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Journal of Pediatric Urology May 2024Desmopressin is well accepted as first-line medical therapy for enuresis. If ineffective, combination therapy of desmopressin + oxybutynin or...
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.
PubMed: 38871547
DOI: 10.1016/j.jpurol.2024.05.024 -
European Journal of Pharmacology Dec 2023Many drugs have been explored for their role in improving skin flap survival. 1-deamino-8-D-arginine vasopressin (DDAVP or desmopressin) is a synthesized form of...
BACKGROUND
Many drugs have been explored for their role in improving skin flap survival. 1-deamino-8-D-arginine vasopressin (DDAVP or desmopressin) is a synthesized form of anti-diuretic hormone (ADH) and a selective agonist for vasopressin type-2 receptors (V2 receptors). Desmopressin has been shown to improve endothelial function, induce vasodilation, and reduce inflammation. We aimed to evaluate its efficacy in enhancing flap survival and assess the role of vasopressin receptors in this process.
MATERIALS AND METHODS
We randomly assigned six male Wistar rats to each study group. Different doses of desmopressin were injected intraperitoneally to find the most effective amount (8 μg/rat). SR-49059, a selective V1a receptor antagonist, was given at 2μg/rat before providing the most effective dose of desmopressin (8μg/rat). Histopathological assessments, quantitative measurements of interleukin-1β (IL-1β), Tumor necrosis factor-alpha (TNF-α), and Nuclear Factor-κB (NF-κB), optical imaging, and measurement of the expression levels of V2 receptor in the rat skin tissue were performed.
RESULTS
Desmopressin (8μg/rat) significantly reduced the mean percentage of necrotic area compared to the control group (19.35% vs 73.57%). Histopathological evaluations revealed a notable reduction in tissue inflammation, edema, and degeneration following administration of desmopressin (8). The expression of the V2 receptor was increased following desmopressin administration. It also led to a reduction in IL-1β, TNF-α, and NF-κB levels. The protective effect of desmopressin on flap survival was reversed upon giving SR-49059. The optical imaging revealed enhanced blood flow in the desmopressin group compared to the control group.
CONCLUSIONS
Desmopressin could be repurposed to improve flap survival. V1a and V2 receptors probably mediate this effect.
Topics: Rats; Male; Animals; Deamino Arginine Vasopressin; Receptors, Vasopressin; NF-kappa B; Tumor Necrosis Factor-alpha; Rats, Wistar; Antidiuretic Hormone Receptor Antagonists; Vasopressins; Inflammation
PubMed: 37979830
DOI: 10.1016/j.ejphar.2023.176203 -
Frontiers in Endocrinology 2024We evaluated the accuracy of the 10 μg desmopressin test in differentiating Cushing disease (CD) from non-neoplastic hypercortisolism (NNH) and ectopic ACTH syndrome... (Meta-Analysis)
Meta-Analysis
UNLABELLED
We evaluated the accuracy of the 10 μg desmopressin test in differentiating Cushing disease (CD) from non-neoplastic hypercortisolism (NNH) and ectopic ACTH syndrome (EAS). A systematic review of studies on diagnostic test accuracy in patients with CD, NNH, or EAS subjected to the desmopressin test obtained from LILACS, PubMed, EMBASE, and CENTRAL databases was performed. Two reviewers independently selected the studies, assessed the risk of bias, and extracted the data. Hierarchical and bivariate models on Stata software were used for meta-analytical summaries. The certainty of evidence was measured using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation Working Group) approach. In total, 14 studies were included: 3 studies on differentiated CD versus NNH and 11 studies on differentiated CD versus EAS. Considering ΔACTH in 8 studies involving 429 patients, the pooled sensitivity for distinguishing CD from EAS was 0.85 (95% confidence interval [CI]: 0.80-0.89, I2 = 17.6%) and specificity was 0.64 (95% CI: 0.49-0.76, I2 = 9.46%). Regarding Δcortisol in 6 studies involving 233 participants, the sensitivity for distinguishing CD from EAS was 0.81 (95% CI: 0.74-0.87, I2 = 7.98%) and specificity was 0.80 (95% CI: 0.61-0.91, I2 = 12.89%). The sensitivity and specificity of the combination of ΔACTH > 35% and Δcortisol > 20% in 5 studies involving 511 participants were 0.88 (95% CI: 0.79-0.93, I2 = 35%) and 0.74 (95% CI: 0.55-0.87, I2 = 27%), respectively. The pooled sensitivity for distinguishing CD from NNH in 3 studies involving 170 participants was 0.88 (95% CI: 0.79-0.93) and the specificity was 0.94 (95% CI: 0.86-0.97). Based on the desmopressin test for differentiating CD from EAS, considering ΔACTH, Δcortisol, or both percent increments, 15%, 19%, or 20% of patients with CD, respectively, would be incorrectly classified as having EAS. For CD versus NNH, 11% of patients with CD would be falsely diagnosed as having NNH, whereas 7% of patients with NNH would be falsely diagnosed as having CD. However, in all hierarchical plots, the prediction intervals were considerably wider than the confidence intervals. This indicates low confidence in the estimated accuracy, and the true accuracy is likely to be different.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=85634, identifier CRD42018085634; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=68317, identifier CRD42017068317.
Topics: Humans; Cushing Syndrome; Deamino Arginine Vasopressin; Diagnosis, Differential; ACTH Syndrome, Ectopic; Pituitary ACTH Hypersecretion
PubMed: 38352712
DOI: 10.3389/fendo.2024.1332120 -
Blood Jan 2024von Willebrand disease (VWD) is the most common bleeding disorder and especially milder type 1 VWD might not be cared for in specialty clinics. VW factor levels rise...
von Willebrand disease (VWD) is the most common bleeding disorder and especially milder type 1 VWD might not be cared for in specialty clinics. VW factor levels rise with age, but the rise of these levels does not necessarily correlate with bleeding risk. A recent bleeding history combined with recent labs are important for hemostatic management decision during surgical interventions. Antifibrinolytics appear safe in the population of older adults, whereas desmopressin (DDAVP) should be used cautiously. Where needed, factor concentrates present a great treatment option. Acquired von Willebrand syndrome is vastly underrecognized, but likely to surface in the aging, especially in the setting of comorbidities, such as plasma-cell dyscrasias. Intravenous immunoglobulin can be an effective treatment in this scenario, but potentially increases thrombotic risk.
Topics: Humans; Aged; von Willebrand Diseases; von Willebrand Factor; Hemorrhage; Deamino Arginine Vasopressin; Hemostatics
PubMed: 37672774
DOI: 10.1182/blood.2022018534 -
Journal of Cardiothoracic and Vascular... Jul 2024Patient blood management (PBM) guidelines for patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) have increased during the past decade, and... (Review)
Review
Patient blood management (PBM) guidelines for patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) have increased during the past decade, and pharmacotherapy plays an important role in PBM. In the face of the undefined consistency in the methodologic quality and pharmacotherapy recommendations across multiple guidelines, this study exclusively evaluated methodologies of the related guideline development process, and compiled medication recommendations of PBM for cardiac surgery patients. PBM guidelines for cardiac surgery under CPB were searched through some mainstream literature and guideline databases from database establishment to May 15, 2023. Nine guidelines meeting inclusion criteria were included in this study. The quality of the guidelines was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. "Stakeholder involvement" received the lowest mean score of 49.38% in the AGREE II scoring among the guidelines. PBM for cardiac surgery patients spans the perioperative phase. Drug therapy strategies of PBM for cardiac surgery patients involve anemia therapy, perioperative administration of antithrombotic drugs, intraoperative anticoagulation, and the use of hemostatic drugs. Unlike for adults, there is less evidence about the management of antithrombotic drugs and hemostatic drugs for pediatric cardiac surgery patients. Recombinant activated factor VII (rFVIIa) and desmopressin (DDAVP) are not recommended after pediatric cardiac surgery, whereas prothrombin complex concentrate could be considered in clinical trials. As for the controversies regarding the administration of rFVIIa and DDAVP after adult cardiac surgery by different societies, clinicians should exercise their clinical judgment based on individual patient features.
Topics: Humans; Cardiopulmonary Bypass; Cardiac Surgical Procedures; Practice Guidelines as Topic
PubMed: 38594156
DOI: 10.1053/j.jvca.2024.03.011 -
Value in Health Regional Issues Sep 2023This study aimed to estimate the cost-utility of effective interventions for enuresis treatment in children and adolescents and to calculate the incremental cost-utility... (Meta-Analysis)
Meta-Analysis
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...
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.
Topics: Humans; Child; Adolescent; Brazil; Deamino Arginine Vasopressin; Tolterodine Tartrate; Enuresis
PubMed: 37099838
DOI: 10.1016/j.vhri.2023.03.004 -
Journal of Evidence-based Medicine Jun 2024Thiazides are the first-line treatment for hypertension, however, they have been associated with hospitalizations for thiazide-associated hyponatremia (TAH). The aim of...
OBJECTIVE
Thiazides are the first-line treatment for hypertension, however, they have been associated with hospitalizations for thiazide-associated hyponatremia (TAH). The aim of this study was to evaluate the risk of TAH and other drug-associated hyponatremia in a Korean population.
METHODS
The study used big data from the National Health Insurance Sharing Service of 1,943,345 adults treated for hypertension from January 2014 to December 2016. The participants were divided into two groups based on the use of thiazides. Cox proportional hazard models were used to identify independent risk factors for the occurrence of hyponatremia.
RESULTS
The study found that hyponatremia-related hospitalizations were significantly higher in the thiazide group than the control group (2.19% vs. 1.45%). The risk increased further with concurrent use of other diuretics or desmopressin, and thiazide+spironolactone+desmopressin and hospitalization risk further increased (4.0 and 6.9 times). Multivariate analysis showed that hyponatremia occurrence increased with age, diabetes mellitus, depression, and thiazide use (hazard ratio = 1.436, p < 0.001). The thiazide group had better 6-year overall survival than the control group but had more fractures and hyponatremia.
CONCLUSIONS
Thiazide use is associated with an increased risk of hyponatremia and related complications. However, the mortality rate decreased in those who received thiazides, suggesting that thiazide use itself is not harmful and may help decrease complications and improve prognosis with proper, cautious use in high-risk patients.
Topics: Humans; Hyponatremia; Female; Male; Middle Aged; Hypertension; Aged; Thiazides; Republic of Korea; Cohort Studies; Risk Factors; Sodium Chloride Symporter Inhibitors; Hospitalization; Adult; Proportional Hazards Models; Antihypertensive Agents
PubMed: 38566339
DOI: 10.1111/jebm.12601 -
Paediatrics & Child Health Oct 2023Pour évaluer l'énurésie, un trouble pédiatrique courant, il faut en distinguer la forme monosymptomatique de la forme non monosymptomatique et établir la présence... (Review)
Review
Pour évaluer l'énurésie, un trouble pédiatrique courant, il faut en distinguer la forme monosymptomatique de la forme non monosymptomatique et établir la présence d'affections concomitantes. La prise en charge simultanée des facteurs cooccurrents est le meilleur moyen pour obtenir un résultat satisfaisant. Le traitement commence par l'éducation du patient et de sa famille sur l'évolution naturelle de l'énurésie et par des conseils pratiques sur le comportement. Les données probantes en appui à des interventions particulières sont limitées, et les enfants et les familles devraient participer au choix du traitement approprié. Les dispositifs d'alarme contre l'énurésie et la desmopressine représentent des possibilités thérapeutiques lorsqu'une intervention plus active est souhaitée. Des améliorations cliniques et des traitements combinés sont en voie de se dégager.
PubMed: 37744754
DOI: 10.1093/pch/pxad024 -
Journal of Pediatric Surgery Oct 2023To compare the efficacy and tolerability of Solifenacin plus Desmopressin and Desmopressin alone in the treatment of primary monosymptomatic nocturnal enuresis (PMNE). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To compare the efficacy and tolerability of Solifenacin plus Desmopressin and Desmopressin alone in the treatment of primary monosymptomatic nocturnal enuresis (PMNE).
METHODS
A total of 88 children, 5-14 years old, diagnosed with PMNE were enrolled in this randomized control trial (RCT) from June 2017 to June 2020. After informed written consent patients were randomized to one of the two therapeutic groups. Group 1 received one puff of desmopressin nasal spray 1 h before bedtime every night. Group 2 received one pill of solifenacin 5 mg plus one puff of desmopressin nasal spray 1 h before bedtime every night. All patients were evaluated after three months for their response to treatment and drug side effects.
RESULTS
The mean age in desmopressin alone group and solifenacin plus desmopressin group was 8.1 ± 2.2 (5-14) and 7.9 ± 2.2 (5-14) years respectively (p-value >0.05). In group 2, 37/44 (84.09%) patients achieved complete response after three months of treatment in comparison to group 1 in which 27/44 (61.36%) patients showed complete response (p-value <0.05). In group 1, 8/44 (18.18%) patients developed treatment related side effects whereas in group 2, 12/44 (27.27%) patients developed side effects (p-value >0.05). No case of discontinuation of treatment due to side effects was observed in any of the two groups. The recurrence rate was also significantly lower in group 2 in comparison to group 1 (8.1% vs 33.3%, p-value <0.05).
CONCLUSION
Our study demonstrated that the combination of Solifenacin plus Desmopressin is more effective than desmopressin monotherapy in the treatment of PMNE with an acceptable tolerability profile.
LEVEL OF EVIDENCE
Level I.
Topics: Child; Humans; Child, Preschool; Adolescent; Deamino Arginine Vasopressin; Nocturnal Enuresis; Solifenacin Succinate; Nasal Sprays
PubMed: 37041092
DOI: 10.1016/j.jpedsurg.2023.03.010 -
Transfusion and Apheresis Science :... Oct 2023Four-factor prothrombin complex concentrate (4F-PCC) may be an option for patients with bleeding unrelated to therapeutic anticoagulation to help with bleeding cessation... (Observational Study)
Observational Study
INTRODUCTION
Four-factor prothrombin complex concentrate (4F-PCC) may be an option for patients with bleeding unrelated to therapeutic anticoagulation to help with bleeding cessation and reduce blood component requirements.
MATERIALS AND METHODS
Retrospective, observational study of adult patients who received 4F-PCC for bleeding not associated with therapeutic anticoagulation between June 2019 and July 2021. Primary outcome was to describe off-label 4F-PCC use in patients not on therapeutic anticoagulation for bleeding management in surgical and non-surgical patients. Additional outcomes evaluated were blood product use, chest tube and drainage output, and coagulation studies before and after 4F-PCC administration as well as other hemostatic agent use and thromboembolic events.
RESULTS
Seventy-six patients were included; median age 64 years (IQR 50-69), 66% of bleeding events were associated with surgery, and the majority of 4F-PCC doses ordered by cardiac surgery (68.4%). A total of 110 4F-PCC doses were administered; median 1 dose/patient (IQR 1-2), median total dose 1000 units (IQR 500-1484). Other hemostatic agents commonly administered were protamine (59%), desmopressin (43%), and tranexamic acid (42%). Packed red blood cells, fresh frozen plasma, platelet, and cell saver blood administration and prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (aPTT) were significantly reduced following 4F-PCC administration. Eight patients (11%) experienced thromboembolic complications.
CONCLUSION
Relatively low doses of 4F-PCC (median total dose 1000 units) were associated with decreased blood component requirements and improved PT, INR, and aPTT values in patients with bleeding unrelated to therapeutic anticoagulation. Other hemostatic agent use was common and thromboembolic complications occurred.
Topics: Adult; Humans; Middle Aged; Anticoagulants; Retrospective Studies; Blood Coagulation Factors; Hemorrhage; Factor IX; Hemostatics; Thromboembolism; International Normalized Ratio
PubMed: 37453907
DOI: 10.1016/j.transci.2023.103759