Eficácia E Custo-Utilidade De Intervenções Para O Tratamento Da Enurese Em Crianças E Adolescentes Sob A Perspectiva Do Sistema Único De Saúde Brasileiro: Effectiveness and Cost-Utility of Interventions for Enuresis Treatment in Children and Adolescents From the Brazilian Single Health System Perspective.

OBJECTIVES: This study aimed to estimate the cost-utility of effective interventions for enuresis treatment in children and adolescents and to calculate the incremental cost-utility ratio from the perspective of the Brazilian Unified Health System in a 1-year time horizon. METHODS: The economic analysis is in 7 stages: (1) survey of evidence of treatments for enuresis, (2) performing the network meta-analysis, (3) estimation of the probability of cure, (4) cost-utility analysis, (5) model sensitivity analysis, (6) analysis of acceptability of interventions by acceptability curve, and (7) monitoring the technological horizon. RESULTS: The association between desmopressin and oxybutynin is the therapeutic strategy with the highest probability of success in the treatment of enuresis in children and adolescents compared with placebo (relative risk [RR] 2.88; 95% confidence interval [CI] 1.65-5.04), followed by the combination therapy between desmopressin and tolterodine (RR 2.13; 95% CI 1.13-4.02), alarm (RR 1.59; 95% CI 1.14-2.23), and neurostimulation (RR 1.43; 95% CI 1.04-1.96). Combination therapy between desmopressin and tolterodine was the only 1 considered not to be cost-effective. Neurostimulation, alarm therapy, and therapy had the respective incremental cost-utility ratio values: R$5931.68, R$7982.92, and R$29 050.56/quality-adjusted life-years. CONCLUSION: Among the therapies that are on the borderline of efficiency, the combined therapy between desmopressin and oxybutynin presents the greatest incremental benefit at an incremental cost that is still feasible, given that it does not exceed the reference value of the cost-effectiveness threshold established in Brazil.

Association between winter season and desmopressin treatment efficiency in children with monosymptomatic nocturnal enuresis: a pilot study

ABSTRACT Objectives: The purpose of our study was to assess the association between the winter season and desmopressin treatment failure in South Chinese children with monosymptomatic nocturnal enuresis (MNE). Materials and Methods: A retrospective study was conducted to analyze the clinical data of children with monosymptomatic nocturnal enuresis who have visited our urology clinic from January to December 2019. All patients received desmopressin treatment. Final treatment outcomes were categorized as successful (complete response) or failed (absent and partial response). The relationship between winter season and treatment response to desmopressin was evaluated. Additionally, associated risk factors were investigated with both univariate and multivariate regression analysis. Results: In total, 393 patients diagnosed with MNE were included in the present study. There were no statistically significant differences in pretreatment variables at first visit between patients who visited the clinic in winter and those who did so in other seasons. However, the treatment failure rate of MNE in the winter season was higher than that of other seasons (77.50% vs. 52.74%). Multivariate logistic regression analysis demonstrated that the severity of symptoms and an initial clinic visit in the winter season were significantly related to desmopressin treatment failure in MNE patients. Conclusion: Winter season and severity of symptoms are two risk factors associated with desmopressin treatment failure in MNE patients.

Association between winter season and desmopressin treatment efficiency in children with monosymptomatic nocturnal enuresis: a pilot study.

OBJECTIVES: The purpose of our study was to assess the association between the winter season and desmopressin treatment failure in South Chinese children with monosymptomatic nocturnal enuresis (MNE). MATERIALS AND METHODS: A retrospective study was conducted to analyze the clinical data of children with monosymptomatic nocturnal enuresis who have visited our urology clinic from January to December 2019. All patients received desmopressin treatment. Final treatment outcomes were categorized as successful (complete response) or failed (absent and partial response). The relationship between winter season and treatment response to desmopressin was evaluated. Additionally, associated risk factors were investigated with both univariate and multivariate regression analysis. RESULTS: In total, 393 patients diagnosed with MNE were included in the present study. There were no statistically significant differences in pretreatment variables at first visit between patients who visited the clinic in winter and those who did so in other seasons. However, the treatment failure rate of MNE in the winter season was higher than that of other seasons (77.50% vs. 52.74%). Multivariate logistic regression analysis demonstrated that the severity of symptoms and an initial clinic visit in the winter season were significantly related to desmopressin treatment failure in MNE patients. CONCLUSION: Winter season and severity of symptoms are two risk factors associated with desmopressin treatment failure in MNE patients.

Variability in Oral Desmopressin Dose Requirements in Children with Central Diabetes Insipidus.

There is inconsistency in the amount of oral desmopressin that children with central diabetes insipidus require. We investigated whether clinical characteristics influenced desmopressin dose requirements in 100 children with central diabetes insipidus. Extremely large doses were associated with acquired etiology (P = .04), greater body mass index z score, intact thirst, and additional pituitary hormone deficiencies (P < .001).

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.

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.

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.

Monitoramento do horizonte tecnológico: Medicamentos em desenvolvimento para o tratamento da Hemofilia A / Monitoring the technological horizon: Drugs under development for the treatment of Hemophilia A

A DOENÇA: A hemofilia A (HA) é uma doença genética hemorrágica, com herança ligada ao cromossomo X. Uma vez que os homens apresentam apenas um cromossomo X e não há alelo homólogo correspondente no cromossomo Y, a hemofilia A acomete principalmente indivíduos do sexo masculino. Ela é caracterizada pela deficiência ou anormalidade da atividade coagulante do fator VIII. Os pacientes tendem a ter sangramento recorrente de gravidade variável, que ocorre espontânea ou pós-traumaticamente em qualquer órgão ou tecido. A gravidade dos episódios hemorrágicos varia de acordo com a atividade residual coagulante do fator VIII. A maioria envolve sangramento intra-articular e hemartrose, a qual, quando recorrente e tratada de forma inadequada, resulta em dano permanente à cartilagem articular. No Brasil, em 2019, havia 10.821 pessoas diagnosticadas com HA, sendo 98,5% do sexo masculino e 36,6% tendo seu quadro clínico classificado como grave. A prevalência da HA estimada é de, aproximadamente, um caso em cada 10.000 nascimentos do sexo masculino. Dentre as coagulopatias hereditárias no Brasil, a HA é a mais frequente, correspondendo à 38,7% do total (4). No país, entre 1999 e 2016, ocorreram 927 óbitos masculinos relacionados à hemofilia, sendo 45,1% como causa básica e 54,9% como causa associada ao óbito. A principal causa associada foi hemorragia intracraniana, seguida de doenças infecciosas e parasitárias, prevalecendo a doença pelo vírus da imunodeficiência humana (HIV) e a hepatite viral. TRATAMENTO RECOMENDADO: No Brasil, as recomendações a respeito do tratamento da HA estão dispostas na segunda edição do manual de hemofilia, publicado pelo Ministério da Saúde em 2015. Também estão disponíveis o Protocolo de uso de Profilaxia Primária para Hemofilia Grave e o Protocolo de uso de indução de imunotolerância para pacientes com hemofilia A e inibidor. O tratamento da hemofilia inclui prevenção de sangramento e danos nas articulações e gerenciamento imediato de episódios hemorrágicos. O principal pilar é a reposição do fator de coagulação deficiente ­ no caso da HA, a reposição do fator VIII. A profilaxia com concentrados de fator de coagulação é referida como terapia de reposição regular, enquanto a terapia de reposição episódica ou terapia sob demanda caracteriza-se pela administração do fator apenas no momento de um sangramento. Diferentes terapias de coagulação estão disponíveis para o tratamento da hemofilia. Há os derivados de plasma humano (hemoderivados), os quais são submetidos a técnicas de diagnóstico, inativação viral e purificação; ou concentrados recombinantes, desenvolvidos por técnicas de biologia molecular. Dos recombinantes, há fatores de coagulação com meia-vida estendida, que aumentam a segurança hemostática na profilaxia e mantêm os níveis do fator mais elevados. Em eventos hemorrágicos, outros agentes são também recomendados, como o acetato de desmopressina e os antifribinolíticos (ácido tranexâmico e ácido épsilon-aminocaproico). ESTRATÉGIA DE BUSCA: Para identificar os medicamentos em pesquisa clínica para HA, foi consultado o sítio eletrônico ClinicalTrials.gov, em 07 de maio de 2021, empregando os termos "hemophilia" e "haemophilia". Foram considerados medicamentos que estão em fase 3 de pesquisa clínica, com a HA como alvo e sem registro para essa indicação terapêutica no Brasil. Para a pesquisa de resultados publicados dos ensaios clínicos, utilizaram-se os códigos de registro do ClinicalTrials.gov referentes aos estudos identificados na etapa anterior e os nomes de cada um dos medicamentos. Entre 13 e 20 de maio de 2020, foram feitas buscas nas bases de dados MEDLINE (via Pub Med), EMBASE e, também, o Google Acadêmico. De forma complementar, anais de congressos científicos, diretrizes clínicas internacionais e a base de dados CortellisTM foram consultados. Os estados regulatórios das terapias selecionadas foram consultados nos sítios eletrônicos da Agência Nacional de Vigilância Sanitária (Anvisa), European Medicines Agency (EMA) e Food and Drug Administration (FDA). NOVAS TERAPIAS: terapias alternativas (sem reposição de fator) que inibem as vias anticoagulantes: Concizumabe. Fitusiran. Marstacimabe. Terapia gênica. Giroctocogene fitelparvovec. Fatores de coagulação VIII com meia-vida estendida. LIMITAÇÕES: A maioria dos estudos de fase 3 localizados nesse informe ainda está em andamento. Embora alguns deles já possuam resultados publicados, esses estão disponíveis apenas sob forma de resumo ou apresentações em eventos científicos. As conclusões sobre a eficácia e segurança das tecnologias ainda são prematuras. Pacientes com hemofilia têm qualidade de vida reduzida devido, principalmente, a dor e às limitações físicas, com repercussão potencial na educação, no emprego e nos relacionamentos interpessoais (56). Avanços em técnicas de biologia molecular e terapias gênicas vêm mudando o cenário dos tratamentos disponíveis para a hemofilia. As melhorias nos fatores de coagulação de reposição permitem, por exemplo, a redução da frequência da infusão e a melhora da atividade biológica. O desenvolvimento de terapias de reposição sem fator de coagulação começou recentemente a oferecer uma abordagem alternativa de tratamento para pacientes com hemofilia. A terapia gênica oferece o potencial de uma cura vitalícia, uma melhor qualidade de vida e liberdade de várias morbidades relacionadas, embora com efeitos de longo prazo ainda desconhecidos. Os dois anticorpos monoclonais (concizumabe e marstacimabe) e o iRNA (fitusiran) são terapias de administração subcutânea que inibem as vias anticoagulantes, reduzindo ou cessando a necessidade de reposição do fator de coagulação. Estudos de fase 2 e resultados preliminares de estudos de fase 3 vêm demonstrando uma redução da taxa de sangramento anual de pacientes com HA que fizeram uso dessas tecnologias. Em relação à terapia gênica, o valoctocogene roxaparvovec e o giroctocogene fitelparvovec estão em fase 3 de desenvolvimento, e demonstram resultados promissores. Dados de estudos de fase 3 publicados em resumos e apresentações de congresso mostram níveis de atividade de FVIII substanciais e sustentados, reduções em episódios de sangramento autorrelatados, reduções em infusões de reposição de FVIII e perfil de segurança bem tolerado após a terapia com valoctocogene roxaparvovec. Os fatores de coagulação VIII com meia-vida estendida permitem a conveniência da redução na frequência da infusão do fator. No entanto, em geral, essas reduções são modestas. Foi apresentado o efanesoctocog alfa que possui três a quatro vezes a meia-vida relacionada a outros fatores VIII, permitindo a sua administração uma vez por semana. Os dados publicados abordam, em geral, a farmacocinética do medicamento, não permitindo conclusões sobre a sua eficácia e segurança. As tecnologias abordadas nesse informe de MHT estão em estudos de fase 3. Em geral, os resultados publicados são dos estudos de fase 2 ou são resultados preliminares de estudos de fase 3, publicados como resumos de eventos científicos. Em relação aos registros sanitários em outros países, das terapias avaliadas, apenas o Valoctocogene roxaparvovec tem a autorização de comercialização solicitada no EMA. No FDA, a autorização foi solicitada, mas a agência pediu dados suplementares e a empresa ainda não submeteu o pedido novamente (58). Nenhuma outra terapia discutida nesse MHT está registrada no EMA ou no FDA até a data de consulta. O desenvolvimento de novos tratamentos para a HA vem permitindo o maior controle da doença e de seus impactos. Caso tenham o registro aprovado por agências regulatórias e solicitada a incorporação destas tecnologias, análises cuidadosas devem ser feitas quanto ao perfil de eficácia/efetividade comparativa e segurança, além do impacto econômico que poderiam gerar ao sistema de saúde.

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)

Pituitary dysfunction in granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis of small vessels that affect the pituitary gland in less than 1% of cases being exceptionally rare. To describe the clinical, biochemical, radiological findings, treatment, and outcomes of 4 patients with GPA-related hypophysitis. A systematic review of published cases with the same diagnosis is presented as well. A cross-sectional case series of patients with hypophysitis due to GPA from 1981 to 2018 at a third level specialty center. Literature review was performed searching in seven different digital databases for terms "granulomatosis with polyangiitis" and "pituitary gland" or "hypophysitis," including in the analysis all published cases between 1950 and 2019 with a minimum follow-up of 6 months. We found 197 patients with GPA in our institution of whom 4 patients (2.0%) had pituitary involvement. Clinical characteristics and outcomes are described. We also reviewed 7 case series, and 36 case reports describing pituitary dysfunction related to GPA from 1953 to 2019, including the clinical picture of an additional 74 patients. Pituitary dysfunction due to GPA is rare. Treatment is targeted to control systemic manifestations; nevertheless, the outcome of the pituitary function is poor. Central diabetes insipidus, particularly in younger women with other systemic features, should raise suspicion of GPA.Key Points• Involvement of the pituitary gland is an uncommon manifestation in GPA patients. The presence of central diabetes insipidus in the setting of systemic symptoms should prompt its suspicion.• In patients with pituitary involvement due to GPA, affection of other endocrine glands is rare, neither concomitant nor in different times during the disease course. This may arise the hypothesis of a local or regional pathogenesis affection of the gland.• There is no consensus on the best therapy strategy for GPA hypophysitis. Although the use of glucocorticoids with CYC is the most common drug combination, no differences in the outcome of the pituitary function and GPA disease course are seen with other immunosuppressants.• Poor prognosis regarding pituitary function is expected due to possible permanent pituitary tissue damage that results in the need of permanent hormonal replacement.

Brazilian consensus in enuresis-recomendations for clinical practice

ABSTRACT Introduction Enuresis, defined as an intermittent urinary incontinence that occurs during sleep, is a frequent condition, occurring in about 10% of children at 7 years of age. However, it is frequently neglected by the family and by the primary care provider, leaving many of those children without treatment. Despite of many studies in Enuresis and recent advances in scientific and technological knowledge there is still considerable heterogeneity in evaluation methods and therapeutic approaches. Materials and Methods The board of Pediatric Urology of the Brazilian Society of Urology joined a group of experts and reviewed all important issues on Enuresis and elaborated a draft of the document. On September 2018 the panel met to review, discuss and write a consensus document. Results and Discussion Enuresis is a multifactorial disease that can lead to a diversity of problems for the child and family. Children presenting with Enuresis require careful evaluation and treatment to avoid future psychological and behavioral problems. The panel addressed recommendations on up to date choice of diagnosis evaluation and therapies.

Brazilian consensus in enuresis-recomendations for clinical practice.

INTRODUCTION: Enuresis, defined as an intermittent urinary incontinence that occurs during sleep, is a frequent condition, occurring in about 10% of children at 7 years of age. However, it is frequently neglected by the family and by the primary care provider, leaving many of those children without treatment. Despite of many studies in Enuresis and recent advances in scientific and technological knowledge there is still considerable heterogeneity in evaluation methods and therapeutic approaches. MATERIALS AND METHODS: The board of Pediatric Urology of the Brazilian Society of Urology joined a group of experts and reviewed all important issues on Enuresis and elaborated a draft of the document. On September 2018 the panel met to review, discuss and write a consensus document. RESULTS AND DISCUSSION: Enuresis is a multifactorial disease that can lead to a diversity of problems for the child and family. Children presenting with Enuresis require careful evaluation and treatment to avoid future psychological and behavioral problems. The panel addressed recommendations on up to date choice of diagnosis evaluation and therapies.

Preclinical Efficacy of [V4 Q5 ]dDAVP, a Second Generation Vasopressin Analog, on Metastatic Spread and Tumor-Associated Angiogenesis in Colorectal Cancer.

PURPOSE: Control of metastatic spread of colorectal cancer (CRC) remains as a major therapeutic challenge. [V4 Q5 ]dDAVP is a vasopressin peptide analog with previously reported anticancer activity against carcinoma tumors. By acting as a selective agonist of arginine vasopressin type 2 membrane receptor (AVPR2) present in endothelial and tumor cells, [V4Q5]dDAVP is able to impair tumor aggressiveness and distant spread. Our aim was to evaluate the potential therapeutic benefits of [V4Q5]dDAVP on highly aggressive CRC disease using experimental models with translational relevance. MATERIALS AND METHODS: Murine CT-26 and human Colo-205 AVPR2-expressing CRC cell lines were used to test the preclinical efficacy of [V4Q5]dDAVP, both in vitro and in vivo. RESULTS: In syngeneic mice surgically implanted with CT-26 cells in the spleen, sustained intravenous treatment with [V4Q5]dDAVP (0.3 µg/kg) dramatically impaired metastatic progression to liver without overt signs of toxicity, and also reduced experimental lung colonization. The compound inhibited in vivo angiogenesis driven by Colo-205 cells in athymic mice, as well as in vitro endothelial cell migration and capillary tube formation. [V4Q5]dDAVP exerted AVPR2-dependent cytostatic activity in vitro (IC50 1.08 µM) and addition to 5-fluorouracil resulted in synergistic antiproliferative effects both in CT-26 and Colo-205 cells. CONCLUSION: The present preclinical study establishes for the first time the efficacy of [V4Q5]dDAVP on CRC. These encouraging. RESULTS: suggest that the novel second generation vasopressin analog could be used for the management of aggressive CRC as an adjuvant agent during surgery or to complement standard chemotherapy, limiting tumor angiogenesis and metastasis and thus protecting the patient from CRC recurrence.

Enuresis Management in Children: Retrospective Clinical Audit of 2861 Cases Treated with Practitioner-Assisted Bell-and-Pad Alarm.

OBJECTIVE: To establish the treatment efficacy of practitioner-assisted bell-and-pad alarm therapy in children with enuresis between the ages of 5 and 16 years by retrospective medical chart review of 2861 children in multiple clinical settings. STUDY DESIGN: This review was conducted across 7 Australian clinical practices. The primary outcome measure was the time taken for children with either primary, secondary, monosymptomatic, or nonmonosymptomatic enuresis to be dry for 14 consecutive nights. The secondary outcome measure was to determine relapse rates, defined as 1 symptom recurrence per month post interruption of treatment. Data were analyzed by correlation and χ2 test via IBM SPSS Statistics (version 22). RESULTS: The overall success rate of the bell and pad treatment was 76%, irrespective of age. The mean treatment time to achieve dryness was 62.1 ± 30.8 days, and the relapse rate was 23%. Concurrent bowel dysfunction was associated with a slightly lower success rate (74%). Concurrent lower urinary tract symptoms were associated with a lower success rate (73%) and greater relapse (1.75 times more likely to relapse). Children with secondary enuresis had significantly greater success than those with primary enuresis (82% vs 74%). CONCLUSION: The type of alarm therapy reported in this study is highly effective. This study will provide the basis for clinical guidelines and practice tools for clinicians, which will help to reduce variation in care pathways for alarm treatment for enuresis.

Desmopressina oral para o tratamento de diabetes insípido central / Oral desmopressin for the treatment of central diabetes insipidus

A DOENÇA: O diabetes insípido é uma síndrome caracterizada pela incapacidade de concentração do filtrado urinário, com consequente desenvolvimento de urina hipotônica e aumento de volume urinário (1). Pode ocorrer por deficiência do hormônio antidiurético (ADH) [também conhecido como arginina vasopressina (AVP)] ou por resistência à sua ação nos túbulos renais. Quando há deficiência na síntese do ADH, o diabetes insípido é chamado central, neurohipofisário ou neurogênico (DIC); quando há resistência à sua ação nos túbulos renais, é dito renal ou nefrogênico. É uma doença rara que pode afetar todas as faixas etárias. A TECNOLOGIA: A desmopressina é um análogo sintético do ADH com maior tempo de ação, maior potência antidiurética e menor efeito pressórico quando comparado ao ADH. O tratamento do diabetes insípido com desmopressina tem embasamento em séries de casos. O primeiro relato de seu uso no tratamento de diabetes insípido central envolveu uma série de 10 pacientes com a condição. Nesse estudo, que utilizou como controles os dados históricos dos 10 pacientes no período em que usavam o ADH como tratamento, a desmopressina mostrou-se segura e apresentou vantagens em relação ao ADH, principalmente quanto ao número de aplicações do medicamento (6-10 doses/dia com ADH e 1-3 doses/dia com desmopressina) e aos efeitos adversos (comuns com ADH e não detectados com desmopressina). Pela inequívoca demonstração de tratar-se de um fármaco com perfil de segurança e efetividade favoráveis, a desmopressina no tratamento do diabetes insípido central foi amplamente adotada, não existindo ensaios clínicos randomizados comparando ADH e desmopressina no tratamento da condição. CONSIDERAÇÕES: Solicita-se a incorporação no PCDT de diabetes insípido da apresentação na forma comprimidos para o uso oral da desmopressina para propiciar mais uma opção de via de administração no tratamento dos pacientes com diabetes insípido. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na reunião do plenário do dia 03/08/2017 deliberaram, por unanimidade, por recomendar a incorporação de desmopressina oral para diabetes insípido desde que o custo de tratamento não seja superior à desmopressina já disponível no SUS. DECISÃO: PORTARIA Nº 61, DE 19 DE DEZEMBRO DE 2017. Torna pública a decisão de incorporar a desmopressina oral para Diabetes Insípido, mediante negociação de preço, no âmbito do Sistema Único de Saúde ­ SUS.

Infundibuloneurohipofisitis: caso clínico y revisión de la literatura / Infundibuloneurohypophysitis: clinical report and literature review

Infundibuloneurohypophysitis is a rare condition, which is part of the group of hypophysitis, of relatively recent description (1993). The main clinical manifestation is diabetes insipidus, whose natural evolution is towards chronicity. The differential diagnosis with other thickening of the hypophysial stem is very important, where the clinic, imaging, laboratory and eventually biopsy are a main support for a correct diagnosis. We present a clinical case that shows the usual picture of infundibuloneurohypophysitis, and illustrates the imaging evolution in a female patient, with diabetes insipidus as the main clinical manifestation

Monosymptomatic nocturnal enuresis in pediatric patients: multidisciplinary assessment and effects of therapeutic intervention.

BACKGROUND: Few studies manage patients with isolated monosymptomatic enuresis (MNE) with multidisciplinary evaluation and pre- and long-term post-intervention monitoring. METHODS: This was a prospective study of MNE patients, aged 6-16 years, diagnosed by multidisciplinary assessment. Of the 140 initial applicants (58.6%) with MNE, 82 were included in the study and randomized for therapeutic intervention in three treatment groups, namely: alarm, desmopressin and alarm + desmopressin. Therapeutic response was evaluated 12 months after treatment withdrawal. RESULTS: Of the 82 patients [mean age 9.5 (SD ± 2.6) years, n = 62 males (75.6%)], 91.1% had a family history of nocturnal enuresis (NE) in first-/second-degree relatives, 81.7% had constipation and 40.7% had mild-to-moderate apnea. Prior to randomization, management of constipation and urotherapy led to remission in seven of the 82 patients; 75 patients were randomized to intervention. There were 14/75 (18.7%) dropouts during the intervention, especially in the alarm group (p = 0.00). Initial complete/partial response was achieved in 56.6% of the alarm group, 70% of the desmopressin group and 64% in the combined group (p = 0.26). Continued success occurred in 70% of the alarm group, 84.2% of the desmopressin group and 100% of the combined group (p = 0.21). Recurrence occurred in 3/20 (15%) patients in the alarm group and 1/19 (5.2 %) patients of the desmopressin group. Post-intervention Child Behavior Checklist (CBCL) and PedsQL 4.0 scores showed significant improvement. CONCLUSIONS: The three therapeutic modalities were effective in managing MNE with low relapse rates; the alarm group showed the highest dropout rate. Therapeutic success was associated with improvement of behavioral problems and quality of life scores.

Clotting factor XIII and desmopressin improve hemostasis in uncontrolled bleeding.

PURPOSE: To investigate hemostatic effects of supplementary factor XIII and desmopressin (DDAVP) in resuscitation of uncontrolled bleeding. METHODS: Fifty-four rabbits were randomized in nine groups: G1: Sham; G2: FXIII and normotensive resuscitation (NBP); G3: FXIII and permissive hypotension (PH) (MAP 60% baseline); G4: FXIII/DDAVP/NBP; G5: FXIII/DDAVP/PH; G6: NBP only; G7: FXIII no hemorrhage; G8: FXIII/DDAVP no hemorrhage; G9: PH only. Thromboelastometry and intra-abdominal blood loss were assessed. Scanning electron microscopy (EM) of the clots was performed. RESULTS: Compared to Sham, only G8 (FXIII/DDAVP w/o hemorrhage) showed clotting time (CT) significantly lower (p<0.05). NBP alone (G6) resulted in significantly prolonged CT compared to G2, G3 and G5 (p<0.05). Similarly, median alpha angle was significantly larger in G3,4,5, and 9 compared to G6 (p<0.05). Area under the curve was significantly greater in G5 than G2. Intra-abdominal blood loss was lower in G5 and G9 compared to G2 and G6. FXIII/DDAVP and PH resulted in more robust fibrin mesh by EM. CONCLUSIONS: Normotensive resuscitation provokes more bleeding and worsens coagulation compared to pH, that is partially reversed by factor XIII and desmopressin. FXIII and DDAVP can synergistically improve coagulation. Permissive hypotension reduces bleeding regardless of those agents.