Uso preoperatorio de fármacos hemostáticos para disminuir la transfusión de hemocomponentes en histerectomía total abdominal / Preoperative use of hemostatic drugs to reduce hemocomponent transfusion in total abdominal hysterectomy

Resumen: Introducción: en la actualidad se usan fármacos para disminuir el sangrado transoperatorio, la transfusión de hemoderivados como el ácido tranexámico que es un antifibrinolítico análogo de la lisina y desmopresina que actúa incrementando de forma autóloga el factor VIII y el factor de Von Willebrand (FVW) en individuos sanos. Objetivo: demostrar la eficacia del uso y seguridad del ácido tranexámico vs desmopresina para disminuir la transfusión de hemocomponentes en pacientes sometidos a histerectomía total abdominal electiva. Material y métodos: se estudiaron 72 pacientes, los cuales se dividieron en dos grupos (36 pacientes cada uno) asignados al azar para recibir ácido tranexámico 10 mg/kg de peso o desmopresina 0.3 mg/kg de peso, ambos por vía intravenosa 20 minutos previo al evento quirúrgico. Resultados: en comparación del ácido tranexámico contra desmopresina para la disminución del sangrado transoperatorio, 100% de las pacientes a las que se les administró el ácido tranexámico no requirieron transfusión de hemoderivados y presentado el 100% de efectividad siendo estadísticamente significativos con un valor de p < 0.05. Conclusiones: la administración de ácido tranexámico resultó más eficaz para disminuir la administración de hemoderivados en pacientes sometidos a histerectomía total abdominal electiva. Además, no se presentaron efectos adversos graves durante su administración.

Abstract: Introduction: drugs are currently used to reduce intraoperative bleeding, transfusion of blood products such as tranexamic acid, which is an antifibinolytic lysine analogue, and desmopressin, which acts by autologously increasing factor VIII and VWF in healthy individuals. Objective: demonstrate the efficacy of the use and safety of tranexamic acid vs desmopressin to reduce the transfusion of blood components in patients undergoing elective total abdominal hysterectomy. Material and methods: 72 patients were studied, divided into two groups (36 patients each one) randomly assigned to receive tranexamic acid 10 mg/kg weight or desmopressin 0.3 mg/kg weight, both intravenously 20 minutes prior to the surgical event. Results: the comparison of tranexamic acid against desmopressin for the reduction of intraoperative bleeding, 100% of the patients who were administered tranexamic acid did not require transfusion of blood products and presented 100% effectiveness, being statistically significant with a value of p < 0.05. Conclusions: the administration of tranexamic acid was more effective in reducing the administration of blood products in patients undergoing elective total abdominal hysterectomy.

cAMP-Epac1 signaling is activated in DDAVP-induced endolymphatic hydrops of guinea pigs

Abstract Objective To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. Methods Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 μg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. Results Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p< 0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p< 0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p< 0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. Conclusion DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 5.

Voiding diary predicts the therapeutic effects on primary monosymptomatic nocturnal enuresis / 现代泌尿外科杂志

【Objective】 To investigate the possibility of using voiding diary (VD) to predict desmopressin diacetate arginine vasopressin (DDAVP) and enuresis alarm (EA) in the treatment of primary monosymptomatic nocturnal enuresis (PMNE). 【Methods】 A total of 100 children (aged 6 to 14 years) with PMNE treated during Jan.2018 and Oct.2022 were involved. Bladder type was classified with two-week VD. Pseudo-randomization was performed using the Danish REDCap system to group patients into the randomized group and VD group. All patients were treated for 8 weeks. 【Results】 A total of 82 cases met the inclusive criteria. The effective rate was 82.50% (33/40) and 59.52% (25/42) in the VD and randomized groups, respectively, with significant difference (χ2=5.224, P=0.022). In the randomized group, if VD was not considered, the effective rate in the DDAVP and EA subgroups was 81.82% (18/22) and 25.00% (5/20), respectively, with significant difference (χ2=13.625, P=0.000). 【Conclusion】 VD can predict the therapeutic effects of PMNE. It is necessary to record VD for two weeks before selecting appropriate treatment methods. For patients who choose treatment without reference to VD, DDAVP shows better response than EA, but the recurrence rate after discontinuation of treatment requires further follow-up.

Approach to the patient with Cushing′s disease with a false negative result in inferior petrosal sinus sampling / 中华内分泌代谢杂志

Bilateral inferior petrosal sinus sampling(BIPSS), with or without desmopressin stimulation, is the gold standard in the diagnosis of Cushing′s disease. A few of patients with Cushing′s disease present a false negative result in BIPSS. These patients are often misdiagnosed as ectopic adrenocorticotropin(ACTH) syndrome(EAS). Here we report a case of Cushing′s disease with a false negative BIPSS, in the hope to aid clinical physicians in the differential diagnosis and treatment of ACTH-dependent Cushing′s syndrome.

Desmopressin acetate use in von Willebrand's disease: a survey on current practices in Brazil

ABSTRACT Introduction: von Willebrand's disease (VWD) is the most common inherited bleeding disorder. The 1-desamino-8-d-arginine vasopressin (DDAVP) is the treatment of choice for most responsive patients with VWD. The aim of this study was to evaluate DDAVP use in the management of VWD. Method: We implemented a survey targeting medical doctors involved in the management of VWD in Brazil. Data was collected during a national congress on Hematology in November 2017. Main results: A total of 51/80 (63.8%) questionnaires were collected. Most participants (76.2%) were hematologists who assisted adult patients and approximately 60% worked at hemophilia treatment centers (HTCs). Approximately half of participants who reported treating patients with VWD, assisted on average, less than 5 patients per month, and approximately 60% declared not having used any DDAVP for treating VWD in the previous year. However, most participants (70%) prescribed FVIII-containing VWF concentrate (VWF/FVIII) for 1-10 patients in the previous year. More than 80% of the participants recognized the main indications for DDAVP. Physicians who recognized indication for DDAVP for type 1 VWD more often had prescribed DDAVP in previous year (p = 0.03). Barriers for prescribing DDAVP varied and included unavailability of laboratory facilities and consumables for DDAVP testing and lack of skills on its prescription. Conclusion: The DDAVP is currently underused in Brazil, as opposed to the excessive use of VWF/FVIII in VWD patients. We suggest the adoption of measures targeting educational and auditing programs. Furthermore, availability of laboratory reagents is needed to evaluate response and increment the correct use of DDAVP.

A comparison of the efficacy and tolerability of treating primary nocturnal enuresis with Solifenacin Plus Desmopressin, Tolterodine Plus Desmopressin, and Desmopressin alone: a randomized controlled clinical trial

ABSTRACT Introduction: Nocturnal enuresis (enuresis) is one of the most common developmental problems of childhood, which has often a familial basis, causes mental and psychological damage to the child and disrupts family solace. Objectives: In this study, we compared therapeutic efficacy and tolerability of treating primary nocturnal enuresis (PNE) with solifenacin plus desmopressin, tolterodine plus desmopressin, and desmopressin alone. Because we don't have enough information about this comparison especially about solifenacin plus desmopressin. Patients and Methods: This clinical trial study was performed on 62 patients with enuresis aged 5-15 years who referred to the urology clinic of Imam Khomeini Hospital in Ahwaz in 2017-2018. Patients were randomly assigned to one of the three different therapeutic protocols and any participants were given a specific code. After that, we compared the therapeutic response and the level of satisfaction of each therapeutic group in different months. Data were analyzed using SPSS 22 software and descriptive and analytical statistics. Results: The mean age of patients was 8.70±66 years. In the therapeutic group with desmopressin and solifenacin, 19 of 20 patients (95%) achieved complete remission (1) after a 3-month treatment in comparison with monotherapy group in which 14 of 22 patients (63.63%) achieved complete remission; and in the combination therapy group of desmopressin and tolterodine, in the study and the evaluation of the consequences of 3-month treatment of this group, it was found that 17 of 20 patients (85%) had complete remission. Overall, the therapeutic response in combination therapy groups of desmopressin plus anticholinergic was higher than the monotherapy group of desmopressin alone. Conclusion: Our results demonstrate that the combination of desmopressin and an anticholinergic agent is highly effective in treatment of children with PMNE. Although desmopressin has long been a first - line treatment for PMNE, desmopressin monotherapy often fails to achieve a successful response in patients with PMNE.

Cateterismo de senos petrosos en el diagnóstico etiológico de síndrome de Cushing: primera experiencia en Uruguay / Petrosal sinus sampling for etiological diagnosis of Cushing's syndrome: first experience in Uruguay / Cateterismo dos seios petrosos no diagnóstico etiológico da síndrome de Cushing: primeira experiência no Uruguai

Resumen: Identificar la causa de un síndrome de Cushing dependiente de adrenocorticotropina (ACTH) es esencial para realizar un tratamiento correcto. La hipersecreción de ACTH es debida en su mayoría a un tumor hipofisario (enfermedad de Cushing) o, en un 10%-20%, a tumores con producción ectópica de esta hormona. Los test no invasivos tienen baja sensibilidad y especificidad para diferenciar estas dos etiologías. El patrón oro lo constituye el cateterismo bilateral de los senos petrosos inferiores (CSP). Mediante el CSP se demuestra la hipersecreción de ACTH a nivel hipofisario al documentar un gradiente de ACTH central a periférico en el drenaje del tumor. Se recomienda realizarlo en todo síndrome de Cushing ACTH dependiente, aunque suele reservarse para pacientes con diagnóstico de hipercortisolismo y hallazgos negativos o equívocos en la resonancia nuclear magnética (RNM) de la región selar. Presentamos el primer caso en Uruguay en que se utilizó el CSP como método diagnóstico, una mujer de 55 años que presentó un hipercortisolismo ACTH-dependiente con una imagen adenohipofisaria <6 mm. El gradiente petroso-periférico confirmó el diagnóstico de enfermedad de Cushing y no hubo complicaciones durante el procedimiento. Posteriormente se realizó la resección del adenoma mediante cirugía transesfenoidal, con buena evolución y confirmación inmunohistoquímica del tumor.

Summary: Identifying the cause of adrenocorticotropin (ACTH)-dependent Cushing's syndrome is key to define the appropriate treatment. Hypersecretion of the adrenocorticotropic hormone (ACTH) is mainly caused by a pituitary tumor (Cushing's syndrome) or, in 10% to 20% of cases, by tumors with ectopic production of this hormone. Differentiation between these two etiologies may not be easy due to the low sensitivity and specificity of non- invasive tests. Bilateral sampling of the lower petrosal sinus is the gold standard to differentiate between a pituitary and an ectopic origin, showing the pituitary ACHT hypersecretion and recording the central-to-peripheral ACTH gradient in the tumor's drainage. Despite it being highly recommended for all cases of ACTH-dependent Cushing's syndrome, it is reserved for patients with a diagnosis of hypercortisolism and negative or misleading findings in the MRI of the sellar region. The study presents the first case of petrosal sinus sampling for diagnostic purposes in Uruguay, in a 55-year-old woman with ACHT-dependent hypercortisolism showing an adenohypophysis image < 6 mm. The petrosal-peripheral gradient confirmed the diagnosis of Cushing's syndrome and no complications arose during the procedure. Afterwards a transsphenoidal surgery was performed for resection of the adenoma. Evolution was good and immunochemistry confirmed the tumor's etiology.

Resumo: Identificar a causa da síndrome de Cushing dependente de adrenocorticotropina (ACTH) é essencial para o tratamento adequado. A hipersecreção de ACTH se deve principalmente a um tumor hipofisário (doença de Cushing) ou, em 10%-20%, a tumores com produção ectópica desse hormônio. Os testes não invasivos apresentam baixa sensibilidade e especificidade para diferenciar essas duas etiologias. O padrão ouro é o cateterismo bilateral dos seios petrosos inferiores (CEP). O CSP demonstra hipersecreção de ACTH no nível da hipófise, documentando um gradiente de ACTH central a periférico na drenagem do tumor. É recomendado nos casos de síndrome de Cushing dependente de ACTH, embora seja geralmente reservado para pacientes com diagnóstico de hipercortisolismo e achados negativos ou duvidosos na ressonância magnética (RNM) da região selar. Apresentamos o primeiro caso no Uruguai em que o CSP foi usado como método diagnóstico, uma mulher de 55 anos que apresentava hipercortisolismo ACTH dependente com imagem da hipófise anterior <6 mm. O gradiente petroso-periférico confirmou o diagnóstico de doença de Cushing e não houve complicações durante o procedimento. A seguir, o adenoma foi ressecado por cirurgia transesfenoidal, com boa evolução e confirmação imunohistoquímica do tumor.

Hemostatic evaluation of rabbits envenomed with Bothrops alternatus treated with anti-bothropic serum, desmopressin and tranexamin acid / Avaliação hemostática de coelhos envenenados com Bothrops alternatus e tratados com soro antibotrópico, desmopressina e ácido tranexâmico

In Brazil, snakes from the Bothrops genus are responsible for thousands of accidents, and their venoms are mainly composed of proteolytic enzymes. Although the antibothropic serum produced by the Brazilian Institutes is remarkably efficient, more studies are necessary, especially in veterinary medicine. The venom contain enzymes and non-enzymatic proteins that interfere with hemostasis leading to hemorrhage or even thrombosis. Possible treatment associations with known bothropic antivenom were the reason for the development of the present study. The aim of this study was to evaluate hemostasis alterations caused by Bothrops alternatus venom in rabbits followed by treatments with anti-bothropic serum, tranexamic acid and desmopressin. Twenty New Zealand rabbits were distributed into five groups (n=4) that were experimentally envenomed with 150mcg/kg of B. alternatus venom via intramuscular injection and treated as follow: Group 1 (G1) was the positive control and received venom and PBS/BSA; Group 2 (G2) was treated with tranexamic acid; Group 3 (G3) with desmopressin; Group 4 (G4) with tranexamic acid and anti-bothropic serum; and Group 5 (G5) with anti-bothropic serum and desmopressin. Blood samples were collected before venom administration, and one, four, eight and 12 hours after, for Partial activated partial thromboplastin time, Prothrombin Time, Thrombin Time and fibrinogen evaluation. Thrombin generation (TG) test was carried out with a pool of samples from final times (8 and 12h). At the end of 12h, all animals were euthanized and necropsy was conducted. Samples from muscle tissue, heart, lungs and kidney were analyzed. Classic coagulation tests showed no significant differences amongst groups and times. However, TG indicated that the venom causes a hypocoagulability state, which was not reversed by proposed treatments. Histology showed muscle inflammation, hemorrhage and necrosis, as well as hemorrhage in other tissues with no differences amongst groups. B. alternatus envenomation causes hypocoagulability detected by TG assay, but not through classical coagulation tests. The use of tranexamic acid and desmopressin for hemostasis stabilization after inoculation of the venom did not show advantage in coagulation restoration.(AU)

No Brasil, as serpentes do gênero Bothrops são responsáveis por milhares de acidentes, e seus venenos são compostos principalmente de enzimas proteolíticas. Embora o soro antiofídico produzido pelos institutos brasileiros seja notavelmente eficiente, mais estudos são necessários, especialmente na medicina veterinária. O veneno contem enzimas e proteínas não-enzimáticas que interferem com a hemostasia levando a hemorragias ou trombose. A associação de outros tratamentos ao soro antibotrópico foi a razão para o desenvolvimento do presente estudo. O objetivo deste estudo foi avaliar as alterações da hemostasia causadas pelo veneno de Bothrops alternatus em coelhos, após tratamento com soro antibotrópico, ácido tranexâmico e desmopressina. Vinte coelhos da Nova Zelândia foram distribuídos em cinco grupos (n = 4) que foram submetidos a experimentos com 150mcg/kg de veneno de B. alternatus por injeção intramuscular. O Grupo 1 (G1) foi o controle positivo e recebeu veneno e PBS / BSA, enquanto o Grupo 2 (G2) foi tratado com ácido tranexâmico, o Grupo 3 (G3) com desmopressina, o Grupo 4 (G4) com ácido tranexâmico e soro antibotrópico, e o Grupo 5 (G5) com soro antibotrópico e desmopressina. As amostras de sangue foram coletadas antes da administração do veneno, e uma, quatro, oito e 12 horas após os tratamentos para realização de tempo de tromboplastina parcial ativada parcial (TTPa), tempo de protrombina (TP), tempo de trombina (TT) e mensuração de fibrinogênio. Para o ensaio de geração de trombina (TG) foi realizado com um pool de amostras nos tempos finais (8 e 12h). Ao final das 12h, todos os animais foram sacrificados e a necropsia foi realizada. Amostras de tecido muscular, coração, pulmões e rins foram analisadas. Os testes TTPa, TP, TT e fibrinogênio não mostraram diferenças significativas entre os grupos e os tempos. No entanto, o TG indicou que o veneno causa um estado de hipocoagulabilidade, que não foi revertido pelos tratamentos propostos. Na histologia, foram observadas inflamação muscular, hemorragia e necrose, além de hemorragia em outros tecidos, sem diferenças entre os grupos. O envenenamento por B. alternatus causa hipocoagulabilidade detectada mais precocemente pelo teste de geração de trombina. O uso de ácido tranexâmico e desmopressina para estabilização da hemostasia após a inoculação do veneno não mostrou vantagem na restauração da coagulação.(AU)

Respuesta a la prueba de desmopresina: estudio de cohorte en un hospital de Bogotá / Response to the desmopressin test: cohort study in a Bogota hospital

Introducción: La desmopresina es un análogo sintético de la vasopresina que aumenta los niveles plasmáticos del factor VIII y del factor de von Willebrand. Algunos autores señalan el tiempo de mantenimiento del efecto hemostático entre 6 y 8 h, por lo que es necesario estudiar su efecto en el tiempo. Objetivo: Determinar la variación de las variables de laboratorio de pacientes con enfermedad de von Willebrand y hemofilia tipo A posterior a la administración de desmopresina. Métodos: Estudio de cohorte retrospectivo en un hospital universitario en Bogotá. Se realizó un muestreo no aleatorio, se incluyeron 24 pacientes mayores de 18 años con diagnóstico de enfermedad de von Willebrand (67 por ciento) y hemofilia tipo A no grave (33 por ciento), a quienes se les realizó la prueba de desmopresina. Se conformaron dos grupos de pacientes, independientemente del diagnóstico: 15 pacientes con valores basales de factor VIII ; 50 UI y 13 pacientes con valores basales de antígeno von Willebrand lt; 50 UI. Se efectúo análisis estadístico descriptivo y correlacional en Stata 13. Resultados: El 87 por ciento de los pacientes del grupo I alcanzó el valor terapéutico a las 2 h de administrada la desmopresina (p= 0,000), el cual se mantuvo hasta 6 h en el 77 por ciento (p= 0,000). En el grupo II el 92 por ciento logró el valor terapéutico en 2 h (p= 0,003), que continuó hasta las 6 h en el 83 por ciento (p= 0,000). Conclusiones: La respuesta a la administración de desmopresina fue máxima a las 2 h posteriores, cuando comenzó a disminuir progresivamente, pero mantuvo el efecto terapéutico. Aunque no se encontraron efectos adversos, existe variabilidad de respuesta entre pacientes(AU)

Introduction: Desmopressin is a synthetic analog for vasopressin that increases the plasma levels of factor VIII and of von Willebrand factor. Some authors indicate maintenance time of hemostatic effect between 6 and 8 hours, so it is necessary to study its effect over time. Objective: To determine the variation of laboratory variables in patients with von Willebrand disease and type A hemophilia after desmopressin administration. Methods: Retrospective cohort study carried out in a university hospital in Bogotá. Nonrandomized sampling was used, including 24 patients older than 18 years and with a diagnosis of von Willebrand disease (67 percent) and non-severe type A hemophilia (33 percent), who underwent the desmopressin test. Two groups of patients were created, regardless of diagnosis: 15 patients with baseline values of factor-VIII 8203; #8203;lower than 50 IU and 13 patients with baseline values of von Willebrand antigen8203;8203;lower than 50 IU. Descriptive and correlational statistical analysis was performed in Stata 13. Results: 87 percent of patients in group I reached the therapeutic value two hours after desmopressin administration (p=0.000), which was maintained for up to six hours in 77 percent (p=0.000). In group II, 92 percent achieved the therapeutic value in two hours (p=0.003), which continued until six hours in 83 percent (p=0.000). Conclusions: Response to desmopressin administration was maximum at two hours, when it began to decrease progressively, but maintained the therapeutic effect. Although no adverse effects were found, there is variability of response among patients(AU)

Study of the profile of behavioral problems and quality of life indexes in a pediatric cohort of monosymptomatic enuresis / Estudo do perfil dos problemas de comportamento e dos índices de qualidade de vida numa coorte pediátrica de enurese monossintomática

Abstract Objective: To evaluate and correlate, before and after the therapeutic intervention, the behavioral problem scores evaluated by the CBCL/6-18 questionnaire and the quality of life indexes evaluated by the PedsQL™ 4.0 in patients with monosymptomatic nocturnal enuresis. Method: After the initial evaluation and completion of the CBCL/6-18 questionnaire, a multidisciplinary evaluation and completion of the PedsQL™ 4.0 questionnaire was performed. Of the initially evaluated 140 children and adolescents aged 6-16 years, 58 were excluded due to non-monosymptomatic enuresis or associated comorbidities. Of the initially included 82 patients, who were randomized to three treatment groups, 59 completed the CBCL/6-18 and PedsQL™ 4.0 questionnaires at the end of the treatment and were included in this study. The α error was set at 5% for ruling out the null hypothesis. Results: Of the total of 59 participants, 45.8% responded with total success, 23.7% were partially successful, 23.7% did not reach the improvement criteria, and 6.8% gave up the treatment. There was a significant increase in quality of life indexes and a reduction of post-intervention behavioral problem scores, in the three proposed modalities, in patients who had a total or partial response to treatment. There was no correlation between higher scores of pre-treatment behavior problems and therapeutic failure. Conclusions: Only the participants who successfully responded to interventions showed improvement in quality of life and behavioral problems, which indicates that enuresis is a primary problem that has a negative impact on these parameters. The authors suggest that it is possible to achieve success in the treatment of monosymptomatic enuresis, even in patients with high pre-intervention behavioral problem scores.

Resumo Objetivo: Avaliar e relacionar, pré e pós-intervenção terapêutica, em pacientes com enurese noturna monossintomática, os escores de problemas de comportamento, avaliados pelo questionário CBCL/6-18, e os índices de qualidade de vida, avaliados pelo PedsQL™ 4.0. Método: Após avaliação inicial e preenchimento CBCL6/18, procedeu-se avaliação multidisciplinar e preenchimento do PedsQL™ 4.0. Das 140 crianças e adolescentes de 6 a 16 anos inicialmente avaliados, 58 foram excluídos por enurese não monossintomática ou comorbidades associadas. Dos 82 pacientes inicialmente incluídos e randomizados em três grupos de tratamento, 59 preencheram o CBCL/6-18 e PedsQL™ 4.0 no fim do tratamento e puderam ser incluídos neste trabalho. O erro alfa foi estabelecido em 5% para descarte da hipótese de nulidade. Resultados: Dos 59 participantes 45,8% responderam com sucesso total, 23,7% tiveram sucesso parcial, 23,7% não atingiram critério de melhoria e 6,8% desistiram do tratamento. Verificou-se aumento significativo dos índices de qualidade de vida e redução dos escores de problemas de comportamento pós-intervenção, nas três modalidades propostas, nos pacientes que obtiveram resposta total ou parcial ao tratamento. Não se demonstrou correlação entre maiores escores de problemas de comportamento pré-tratamento e insucesso terapêutico. Conclusões: Apenas os participantes que responderam com sucesso às intervenções melhoraram em sua qualidade de vida e problemas comportamentais, o que indica que a enurese é um problema primário que impacta negativamente esses parâmetros. Sugere-se que é viável obter sucesso no tratamento da enurese monossintomática, mesmo em pacientes com altos escores de problemas de comportamento pré-intervenção.

Clinical observation of desmopressin in the treatment of 15 patients with DDAVP / 中华血液学杂志

Objective@#To assess the significance of DDAVP use in the diagnosis and treatment of VWD.@*Methods@#An analysis of 15 VWD cases who referred to Hematology Division of First affiliated Hospital of Soochow University and treated with DDAVP from March 2016 to August 2018 was conducted. Efficacy and treatment response of DDAVP were monitored by observations of changes in factor Ⅷ procoagulant (FⅧ∶C) and von Willebrand Factor (VWF) related indicators before and 2 h after DDAVP injection.@*Results@#Of 15 cases with VWD, 7 males and 8 females with a median age of 23 (6-46) years, 7 of 9 type I VWD patients achieved complete response (CR) , 1 type 2A VWD case CR, 5 type 3 VWD ones no response (NR) . The VWF multimer analysis in 5 patients combined with other plasma VWF values were in accordance with the known diagnosis.@*Conclusions@#DDAVP was effective in most type 1 patients, and ineffective in some type 2 and almost all type 3 cases. It was helpful for diagnosis and subsequent treatment planning.

Clinical observation of desmopressin in the treatment of 15 patients with DDAVP / 中华血液学杂志

Objective: To assess the significance of DDAVP use in the diagnosis and treatment of VWD. Methods: An analysis of 15 VWD cases who referred to Hematology Division of First affiliated Hospital of Soochow University and treated with DDAVP from March 2016 to August 2018 was conducted. Efficacy and treatment response of DDAVP were monitored by observations of changes in factor Ⅷ procoagulant (FⅧ∶C) and von Willebrand Factor (VWF) related indicators before and 2 h after DDAVP injection. Results: Of 15 cases with VWD, 7 males and 8 females with a median age of 23 (6-46) years, 7 of 9 type I VWD patients achieved complete response (CR) , 1 type 2A VWD case CR, 5 type 3 VWD ones no response (NR) . The VWF multimer analysis in 5 patients combined with other plasma VWF values were in accordance with the known diagnosis. Conclusions: DDAVP was effective in most type 1 patients, and ineffective in some type 2 and almost all type 3 cases. It was helpful for diagnosis and subsequent treatment planning.

A network meta-analysis of desmopressin, alarm, and combination of both in the treatment of monosymptomatic nocturnal enuresis in children / 临床儿科杂志

Objective To systematically explore the efficacy of four intervention regiments including desmopressin, alarm, desmopressin combined with alarm, and desmopressin combined with anticholinergic drugs in the treatment of monosymptomatic nocturnal enuresis in children by network meta-analysis. Methods The databases of PubMed, Cochrance Library, EMBase and Web of Science were systematically searched and retrieved upto August 1, 2017. Included were the randomized controlled trials (RCTs) which had any two or more of four intervention regiments (desmopressin, alarm, desmopressin combined with alarm, and desmopressin combined with anticholinergic drugs) for treatment of monosymptomatic nocturnal enuresis in children. The literature was screened according to the established inclusion and exclusion criteria, and the data extraction and quality evaluation were performed for the final inclusion of RCT. Software R 3.3.2 and STATA 14.0 were used for data analysis. Results Fifteen RCTs were included with a total of 1505 children. Network meta-analysis showed that the complete response rate and success rate of desmopressin combined with anticholinergic drugs were higher than those of desmopressin (complete reaction rate: OR=2.8, 95％ CI :1.5～5.4; success rate: OR=3.5, 95％ CI :1.7～7.5) and alarm (complete response rate: OR=2.7, 95％ CI :1.1～6.6; success rate: OR=3.8, 95％ CI: 1.6～9.0. The success rate of desmopressin combined with alarm was higher than that of alarm (OR=1.9, 95％CI: 1.1～3.4) . The recurrence rate of alarm after treatment was significantly lower than that of desmopressin (OR=0.15, 95％CI: 0.03～0.53) . The ranking results showed that the complete response rate and success rate of desmopressin combined with anticholinergic drugs were the best. The desmopressin combined with alarm can minimize the number of bed-wetting episodes per week and the recurrence rate of alarm was the lowest among the four regiments. Conclusion The effect of desmopressin combined with anticholinergic drugs is significantly better than that of alarm or desmopressin alone. The combination of desmopressin and alarm has a slight advantage or similar effect to that of single alarm or desmopressin treatment. The effect of desmopressin is similar to that of alarm. Alarm treatment has the lowest recurrence rate.

Tratamiento con desmopresina sublingual en dos lactantes con hidranencefalia y diabetes insípida central / Treatment with sublingual desmopressin in two infants with hydranencephaly and central diabetes insipidus

La diabetes insípida central es una patología infrecuente en pediatría ocasionada por un déficit de vasopresina. Sus manifestaciones clínicas principales son poliuria y polidipsia. Las malformaciones cerebrales son una de las principales causas. La desmopresina es la droga sintética de elección para el tratamiento. Una de las vías de administración es la sublingual y su uso en lactantes es muy limitado. Se describe a dos lactantes con hidranencefalia y diabetes insípida central que fueron tratados satisfactoriamente con desmopresina sublingual.

Central diabetes insipidus is a rare disease in children caused by a deficiency of vasopressin. Its main clinical manifestations are polyuria and polydipsia. Brain malformations are one of the main causes. Desmopressin is the synthetic drug of choice for the treatment. One of the routes of administration is sublingual and its use in infants is very limited. We describe two infants with central diabetes insipidus and hydranencephaly who were successfully treated with sublingual desmopressin.

Effects and safeties of desmopressin on nocturia in medium-elderly men / 中华泌尿外科杂志

Objective To explore the effects and safeties of desmopressin on nocturia in elderly men.Methods We used random number table to divide patients into 2 groups.The patient in treatment group took desmopressin acetate tablets 0.2 mg orally and the patient in control group took tamsulosin hydmchloride sustained release capsule 0.2 mg orally before sleep for 4 weeks.The patient recorded 24 hours voiding diaries for 3 days and worked out mean number of nocturnal voids,hours of undisturbed sleep (HUS) before treatment and before subsequent visit weekly.Before treatment and 1 to 4 weeks after treatment,mean number of nocturnal voids,HUS,night quality of life (NQOL),quality of life (QOL),adverse event were recorded.Before treatment,1 week and 4 weeks after treatment,blood serum sodium was checked in treatment group.Results 42 men had been diagnosed with nocturia in outpatient department of investigator from December 2014 to March 2016,34 of them were recruited in our study and randomly enter the treatment group or control group.Each group consisted of 17 cases.There was no statistical difference in the baseline data between two groups (all P ＞ 0.05).The average ages of treatment group and the control group were (65.1 ± 11.2) and (63.9 ± 9.3) years old,the courses of disease were (3.0 ± 5.0) and (2.3 ± 2.6) years,respectively.Before treatment mean numbers of nocturnal voids were (3.8 ± 1.2) and (3.2 ± 1.4) times,HUS were (1.8 ± 1.7) and (1.8 ± 0.6) h,NQOL were (51.8 ± 13.8) and (41.2 ± 13.6),QOL were (4.0 ± 1.0) and (3.9 ± 0.9),respectively.Four weeks after treatment,mean numbers of nocturnal voids decreased to (1.6 ± 1.0) and (2.0 ± 0.9) times,HUS increased to (4.0 ± 0.7) and (2.6 ± 0.7) h,NQOL decreased to (20.9 ± 12.0) and (30.6 ± 12.4),QOL decreased to (1.4 ± 1.1) and (2.9 ± 1.0) in treatment group and control group,respectively.Every index of the two groups were statistically significant differences compared with that before treatment (P ＜ 0.05).There were statistically significant differences in the degree of improvement between treatment group and control group from 2 weeks to 4 weeks after treatment (P ＜ 0.05).Therefore,the degree of improvement of treatment group was superiored to the control group.Before treatment and both 1 week and 4 weeks after treatment,the blood serum sodium of patients in treatment group were (140.3 ± 3.9),(139.2 ± 4.3) and (140.6 ± 3.1) mmol/ L,respectively.Two patients of treatment group appeared dizzy during the follow-up period.In one of both,the symptom disappeared after the dose decreased from 0.2 mg to 0.1 mg per night.The symptom sustained and the dose was not changed in the other one.In treatment group,two other patients suffered from dyspepsia,one palpitation and one thirst.Those symptoms could be tolerated and the dose was not changed.In control group,2 patients suffered from thirst,one nasal congestion,one dizzy and one short of breath.All of those symptoms could be tolerated and the dose was not changed.There was not statistical differencebetween the occurrence rate of adverse events in the 2 groups (P =0.714).Conclusions Desmopressin can improve the symptoms of nocturia in elderly men,improve the quality of life of patients,and has goodsafety.

Clinical effect of 1-desamino-8-D-Arginine Vasopressin different withdrawal ways in primary monosymptomatic nocturnal enuresis / 中国综合临床

Objective To explore the effect and compare the relapse rates of 1-desamino-8-D-Arginine Vasopressin(DDAVP) different withdrawal ways after initial 3 months in primary monosymptomatic nocturnal enuresis(PMNE) patients,in order to provide some evidences and references to use DDAVP to cure PMNE preferably.Methods Two hundred and fifty-six cases PMNE patients who were treated in Hubei Maternal and Child Health Hospital from November 2014 to June 2016 were selected and randomly divided into group A (DDAVP immediate withdrawal group,65 cases),group B(DDAVP day reduction group,58 cases) and group C (DDAVP step reduction group,60 cases).All patients were given DDAVP tables for 3 months.After 3 months for DDAVP,patients who were effective (full respond and partial respond) to DDAVP continued to undergo a withdrawal stage,those in group A underwent immediate cessation,those in group B continued to receive the effective dose every other day for 2 months and those in group C were step by step tapered by 0.05-0.10 mg every 2-4 weeks until completely stopped,the period was not more than 3 months.All patients had a follow-up visit for 3 months after cessation of DDAVP.Results A total of 183 patients completed the study finally,there were 65 patients in group A,58 patients in group B and 60 patients in group C.Initial 3 months the effective rates of group A,B and C were respectively 89.23％ (58/65),89.66％ (52/58) and 86.67％ (52/60),there were not statistically significant difference(x2 =0.309,P =0.857).There were 58 patients in group A,52 patients in group B and 52 patients in group C continued to undergo the withdrawal stage.One month after cessation of DDAVP,the effective rates of group B (88.46％,46/52) and group C (92.31％,48/52) were significantly higher than group A(67.24％,39/58) (x2 =7.030,P=0.008;x2 =10.417,P=0.001),while the relapse rates of group B(19.23％,10/52) and group C(17.31％,9/52) were significantly less than group A(36.21％,21/58) (x2=3.904,P=0.048;x2=4.937,P =0.026).Three months after cessation of DDAVP,the effective rates of group C (78.85％,41/52) were significantly higher than group A (50.00％,29/58) and group B (57.69％,30/52) (x2 =9.859,P=0.002;x2 =5.371,P=0.020),and the relapse rates of group C(32.69％,17/52) were significantly less than group A (55.17％,32/58) and group B (51.92％,27/52) (x2 =5.609,P =0.018;x2 =3.939,P =0.047),while the effective rates and relapse rates were not statistically significant difference between group A and group B(x2 =0.652,P =0.419;x2 =0.116,P =0.733).Severe adverse events related to DDAVP were not observed in any patients.Conclusion Gradual withdrawal after initial 3 months of DDAVP may improve the effect and reduce the relapse rates,the short-term and long-term curative effects of step-by-step withdrawal treatment are both well,while long-term curative effects of every other day withdrawal treatment is not obviously well.

Pharmacological therapy of nocturnal enuresis

Nocturnal enuresis is a common problem of children during sleeping at preschool or school age. It may affect negatively the psychosocial development of children. Children with enuresis may have lower self-esteem and lower quality of life. There are three main factors of the pathophysiology of enuresis: high nocturnal urine production, nocturnal low bladder capacity or increased detrusor muscle activity, and arousal disorder. As pharmacological therapy for nocturnal enuresis, several medications including desmopressin, anticholinergics, imipramine have been used for a long time. As first-line therapy, desmopressin combined with anticholinergics has good response in primary monosymptomatic nocturnal enuresis. Because imipramine has serious and lethal cardiotoxic effect with overdosage, imipramine should be prescribed after EKG to rule out the conduction problem of heart.

Highly sensitive assay for the determination of therapeutic peptide desmopressin in human plasma by UPLC–MS/MS / 药物分析学报

An analytical method based on ultra-performance liquid chromatography with positive ion electrospray ionization (ESI) coupled with tandem mass spectrometry (UPLC–MS/MS) was developed and validated for the determination of therapeutic peptide desmopressin in human plasma. A desmopressin stable labeled isotope (desmopressin d8) was used as an internal standard. Analyte and the internal standard were extracted from 200 μL of human plasma via solid-phase extraction technique using Oasis WCX cartridges. The chromatographic separation was achieved on an Aquity UPLC HSS T3 column by using a gradient mixture of methanol and 1 mM ammonium formate buffer as the mobile phase. The calibration curve obtained was linear (r2≥0.99) over the concentration range of 1.01–200 pg/mL. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. The proposed method was successfully applied to pharmacokinetic studies in humans.

Melatonin's Effect on the Efficacy of Desmopressin in the Treatment of Enuresis / 대한배뇨장애요실금학회지

PURPOSE: This study aims to evaluate and compare the efficacy of exogenous melatonin associated with desmopressin (dDAVP) and dietary recommendations. METHODS: A total of 189 patients were enrolled from the Service of Pediatrics, Campus Bio-Medico University Hospital of Rome, from January 2013 to June 2015. Of the 189 original patients, 153 children, aged between 5 and 14 years (mean age, 8.7 years) were included in the study. After clinical evaluation and a 3-month period of observation without treatment, children were assigned to receive treatment in one of 3 groups: group 1, dDAVP at a dose of 120 mcg a day (Minirin); group 2, dDAVP at a dose of 120 mcg and dietary recommendations; or group 3, dDAVP at a dose of 120 mcg, dietary recommendations, and melatonin at a dose of 1 mg a day (Melamil plus). Each patient was treated for 3 months. RESULTS: After the 3 months of therapy, a desiderable response was achieved in 30 of 51 patients (58.82%) treated with dDAVP, 35 of 53 patients (66.04%) treated with dDAVP and dietary recommendations, and 35 of 49 patients (71.43%) treated with dDAVP, dietary recommendations, and melatonin. CONCLUSIONS: Although not statistically significant, the results show that the association between dDAVP treatment with dietary recommendations and melatonin could be considered a safe and effective treatment of NE. Considering that the statistically insignificant results might be due to the small sample size, the study will be continued to increase the number of subjects.

A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report

A 14-year-old girl was referred for evaluation of the etiology of Cushing syndrome. During the previous 2 years, she had experienced weight gain, secondary amenorrhea, growth retardation, and back pain. Random serum cortisol level, 24-hour urinary free cortisol excretion, and overnight and low-dose dexamethasone suppression tests suggested Cushing syndrome. Midnight adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance imaging was suspicious for microadenoma. To eliminate ectopic ACTH syndrome, and lateralize the pituitary tumor, inferior petrosal sinus sampling (IPSS) was performed by desmopressin use to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to ACTH-secreting pituitary microadenoma, lateralized to the left side; subsequently underwent transsphenoidal surgery. Here we report a case of a 14-year-old girl diagnosed with Cushing disease with a pituitary tumor lateralized by IPSS using desmopressin, which is very rare in pediatric Cushing disease.