and is associated with increased morbidity, mortality, and health care costs. There is a limited number of studies addressing strategies for hyperglycemia management in this population, with a few articles emerging recently. METHODS: We performed a PubMed search of studies published in English addressing hyperglycemia management of PTDM/new-onset diabetes after transplant (NODAT). Relevant cited articles were also retrieved. RESULTS: Most of the 25 publications eligible for review were retrospective studies. Insulin therapy during the early posttransplantation period showed promise in preventing PTDM development. Thiazolidinediones have been mostly shown to exert glycemic control in retrospective studies, at the expense of weight gain and fluid retention. Evidence with metformin, sulfonylureas, and meglitinides is very limited. Incretins have shown promising results in small prospective studies using sitagliptin, linaglitpin, and vildagliptin and a case series using liraglutide. CONCLUSION: Prospective randomized studies assessing the management of hyperglycemia in PTDM are urgently needed. In the meantime, clinicians need to be aware of the high risk of PTDM and associated complications and current concepts in management.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/etiología , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Trasplante de Órganos/efectos adversos , Diabetes Mellitus Tipo 2/epidemiología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Humanos , Hiperglucemia/clasificación , Hiperglucemia/diagnóstico , Hiperglucemia/epidemiología , Insulina/uso terapéutico , Metformina/uso terapéutico , Trasplante de Órganos/estadística & datos numéricos , Compuestos de Sulfonilurea/uso terapéutico , Tiazolidinedionas/uso terapéuticoRESUMEN
OBJECTIVE: To establish the prevalence of reliable self-monitored blood glucose (r-SMBG) data at office visits for diabetes and to determine whether r-SMBG is associated with changes in glycemic control and other clinical parameters. METHODS: We conducted a chart review of 500 patients followed in an Endocrinology Faculty/Commercial Insurance Practice (FP) or a Managed Medicare/Medicaid Diabetes Clinic (MDC). Follow-up visits for patients with type 1 or type 2 diabetes from January 1, 2012 to June 30, 2012 were analyzed for anthropometric data, creatinine (Cr), glomerular filtration rate (GFR), low-density lipoprotein cholesterol (LDL-C), medications, hemoglobin A1C (A1C), change in A1C from the previous visit (ΔA1C), and availability of r-SMBG data at the visit. RESULTS: Our sample was composed of 215 MDC patients (43%) and 285 FP patients (57%). Overall, 151 patients (30%) provided r-SMBG data at their visit, with no difference between MDC or FP patients. Mean A1C at MDC was 9.1%, while mean A1C at FP was 7.9% (P<.001). MDC patients with A1C >8.0% demonstrated an A1C reduction of 1.2% if they provided r-SMBG, compared to an increase of 0.1% for MDC patients who did not (P<.05). Providing r-SMBG did not affect A1C in FP patients in any A1C range. CONCLUSION: Only a minority of diabetes patients, mostly insulin-treated, made r-SMBG data available to their providers. Insulin-requiring Managed Medicare/Medicaid patients with poorly controlled diabetes had an A1c reduction associated with r-SMBG. Prospective studies are needed to determine whether this patient population may be more likely to benefit from r-SMBG at their visits.
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Automonitorización de la Glucosa Sanguínea , Glucemia/análisis , Diabetes Mellitus/sangre , Adulto , Anciano , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
INTRODUCTION: Interprofessional consultations ("eConsults") can reduce healthcare utilization. However, the impact of eConsults on healthcare utilization remains poorly characterized among patients with headache. METHODS: We performed a retrospective, 1:1 matched cohort study comparing patients evaluated for headache via eConsult request or in-person referral at the Mount Sinai Health System in New York. Groups were matched on clinical and demographic characteristics. Our primary outcome was one or more outpatient headache-related encounters in 6 months following referral date. Secondary outcomes included one or more all-cause outpatient neurology and headache-related emergency department (ED) encounters during the same period. We used univariable and multivariable logistic regression to model associations between independent variables and outcomes. RESULTS: We identified 74 patients with headache eConsults who were matched to 74 patients with in-person referrals. Patients in the eConsult group were less likely to achieve the primary outcome (29.7% vs 62.2%, P < 0.0001) or have an all-cause outpatient neurology encounter (33.8% vs 79.7%, P < 0.0001) than patients in the comparison group. Both groups did not significantly differ by headache-related ED encounters. In multivariable analyses, patients in the eConsult group had significantly lower odds of having one or more headache-related or all-cause neurology encounters than patients in the comparison group (odds ratio (OR) 0.3, 95% confidence interval (CI) 0.1-0.6; OR 0.1, 95% CI 0.1-0.3, respectively). DISCUSSION: In comparison to in-person referrals, eConsult requests for headache were associated with reduced likelihood of outpatient neurology encounters in the short-term but not with differential use of headache-related ED encounters. Larger-scale, prospective studies should validate our findings and assess patient outcomes.
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BACKGROUND: Both diabetes and glucose-lowering medications have been associated with an increased risk of cancer incidence. This study will compare cancer incidence rates in individuals with and without diabetes; and will investigate, in individuals with diabetes, an association between glucose control and cancer incidence; and between the use of specific glucose-lowering medications, as well as no drug exposure, and cancer incidence. METHODS/DESIGN: This is a population based historical cohort study of all individuals aged 21 years or older (about 2,300,000) who were insured by Clalit Health Services, the largest health maintenance organization in Israel during a ten-year study period. Four study groups will be established according to the status of diabetes and cancer at study entry, Jan 1, 2002: cancer free, diabetes free; cancer free, diabetes prevalent; cancer prevalent, diabetes free; and cancer prevalent, diabetes prevalent. Individuals without diabetes at study entry will be followed for diabetes incidence, and all four groups will be followed for specific cancer incidence, including second primary neoplasms. Glucose control will be assessed by HbA1c and by fasting plasma glucose levels. Time dependent regression models for cancer incidence will account for glucose-lowering medications as they are added and changed over the follow-up period. A large number of demographic and clinical variables will be considered, including: age, gender, BMI, smoking status, concomitant medications, glucose control (assessed by HbA1c and by fasting plasma glucose) and cancer screening tests. DISCUSSION: Strengths of this study include the large population; high quality comprehensive data; comparison to individuals without diabetes, and to those with diabetes but not treated with glucose-lowering medications; and the extensive range of variables available for analysis. The great increases in diabetes prevalence and in treatment options render this study particularly relevant and timely. The Israeli national healthcare system, characterized by high standard and uniform healthcare, offers an advantageous environment for its conduct.
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Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Neoplasias/complicaciones , Neoplasias/epidemiología , Glucemia , Estudios de Cohortes , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estudios de Seguimiento , Humanos , Hipoglucemiantes/uso terapéutico , Incidencia , Israel/epidemiología , RiesgoRESUMEN
BACKGROUND: Large clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia. OBJECTIVES: The purpose of this study was to assess the effect of empagliflozin on left ventricular (LV) function and volumes, functional capacity, and quality of life (QoL) in nondiabetic HFrEF patients. METHODS: In this double-blind, placebo-controlled trial, nondiabetic HFrEF patients (n = 84) were randomized to empagliflozin 10 mg daily or placebo for 6 months. The primary endpoint was change in LV end-diastolic and -systolic volume assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life. RESULTS: Empagliflozin was associated with a significant reduction of LV end-diastolic volume (-25.1 ± 26.0 ml vs. -1.5 ± 25.4 ml for empagliflozin vs. placebo, respectively; p < 0.001) and LV end-systolic volume (-26.6 ± 20.5 ml vs. -0.5 ± 21.9 ml for empagliflozin vs. placebo; p < 0.001). Empagliflozin was associated with reductions in LV mass (-17.8 ± 31.9 g vs. 4.1 ± 13.4 g, for empagliflozin vs. placebo, respectively; p < 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 ± 4.2 vs. -0.1 ± 3.9; p < 0.001). Patients who received empagliflozin had significant improvements in peak O2 consumption (1.1 ± 2.6 ml/min/kg vs. -0.5 ± 1.9 ml/min/kg for empagliflozin vs. placebo, respectively; p = 0.017), oxygen uptake efficiency slope (111 ± 267 vs. -145 ± 318; p < 0.001), as well as in 6-min walk test (81 ± 64 m vs. -35 ± 68 m; p < 0.001) and quality of life (Kansas City Cardiomyopathy Questionnaire-12: 21 ± 18 vs. 2 ± 15; p < 0.001). CONCLUSIONS: Empagliflozin administration to nondiabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status. (Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity? [ATRU-4] [EMPA-TROPISM]; NCT03485222).
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Compuestos de Bencidrilo/uso terapéutico , Glucósidos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Volumen Sistólico/efectos de los fármacos , Anciano , Compuestos de Bencidrilo/farmacología , Técnicas de Imagen Cardíaca , Método Doble Ciego , Prueba de Esfuerzo , Femenino , Glucósidos/farmacología , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacologíaRESUMEN
BACKGROUND: Diabetes mellitus (DM) and obesity affect large parts of the population in the United States and around the world. These disorders are among the most common risk factors for erectile dysfunction (ED), because of their effects on the vasculature and the hormonal milieu. OBJECTIVE: This article reviews the current literature on the connection between DM, obesity, and ED. METHODS: Using the search terms erectile dysfunction, endothelial dysfunction, hypogonadism, diabetes, and obesity, a systematic review of the available literature in the PubMed database was conducted. Relevant English-language publications (to August 2008) were identified. RESULTS: ED is highly prevalent in men with both DM and obesity, and may act as a harbinger for cardiovascular disease (CVD) in this high-risk population. In addition to male hypogonadism and macrovascular disease, endothelial dysfunction is central to the connection between the metabolic syndrome and ED. Conversely, improved glycemic control and weight loss have been found to improve erectile function. CONCLUSION: ED is very prevalent in men with DM and obesity. It is increasingly being recognized as an early clinical indicator and motivator for patients with CVD. The role of pharmacologic ED treatments in improving endothelial function is currently being investigated.
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Diabetes Mellitus Tipo 2/epidemiología , Disfunción Eréctil/epidemiología , Obesidad/epidemiología , Testosterona/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Endotelio/fisiopatología , Disfunción Eréctil/etiología , Disfunción Eréctil/fisiopatología , Humanos , Hipogonadismo , Masculino , Obesidad/complicaciones , Obesidad/fisiopatología , Prevalencia , Factores de Riesgo , Estados Unidos/epidemiologíaAsunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Liderazgo , Femenino , Humanos , MasculinoRESUMEN
Dietary supplements and nutraceuticals are commonly used by men with erectile dysfunction, decreased libido, BPH, and concerns about developing prostate cancer. Many preparations do not contain the advertised dosages of the active ingredient or are contaminated. Dietary supplements and nutraceuticals, particularly those addressing erectile dysfunction and libido, need to undergo rigorous testing before they can be wholeheartedly recommended.
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Dieta , Suplementos Dietéticos , Disfunción Eréctil/dietoterapia , Libido , Enfermedades de la Próstata/prevención & control , Disfunciones Sexuales Psicológicas/dietoterapia , Antioxidantes/uso terapéutico , Arginina/uso terapéutico , Carnitina/uso terapéutico , Deshidroepiandrosterona/uso terapéutico , Ginkgo biloba , Humanos , Masculino , Panax , Fitoterapia/métodos , Extractos Vegetales/uso terapéutico , Enfermedades de la Próstata/dietoterapia , Serenoa , Yohimbina/uso terapéuticoRESUMEN
BACKGROUND: The Action for Health in Diabetes (Look AHEAD) trial investigated whether long-term cardiovascular disease morbidity and mortality could be reduced through a weight loss intervention among people with type 2 diabetes. Despite finding no significant reduction in cardiovascular events on average, it is possible that some subpopulations might have derived benefit. In this post-hoc analysis, we test the hypothesis that the overall neutral average treatment effect in the trial masked important heterogeneous treatment effects (HTEs) from intensive weight loss interventions. METHODS: We used causal forest modelling, which identifies HTEs, using a random half of the trial data (the training set). We applied Cox proportional hazards models to test the potential HTEs on the remaining half of the data (the testing set). The analysis was deemed exempt from review by the Columbia University Institutional Review Board, Protocol ID# AAAO3003. FINDINGS: Between Aug 22, 2001, and April 30, 2004, 5145 patients with type 2 diabetes were enrolled in the Look AHEAD randomised controlled trial, of whom 4901 were included in the The National Institute of Diabetes and Digestive and Kidney Diseases Repository and included in our analyses: 2450 for model development and 2451 in the testing dataset. Baseline HbA1c and self-reported general health distinguished participants who differentially benefited from the intervention. Cox models for the primary composite cardiovascular outcome revealed a number needed to treat of 28·9 to prevent 1 event over 9·6 years among participants with HbA1c 6·8% or higher, or both HbA1c less than 6·8% and Short Form Health Survey (SF-36) general health score of 48 or more (2101 [86%] of 2451 participants in the testing dataset; 167 [16%] of 1046 primary outcome events for intervention vs 205 [19%] of 1055 for control, absolute risk reduction of 3·46%, 95% CI 0·21-6·73%, p=0·038) By contrast, participants with HbA1c less than 6·8% and baseline SF-36 general health score of less than 48 (350 [14%] of 2451 participants in the testing data; 27 [16%] of 171 primary outcome events for intervention vs 15 [8%] of 179 primary outcome events for control) had an absolute risk increase of the primary outcome of 7·41% (0·60 to 14·22, p=0·003). INTERPRETATION: Look AHEAD participants with moderately or poorly controlled diabetes (HbA1c 6·8% or higher) and subjects with well controlled diabetes (HbA1c less than 6·8%) and good self-reported health (85% of the overall study population) averted cardiovascular events from a behavioural intervention aimed at weight loss. However, 15% of participants with well controlled diabetes and poor self-reported general health experienced negative effects that rendered the overall study outcome neutral. HbA1c and a short questionnaire on general health might identify people with type 2 diabetes likely to derive benefit from an intensive lifestyle intervention aimed at weight loss. FUNDING: None.
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Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Programas de Reducción de Peso , Enfermedades Cardiovasculares/etiología , Manejo de la Enfermedad , Femenino , Humanos , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Pérdida de PesoRESUMEN
Glucocorticoids have been the main agents for preventing organ rejection,but unfortunately they possess serious side effects. Newer immunosuppressive agents have therefore been introduced to overcome these effects and have had a dramatic impact on reducing the incidence of organ rejection, enhancing donor organ acceptance, and hence patient survival posttransplantation. However, calcineurin inhibitors (CIs), such as cyclosporine and tacrolimus, also have serious effects causing rapid and severe bone loss in animal models and humans. The mechanism accounting for this action is unclear at present, but the role of T lymphocyte action via RANKL seems to be of essence in triggering bone loss. The mechanism is complex and in vitro studies often produce results that are opposite to those seen in vivo. In addition to acute, rapid, and severe bone loss (ARSBL), the clinical picture shows an extremely high incidence of fractures at all sites, and depends upon the organ transplanted, preexisting bone disease, interval before transplantation, and the dose and duration of multiple immunosuppressive drugs. Other immune-modifying drugs, such as azathioprine, mycophenolate mofetil, and sirolimus, which are used in conjunction with glucocorticoids and CIs have not been shown to promote bone loss experimentally or clinically. With the exception of glucocorticoids, all of the agents discussed here demand further investigation with regard to their effects on bone health in the clinical setting.
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Enfermedades Óseas/inmunología , Factores Inmunológicos/uso terapéutico , Inmunosupresores/farmacología , Resorción Ósea/inmunología , Huesos/efectos de los fármacos , Huesos/inmunología , Humanos , Osteoporosis/inmunología , Linfocitos T/inmunologíaRESUMEN
OBJECTIVE: To determine the relationship between chronic pain patients' responses to self-report measures of pain intensity, and self-reported strategies when completing such measures. PARTICIPANTS: Ambulatory outpatients suffering from one of the following chronic pain conditions: painful HIV neuropathy, painful diabetic neuropathy, chronic Low-Back Pain. METHOD: As part of a previously reported study using qualitative methods, participants completed standard pain intensity questionnaires as well as a measure of pain related disturbances in activities of daily living. In the previous study, participants' responses during a focus group were then used to identify their strategies and beliefs about their approach to completing the questionnaires. Among the beliefs were: (1) difficulties averaging pain over different time periods (i.e., "what was your average pain during the last 24h" versus "what was your average pain during the last 2 weeks"); (2) difficulty in comparing pain from different etiologies; (3) difficulties in reporting sensations of pain in a manner unaffected by issues and situations secondary to the pain experience, such as difficulties in activities of daily living. In the present paper we use ANOVA (analysis of variance) and partial correlation to determine whether the qualitatively derived perceptions are reflected in the quantitative pain intensity scores. RESULTS: Participants' belief that it was difficult to "average" pain intensity over different time periods was supported. The data do not support their belief that pain intensity scores are affected by other factors: their specific pain diagnosis, and the extent to which pain interfered with their activities of daily living. CONCLUSIONS: (1) Patients tend to report different levels of pain intensity when asked to report their pain over different periods; (2) insofar as it can be said to exist, the relationship between measures of intensity and interference with activities of daily living is minimal; (3) participants tend to report similar levels of pain intensity, irrespective of etiology. IMPLICATIONS: (1) Chronic pain patients' elicited beliefs and strategies concerning how they complete pain intensity questionnaires are sometimes, but not invariably, reflected in their responses to these measures. Thus, purely qualitative methodologies alone cannot provide completely reliable information and point to the need to use a "mixed methods" approach combining both qualitative and quantitative data; (2) the lack of association between pain intensity measures and interference with activities of daily living, as well as relative insensitivity to different etiologies underlines the problem in relying on pain intensity measures as the primary means of evaluating the success of a treatment, either for pain management or in clinical research.
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Dolor Crónico/terapia , Dimensión del Dolor , Medición de Resultados Informados por el Paciente , Actividades Cotidianas , Humanos , Pacientes Ambulatorios , Encuestas y CuestionariosRESUMEN
Type 2 diabetes (T2D) is a heterogeneous complex disease affecting more than 29 million Americans alone with a rising prevalence trending toward steady increases in the coming decades. Thus, there is a pressing clinical need to improve early prevention and clinical management of T2D and its complications. Clinicians have understood that patients who carry the T2D diagnosis have a variety of phenotypes and susceptibilities to diabetes-related complications. We used a precision medicine approach to characterize the complexity of T2D patient populations based on high-dimensional electronic medical records (EMRs) and genotype data from 11,210 individuals. We successfully identified three distinct subgroups of T2D from topology-based patient-patient networks. Subtype 1 was characterized by T2D complications diabetic nephropathy and diabetic retinopathy; subtype 2 was enriched for cancer malignancy and cardiovascular diseases; and subtype 3 was associated most strongly with cardiovascular diseases, neurological diseases, allergies, and HIV infections. We performed a genetic association analysis of the emergent T2D subtypes to identify subtype-specific genetic markers and identified 1279, 1227, and 1338 single-nucleotide polymorphisms (SNPs) that mapped to 425, 322, and 437 unique genes specific to subtypes 1, 2, and 3, respectively. By assessing the human disease-SNP association for each subtype, the enriched phenotypes and biological functions at the gene level for each subtype matched with the disease comorbidities and clinical differences that we identified through EMRs. Our approach demonstrates the utility of applying the precision medicine paradigm in T2D and the promise of extending the approach to the study of other complex, multifactorial diseases.
Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/genética , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Infecciones por VIH/etiología , Infecciones por VIH/genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Pruritus is a risk factor for self-injury behavior (SIB) in sensory polyneuropathies. Although diabetes patients have elevated risk for pruritus, there are no reports of SIB in diabetic neuropathy. We present the case of a diabetes patient with neuropathy, whose pruritus induced SIB, resulted in partial amputation of a toe.
Asunto(s)
Amputación Quirúrgica , Diabetes Mellitus Tipo 1/complicaciones , Pie Diabético/cirugía , Neuropatías Diabéticas/complicaciones , Prurito/complicaciones , Conducta Autodestructiva/etiología , Dedos del Pie/cirugía , Neuropatías Diabéticas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Prurito/patología , Factores de Riesgo , Conducta Autodestructiva/diagnóstico , Conducta Autodestructiva/cirugíaRESUMEN
We reviewed diabetes apps for Android smartphones. We compiled a list of free and paid apps in April 2011 by searching the Android Market for apps which could track self-monitoring of blood glucose (SMBG), diabetes medications or calculate prandial insulin dosages. Two reviewers independently evaluated six features per app, using a five-point Likert scale. The sum of the six ratings was the composite usability score, and the mean score of an app's features was the average usability score. Of the 80 Android diabetes apps identified, 42 unique apps were eligible for the study. SMBG recording was present in 36 (86%) of the apps, a tool to track insulin or oral diabetic medications was found in 19 (45%) apps, and a prandial insulin dose calculator existed for 11 (26%) apps. Eighteen apps were free of charge and the other 24 apps had a mean purchase price of $2.86 (range 0.99-6.99). The mean composite usability score was 11.3 out of a possible 30. The mean average usability score was 3.0 out of a possible 5.0. Only four of the 42 apps had a composite usability score above 20 and none offered direct data input from glucometers, suggesting that few provided a comprehensive method of diabetes management. The apps Glucool Diabetes, OnTrack Diabetes, Dbees and Track3 Diabetes Planner were the highest rated. Clinicians may find it useful to recommend these apps.
Asunto(s)
Teléfono Celular , Computadoras de Mano , Diabetes Mellitus/terapia , Programas Informáticos , Automonitorización de la Glucosa Sanguínea/métodos , Computadoras de Mano/normas , Humanos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Insulina/análisis , Internet , Programas Informáticos/economíaRESUMEN
BACKGROUND: Inpatient dysglycemia is associated with increased morbidity, mortality and cost. Medical education must not only address knowledge gaps, but also improve clinical care. METHODS: All 129 medicine residents at a large academic medical center were offered a case-based online curriculum on the management of inpatient dysglycemia in the fall of 2009. First-year residents took a 3-h course with 10 modules. Second and third-year residents, who had been educated the prior year, underwent abbreviated training. All residents were offered a 20-min refresher course in the spring of 2009. We assessed resident knowledge, resident confidence, and patient glycemia on two teaching wards before and after the initial intervention, as well as after the refresher course. RESULTS: A total of 117 residents (91%) completed the initial training; 299 analyzed admissions generated 11, 089 blood glucose values and 4799 event blood glucose values. Admissions with target glycemia increased from 19.4% to 33.0% (P = 0.035) by the end of the curriculum. There was a strong downward trend in hyperglycemia from 22.4% to 11.3% (P = 0.055) without increased hypoglycemia. Confidence and knowledge increased significantly among first-time and repeat participants. Residents rated the intervention as highly relevant to their practice and technologically well implemented. CONCLUSION: Optimization of an online curriculum covering the management of inpatient glycemia over the course of 2 years led to significantly more admissions in the target glycemia range. Given its scalability, modularity and applicability, this web-based educational intervention may become the standard curriculum for the management of inpatient glycemia.