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Serum sodium levels and related treatment-emergent adverse events during eslicarbazepine acetate use in adults with epilepsy.
Wechsler, RT, Radtke, RA, Smith, M, Vossler, DG, Strom, L, Trinka, E, Cheng, H, Grinnell, T, Blum, D, Vieira, M, et al
Epilepsia. 2019;(7):1341-1352
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Abstract
OBJECTIVE To examine the frequency of hyponatremia and potentially related symptoms in clinical trials of eslicarbazepine acetate (ESL) in adults with focal- (partial-) onset seizures. METHODS This post hoc, exploratory analysis included data from three controlled phase 3 trials of adjunctive ESL (400-1200 mg once daily), two phase 3 trials of ESL monotherapy (1200-1600 mg once daily), and their open-label extension studies. Exploratory endpoints included clinical laboratory measurements of serum sodium concentrations ([Na+ ]), incidences of hyponatremia-related treatment-emergent adverse events (TEAEs), and incidences of TEAEs that are potential symptoms of hyponatremia. RESULTS The controlled trials of adjunctive ESL and ESL monotherapy included 1447 (placebo, n = 426; ESL, n = 1021) and 365 (ESL, n = 365) patients, respectively; 639 and 274 patients continued onto uncontrolled, open-label extensions. In the controlled and uncontrolled trials ≤3.3% of patients taking ESL had a minimum postdose [Na+ ] measurement ≤125 mEq/L, <9% had a >10 mEq/L decrease in [Na+ ] from baseline, <6% had a hyponatremia-related TEAE, and <2% discontinued the controlled trials due to a hyponatremia-related TEAE. Hyponatremia appeared to be more frequent in the monotherapy (vs adjunctive therapy) trials; in the controlled trials of adjunctive ESL and ESL monotherapy, incidence generally increased with increasing ESL dose. The majority of patients with an investigator-reported TEAE of "hyponatremia" or "blood sodium decreased" did not have a corresponding laboratory [Na+ ] measurement ≤125 mEq/L. Some symptoms potentially related to hyponatremia (including nausea and vomiting) were more frequent in patients with a minimum postdose [Na+ ] measurement ≤125 mEq/L. SIGNIFICANCE Reductions in serum sodium concentrations and hyponatremia-related TEAEs occurred in a small number of patients taking ESL. Suspected hyponatremia should be confirmed and monitored via [Na+ ] measurements.
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Hyponatremia associates with poor outcome in metastatic renal cell carcinoma patients treated with everolimus: prognostic impact.
Penttilä, P, Bono, P, Peltola, K, Donskov, F
Acta oncologica (Stockholm, Sweden). 2018;(11):1580-1585
Abstract
BACKGROUND The prognostication of metastatic renal cell carcinoma (mRCC) is based on Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classifications. Research has shown that hyponatremia is associated with worse prognosis in cancer. We analyzed the association of hyponatremia and outcome in everolimus-treated mRCC patients. PATIENTS AND METHODS Baseline and on-treatment (≤12 weeks) sodium in 233 mRCC patients was analyzed using Kaplan-Meier, Cox regression and logistic regression. Baseline sodium was correlated with baseline thrombocyte and neutrophil values. RESULTS 65 (28%) and 41 (18%) patients had sodium < lower limit of normal (LLN) at baseline and on-treatment, respectively. Baseline sodium < LLN was associated with shorter overall survival (OS) (6.1 vs. 10.3 months; p < .001) and progression-free survival (PFS) (2.8 vs. 3.5 months; p = .04). On-treatment sodium < LLN was associated with shorter OS (5.4 vs. 9.9 months; p < .001) and PFS (2.8 vs. 4.0 months; p < .001). In multivariate analyses adjusted for IMDC factors, baseline and on-treatment sodium < LLN were significantly associated with shorter OS (adjusted HR 1.46 (95% CI 1.04-2.05); p = .02; adjusted HR 1.80 (95% CI 1.23-2.61); p = .002; respectively). On-treatment sodium < LLN was significantly associated with progressive disease (OR 0.23 (95% CI 0.10-0.56); p = .001). A landmark analysis demonstrated that on-treatment hyponatremia was significantly associated with shorter OS and PFS (p = .01 and p = .03, respectively). On-treatment normalization of hyponatremia was associated with improved OS (unadjusted HR 0.61 (95% CI 0.35-0.98); p = .04), as compared to patients with sustained hyponatremia throughout follow-up. CONCLUSIONS Hyponatremia associates with poor outcome in mRCC patients treated with everolimus. On-treatment normalization of hyponatremia to normal sodium values associates with favorable outcome.
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Development of a computer-interpretable clinical guideline model for decision support in the differential diagnosis of hyponatremia.
González-Ferrer, A, Valcárcel, MÁ, Cuesta, M, Cháfer, J, Runkle, I
International journal of medical informatics. 2017;:55-64
Abstract
INTRODUCTION Hyponatremia is the most common type of electrolyte imbalance, occurring when serum sodium is below threshold levels, typically 135mmol/L. Electrolyte balance has been identified as one of the most challenging subjects for medical students, but also as one of the most relevant areas to learn about according to physicians and researchers. We present a computer-interpretable guideline (CIG) model that will be used for medical training to learn how to improve the diagnosis of hyponatremia applying an expert consensus document (ECDs). METHODS We used the PROForma set of tools to develop the model, using an iterative process involving two knowledge engineers (a computer science Ph.D. and a preventive medicine specialist) and two expert endocrinologists. We also carried out an initial validation of the model and a qualitative post-analysis from the results of a retrospective study (N=65 patients), comparing the consensus diagnosis of two experts with the output of the tool. RESULTS The model includes over two-hundred "for", "against" and "neutral" arguments that are selectively triggered depending on the input value of more than forty patient-state variables. We share the methodology followed for the development process and the initial validation results, that achieved a high ratio of 61/65 agreements with the consensus diagnosis, having a kappa value of K=0.86 for overall agreement and K=0.80 for first-ranked agreement. CONCLUSION Hospital care professionals involved in the project showed high expectations of using this tool for training, but the process to follow for a successful diagnosis and application is not trivial, as reported in this manuscript. Secondary benefits of using these tools are associated to improving research knowledge and existing clinical practice guidelines (CPGs) or ECDs. Beyond point-of-care clinical decision support, knowledge-based decision support systems are very attractive as a training tool, to help selected professionals to better understand difficult diseases that are underdiagnosed and/or incorrectly managed.
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Paroxetine-induced hyponatremia in the elderly due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH).
Fabian, TJ, Amico, JA, Kroboth, PD, Mulsant, BH, Reynolds, CF, Pollock, BG
Journal of geriatric psychiatry and neurology. 2003;(3):160-4
Abstract
This study investigated the development of hyponatremia and its underlying mechanism in elderly patients prescribed paroxetine. Patients were 15 men and women (mean age, 75.7 +/- 5.3 years) who were participants in a treatment study of late-life depression and who were without medical illness or other medications known to cause hyponatremia or alter antidiuretic hormone (ADH) secretion. Blood samples for measurement of plasma sodium, ADH, blood urea nitrogen (BUN), creatinine, glucose, and osmolality were determined prior to initiation of paroxetine (week 0) and at 2, 4, 6, and 12 weeks of treatment with paroxetine. Hyponatremia (serum sodium < 135 mEq/L) was identified in 6 of 15 patients after 2 weeks of treatment with paroxetine. Despite low plasma osmolality, ADH levels were not suppressed appropriately. Data suggest hyponatremia is a common adverse event in elderly patients prescribed paroxetine and implicates inappropriate secretion of ADH as the potential mechanism.
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Risperidone failed to improve polydipsia-hyponatremia of the schizophrenic patients.
Kawai, N, Baba, A, Suzuki, T
Psychiatry and clinical neurosciences. 2002;(1):107-10
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Abstract
The effect of risperidone on polydipsia-hyponatremia was evaluated in six hospitalized schizophrenic patients. The normalized diurnal weight gain (NDWG), urine-specific gravity (USG), urine and plasma osmolarity, and serum sodium were monitored during 9 months of risperidone treatment. The dose of risperidone (mean +/- SD=8.0 +/- 1.0, range=6-9 mg/day) was determined as approximately half of the haloperidol-equivalent dose of previous neuroleptics. Before risperidone treatment, the mean (+/- SD) BPRS score was 23.5 +/- 7.1; no significant improvement was observed after risperidone (22.0 +/- 7.5). The subjects showed relatively high serum prolactin before risperidone treatment (mean +/- SD=16.5 +/- 9.7 ng/mL), that was not significantly decreased by risperidone (14.2 +/- 7.9 ng/mL). The monthly means (+/- SD) of NDWG and USG before risperidone were 5.5 +/- 1.5 (%) and 1.002 +/- 0.001, respectively. These and other indices did not significantly improve throughout the study period. Although the sample size is relatively small, our preliminary data showed that risperidone might not be effective on polydipsia-hyponatremia of schizophrenic patients.