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INTRODUCTION: Childhood cancer survivors (CCS) are at risk of experiencing lower quality-of-life, fatigue, and depression. Few randomized controlled trials have studied the effect of physical activity (PA) on these in adult long-term CCS. This study investigated the effect of a 1-year individualized PA intervention on health-related quality-of-life (HRQOL), fatigue, and distress symptoms in adult CCS. METHODS: The SURfit trial randomized 151 CCS ≥16 years old, <16 at diagnosis and ≥5 years since diagnosis, identified through the Swiss Childhood Cancer Registry. Intervention participants received personalized PA counselling to increase intense PA by ≥2.5 h/week for 1 year. Controls maintained usual PA levels. The authors assessed physical- and mental-HRQOL, fatigue, and distress symptoms at baseline, 3, 6, and 12 months. T-scores were calculated using representative normative populations (mean = 50, standard deviation = 10). Generalized linear mixed-effects models with intention-to-treat (ITT, primary), and three per-protocol allocations were used. RESULTS: At 12 months, ITT (-3.56 larger decrease, 95% confidence interval -5.69 to -1.43, p = .001) and two per-protocol analyses found significantly lower fatigue. Physical-HRQOL improved significantly in two per-protocol analyses at 12 months. No other effects were found. CONCLUSION: SURfit showed that increased intense PA over 1 year improved fatigue in adult CCS. Survivors should be recommended PA to reduce the burden of late-effects.
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Supervivientes de Cáncer , Ejercicio Físico , Fatiga , Calidad de Vida , Humanos , Supervivientes de Cáncer/psicología , Fatiga/terapia , Fatiga/etiología , Femenino , Masculino , Adulto , Adolescente , Neoplasias/psicología , Neoplasias/terapia , Adulto Joven , NiñoRESUMEN
Alcohol consumption influences sodium-water homeostasis. However, the effect of alcohol on vasopressin levels is controversial. The aim of the present study was to evaluate physiological changes of alcohol consumption on the stable vasopressin surrogate marker copeptin. In addition, we aimed at investigating the effect of additional sodium and/or water consumption on plasma sodium, osmolality, and copeptin levels. Ten healthy men underwent four interventions in random order: 1) beer consumption only, 2) beer consumption with additional water, 3) beer consumption with additional stock, or 4) water consumption only. Fluid consumption was equal between interventions and calculated to reach a blood alcohol concentration of 0.8 in the beer interventions. Blood and urinary samples were taken at six time points over the observation period of 720 min. The primary end point was the mean difference in copeptin levels 90 min after the start of fluid consumption, which showed no in-between group differences (P = 0.4). However, a higher total urinary volume excretion in all alcohol compared with water interventions was observed (P = 0.01). Furthermore, plasma copeptin, sodium, and urinary osmolality levels increased significantly at the end of the observation period in all alcohol compared with water-only interventions (P = 0.02). In conclusion, initial copeptin suppression does not differ between alcohol or water interventions but seems to be prolonged in the alcohol interventions. This leads to increased volume loss followed by a counterregulation with increased copeptin levels and water retention after 720 min in alcohol compared with interventions. Additional sodium and/or water consumption with alcohol did not change the observed alcohol-induced effects.
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Cerveza , Glicopéptidos/metabolismo , Sodio/sangre , Equilibrio Hidroelectrolítico , Agua , Adulto , Consumo de Bebidas Alcohólicas , Ingestión de Líquidos , Glicopéptidos/genética , Homeostasis/efectos de los fármacos , Humanos , Masculino , Adulto JovenRESUMEN
Background: Smoking cessation is challenging, despite making use of established smoking cessation therapies. Preclinical studies and one clinical pilot study suggest the antidiabetic drug glucagon-like peptide-1 (GLP-1) analogue to modulate addictive behaviours and nicotine craving. Previously, we reported the short-term results of a randomised, double-blind, placebo-controlled trial. Herein we report long-term abstinence rates and weight developments after 24 and 52 weeks. Methods: This single-centre, randomised, double-blind, placebo-controlled, parallel group trial was done at the University Hospital Basel in Switzerland. We randomly assigned (1:1) individuals with at least a moderate nicotine dependence willing to quit smoking to either a 12-week treatment with dulaglutide 1.5 mg or placebo subcutaneously once weekly in addition to standard of care smoking cessation therapy (varenicline 2 mg/day and behavioural counselling). After 12 weeks, dulaglutide or placebo injections were discontinued and the participants were followed up at week 24 and 52. The primary outcome of self-reported and biochemically confirmed point prevalence abstinence rate, and secondary outcome of secondary outcome of weight change were assessed at weeks 24 and 52. All participants who received one dose of the study drug were included in the intention to treat set and participants who received at least 10/12 doses of the study drug formed the per protocol set. The trial was registered at ClinicalTrials.gov, NCT03204396. Findings: Of the 255 participants who were randomly assigned between June 22, 2017 and December 3, 2020, 63% (80/127) (dulaglutide group) and 65% (83/128) (placebo group) were abstinent after 12 weeks. These abstinence rates declined to 43% (54/127) and 41% (52/128), respectively, after 24 weeks and to 32% (41/127) and 32% (41/128), respectively, after 52 weeks. Post-cessation weight gain was prevented in the dulaglutide group (-1.0 kg, standard deviation [SD] 2.7) as opposed to the placebo group (+1.9 kg, SD 2.4) after 12 weeks. However, at week 24, increases in weight from baseline were observed in both groups (median, interquartile range [IQR]: dulaglutide: +1.5 kg, [-0.4, 4.1], placebo: +3.0 kg, [0.6, 4.6], baseline-adjusted difference in weight change -1.0 kg (97.5% CI [-2.16, 0.16])), and at week 52 the groups showed similar weight gain (median, IQR: dulaglutide: +2.8 kg [-0.4, 4.7], placebo: +3.1 kg [-0.4, 6.0], baseline-adjusted difference in weight change: -0.35 kg (95% CI [-1.72, 1.01])). In the follow-up period (week 12 to week 52) 51 (51%) and 48 (48%) treatment-unrelated adverse events were recorded in the dulaglutide and the placebo group, respectively. No treatment-related serious adverse events or deaths occurred. Interpretation: Dulaglutide does not improve long-term smoking abstinence, but has potential to counteract weight gain after quitting. However, 3 months of treatment did not have a sustained beneficial effect on weight at 1 year. As post-cessation weight gain is highest in the first year after quitting smoking, future studies should consider a longer treatment duration with a GLP-1 analogue in abstinent individuals. Funding: Swiss National Science Foundation, the Gottfried and Julia Bangerter-Rhyner Foundation, the Goldschmidt-Jacobson Foundation, the Hemmi-Foundation, the University of Basel, the Swiss Academy of Medical Sciences.
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Background: Quitting smoking is difficult due to barriers such as craving for cigarettes and post-cessation weight gain. Recent experimental data suggest a role of glucagon-like peptide-1 (GLP-1) in the pathophysiology of addiction in addition to appetite regulation and weight control. We hypothesized that a pharmacological intervention with the GLP-1 analogue dulaglutide during smoking cessation may improve abstinence rates and reduce post-cessation weight gain. Methods: This is a single-centre, randomized, double-blind, placebo-controlled, parallel group, superiority study conducted in the University Hospital Basel in Switzerland. We included adult smokers with at least moderate cigarette dependence who wanted to quit. Participants were randomly assigned to a 12-week treatment with dulaglutide 1.5 mg once weekly or placebo subcutaneously in addition to standard of care including behavioural counselling and oral varenicline pharmacotherapy of 2 mg/day. The primary outcome was self-reported and biochemically confirmed point prevalence abstinence rate at week 12. Secondary outcomes included post-cessation weight, glucose metabolism, and craving for smoking. All participants who received one dose of study drug were included in the primary and safety analyses. The trial was registered on ClinicalTrials.gov (NCT03204396). Findings: Between June 22, 2017, and December 3, 2020, 255 participants were enrolled and randomly assigned to each group (127 in the dulaglutide group and 128 in the placebo group). After 12 weeks, 63% (80/127) participants on dulaglutide and 65% (83/128) on placebo treatment were abstinent (difference in proportions -1.9% [95% Confidence interval (CI) -10.7, 14.4], p-value (p) = 0.859). Dulaglutide decreased post-cessation weight (-1 kg [standard deviation (SD) 2.7]), while weight increased on placebo (+1.9 kg [SD 2.4]). The baseline-adjusted difference in weight change between groups was -2.9 kg (95% CI -3.59, -2.3, p < 0.001). Haemoglobin A1c (HbA1c) level declined on dulaglutide treatment (baseline-adjusted median difference in HbA1c between groups -0.25% [interquartile range (IQR) -0.36, -0.14], p < 0.001). Craving for smoking declined during treatment without any difference between the groups. Treatment-emergent gastrointestinal symptoms were very common in both groups: 90% (114/127) of participants on dulaglutide and 81% (81/128) on placebo). Interpretation: Dulaglutide had no effect on abstinence rates but prevented post-cessation weight gain and decreased HbA1c levels. GLP-1 analogues may play a role in future cessation therapy targeting metabolic parameters such as weight and glucose metabolism. Funding: Swiss National Science Foundation, the Gottfried Julia Bangerter-Rhyner Foundation, the Goldschmidt-Jacobson Foundation, the Hemmi-Foundation, the University of Basel, the Swiss Academy of Medical Sciences.
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CONTEXT: Arginine stimulates pituitary hormones, like growth hormone and vasopressin, but its effect on the hypothalamic-pituitary-adrenal (HPA) axis is unknown. Arginine may also stimulate the HPA axis, possibly through a mechanism involving vasopressin. OBJECTIVE: To investigate the effect of arginine on adrenocorticotropic hormone (ACTH) and cortisol in subjects with and without vasopressin deficiency. DESIGN: Prospective study, University Hospital Basel. PARTICIPANTS: 38 patients with central diabetes insipidus, 58 patients with primary polydipsia, and 50 healthy controls. INTERVENTION: Arginine infusion with measurement of ACTH, cortisol and copeptin at baseline and 30, 45, 60, 90, and 120 minutes. RESULTS: We found different response patterns to arginine: in patients with diabetes insipidus (and low stimulated copeptin levels) median (interquartile range [IQR]) ACTH and cortisol increased from 22.9 (16.8, 38.7) to 36.6 (26.2, 52.1) ng/L and from 385 (266, 463) to 467 (349, 533) nmol/L, respectively. In contrast, median (IQR) ACTH and cortisol levels decreased in patients with primary polydipsia (despite high stimulated copeptin levels): ACTH from 17.3 (12.3, 23) to 14.8 (10.9, 19.8) ng/L and cortisol from 343 (262, 429) to 272 (220.8, 360.3) nmol/L; likewise, in healthy controls: ACTH from 26.5 (17.6, 35.7) to 14.8 (12.1, 22.7) ng/L and cortisol from 471 (393.3, 581.8) to 301.5 (206.5, 377.8) nmol/L. CONCLUSION: Diabetes insipidus is associated with increased responsiveness of ACTH/cortisol to arginine. In contrast, arginine does not stimulate the HPA axis in healthy controls or in primary polydipsia.