RESUMO
BACKGROUND: Androgen deprivation therapy (ADT) in prostate cancer (PCa) has been associated with development of insulin resistance. However, the predominant site of insulin resistance remains unclear. METHODS: The ADT & Metabolism Study was a single-center, 24-week, prospective observational study that enrolled ADT-naive men without diabetes who were starting ADT for at least 24 weeks (ADT group, n = 42). The control group comprised men without diabetes with prior history of PCa who were in remission after prostatectomy (non-ADT group, n = 23). Prevalent diabetes mellitus was excluded in both groups using all three laboratory criteria defined in the American Diabetes Association guidelines. All participants were eugonadal at enrollment. The primary outcome was to elucidate the predominant site of insulin resistance (liver or skeletal muscle). Secondary outcomes included assessments of body composition, and hepatic and intramyocellular fat. Outcomes were assessed at baseline, 12, and 24 weeks. RESULTS: At 24 weeks, there was no change in hepatic (1.2; 95% confidence interval [CI], -2.10 to 4.43; p = .47) or skeletal muscle (-3.2; 95% CI, -7.07 to 0.66; p = .10) insulin resistance in the ADT group. No increase in hepatic or intramyocellular fat deposition or worsening of glucose was seen. These changes were mirrored by those observed in the non-ADT group. Men undergoing ADT gained 3.7 kg of fat mass. CONCLUSIONS: In men with PCa and no diabetes, 24 weeks of ADT did not change insulin resistance despite adverse body composition changes. These findings should be reassuring for treating physicians and for patients who are being considered for short-term ADT.
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BACKGROUND: Very early onset inflammatory bowel disease (VEOIBD) is defined as disease onset in patients younger thanâ 6 years. Challenges in treatment of VEOIBD include lack of approved therapies and increased incidence of monogenic immunodeficiencies. We report on patterns of anti-TNF use, efficacy, and safety in a large cohort of patients with VEOIBD. METHODS: Very early onset inflammatory bowel disease patients receiving care at a single center were prospectively enrolled in a data registry and biorepository starting in 2012. Whole exome sequencing was available to all patients. Clinical data including IBD medication use and response were extracted from the medical record. We examined antitumor necrosis factor (anti-TNF) cumulative exposure and time to failure and evaluated the effect of covariates on anti-TNF failure using Cox proportional hazard regression. RESULTS: In this cohort of 216 VEOIBD patients with median 5.8-year follow-up, 116 (53.7%) were TNF-exposed. Sixty-two TNF-exposed patients (53.4%) received their first dose atâ younger thanâ 6 years. Cumulative exposure to anti-TNF was 23.6% at 1 year, 38.4% at 3 years, and 43.4% at 5 years after diagnosis. Cumulative exposure was greater in patients with Crohn's disease (P = .0004) and in those diagnosed in 2012 or later (P < .0001). Tumor necrosis factor failure occurred in 50.9% of those exposed. Features predictive of anti-TNF failure included ulcerative colitis/IBD-unclassified (hazard ratio, 1.94; P = .03), stricturing (hazard ratio, 2.20; P = .04), and younger age at diagnosis (hazard ratio, 1.25; P = .01). Adverse events occurred in 22.6% of infliximab-exposed and 14.3% of adalimumab-exposed. CONCLUSIONS: Efficacy and safety of anti-TNFs in VEOIBD is comparable to what has previously been reported in older patients.
Half of VEOIBD patients followed for a median 5.8 years used anti-TNF. Anti-TNF failure occurred in half of those exposed. Stricturing, UC/IBD-U, and younger age at diagnosis were predictors of failure. Adverse events were similar to those reported in older patients.
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Androgen deprivation therapy (ADT), a cornerstone of treatment for patients with locally advanced and metastatic prostate cancer, is associated with many adverse effects, including osteoporosis, sexual dysfunction, fatigue, and vasomotor symptoms. It is also associated with loss of muscle mass and increased adiposity. This change in body composition is likely the inciting event in the development of insulin resistance, an independent risk factor for diabetes mellitus and cardiovascular disease. Although the occurrence of insulin resistance during ADT has been reported, it remains unclear whether this insulin resistance is primarily hepatic or muscular. Similarly, the mechanisms that lead to insulin resistance also remain unknown. The ADT & Metabolism Study was designed to address these knowledge gaps, as the elucidation of the predominant site of insulin resistance will allow prevention strategies and the use of targeted, tissue-specific insulin-sensitizing agents in patients undergoing ADT. This prospective, mechanistic, single-center, 24-week, observational cohort study will enroll treatment-naïve adult men with prostate cancer about to undergo surgical or medical ADT for at least 24 weeks (ADT group; n = 50) and a control group of men who had undergone radical prostatectomy and are in remission (non-ADT group, n = 25). The primary outcome is to determine the site of insulin resistance (skeletal muscle or liver) using frequent sampling oral glucose tolerance test at baseline and 12 and 24 weeks after commencement of ADT (ADT group) or after enrollment in the study (non-ADT group). Secondary outcomes will assess changes in hepatic and intramyocellular fat (using magnetic resonance spectroscopy), inflammatory markers, adipokines, free fatty acids, and changes in body composition (assessed using dual-energy x-ray absorptiometry) and their correlation with the development of insulin resistance. Exploratory outcomes will include changes in muscle performance, physical function, physical activity, vitality, and sexual drive.
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Resistência à Insulina , Neoplasias da Próstata , Masculino , Humanos , Idoso , Neoplasias da Próstata/metabolismo , Androgênios , Resistência à Insulina/fisiologia , Antagonistas de Androgênios/efeitos adversos , Estudos de Coortes , Estudos Prospectivos , Antineoplásicos Hormonais/uso terapêutico , Estudos Observacionais como AssuntoRESUMO
CONTEXT: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with increased cardiovascular mortality and sudden cardiac death, with some events occurring early after initiation of ADT. Testosterone levels are inversely associated with corrected QT (QTc) interval duration; therefore, prolongation of QTc duration could be responsible for some of these events during ADT. OBJECTIVE: To evaluate changes in QTc duration during ADT. DESIGN AND INTERVENTIONS: A 6-month prospective cohort study that enrolled men with PCa about to undergo ADT (ADT group) and a control group of men who previously underwent prostatectomy for PCa and never received ADT (non-ADT group). PATIENTS: At study entry, all participants were eugonadal and had no history of cardiac arrhythmias or complete bundle branch block. OUTCOMES: Difference in change in QTc duration from baseline on a 12-lead electrocardiogram at 6, 12, and 24 weeks after initiation of ADT compared with electrocardiograms performed at the same intervals in the non-ADT group. PR, QRS, and QT interval durations were also evaluated. RESULTS: Seventy-one participants formed the analytical sample (33 ADT and 38 non-ADT). ADT was associated with prolongation of the QTc by 7.4 ms compared with the non-ADT group [95% confidence interval (CI) 0.08 to 14.7 ms; P = 0.048]. ADT was also associated with shortening of the QRS interval by 2.4 ms (95% CI -4.64 to -0.23; P = 0.031). Electrolytes did not change. CONCLUSIONS: Men undergoing ADT for PCa experienced prolongation of the QTc. These findings might explain the increased risk of sudden cardiac death seen in these patients.
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CONTEXT: Previous animal and human research suggests that testosterone has antinociceptive properties. Castration in male rodents increases pain perception which is reversed by testosterone replacement. Pain perception also improves in hypogonadal men with testosterone therapy. However, it remains unclear whether androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with an increase in pain perception. OBJECTIVES: To evaluate the effects of ADT on pain perception, depression and quality of life (QOL) in men with PCa. METHODS: Thirty-seven men with PCa about to undergo ADT with leuprolide acetate (ADT group) were followed prospectively for six months to evaluate changes in clinical and experimental pain. Forty men who had previously undergone prostatectomy for localized PCa and were in remission served as controls (non-ADT group). All participants were eugonadal at study entry. Primary outcomes were changes in clinical pain (assessed with Brief Pain Inventory questionnaire) and experimental pain (assessed with quantitative sensory testing). Secondary outcomes included evaluation of depression, anxiety levels, and quality of life. RESULTS: Serum testosterone levels significantly decreased in the ADT group but remained unchanged in the non-ADT group. There were no significant changes in pain thresholds, ratings, or other responses to quantitative sensory tests over the 6-month course of the study. Clinical pain did not differ between the two groups, and no changes from baseline were observed in either group. Men undergoing ADT did experience worsening of depression (0.93; 95% CI = 0.04-1.82; P = 0.042) and QOL related to physical role limitation (-18.28; 95% CI = -30.18 to -6.37; P = 0.003). CONCLUSION: ADT in men with PCa is associated with worsening of depression scores and QOL but is not associated with changes in clinical pain or pain sensitivity.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Depressão , Percepção da Dor/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/psicologia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Depressão/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Estudos Prospectivos , Qualidade de Vida , Testosterona/sangue , Resultado do TratamentoRESUMO
The dietary practices of diverse population groups, associated with the nutritional transition and the rapid demographic changes occurring globally require more attention to the food preferences of migrant groups such as Latinos living in the United States United States of America (US). This work aimed at the performance of an instrument utilized to measure availability of healthy food options in Latino stores located in the town of Somerville, state of Massachusetts. The methodology included the application of two versions: Guatemalan and US of the Nutrition Environment Measures Survey for Stores (NEMS-S), for the assessment of the availability of healthy food options in three Latino stores. Data were analyzed using descriptive statistics. The results indicated that foods sold in Latino stores were identified more successfully with the Guatemalan-NEMS-S than with the US NEMS-S. There was a general lack of healthy food options found when using the US survey, as well as a relatively narrow selection of fruits and vegetables. As conclusion, it was found that the US NEMS-S tended to identify a lower number of healthy food options, as compared to a larger number of similar options when a culturally-appropriate survey was used. These findings illustrate a manner in which a culture-specific instrument perform more appropriately than similar instruments adapted for other population groups, especially when the results are to be applied to support development of healthy food policies(AU)
Las prácticas alimentarias de diversos grupos de población, asociadas a la transición nutricional, y a los rápidos cambios demográficos que se producen a nivel mundial, exigen más atención a las preferencias alimentarias de grupos migrantes, como por ejemplo Latinos en los Estados Unidos de Norteamérica (EU). Este trabajo documenta los resultados de aplicar un instrumento para medir disponibilidad de alimentos saludables en tres tiendas latinas ubicadas en la ciudad de Somerville, estado de Massachusetts. La metodología utilizada incluyó la aplicación de dos versiones: guatemalteca y EU de la Encuesta para Medir Ambiente Nutricional en Tiendas (NEMS-S, siglas en inglés), para evaluar la disponibilidad de alimentos saludables. Los datos se analizaron con estadísticas descriptivas. Los resultados indicaron que los alimentos vendidos en las tiendas latinas fueron identificados con más acierto con el NEMS-S guatemalteco que con el NEMS-S de EU. Con este último instrumento, se obtuvo un número menor de opciones saludables y una selección limitada de frutas y de vegetales. Como conclusión, se encontró que el NEMS-S de EU identificaba un menor número de opciones de alimentos saludables, en comparación con el instrumento culturalmente apropiado. Estos hallazgos ilustran la importancia de utilizar instrumentos específicos para determinar disponibilidad de alimentos saludables, especialmente cuando los resultados se utilicen para apoyar el desarrollo de políticas alimentarias(AU)