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BACKGROUND: Several SGLT2i (sodium-glucose transport protein 2 inhibitors) and GLP1-RA (glucagon-like peptide-1 receptor agonists) reduce cardiovascular events and improve kidney outcomes in patients with type 2 diabetes; however, utilization remains low despite guideline recommendations. METHODS: A randomized, remote implementation trial in the Mass General Brigham network enrolled patients with type 2 diabetes with increased cardiovascular or kidney risk. Patients eligible for, but not prescribed, SGLT2i or GLP1-RA were randomly assigned to simultaneous virtual patient education with concurrent prescription of SGLT2i or GLP1-RA (ie, Simultaneous) or 2 months of virtual education followed by medication prescription (ie, Education-First) delivered by a multidisciplinary team driven by nonlicensed navigators and clinical pharmacists who prescribed SGLT2i or GLP1-RA using a standardized treatment algorithm. The primary outcome was the proportion of patients with prescriptions for either SGLT2i or GLP1-RA by 6 months. RESULTS: Between March 2021 and December 2022, 200 patients were randomized. The mean age was 66.5 years; 36.5% were female, and 22.0% were non-White. Overall, 30.0% had cardiovascular disease, 5.0% had cerebrovascular disease, and 1.5% had both. Mean estimated glomerular filtration rate was 77.9 mL/(minâ§1.73 m2), and mean urine/albumin creatinine ratio was 88.6 mg/g. After 2 months, 69 of 200 (34.5%) patients received a new prescription for either SGLT2i or GLP1-RA: 53.4% of patients in the Simultaneous arm and 8.3% of patients in the Education-First arm (P<0.001). After 6 months, 128 of 200 (64.0%) received a new prescription: 69.8% of patients in the Simultaneous arm and 56.0% of patients in Education-First (P<0.001). Patient self-report of taking SGLT2i or GLP1-RA within 6 months of trial entry was similarly greater in the Simultaneous versus Education-First arm (69 of 116 [59.5%] versus 37 of 84 [44.0%]; P<0.001) Median time to first prescription was 24 (interquartile range [IQR], 13-50) versus 85 days (IQR, 65-106), respectively (P<0.001). CONCLUSIONS: In this randomized trial, a remote, team-based program identifies patients with type 2 diabetes and high cardiovascular or kidney risk, provides virtual education, prescribes SGLT2i or GLP1-RA, and improves guideline-directed medical therapy. These findings support greater utilization of virtual team-based approaches to optimize chronic disease management. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06046560.
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Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Feminino , Masculino , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Guias de Prática Clínica como Assunto , Doenças Cardiovasculares , Telemedicina , Fidelidade a Diretrizes , Resultado do TratamentoRESUMO
We describe the strategies used to identify and enroll participants in a remote health management program aimed at optimizing diabetes care in patients at high cardiovascular and kidney risk. Using a combination of digital and traditional outreach methods, including patient portals, emails, mailed letters, and provider referrals, we successfully enrolled 200 participants. Our experience highlights the effectiveness of a hybrid approach in achieving enrollment targets, addressing the challenges of identification of eligible candidates and engagement while integrating traditional methods for inclusivity.
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Chronic caloric deprivation and obesity are complicated by hypercortisolemia. The effects of acute overfeeding and fasting on circulating free cortisol levels and conversion of cortisone to free cortisol are unknown. We hypothesized that serum-free cortisol and free cortisol-to-cortisone ratio would increase after both overfeeding and fasting. This is a prospective study of 22 healthy volunteers who completed a 10-day high-calorie protocol followed by a 10-day fast, separated by a 2-wk washout. Morning free and total cortisol and free cortisone levels (LC/MS) were measured at baseline and after 10 days of each intervention. Both high-calorie feeding and fasting increased total and free cortisol and the free cortisol-to-free cortisone ratio (P = 0.001 to P = 0.046). There were sex interactions, with significant effects in men (P < 0.001), but not in women (P = 0.898 and 1.000, respectively) in subset analyses examining the effects of fasting on free cortisol and the free-to-total cortisol ratio. Overfeeding and fasting both increase circulating free cortisol levels and appear to alter the balance between cortisol and its inactive metabolite, cortisone. Further study is warranted to determine whether elevated cortisol levels contribute to complications of starvation and obesity, such as bone fragility.NEW & NOTEWORTHY Overfeeding and fasting both increase circulating free cortisol levels and appear to alter the balance between cortisol and its inactive metabolite, cortisone. The effect of fasting on free cortisol levels is modified by sex. Further study is needed to determine the mechanisms driving the increases in cortisol.
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Cortisona , Hidrocortisona , Masculino , Humanos , Feminino , Hidrocortisona/metabolismo , Cortisona/metabolismo , Estudos Prospectivos , Obesidade , JejumRESUMO
OBJECTIVE: We aimed to (1) examine the diagnosis of opioid-induced adrenal insufficiency, and (2) investigate the diagnostic value of a morning cortisol <83 nmol/L (3 µg/dl) for the diagnosis of adrenal insufficiency, using newer more specific cortisol assays and cut-offs. DESIGN: Retrospective study (5/2015-10/2020). PARTICIPANTS: Cohort 1 (N = 75): adults who underwent cosyntropin stimulation testing and opioid exposure for >30 days. Cohort 2 (N = 854): adults, with or without opioid exposure, who had a morning cortisol level measured the same day as stimulation testing. MEASUREMENTS: Peak cortisol during cosyntropin stimulation testing. Sensitivity and specificity of morning serum cortisol for adrenal insufficiency. RESULTS: The prevalence of adrenal insufficiency in patients with chronic opioid exposure who underwent cosyntropin stimulation testing was 4.0% using a cortisol cutoff of <405 nmol/L (14.7 µg/dl) versus 19% using the traditional cutoff of <500 nmol/L (18.1 µg/dl). For hospitalized patients with and without opioid-exposure, 14 of 22 (64%) patients with morning cortisol levels of <83 nmol/L (3 µg/dl) passed cosyntropin stimulation testing. A morning cortisol level of <348 nmol/L (12.6 µg/dl) had 100% sensitivity (95% confidence interval: 84.5%-100%) for the diagnosis of adrenal insufficiency. CONCLUSION: Applying a cutoff of <405 nmol/L (14.7 µg/dl), opioid-induced adrenal insufficiency is rare. Nearly 1 out of 6 patients would be reclassified as having adrenal insufficiency applying the guideline-recommended cutoff of <500 nmol/L (18.1 µg/dl). Serum morning cortisol <83 nmol/L (3 µg/dl) is not a valid diagnostic test for adrenal insufficiency in hospitalized patients, whether or not receiving opioids.
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Insuficiência Adrenal , Analgésicos Opioides , Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/diagnóstico , Adulto , Analgésicos Opioides/efeitos adversos , Cosintropina , Hospitalização , Humanos , Hidrocortisona , Estudos RetrospectivosRESUMO
OBJECTIVE: Anorexia nervosa (AN) is a serious condition characterized by undernutrition, complicated by endocrine dysregulation, and with few predictors of recovery. Urinary free cortisol (UFC) is a predictor of weight gain, but 24-h urine samples are challenging to collect. We hypothesized that serum dehydroepiandrosterone sulfate (DHEAS), which like cortisol is regulated by adrenocorticotropic hormone (ACTH), would predict weight gain and increases in fat mass in women with AN. METHODS: We prospectively studied 34 women with AN and atypical AN, mean age 27.4 ± 7.7 years (mean ± SD), who received placebo in a 6-month randomized trial. Baseline DHEAS and 24-h UFC were measured by liquid chromatography with tandem mass spectrometry. Body composition was assessed at baseline and 6 months by DXA and cross-sectional abdominal CT at L4. RESULTS: Mean baseline DHEAS level was 173 ± 70 µg/dl (0.7 ± 0.3 times the mean normal range for age) and mean baseline UFC (n = 15) was 20 ± 18 µg/24 h (normal: 0-50 µg/24 h). Higher DHEAS levels predicted weight gain over 6 months (r = 0.61, p < .001). DHEAS levels also predicted increases in fat mass (r = 0.40, p = .03), appendicular lean mass (r = 0.38, p = .04), and abdominal adipose tissue (r = 0.60, p < .001). All associations remained significant after controlling for age, baseline BMI, OCP use, duration of AN, and SSRI/SNRI use. DHEAS levels correlated with UFC (r = 0.61, p = .02). DISCUSSION: In women with AN, higher serum DHEAS predicts weight gain and increases in fat and muscle mass. Additional studies are needed to confirm these findings and further elucidate the association between DHEAS and weight gain. PUBLIC SIGNIFICANCE: Anorexia nervosa is a severe psychiatric condition, and predictors of weight recovery are needed to improve prognostication and guide therapeutic decision making. While urinary cortisol is a predictor of weight gain, 24-h urine collections are challenging to obtain. Like cortisol, dehydroepiandrosterone sulfate (DHEAS) is a hormone produced by the adrenal glands. As a readily available blood test, DHEAS holds promise as more practical biomarker of weight gain in anorexia nervosa.
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Anorexia Nervosa , Adulto , Estudos Transversais , Sulfato de Desidroepiandrosterona , Feminino , Humanos , Hidrocortisona/urina , Aumento de Peso , Adulto JovemRESUMO
PURPOSE: To investigate advanced neoplasia (AN) after endoscopic mucosal resection (EMR) of colonic laterally spreading lesions (LSLs). METHODS: A retrospective study of patients who underwent injection-assisted EMR of colonic LSLs ≥ 10 mm was performed. Primary outcome was overall rate of AN at initial surveillance colonoscopy. Secondary outcomes were the rates of residual AN (rAN) at the EMR site and metachronous AN (mAN), and analysis of risk factors for AN, including effect of surveillance guidance. RESULTS: Three hundred seventy-four patients underwent successful EMR for 388 LSLs. AN occurred in 66/374 (17.6%) patients on initial surveillance colonoscopy at median follow-up of 364.5 days. Two patients had both rAN and mAN, for a total of 68 instances of AN, including 30/374 (8.0%) cases of rAN and 38/374 (10.2%) cases of mAN. On multivariate analysis, use of piecemeal resection was associated with increased likelihood of residual AN (P = 0.003, OR 9.2, 95% CI 2.1-33.3). Twenty-nine out of thirty cases (96.7%) of rAN were successfully endoscopically managed at surveillance colonoscopy. CONCLUSIONS: AN occurred in 17.6% of all patients at initial surveillance colonoscopy at a median of 1 year after EMR. Roughly half of the instances of AN were metachronous lesions. Our data support a 1-year surveillance interval after EMR of LSLs ≥ 10 mm with careful inspection of the entire colon, not just the prior resection site.
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Neoplasias do Colo , Colonoscopia , Ressecção Endoscópica de Mucosa/efeitos adversos , Recidiva Local de Neoplasia , Neoplasia Residual , Segunda Neoplasia Primária , Idoso , Colo/patologia , Colo/cirurgia , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Colonoscopia/métodos , Colonoscopia/estatística & dados numéricos , Ressecção Endoscópica de Mucosa/métodos , Feminino , Humanos , Incidência , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/epidemiologia , Neoplasia Residual/patologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/patologia , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
AIM: Describe the rationale for and design of Diabetes Remote Intervention to improVe use of Evidence-based medications (DRIVE), a remote medication management program designed to initiate and titrate guideline-directed medical therapy (GDMT) in patients with type 2 diabetes (T2D) at elevated cardiovascular (CV) and/or kidney risk by leveraging non-physician providers. METHODS: An electronic health record based algorithm is used to identify patients with T2D and either established atherosclerotic CV disease (ASCVD), high risk for ASCVD, chronic kidney disease, and/or heart failure within our health system. Patients are invited to participate and randomly assigned to either simultaneous education and medication management, or a period of education prior to medication management. Patient navigators (trained, non-licensed staff) are the primary points of contact while a pharmacist or nurse practitioner reviews and authorizes each medication initiation and titration under an institution-approved collaborative drug therapy management protocol with supervision from a cardiologist and/or endocrinologist. Patient engagement is managed through software to support communication, automation, workflow, and standardization. CONCLUSION: We are testing a remote, navigator-driven, pharmacist-led, and physician-overseen management strategy to optimize GDMT for T2D as a population-level strategy to close the gap between guidelines and clinical practice for patients with T2D at elevated CV and/or kidney risk.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Farmacêuticos , Rim , Insuficiência Renal Crônica/diagnóstico , Gerenciamento Clínico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologiaRESUMO
Importance: Immune checkpoint inhibitors (ICIs) have revolutionized cancer care; however, accompanying immune-related adverse events (irAEs) confer substantial morbidity and occasional mortality. Life-threatening irAEs may require permanent cessation of ICI, even in patients with positive tumor response. Therefore, it is imperative to comprehensively define the spectrum of irAEs to aid individualized decision-making around the initiation of ICI therapy. Objective: To define incidence, risk factors, and clinical spectrum of an irreversible and life-threatening irAE: ICI-induced diabetes. Design, Setting, and Participants: This cohort study, conducted at an academic integrated health care system examined 14â¯328 adult patients treated with ICIs, including 64 patients who developed ICI-induced diabetes, from July 2010 to January 2022. The data were analyzed from 2022 to 2023. Cases of ICI-induced diabetes were manually confirmed; detailed clinical phenotyping was performed at diagnosis and 1-year follow-up. For 862 patients, genotyping data were available, and polygenic risk for type 1 diabetes was determined. Main Outcomes and Measures: For ICI-induced diabetes cases and controls, demographic characteristics, comorbidities, tumor category, and ICI category were compared. Among ICI-induced diabetes cases, markers of glycemic physiology were examined at diagnosis and 1-year follow-up. For patients with available genotyping, a published type 1 diabetes polygenic score (T1D GRS2) was calculated. Results: Of 14â¯328 participants, 6571 (45.9%) were women, and the median (range) age was 66 (8-106) years. The prevalence of ICI-induced diabetes among ICI-treated patients was 0.45% (64 of 14â¯328), with an incidence of 124.8 per 100â¯000 person-years. Preexisting type 2 diabetes (odds ratio [OR], 5.91; 95% CI, 3.34-10.45) and treatment with combination ICI (OR, 2.57; 95% CI, 1.44-4.59) were significant clinical risk factors of ICI-induced diabetes. T1D GRS2 was associated with ICI-induced diabetes risk, with an OR of 4.4 (95% CI, 1.8-10.5) for patients in the top decile of T1D GRS2, demonstrating a genetic association between spontaneous autoimmunity and irAEs. Patients with ICI-induced diabetes were in 3 distinct phenotypic categories based on autoantibodies and residual pancreatic function, with varying severity of initial presentation. Conclusions and Relevance: The results of this analysis of 14â¯328 ICI-treated patients followed up from ICI initiation determined the incidence, risk factors and clinical spectrum of ICI-induced diabetes. Widespread implementation of this approach across organ-specific irAEs may enhance diagnosis and management of these conditions, and this becomes especially pertinent as ICI treatment rapidly expands to treat a wide spectrum of cancers and is used at earlier stages of treatment.
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Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Neoplasias/tratamento farmacológico , Adulto , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/epidemiologia , Incidência , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Estudos de CoortesRESUMO
Normal aging is linked to various endocrine gland changes, including changes in the adrenal glands. Aging is linked to alterations of the hypothalamic-pituitary-adrenal (HPA) axis, including an increase in cortisol levels, a disruption of the negative cortisol feedback, and attenuation of cortisol's diurnal pattern. In addition, secretion of aldosterone and adrenal androgens [dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)] from the adrenal cortex decreases with aging. In this review, we describe normal adrenal function, the adrenal response to stress and immunomodulation in aging individuals as well as the effects of adrenal aging on body composition, metabolic profile, bone health and cognition.
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Desidroepiandrosterona , Imunossenescência , Humanos , Hidrocortisona/metabolismo , Envelhecimento/fisiologia , Corticosteroides , Sulfato de DesidroepiandrosteronaRESUMO
CONTEXT: Overweight and obesity are associated with relative growth hormone (GH) deficiency, which has been implicated in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD is a progressive disease without effective treatments. OBJECTIVE: We hypothesized that GH administration would reduce hepatic steatosis in individuals with overweight/obesity and NAFLD. METHODS: In this 6-month randomized, double-blind, placebo-controlled trial of low-dose GH administration, 53 adults aged 18 to 65 years with BMI ≥25 kg/m2 and NAFLD without diabetes were randomized to daily subcutaneous GH or placebo, targeting insulin-like growth factor 1 (IGF-1) to the upper normal quartile. The primary endpoint was intrahepatic lipid content (IHL) by proton magnetic resonance spectroscopy (1H-MRS) assessed before treatment and at 6 months. RESULTS: Subjects were randomly assigned to a treatment group (27 GH; 26 placebo), with 41 completers (20 GH and 21 placebo) at 6 months. Reduction in absolute % IHL by 1H-MRS was significantly greater in the GH vs placebo group (mean ± SD: -5.2 ± 10.5% vs 3.8 ± 6.9%; P = .009), resulting in a net mean treatment effect of -8.9% (95% CI, -14.5 to -3.3%). All side effects were similar between groups, except for non-clinically significant lower extremity edema, which was more frequent in the GH vs placebo group (21% vs 0%, P = .02). There were no study discontinuations due to worsening of glycemic status, and there were no significant differences in change in glycemic measures or insulin resistance between the GH and placebo groups. CONCLUSION: GH administration reduces hepatic steatosis in adults with overweight/obesity and NAFLD without worsening glycemic measures. The GH/IGF-1 axis may lead to future therapeutic targets for NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fator de Crescimento Insulin-Like I/metabolismo , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Obesidade/complicações , Obesidade/tratamento farmacológico , Hormônio do Crescimento/uso terapêutico , Método Duplo-Cego , Fígado/metabolismoRESUMO
Type 2 diabetes mellitus (T2DM) is defined by a common end point: hyperglycemia diagnosed by fasting plasma glucose, plasma glucose during an oral glucose tolerance test, or hemoglobin A1c without autoimmune ß-cell destruction.1 Historically, little attention has been paid to the etiologies driving hyperglycemia; as a result, there has been an absence of an elegant pathophysiologically directed diagnostic and therapeutic approach. T2DM has simply been thought to be a result of insulin deficiency and/or peripheral insulin resistance. However, the phenotype of T2DM is heterogeneous, as is the pathophysiology.2,3.
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AIMS: High rates of newly diagnosed diabetes mellitus (NDDM) have been reported in association with coronavirus disease-2019 (COVID-19). Factors associated with NDDM and long-term glycemic outcomes are not known. METHODS: Retrospective review of individuals admitted with COVID-19 and diabetes mellitus (DM; based on labs, diagnoses, outpatient insulin use, or severe inpatient hyperglycemia) between March and September 2020, with follow-up through July 2021. RESULTS: Of 1902 individuals admitted with COVID-19, 594 (31.2%) had DM; 77 (13.0%) of these had NDDM. Compared to pre-existing DM, NDDM was more common in younger patients and less common in those of non-Hispanic White race/ethnicity. Glycemic parameters were lower and inflammatory markers higher in patients with NDDM. In adjusted models, NDDM was associated with lower insulin requirements, longer length of stay, and intensive care unit admission but not death. Of 64 survivors with NDDM, 36 (56.3%) continued to have DM, 26 (40.6%) regressed to normoglycemia or pre-diabetes, and 2 were unable to be classified at a median follow-up of 323 days. CONCLUSIONS: Diabetes diagnosed at COVID-19 presentation is associated with lower glucose but higher inflammatory markers and ICU admission, suggesting stress hyperglycemia as a major physiologic mechanism. Approximately half of such individuals experience regression of DM.
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COVID-19 , Diabetes Mellitus , Hiperglicemia , Glicemia , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/epidemiologia , Fenótipo , Estudos RetrospectivosRESUMO
Objective: Anorexia nervosa is complicated by high bone resorption, low bone mineral density (BMD), and increased fracture risk. We investigated whether off-label antiresorptive therapy with denosumab increases BMD in women with anorexia nervosa. Design: Twelve-month, randomized, double-blind, placebo-controlled study. Methods: Thirty ambulatory women with anorexia nervosa and areal BMD (aBMD) T-score <-1.0 at ≥1 sites were randomized to 12 months of denosumab (60 mg subcutaneously q6 months)(n = 20) or placebo (n = 10). Primary end point was postero-anterior (PA) lumbar spine aBMD by dual-energy x-ray absorptiometry. Secondary end points included femoral neck aBMD, tibia and radius volumetric BMD and bone microarchitecture by high-resolution peripheral quantitative CT, tibia and radius failure load by finite element analysis (FEA), and markers of bone turnover. Results: Baseline mean (±s.d.) age (29 ± 8 (denosumab) vs 29 ± 7 years (placebo)), BMI (19.0 ± 1.7 vs 18.0 ± 2.0 kg/m2), and aBMD (PA spine Z-score -1.6±1.1 vs -1.7±1.4) were similar between groups. PA lumbar spine aBMD increased in the denosumab vs placebo group over 12 months (P = 0.009). The mean (95% CI) increase in PA lumbar spine aBMD was 5.5 (3.8-7.2)% in the denosumab group and 2.2 (-0.3-4.7)% in the placebo group. The change in femoral neck aBMD was similar between groups. Radial trabecular number increased, radial trabecular separation decreased, and tibial cortical porosity decreased in the denosumab vs placebo group (P ≤ 0.006). Serum C-terminal telopeptide of type I collagen and procollagen type I N-terminal propeptide decreased in the denosumab vs placebo group (P < 0.0001). Denosumab was well tolerated. Conclusions: Twelve months of antiresorptive therapy with denosumab reduced bone turnover and increased spine aBMD, the skeletal site most severely affected in women with anorexia nervosa.
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Anorexia Nervosa , Conservadores da Densidade Óssea , Absorciometria de Fóton , Adulto , Anorexia Nervosa/tratamento farmacológico , Densidade Óssea , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea , Osso e Ossos , Denosumab/uso terapêutico , Feminino , Humanos , Adulto JovemRESUMO
CONTEXT: Obesity is a state of relative growth hormone (GH) deficiency, and GH has been identified as a candidate disease-modifying target in nonalcoholic fatty liver disease (NAFLD) because of its lipolytic and anti-inflammatory properties. However, the GH/IGF-1 axis has not been well characterized in NAFLD. OBJECTIVE: We aimed to investigate serum GH and IGF-1 levels in relation to intrahepatic lipid content (IHL) and markers of hepatocellular damage and fibrosis in NAFLD. METHODS: This cross-sectional study included 102 adults (43% women; age 19-67; BMIâ ≥â 25 kg/m2) without type 2 diabetes. IHL was measured by magnetic resonance spectroscopy; NAFLD was defined byâ ≥â 5% IHL. Peak-stimulated GH in response to GH releasing hormone and arginine was assessed as was serum IGF-1 (LC/MS). RESULTS: There was no difference in mean age, BMI, or sex distribution in NAFLD vs controls. Mean (± SD) IHL was higher in NAFLD vs controls (21.8â ±â 13.3% vs 2.9â ±â 1.1%, Pâ <â 0.0001). Mean peak-stimulated GH was lower in NAFLD vs controls (9.0â ±â 6.3 vs 15.4â ±â 11.2 ng/mL, Pâ =â 0.003), including after controlling for age, sex, visceral adipose tissue, and fasting glucose. In a stepwise model, peak-stimulated GH predicted 14.6% of the variability in IHL (Pâ =â 0.004). Higher peak-stimulated GH was also associated with lower ALT. Higher serum IGF-1 levels were associated with lower risk of liver fibrosis by Fibrosis-4 scores. CONCLUSION: Individuals with NAFLD have lower peak-stimulated GH levels but similar IGF-1 levels as compared to controls. Higher peak-stimulated GH levels are associated with lower IHL and less hepatocellular damage. Higher IGF-1 levels are associated with more favorable fibrosis risk scores. These data implicate GH and IGF-1 as potential disease modifiers in the development and progression of NAFLD.
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Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Hormônio do Crescimento Humano , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Fator de Crescimento Insulin-Like I , Lipídeos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Sobrepeso/complicações , Adulto JovemRESUMO
OBJECTIVE: We aimed to identify the proportion of primary care patients meeting criteria for sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) for cardiorenal comorbidities per 2021 American Diabetes Association (ADA) Standards of Care recommendations using readily available electronic health record (EHR) characteristics. RESEARCH DESIGN AND METHODS: We applied 2021 ADA recommendations to a primary care cohort of 13,350 adults with type 2 diabetes (T2D). RESULTS: We found that 33% of patients with diabetes would be eligible for an SGLT2i or GLP-1 RA based on cardiorenal comorbidities, 13% of patients met criteria for an SGLT2i based on heart failure or albuminuric chronic kidney disease (CKD), and 18% of patients met criteria for either agent based on atherosclerotic cardiovascular disease or CKD with an albumin-to-creatinine ratio of ≤300 mg/g. CONCLUSIONS: This EHR algorithm identified one-third of primary care patients with T2D as meeting criteria for SGLT2i and GLP-1 RA based on strict comorbidity definitions according to 2021 ADA recommendations.
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Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Hipoglicemiantes/uso terapêutico , Atenção Primária à Saúde , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Most incidental gastric polyps identified during upper endoscopy are considered low-risk. However, current guidelines recommend sampling all gastric polyps for histopathologic analysis. We aimed to devise a simple narrow-band imaging (NBI) classification to reduce the need for routine biopsies of low-risk gastric polyps. METHODS: Pairs of NBI and white-light images were collected from 73 gastric polyps for which concurrent histopathologic diagnosis was available. A diagnostic accuracy cohort study was performed. Two blinded endoscopists independently analysed NBI features of each polyp for color, vessel pattern, surface pattern, and any combinations thereof to develop a classification scheme to differentiate low-risk polyps (fundic-gland or hyperplastic) from high-risk polyps (adenomatous or adenocarcinoma) and fundic-gland polyps (FGPs) from non-FGPs. RESULTS: An isolated lacy vessel pattern and a homogenous absence of surface pattern successfully differentiated low-risk from high-risk gastric polyps. Combining both descriptors into a single algorithm resulted in a negative predictive value (NPV) of 100% [95% confidence interval (CI): 100%-100%], positive predictive value (PPV) of 13.7% (95% CI: 2.6-24.8), sensitivity of 100% (95% CI: 100%-100%), and specificity of 53.7% (95% CI: 45.3%-62.0%) for high-risk polyps. This would reduce the number of polyps requiring biopsy by 50%, while still capturing all high-risk polyps. Regarding FGPs, using a rule not to biopsy polyps with isolated lacy vessels resulted in a 94.9% NPV (95% CI: 89.2%-100%), 63.2% PPV (95% CI: 47.2%-79.2%), 94.8% sensitivity (95% CI: 89.5%-100%), and 63.6% specificity (95% CI: 51.3%-76.0%) for non-FGPs. CONCLUSION: In this derivation cohort study, NBI is helpful for differentiating between high-risk and low-risk gastric polyps, thereby reducing the need for routine sampling of low-risk polyps. These results need to be validated in a separate test population.
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BACKGROUND: Growth in hospice utilisation has been accompanied by an increase in the proportion of hospice patients who die in an inpatient hospice setting rather than at home. OBJECTIVE: To determine whether this increase in inpatient utilisation is consistent with patient preferences. DESIGN: Retrospective cohort study. SETTING: Seven hospices in the Coalition of Hospices Organised to Investigate Comparative Effectiveness (CHOICE) network. PATIENTS: 70â 488 patients admitted between 1 July 2008 and 31 May 2012. MEASUREMENTS: We measured changes in patients' stated preferences at the time of admission regarding site of death, including weights to adjust for non-response bias. We also assessed patients' actual site of death and concordance with patients' preferences. RESULTS: More patients died receiving inpatient care in 2012 as compared to 2008 (1920 (32.7%), 2537 (18.5%); OR 1.21; 95% CI 1.19 to 1.22; p<0.001). However, patients also expressed an increasing preference for dying in inpatient settings (weighted preferences 27.5% in 2012 vs 7.9% in 2008; p<0.001). The overall proportion of patients who died in the setting of their choice (weighted preferences) increased from 74% in 2008 to 78% in 2012 (p<0.001). LIMITATIONS: This study included only seven hospices, and results may not be representative of the larger hospice population. CONCLUSIONS: Although more patients are dying while receiving inpatient care, these changes in site of death seem to reflect changing patient preferences. The net effect is that patients in this sample were more likely to die in the setting of their choice in 2012 than they were in 2008.