RESUMEN
BACKGROUND: Desmopressin acetate (1-deamino-8-d-arginine vasopressin-DDAVP) is a analogue of the antidiuretic hormone vasopressin. DDAVP is suggested to reduce bleeding after cardiac surgery using cardiopulmonary bypass. The aim of this study was to determine if DDAVP has any negative impact on renal function leading to acute kidney injury (AKI) and therefore increases the need for renal replacement therapy (RRT). METHODS: We performed a retrospective single institutional cohort analysis of 2,179 patients undergoing elective and urgent cardiac surgery with CPB from 2017 to 2021. Logistic regression analysis was used to investigate any association between DDAVP, the incidence of AKI KDIGO class 3 and the need for RRT, respectively. The model was adjusted for relevant covariates, including preexisting renal impairment, pharmacological hemodynamic support with vasopressors, complexity of the surgery and postoperative lactate. Secondary outcomes included, in hospital mortality and the need for allogenic blood transfusion. RESULTS: A total of 992 (45.5%) patients received DDAVP intraoperatively during surgery or shortly thereafter. The use of DDAVP was associated with a significant increase in in AKI KDIGO class 3 (OR 2.27; 95% CI 1.46-3.55; p < 0,001) and the need for RRT (OR 2.19; 95%CI 1.48-3.24; p < 0,001). Both findings persisted after covariate adjusting. No increased in-hospital mortality was associated with DDAVP. CONCLUSION: In cardiac surgery, the use of DDAVP was associated with an increased rate of server AKI and the requirement for RRT. Given the severity of the potential harm associated with DDAVP, an evidence-based reevaluation is needed to enable an accurate risk and benefit assessment.
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Lesión Renal Aguda , Procedimientos Quirúrgicos Cardíacos , Desamino Arginina Vasopresina , Humanos , Estudios Retrospectivos , Desamino Arginina Vasopresina/uso terapéutico , Masculino , Femenino , Procedimientos Quirúrgicos Cardíacos/métodos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Lesión Renal Aguda/epidemiología , Anciano , Persona de Mediana Edad , Mortalidad Hospitalaria , Estudios de Cohortes , Terapia de Reemplazo Renal , Complicaciones Posoperatorias/epidemiologíaRESUMEN
BACKGROUND: Given the role of the placenta in maintaining maternal-fetal equilibrium, changes in maternal sodium levels affect the fetus. Clinicians must also account for the direct impact of maternal conditions and medications on the neonate. Gestational hyponatremia develops in approximately one-third of mothers with preeclampsia with severe features. Additionally, the use of selective antidiuretic (V2 receptor) agonist 1-deamino-8-D-arginine-vasopressin, commonly known as DDAVP, during pregnancy leads to maternal hyponatremia by inhibiting maternal diuresis. We present a case of severe hyponatremia in a premature infant born to a mother with preeclampsia with severe features who was taking DDAVP for von Willebrand Disease (VWD). CASE: A preterm female infant was born at 34 weeks gestation to a mother with pre-eclampsia with severe features treated with magnesium sulfate, and the use of DDAVP for VWD was found to have severe hyponatremia (122 mmol/L). Causes of hyponatremia were explored, such as mineralocorticoid deficiency, renal tubular dysfunction, inappropriate secretion of antidiuretic hormone (SIADH), and renal failure. Initial investigation of the neonatal hyponatremia prompted obtaining a maternal serum sodium level, which also demonstrated severe hyponatremia (122 mmol/L), identical to the infant's serum sodium level. The infant was managed with fluid restriction and close monitoring of serial serum and urine chemistries. Gradually, serum sodium levels increased and normalized by day 4 of life. We speculate that severe maternal hyponatremia induced by preeclampsia with severe features, along with the use of DDAVP during pregnancy, led to fetal and neonatal hyponatremia. CONCLUSION: DDAVP during pregnancy to treat VWD is associated with maternal hyponatremia and subsequent neonatal hyponatremia. It is important to monitor electrolytes in neonates born to mothers treated with DDAVP to promptly correct electrolyte abnormalities.
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Hiponatremia , Recien Nacido Prematuro , Humanos , Hiponatremia/etiología , Femenino , Recién Nacido , Embarazo , Desamino Arginina Vasopresina/uso terapéutico , Adulto , Preeclampsia/tratamiento farmacológicoRESUMEN
ABSTRACT: Diabetes insipidus is a condition characterised by a large volume of diluted urine production and increased thirst. In this case report, a 49-year-old gentleman presented with 3 months of polyuria and polydipsia. He had a repeated history of hypokalemia. On the evaluation of polyuria and polydipsia, he was diagnosed with partial nephrogenic diabetes insipidus based on his inability to concentrate urine after a water deprivation test and his less than 50% response to exogenous desmopressin. On the evaluation of recurrent hypokalemia, the investigation reports met biochemical criteria for the diagnosis of Gitelman syndrome. He was encouraged to increase his fluid intake as required, and potassium chloride supplementation relieved his symptoms. This case report demonstrates the reversibility of nephrogenic diabetes insipidus with a correction of hypokalemia.
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Diabetes Insípida Nefrogénica , Hipopotasemia , Humanos , Masculino , Diabetes Insípida Nefrogénica/diagnóstico , Hipopotasemia/etiología , Hipopotasemia/diagnóstico , Persona de Mediana Edad , Poliuria/etiología , Poliuria/diagnóstico , Cloruro de Potasio/uso terapéutico , Cloruro de Potasio/administración & dosificación , Polidipsia/etiología , Polidipsia/diagnóstico , Desamino Arginina Vasopresina/uso terapéutico , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/complicacionesRESUMEN
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have diverse effects on sodium and water homeostasis. They decrease thirst perception, potentially inhibit arginine vasopressin (AVP) production, and induce natriuresis. We present three cases of AVP deficiency (AVP-D) where GLP-1 RA initiation led to desmopressin dose reduction. CASES: Three patients with AVP-D on stable desmopressin therapy started GLP-1 RAs for type 2 diabetes mellitus or obesity. Following weight loss and decreased thirst, all patients reduced their desmopressin dose while maintaining normal thirst and urine output. DISCUSSION: GLP-1 RAs influence sodium and water homeostasis through various mechanisms. In individuals with intact AVP systems, GLP-1 RAs may directly suppress AVP production and induce natriuresis in the kidney leading to increased water excretion. In AVP-D, with exogenous desmopressin replacing endogenous AVP, the osmotic permeability of collecting ducts is primarily influenced by desmopressin dose. Thus, increased distal fluid delivery may allow for lower desmopressin doses to maintain water balance. CONCLUSION: Our findings indicate a potential interaction between GLP-1 RAs and desmopressin in AVP-D. Clinicians should reassess desmopressin dosage upon initiating GLP-1 RA therapy.
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Arginina Vasopresina , Desamino Arginina Vasopresina , Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Humanos , Desamino Arginina Vasopresina/farmacología , Desamino Arginina Vasopresina/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Masculino , Femenino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Arginina Vasopresina/metabolismo , Adulto , Anciano , Agonistas Receptor de Péptidos Similares al GlucagónRESUMEN
PURPOSE: The desmopressin daily dose requirement is highly variable among patients with arginine vasopressin (AVP) deficiency (i.e. central diabetes insipidus) and few studies to date have evaluated this topic, with often inconclusive results. The aim of our study was to identify clinical and biochemical predictors of such dose requirements in a cohort of patients with a confirmed diagnosis of permanent AVP deficiency who have good and stable control under substitutive treatment. METHODS: We retrospectively analyzed data of all patients with permanent AVP deficiency undergoing regular follow-up at our Division. Inclusion criteria were the presence of stable disease under therapy for at least 12 months and in good biochemical and clinical control. Patients with AVP deficiency who lacked intact thirst or had a disease duration of less than 12 months were excluded from the analysis. RESULTS: Out of the 132 patients initially screened, 96 patients (M/F 44/52; age 51 [37-63] years) met the inclusion criteria. Patients on nasal spray therapy (n = 8) had a significantly longer disease duration (p = 0.002) than patients treated with oral lyophilizate (n = 88). In the bivariate analysis, considering only patients treated with the sublingual formulation, the drug dose was correlated positively with estimated glomerular filtration rate (eGFR) and weight (r = 0.410, p < 0.001; r = 0.224, p = 0.036, respectively) and negatively with age (r = - 0.433, p < 0.001). In the multivariate regression analysis taking into account age, weight, and eGFR, only age emerged as a significant predictor of the required sublingual desmopressin dose (ß = - 1.426, p = 0.044). CONCLUSION: Our data suggest that patient age appears to be the primary factor associated with the daily sublingual desmopressin dose required to achieve adequate clinical and biochemical control in patients with permanent AVP deficiency.
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Arginina Vasopresina , Desamino Arginina Vasopresina , Humanos , Desamino Arginina Vasopresina/administración & dosificación , Desamino Arginina Vasopresina/uso terapéutico , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Arginina Vasopresina/deficiencia , Centros de Atención Terciaria , Fármacos Antidiuréticos/administración & dosificación , Fármacos Antidiuréticos/uso terapéutico , Diabetes Insípida Neurogénica/tratamiento farmacológicoRESUMEN
Background: Desmopressin (1-deamino-8-D-arginine vasopressin [DDAVP]) has demonstrated efficacy as a treatment option for patients with inherited bleeding disorders. Because of individuals' variable response to the medication, it is recommended to complete a challenge to document appropriate hemostatic response to the medication before recommending its use prior to surgical procedures or treatment of bleeding symptoms. The project aimed to reduce the errors in hemostatic response assessments for patients with bleeding disorders undergoing a DDAVP challenge (process outcome), particularly timing and number of blood samples drawn, from an error rate baseline of 36% to 0% by December 2021 and sustained for one year. Method: Plan-Do-Study-Act methodology was employed for this qualitative improvement initiative. Interventions designed and implemented included: an order set with medication doses and corresponding laboratory orders as clinically indicated for the bleeding disorder indication, clinical procedure guidelines for infusion nurses to follow, hemostasis nurse coordination of appointments with patients, and family education. Results: Baseline data on 22 patients who completed a DDAVP challenge demonstrated a 36% error rate not involving doses of medication administered. Errors encountered included improper timing of laboratory draw after DDAVP administration, incomplete laboratory evaluation, laboratory results displayed incorrectly due to testing orders released at once instead of in a sequential manner. These interventions resulted in a reduction of DDAVP challenge errors to 0% that were sustained for one year. Conclusion: Improvement in procedural medication administration and appropriate laboratory evaluation of patients undergoing a DDAVP challenge leads to a complete and reliable assessment of hemostatic response following medication administration.
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Desamino Arginina Vasopresina , Hemostáticos , Mejoramiento de la Calidad , Humanos , Desamino Arginina Vasopresina/uso terapéutico , Desamino Arginina Vasopresina/administración & dosificación , Adolescente , Adulto Joven , Masculino , Femenino , Niño , Hemostáticos/uso terapéutico , Hemostáticos/administración & dosificación , Adulto , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , PreescolarRESUMEN
INTRODUCTION: Antiplatelet agents (AAs) may increase the risk of intracranial hemorrhage (ICH). It is unclear whether reversal of antiplatelet effects (REV = desmopressin acetate [DDAVP] + Platelets) decreases ICH progression. The goal of the study was to determine whether REV was associated with decreased progression of ICH on repeat brain computed tomography (CT) scan. METHODS: This is a clustered study (November 2019 to March 2022) at two regionally distinct trauma centers (TCs) with differing standards of practice in patients with ICH, one reversal with DDAVP + Platelets (REV+) and the other no reversal with DDAVP + Platelets (REV-). Using electronic and manual chart review, data were collected on inpatients aged ≥ 18 y on preinjury AAs with CT proven ICH (abbreviated injury scale head ≥ 2) and no other abbreviated injury scale > 2 injuries, who had at least one repeat CT scan within 120 h of admission. ICH progression on repeat brain CT scan, mortality, and resource utilization were compared via univariate analysis (α = 0.05). RESULTS: One hundred fourteen patients were enrolled: 72 REV+ at the first TC and 42 REV- at the second TC. REV+ group had fewer White patients and a lower proportion on preinjury aspirin but were otherwise similar. ICH progression rate was 24/72 (33.3%) for REV+ and 11/42 (26.2%) for REV- (P = 0.43). Isolated subarachnoid hemorrhage was the most common lesion, followed by isolated subdural hemorrhage. No patients required cranial surgery. All-cause mortality (expired + hospice) was 5/72 (6.9%) and 1/42 (2.4%), respectively (P = 0.29). CONCLUSIONS: In this study of patients on preinjury AAs, REV was not associated with decreased ICH progression, lower mortality, or less resource utilization. These findings should be confirmed in a larger, prospective study.
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Lesiones Traumáticas del Encéfalo , Progresión de la Enfermedad , Hemorragias Intracraneales , Inhibidores de Agregación Plaquetaria , Tomografía Computarizada por Rayos X , Centros Traumatológicos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Centros Traumatológicos/estadística & datos numéricos , Anciano , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/mortalidad , Adulto , Hemorragias Intracraneales/etiología , Hemorragias Intracraneales/inducido químicamente , Desamino Arginina Vasopresina/uso terapéutico , Análisis por ConglomeradosRESUMEN
BACKGROUND: Type 2 Normandy von Willebrand disease (VWD2N) is usually perceived as a mild bleeding disorder that can be treated with desmopressin (DDAVP). However, VWD2N patients can be compound heterozygous or homozygous for different variants, with p.Arg854Gln (R854Q) being the most frequent causative one. There are limited data about the impact of 2N variants on VWD2N phenotype and DDAVP response. OBJECTIVES: This study aims to describe the phenotype of VWD2N, including DDAVP response, according to genotype. METHODS: VWD2N patients with a complete genotype/phenotype characterization by the French reference center for VWD, including MCMDM-1VWD bleeding score, were eligible to be included in the study. Results of the DDAVP trial were also collected. RESULTS: A total of 123 VWD2N patients from the French registry were included in this study. Results were stratified according to the presence (R854QPos, n = 114) or absence (R854QNeg, n = 9) of at least 1 R854Q allele. Three R854QPos subgroups were further individualized: patients homozygous (R854QHmz, n = 55), compound heterozygous for R854Q and a null allele (R854Q/3, n = 48), or compound heterozygous for R854Q and another 2N variant (R854Q/2N, n = 11). FVIII: C levels were significantly lower in R854QNeg and R854Q/3 patients compared with R854QHmz ones (P < .001 and P < .0001, respectively). R854QNeg patients were diagnosed earlier due to bleeding symptoms and had a higher bleeding score than R854QPos patients (P < .001). In DDAVP trial, FVIII:C survival was lower in VWD type 2N than in type 1 patients. R854QPos patients had a heterogeneous DDAVP response, which was best predicted by baseline FVIII:C level. CONCLUSION: The heterogeneous genetic background of VWD2N drives different bleeding phenotypes and response patterns to DDAVP, underlining the clinical relevance of DDAVP trial to identify patients potentially eligible to alternative therapeutic options.
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Desamino Arginina Vasopresina , Genotipo , Hemorragia , Fenotipo , Enfermedad de von Willebrand Tipo 2 , Factor de von Willebrand , Humanos , Desamino Arginina Vasopresina/uso terapéutico , Hemorragia/genética , Hemorragia/inducido químicamente , Hemorragia/sangre , Masculino , Femenino , Enfermedad de von Willebrand Tipo 2/genética , Enfermedad de von Willebrand Tipo 2/tratamiento farmacológico , Enfermedad de von Willebrand Tipo 2/diagnóstico , Enfermedad de von Willebrand Tipo 2/sangre , Factor de von Willebrand/genética , Adulto , Francia , Persona de Mediana Edad , Hemostáticos/uso terapéutico , Adulto Joven , Heterocigoto , Homocigoto , Sistema de Registros , Resultado del Tratamiento , Adolescente , Niño , AncianoRESUMEN
PURPOSE: Nocturnal urine volume and bladder reservoir function are key pathogenic factors behind monosymptomatic nocturnal enuresis (MNE). We investigated the predictive value of these together with other demographic and clinical variables for response to first-line treatments in children with MNE. MATERIALS AND METHODS: A randomized, controlled, international, multicenter study was conducted in 324 treatment-naïve children (6-14 years old) with primary MNE. The children were randomized to treatment with or without prior consideration of voiding diaries. In the group where treatment choice was based on voiding diaries, children with nocturnal polyuria and normal maximum voided volume (MVV) received desmopressin (dDAVP) treatment, and children with reduced MVV and no nocturnal polyuria received an enuresis alarm. In the other group, treatment with dDAVP or alarm was randomly allocated. RESULTS: A total of 281 children (72% males) were qualified for statistical analysis. The change of responding to treatment was 21% higher in children where treatment was individualized compared to children where treatment was randomly selected (risk ratio = 1.21 [1.02-1.45], P = .032). In children with reduced MVV and no nocturnal polyuria (35% of all children), individualized treatment was associated with a 46% improvement in response compared to random treatment selection (risk ratio = 1.46 [1.14-1.87], P = .003). Furthermore, we developed a clinically relevant prediction model for response to dDAVP treatment (receiver operating characteristic curve 0.85). CONCLUSIONS: The present study demonstrates that treatment selection based on voiding diaries improves response to first-line treatment, particularly in specific subtypes. Information from voiding diaries together with clinical and demographic information provides the basis for predicting response. CLINICAL TRIAL REGISTRATION NO.: NCT03389412.
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Fármacos Antidiuréticos , Desamino Arginina Vasopresina , Enuresis Nocturna , Humanos , Enuresis Nocturna/tratamiento farmacológico , Niño , Masculino , Femenino , Desamino Arginina Vasopresina/uso terapéutico , Adolescente , Fármacos Antidiuréticos/uso terapéutico , Resultado del Tratamiento , Alarmas Clínicas , Valor Predictivo de las Pruebas , Micción/efectos de los fármacosRESUMEN
OBJECTIVES: Desmopressin improves nocturia frequency; however, reports on its long-term efficacy and safety are few, and concerns regarding its effect on body composition exist. We thus investigated the efficacy and safety of long-term desmopressin administration and its effect on body composition. METHODS: This retrospective study, conducted at Chikugo City Hospital between August 2020 and December 2022, involved 133 men (mean age, 77.7 years) with nocturnal and persistent nocturia, who were administered an initial dose of 50 µg desmopressin. Efficacy endpoints included nocturnal urinary frequency, nocturnal urinary volume, hours of undisturbed sleep, nocturnal polyuria index, initial nocturnal urinary volume, and daily urinary frequency in a frequency-volume chart (3 days), before treatment and at 1, 4, 12, 24, and 52 weeks after desmopressin administration. Additionally, the effects of desmopressin on body composition were examined, including blood-brain natriuretic peptide and a chest radiography, before and 52 weeks after administration. RESULTS: Treatment improved most efficacy endpoint evaluation parameters. Around 87.6% of patients showed improved symptoms after 52 weeks compared with those before treatment (score ≤ 3). The blood-brain natriuretic peptide level rose; however, cardiothoracic ratio was unchanged. CONCLUSION: Long-term administration of desmopressin is thus effective and safe in older people with nocturnal polyuria, with little effect on body composition.
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Fármacos Antidiuréticos , Desamino Arginina Vasopresina , Nocturia , Humanos , Nocturia/tratamiento farmacológico , Nocturia/etiología , Masculino , Anciano , Desamino Arginina Vasopresina/administración & dosificación , Estudios Retrospectivos , Fármacos Antidiuréticos/administración & dosificación , Anciano de 80 o más Años , Resultado del Tratamiento , Composición Corporal/efectos de los fármacos , Factores de TiempoRESUMEN
von Willebrand disease (VWD) is the most common inherited bleeding disorder. The disorder is characterized by excessive mucocutaneous bleeding. The most common bleeding manifestations of this condition include nosebleeds, bruising, bleeding from minor wounds, menorrhagia or postpartum bleeding in women as well as bleeding after surgery. Other less frequent symptoms include gastrointestinal bleeding, haematomas or haemarthroses. VWD pathophysiology is complex and results from defects in von Willebrand factor (VWF) glycoprotein. Quantitative deficiencies are responsible for type 1 VWD with a partial decrease of VWF and type 3 with the complete absence of VWF. Qualitative abnormalities cause type 2 VWD, being further divided into types 2A, 2B, 2M and 2N. Although common, VWD is at risk of misdiagnosis, overdiagnosis and underdiagnosis owing to several factors, including complex diagnosis, variability of bleeding symptoms, presence of external variables (blood groups and other physiological modifiers such as exercise, thyroid hormones, oestrogens, and ageing), and lack of disease awareness among non-specialist health-care providers. Establishing the correct VWD diagnosis requires an array of specialized phenotypic assays and/or molecular genetic testing of the VWF gene. The management of bleeding includes increasing endogenous VWF levels with desmopressin or infusion of exogenous VWF concentrates (plasma-derived or recombinant). Fibrinolytic inhibitors, topical haemostatic agents and hormonal therapies are used as effective adjunctive measures.
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Enfermedades de von Willebrand , Factor de von Willebrand , Humanos , Enfermedades de von Willebrand/diagnóstico , Enfermedades de von Willebrand/fisiopatología , Factor de von Willebrand/análisis , Desamino Arginina Vasopresina/uso terapéutico , Femenino , Hemostáticos/uso terapéutico , Hemorragia/fisiopatología , Hemorragia/etiología , Hemorragia/diagnósticoRESUMEN
BACKGROUND: Cushing's syndrome (CS) poses diagnostic challenges, particularly in distinguishing pituitary-dependent Cushing's syndrome, Cushing's disease (CD), from the ectopic ACTH syndrome (EAS). This study evaluated the diagnostic value of the desmopressin stimulation test (DST) in patients with ACTH-dependent CS in helping this discrimination. METHODS: Twenty-three ACTH-dependent CS patients underwent sequential DST, bilateral inferior petrosal sinus sampling (BIPSS), and transsphenoidal surgery (TSS). Two definitions of a positive DST results were applied. Diagnostic performance was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios. To avoid bias from predetermined criteria, we generated univariate receiver-operating characteristic (ROC) curves, plotting sensitivity against 1-specificity at various percentage cortisol and ACTH response levels. RESULTS: Against BIPSS, DST demonstrated robust sensitivity (Definition 1: 90.0%, Definition 2: 76.2%) and overall accuracy (Definition 1: 87.0%, Definition 2: 73.9%). PPV was high (Definition 1: 95.0%, Definition 2: 94.1%), but NPV indicated potential false negatives. Compared to TSS, DST showed good sensitivity (Definition 1: 90.9-77.3%) and PPV (100.0%) but limited NPV (16.7%). The likelihood ratios emphasized the diagnostic value of the test. Notably, against TSS, DST showed perfect discriminatory power (AUC 1.000 for percent ACTH, 0.983 for percent cortisol). CONCLUSION: The desmopressin test shows promise in accurately identifying the underlying cause of ACTH-dependent CS, potentially reducing the reliance on invasive procedures and providing a practical solution for managing complex cases. Further research with larger cohorts is required to validate the utility of the DST in routine clinical practice.
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Síndrome de Cushing , Desamino Arginina Vasopresina , Muestreo de Seno Petroso , Sensibilidad y Especificidad , Humanos , Desamino Arginina Vasopresina/farmacología , Femenino , Masculino , Adulto , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/sangre , Persona de Mediana Edad , Muestreo de Seno Petroso/métodos , Muestreo de Seno Petroso/normas , Hormona Adrenocorticotrópica/sangre , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/sangre , Adulto Joven , Anciano , Síndrome de ACTH Ectópico/diagnóstico , Síndrome de ACTH Ectópico/sangreRESUMEN
Objectives: Nocturia with or without asthma is one of the aging diseases. Desmopressin has been used as a nasal spray for patients who are suffering from nocturia. This study determined the effects of desmopressin on isolated tracheal smooth muscle in vitro. Methods: We evaluated desmopressin's efficiency on isolated rat tracheal smooth muscle. Desmopressin was evaluated for the following effects on tracheal smooth muscle: (1) effect on resting tension; (2) effect on contraction brought on by parasympathetic mimetic 10-6 M methacholine; and (3) effect on electrically produced tracheal smooth muscle contractions. Results: As the concentration grew, desmopressin by itself had no impact on the trachea's baseline tension. Addition of desmopressin at doses of 10-5 M or above elicited a significant relaxation response to 10-6 M methacholine-induced contraction. Desmopressin could also inhibit spike contraction of the trachea induced by electrical field. Conclusion: According to this study, desmopressin at high quantities may prevent the trachea's parasympathetic activity. Due to its ability to block parasympathetic activity and lessen the contraction of the tracheal smooth muscle brought on by methacholine, Desmopressin nasal spray might help nocturia sufferers experience fewer asthma attacks.
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Desamino Arginina Vasopresina , Contracción Muscular , Músculo Liso , Rociadores Nasales , Tráquea , Animales , Tráquea/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Desamino Arginina Vasopresina/farmacología , Desamino Arginina Vasopresina/administración & dosificación , Ratas , Contracción Muscular/efectos de los fármacos , Masculino , Cloruro de Metacolina/administración & dosificación , Cloruro de Metacolina/farmacología , Humanos , Sistema Nervioso Parasimpático/efectos de los fármacosRESUMEN
Hyponatraemia, defined as sodium concentration below 135 mmol/l, is one of the most common electrolyte imbalances. Differential diagnosis of hyponatraemia is difficult. We describe 3 cases of children with transient, severe hyponatraemia (< 125 mmol/l). While diagnosing hyponatraemia, it is of major importance to carefully ask in the anamnesis about habits related to the amount of fluid intake and the type of consumed fluids. It should also be noted that a frequent procedure during an infection is to increase fluid ingesting as a prevention of dehydration. One, however, should remember about the possibility of inducing water poisoning in a patient consuming excessive amounts of hypotonic fluids, especially when exposed to non-osmotic antidiuretic hormone stimulus, such as an acute infection or stress, and/or reduced renal excretory capacity. Only the presence of polyuria does not justify a diagnosis of arginine vasopressin deficiency (AVP-D), and especially the implementation of desmopressin treatment before all diagnostic procedures are completed, specifically in the case of hyponatraemia. Desmopressin can be used simultaneously with intravenous 3% saline solution only in the treatment of a very severe hyponatraemia, to avoid overcorrection of natraemia. In patients after profound hyponatraemia, polyuria can be observed after normalisation of fluid intake, but it is temporary.
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Hiponatremia , Humanos , Hiponatremia/etiología , Hiponatremia/diagnóstico , Masculino , Femenino , Niño , Preescolar , Lactante , Desamino Arginina Vasopresina/uso terapéuticoRESUMEN
AIMS: To discuss the role of autocrine/paracrine signaling of urothelial arginine vasopressin (AVP) on mammalian bladder capacities and micturition thresholds, impact of distension on water/urea reabsorption from the bladder, review of the literature to better characterize the central/peripheral effects of AVP, desmopressin (dAVP) toxicity, and urine biomarkers of nocturia. METHODS: This review summarizes discussions during an International Consultation on Incontinence-Research Society 2024 think tank with respect to the role of urothelial AVP in aged individuals with nocturnal polyuria, impact of solute and water reabsorption by the bladder on uninterrupted sleep, central effects of AVP, pharmacological basis of dAVP toxicity, and biomarkers in nocturia/lower urinary tract dysfunction (LUTD) with neurological diseases. RESULTS: Consensus recognized AVP function and pathways in the central nervous system (CNS), pre-proAVP localized using immunohistochemistry in bladder sections from adult/aged noncancerous human punch biopsies and rodent bladder sections is likely to accelerate the systemic uptake of water and urea from the bladder of anesthetized mice instilled with 3H-water and 14C-urea. Mechanisms for charged and uncharged solutes and water transport across the bladder, mechanism of dAVP toxicity, and utility of urine biomarkers in those with neurological diseases/nocturia were determined from literature reviews. CONCLUSION: Pre-proAVP is present in human/rodent bladders and may be involved in water reabsorption from bladder that prevents the sensation of fullness for uninterrupted sleep in healthy adults. The mechanism of action of AVP in the CNS was discussed, as was electrolyte/water transport across the bladder, the basis for dAVP toxicity, and feasibility of urine biomarkers to identify nocturia/LUTD with neurological diseases.
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Síntomas del Sistema Urinario Inferior , Nocturia , Poliuria , Humanos , Nocturia/fisiopatología , Nocturia/metabolismo , Poliuria/fisiopatología , Poliuria/metabolismo , Síntomas del Sistema Urinario Inferior/fisiopatología , Síntomas del Sistema Urinario Inferior/metabolismo , Animales , Vejiga Urinaria/fisiopatología , Vejiga Urinaria/metabolismo , Vejiga Urinaria/efectos de los fármacos , Arginina Vasopresina/metabolismo , Anciano , Desamino Arginina Vasopresina/farmacología , Biomarcadores/orina , Urotelio/metabolismo , Urotelio/efectos de los fármacos , Urotelio/fisiopatologíaRESUMEN
OBJECTIVES: Desmopressin is widely used for nocturia in patients with nocturnal polyuria. We investigated the continuation rate and adherence for desmopressin in patients with overactive bladder and nocturia using a claims database and evaluated factors that improved adherence. METHODS: Patients with nocturia in a Japanese claims database who started desmopressin between September 2019 and July 2021 were evaluated. Drug persistence was assessed using the Kaplan-Meier method for initial prescription of desmopressin. The proportion of days covered (PDC) was also evaluated among patients with prescription persistence. Multivariate analysis was performed using logistic regression analysis to identify factors predicting adherence to desmopressin. RESULTS: The study included 72,888 patients entered into Japan Medical Data Center (JMDC) database between September 2019 and July 2021. For the 236 patients prescribed desmopressin formulations, mean prescription duration was 114 days. Among the total cases, 90 (38.1%) cases were prescribed only once, mean PDC was 0.60, and the number of high-adherence patients (PDC ≥ 0.80) was 108 (45.8%). Desmopressin prescription doses were fixed in 216 patients and adjusted in 20 patients. Multivariate analysis identified prescription dose adjustment for desmopressin as significantly associated with high PDC. CONCLUSION: Desmopressin showed a 38% dropout rate after the first dose. However, high medication continuation and high medication adherence rates (PDC) could be maintained with prescription adjustments. Careful patient monitoring and appropriate adjustment of the desmopressin dosage appear to be important factors in improving nocturia.
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Fármacos Antidiuréticos , Bases de Datos Factuales , Desamino Arginina Vasopresina , Cumplimiento de la Medicación , Nocturia , Vejiga Urinaria Hiperactiva , Humanos , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Desamino Arginina Vasopresina/administración & dosificación , Anciano , Nocturia/tratamiento farmacológico , Fármacos Antidiuréticos/administración & dosificación , Adulto , Japón , Estudios RetrospectivosRESUMEN
An 11-year-old male child who presented with increased frequency of urination, thirst and feeling of incomplete void was initially diagnosed with diabetes mellitus (DM) based on elevated blood sugar. Polyuria and polydipsia were confirmed even after normalisation of blood sugar. A standardised water deprivation test showed presence of central diabetes insipidus (DI) and patient was started on desmopressin. Presence of DM and DI led to suspicion of DIDMOAD/Wolfram syndrome and ophthalmic examination confirmed bilateral optic atrophy. Despite treatment for DM and DI the urinary complaints persisted, and ultrasound showed persistent bilateral hydronephroureterosis. Bladder workup including voiding cystourethrography (VCUG) and urodynamic study reported thickened trabeculated bladder wall along with overactivity, poor compliance and high bladder pressure. Bladder dysfunction has been documented to be associated with Wolfram syndrome and often may lead to chronic kidney disease which can be prevented by early diagnosis and appropriate management. The case highlights the need for comprehensive evaluation of children with urinary symptoms.
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Síndrome de Wolfram , Humanos , Masculino , Niño , Síndrome de Wolfram/diagnóstico , Síndrome de Wolfram/complicaciones , Desamino Arginina Vasopresina/uso terapéutico , Urodinámica , Poliuria/etiología , Poliuria/diagnóstico , Hidronefrosis/etiología , Hidronefrosis/diagnósticoRESUMEN
CONTEXT: Once hypercortisolemia is confirmed, differential diagnosis between Cushing's syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing's syndrome) is crucial. Due to worldwide corticotropin-releasing hormone (CRH) unavailability, accuracy of alternative tests to dexamethasone (Dex)-CRH, is clearly needed. OBJECTIVE: Assess the diagnostic accuracy of Dex-CRH test, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. METHODS: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. DATA SYNTHESIS: A total of 24 articles (1900 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 86% (81-90%; I2 28%) and 90% (84-94%; I2 15%), MSC 91% (85-94%; I2 66%) and 81% (70-89%; I2 71%), and LNSC 80% (67-89%; I2 57%) and 90% (84-93%; I2 21%), respectively. Summary receiver operating characteristics areas under the curve were Dex-CRH 0.949, desmopressin test 0.936, MSC 0.942, and LNSC 0.950 without visual or statistical significance. The overall risk of studies bias was moderate. CONCLUSION: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. When facing this challenging differential diagnosis, the results presented here should increase clinicians' confidence when deciding which test to perform.
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Síndrome de Cushing , Humanos , Síndrome de Cushing/diagnóstico , Hidrocortisona/sangre , Hidrocortisona/metabolismo , Diagnóstico Diferencial , Hormona Liberadora de Corticotropina/metabolismo , Dexametasona , Desamino Arginina VasopresinaRESUMEN
INTRODUCTION AND OBJECTIVE: Desmopressin is well accepted as first-line medical therapy for enuresis. If ineffective, combination therapy of desmopressin + oxybutynin or desmopressin + imipramine has been used. This study assessed the efficacy of adjunct therapy with either imipramine or oxybutynin in the management of enuresis patients who failed desmopressin treatment. STUDY DESIGN: A retrospective chart review of our database for patients with enuresis was performed. Patients who were prescribed desmopressin, oxybutynin, and imipramine over 14 years for enuresis were included. Two cohorts of patients were examined; group OXY was treated with desmopressin and oxybutynin, and group IMP received desmopressin and imipramine. Pretreatment measurement of Vancouver Symptom Scores (VSS) were used to compare groups using the VSS question "I wet my bed at night" where 4: every night, 3: 4-5 nights per week, 2: 1-2 nights per week, 1: 3-4 nights per month, and 0: never. International Children's Continence Society (ICCS) criteria for continence success was utilized to determine outcomes. RESULTS: 2521 patients prescribed one of the 3 medications were identified. Among them, 81 patients (mean age: 10.5 ± 2.8 years) received combination therapy. Of which, 55 were male and 26 female. Specifically, 58 were prescribed both desmopressin and imipramine (group IMP), 23 desmopressin and oxybutynin (group OXY), and 4 transitioned from OXY to IMP. Mean pretreatment VSS showed no difference between groups. Both groups experienced minimal drops in wet nights with desmopressin alone. A comparison revealed that group IMP reduced wet nights significantly more than group OXY (VSS wet night score 0.7 ± 1.2 vs. 2.3 ± 1.1 respectively, p < 0.0001). Non-intent-to-treat complete response rate was 68% vs 5% (OR = 42.5, p < 0.001) (IMP vs. OXY respectively). Intent-to-treat response rates were 58%. DISCUSSION: Although first-line desmopressin treatment for enuresis is effective, it does not work for all patients, and many parents and children desire nighttime dryness. Clinicians have combined desmopressin with oxybutynin or imipramine for improved results, but research comparing these modalities is scarce. Our study suggests that the desmopressin and imipramine combination is superior at reducing nights wet compared to desmopressin and oxybutynin, attributed to imipramine's probable central mechanism rather than its secondary anticholinergic properties. Limitations include a modest sample size, retrospective design, and subjective responses to the Vancouver questionnaire. CONCLUSION: A combination of desmopressin and imipramine was more effective in reducing wet nights and had a complete response rate that was 42.5 times greater than desmopressin and oxybutynin.
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Fármacos Antidiuréticos , Desamino Arginina Vasopresina , Quimioterapia Combinada , Imipramina , Ácidos Mandélicos , Enuresis Nocturna , Humanos , Ácidos Mandélicos/administración & dosificación , Ácidos Mandélicos/uso terapéutico , Desamino Arginina Vasopresina/administración & dosificación , Desamino Arginina Vasopresina/uso terapéutico , Estudios Retrospectivos , Niño , Masculino , Femenino , Imipramina/administración & dosificación , Imipramina/uso terapéutico , Enuresis Nocturna/tratamiento farmacológico , Fármacos Antidiuréticos/administración & dosificación , Fármacos Antidiuréticos/uso terapéutico , Adolescente , Resultado del TratamientoRESUMEN
BACKGROUND: Desmopressin (DDAVP) is used in patients with moderate/mild hemophilia A (PWMHs) to increase their factor VIII (FVIII) level and, if possible, normalize it. However, its effectiveness varies between individuals. The GIDEMHA study aims to investigate the influence of F8 gene variants. MATERIAL AND METHODS: The study collected the trajectory of FVIII levels from therapeutic intravenous DDAVP tests in four French hemophilia treatment centers. A pharmacological analysis was performed associated with efficacy scores according to F8 variants: absolute and relative responses, as well as new scores: absolute duration (based on duration with FVIII ≥ 0.50 IU.mL-1) and relative duration (based on half-life). RESULTS: From enrolled 439 PWMHs, 327 had a hot-spot F8 variant (with ≥5 PWMHs). For these, the median (min-max) basal and peak FVIII were 0.20 (0.02-0.040) and 0.74 (0.14-2.18) IU.mL-1 respectively, with FVIII recovery being 3.80 IU.ml-1 (1.15-14.75). The median FVIII half-life was 3.9 hours (0.7-15.9 hours). FVIII was normalized (≥0.50 IU.mL-1) in 224/327 PWMHs (69%) and the median time with normalized FVIII was 3.9 hours (0.0-54.1 hours). Following the response profiles to DDAVP defined by the four efficacy scores, four groups of F8 variants were isolated, and then compared using survival curves with normalized FVIII (p < 0.0001): "long-lastingly effective" [p.(Glu739Lys), p.(Ser2030Asn), p.(Arg2178His), p.(Gln2208Glu), and T-stretch deletion in intron 13]; "moderately effective" [p.(Ser112Phe), p.(Ala219Thr), p.(Thr2105Ile), p.Phe2146Ser), and p.(Asp2150Asn)]; "moderately ineffective" [p.Ala81Asp), p.(Gln324Pro), p.(Tyr492His), p.(Arg612Cys), p.(Met701Val), p.(Val2035Asn), and p.(Arg2178Cys)]; and "frequently ineffective" [c.-219C > T, p.(Cys2040Tyr), p.(Tyr2169His), p.(Pro2319Leu), and p.(Arg2326Gln)]. CONCLUSION: In view of our data, we propose indications for DDAVP use in PWMH based on F8 variants for minor and major invasive procedures.