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Neurourology and Urodynamics Jan 2024This pooled analysis aims to demonstrate the clinical efficacy and safety of combined desmopressin and anticholinergic therapy in the treatment of pediatric nocturnal... (Review)
Review
OBJECTIVE
This pooled analysis aims to demonstrate the clinical efficacy and safety of combined desmopressin and anticholinergic therapy in the treatment of pediatric nocturnal enuresis (NE).
METHODS
A systematic search was conducted through PubMed, MEDLINE, EMBASE, ResearchGate, and Cochrane Library to identify all randomized controlled trials (RCTs) comparing monotherapy with desmopressin versus combined therapy with desmopressin and anticholinergic agents for the treatment of NE. Data analysis was performed using RevMan version 5.4.1.
RESULTS
This study included 8 RCTs involving a total of 659 patients. The frequencies of complete response (CR), partial response (PR), and nonresponse (NR) were computed for both short-term treatment (1 month) and long-term treatment (3 months). Additionally, alterations in the mean number of NE episodes, adverse events, and relapse were assessed. Our analysis indicates that, in comparison to the monotherapy group, the combination therapy group plays a pivotal role in augmenting the CR odds and diminishing the NR ratios in both short-term and long-term treatments (1 month CR ratio [risk ratio (RR): 1.84; 95% confidence interval (CI): 1.22-2.76; p = 0.003, I = 72%]; 3 months CR ratio [RR: 1.48; 95% CI: 1.25-1.76; p < 0.00001, I = 0%]; 1 month NR ratio [RR: 0.67; 95% CI: 0.55-0.82; p = 0.0001, I = 0%]; 3 months CR ratio [RR: 0.37; 95% CI: 0.19-0.73; p = 0.004, I = 0%]). Furthermore, in both short-term and long-term treatment, the combined therapy group exhibits a greater magnitude of change in the average number of NE episodes compared to patients receiving monotherapy (1 month, mean difference [MD] = -2.97; 95% CI: -4.23 to -1.71, p < 0.0001; 3 months, MD = -4.30; 95% CI: -7.18 to -1.43, p = 0.003). Moreover, the combination therapy group exhibits a significant reduction in the recurrence rate (RR: 0.36; 95% CI: 0.15-0.86; p = 0.02). There is no significant difference in the incidence of adverse events between the two groups (RR: 1.16; 95% CI: 0.58-2.31; p = 0.67).
CONCLUSION
Combining desmopressin with anticholinergic medications is more effective for NE than desmopressin alone, with lower recurrence and minimal adverse effects.
Topics: Child; Humans; Cholinergic Antagonists; Combined Modality Therapy; Deamino Arginine Vasopressin; Drug Therapy, Combination; Nocturnal Enuresis; Pathologic Complete Response
PubMed: 37787540
DOI: 10.1002/nau.25295 -
Scientific Reports Nov 2018This study is to compare the efficacy of enuresis alarm and desmopressin therapy in managing pediatric monosymptomatic enuresis. We performed systematic literature... (Meta-Analysis)
Meta-Analysis
This study is to compare the efficacy of enuresis alarm and desmopressin therapy in managing pediatric monosymptomatic enuresis. We performed systematic literature searches on different databases from inception until April 2017 without language restriction. All randomized control trials comparing an enuresis alarm and desmopressin in managing children with monosymptomatic enuresis were included. A total of 15 studies with 1502 participants (aged 5 to 16 years) were included for pooled analysis. Overall, an enuresis alarm outperformed desmopressin in achieving at least a partial response (>50% reduction in wet nights) in per-protocol analysis (OR: 1.53, 95% CI 1.05 to 2.23) but not in intention-to-treat analysis (OR: 0.97, 95% CI 0.73 to 1.30) as the alarm was hampered by a high dropout rate (OR: 2.20, 95% CI 3.41 to 4.29). However, alarm therapy yielded a better sustained response (OR: 2.89, 95% CI 1.38 to 6.04) and lower relapse rate (OR: 0.25, 95% CI 0.12 to 0.50). In the intention to treat analysis, the results revealed that alarm and desmopressin therapy are comparable in efficacy with regards to achieving >50% reduction in baseline wet nights in enuretic children. However, enuresis alarms offer a superior treatment response and a lower relapse rate in well-motivated children.
Topics: Child; Clinical Alarms; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30425276
DOI: 10.1038/s41598-018-34935-1 -
Reviews in Endocrine & Metabolic... Oct 2022The current gold standard diagnostic method for Cushing disease (CD) is bilateral inferior petrosal sinus sampling (BIPSS) after corticotropin-releasing hormone (CRH)... (Meta-Analysis)
Meta-Analysis Review
Diagnostic accuracy of bilateral inferior petrosal sinus sampling using desmopressin or corticotropic- releasing hormone in ACTH-dependent Cushing's syndrome: A systematic review and meta-analysis.
The current gold standard diagnostic method for Cushing disease (CD) is bilateral inferior petrosal sinus sampling (BIPSS) after corticotropin-releasing hormone (CRH) stimulation. Due to shortages of CRH, BIPSS has been performed with desmopressin (DDAVP) instead. The objective of this systematic review and meta-analysis was to estimate the diagnostic accuracy of BIPSS using DDAVP or CRH for the differential diagnosis of Cushing's syndrome (CS). A literature review was done in PubMed, Scopus, EMBASE, and google scholar databases to derive summary estimates of the overall diagnostic sensitivity and accuracy of BIPSS using DDAVP or CRH in Cushing's syndrome. Pooled sensitivity, specificity, diagnostic odds ratio and summary receiver operating characteristic curves (SROC) for differential diagnosis of Cushing's syndrome in the random-effects models, were computed. Overall, 11 different studies with a total of 612 participants, were eligible for the analysis. Five articles with data on BIPSS using DDAVP, 5 papers on BIPSS using CRH, and another one evaluated the results of stimulation using DDAVP, with or without CRH, for differential diagnosis of Cushing's syndrome. The pooled (95% CI) sensitivity and specificity of BIPSS using DDAVP, were 96% (91-98%) and 1.00 (0.00-1.00), respectively. The area under the SROC curve was 0.95. The pooled (95% CI) sensitivity and specificity of BIPSS using CRH, were 98% (92-99%) and 1.00 (0.00-1.00), respectively, and the area under the SROC curve was 0.98. The I index (95% CI) was 0% (0-100%) for both BIPSS using DDAVP and using CRH. As a result, DDAVP stimulation is a safe, effective, less expensive, valuable and available alternative to CRH in the setting of BIPSS for all age groups of patients with CS. Registration code in PROSPERO: CRD42021292531.
Topics: Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Humans; Petrosal Sinus Sampling
PubMed: 35478451
DOI: 10.1007/s11154-022-09723-y -
The Journal of Clinical Endocrinology... Mar 2020Human reproduction is mainly governed from the hypothalamic-adrenal-gonadal (HPG) axis, which controls both ovarian morphology and function. Disturbances in the...
CONTEXT
Human reproduction is mainly governed from the hypothalamic-adrenal-gonadal (HPG) axis, which controls both ovarian morphology and function. Disturbances in the secretion of other anterior pituitary hormones (and their respective endocrine axes) interfere with HPG activity and have been linked to fertility problems. In normal pregnancy, maintenance of homeostasis is associated with continuous changes in pituitary morphology and function, which need to be considered during hormone replacement in patients with hypopituitarism.
DESIGN
We conducted a systematic PubMed literature review from 1969 to 2019, with the following keywords: fertility and hypopituitarism, pregnancy and hypopituitarism, and ovulation induction and hypopituitarism. Case reports or single-case series of up to 2 patients/4 pregnancies were excluded.
RESULTS
Eleven publications described data on fertility (n = 6) and/or pregnancy (n = 7) in women with hypopituitarism. Women with hypopituitarism often need assisted reproductive treatment, with pregnancy rates ranging from 47% to 100%. In patients achieving pregnancy, live birth rate ranged from 61% to 100%. While glucocorticoids, levothyroxine, and desmopressin are safely prescribed during pregnancy, growth hormone treatment regimens vary significantly between countries, and several publications support a positive effect in women seeking fertility.
CONCLUSIONS
In this first systematic review on fertility, ovulation induction, and pregnancy in patients with hypopituitarism, we show that while literature is scarce, birth rates are high in patients achieving pregnancy. However, prospective studies are needed for evaluating outcomes in relationship to treatment patterns. Replacement therapy in hypopituitarism should always mimic normal physiology, and this becomes challenging with changing demands during pregnancy evolution.
Topics: Female; Fertility; Hormone Replacement Therapy; Humans; Hypopituitarism; Ovulation Induction; Pregnancy; Pregnancy Rate; Prognosis; Reproduction
PubMed: 31652320
DOI: 10.1210/clinem/dgz112 -
Cureus Aug 2023Von Willebrand disease (VWD) and hemophilia A are the most common inherited bleeding disorders. Quantitative or qualitative von Willebrand factor (VWF) anomalies cause... (Review)
Review
Von Willebrand disease (VWD) and hemophilia A are the most common inherited bleeding disorders. Quantitative or qualitative von Willebrand factor (VWF) anomalies cause this disorder in men and women. VWF, a plasma glycoprotein, relies on platelets for primary hemostasis. It also carries and stabilizes factor VIII in the blood. VWD has several categories. Types 1 and 3 have partial or total VWF quantitative deficiencies. However, type 2 and its subtypes have VWF quality issues. The major treatment is desmopressin (DDAVP), which replaces endogenous VWF and factor VIII (FVIII). Plasma-derived VWF/FVIII products may also be substituted exogenously. Treatment with plasma-derived or recombinant VWF concentrates without FVIII is also possible. The purpose of this retrospective, single-center research was to evaluate DDAVP's efficacy in treating VWD based on many criteria established in the current literature. We looked at the results on Google Scholar, the Cochrane Library, and PubMed/Medline. There were a total of 10 papers found, evaluated, and accepted for inclusion in this study. A comprehensive analysis of DDVAP's role in VWD was compiled from the aforementioned papers. Various aspects of DDVAP were captured by including an analysis of complementary treatments used in surgical and clinical settings. We also describe the treatment's intended impact on the different variations of the disease. Given these results, further investigation is required to determine the most effective method for managing VWD so that it may be included in standard clinical practice.
PubMed: 37649925
DOI: 10.7759/cureus.44310 -
The American Journal of Medicine Dec 2015Hyponatremia is common among inpatients and is associated with severe adverse outcomes such as osmotic demyelination syndrome. Current guidelines recommend serum sodium... (Review)
Review
BACKGROUND
Hyponatremia is common among inpatients and is associated with severe adverse outcomes such as osmotic demyelination syndrome. Current guidelines recommend serum sodium concentration correction targets of no more than 8 mEq/L per day in patients at high risk of osmotic demyelination syndrome. Desmopressin is recommended to control high rates of serum sodium concentration correction in severe hyponatremia. However, recommendations are based on limited data. The objective of this study is to review current strategies for DDAVP use in severe hyponatremia.
METHODS
Systematic literature search of 4 databases of peer-reviewed studies was performed and study quality was appraised.
RESULTS
The literature search identified 17 observational studies with 80 patients. We found 3 strategies for desmopressin administration in hyponatremia: 1) proactive, where desmopressin is administered early based on initial serum sodium concentration; 2) reactive, where desmopressin is administered based on changes in serum sodium concentration or urine output; 3) rescue, where desmopressin is administered after serum sodium correction targets are exceeded or when osmotic demyelination appears imminent. A proactive strategy of desmopressin administration with hypertonic saline was associated with lower incidence of exceeding serum sodium concentration correction targets, although this evidence is derived from a small case series.
CONCLUSIONS
Three distinct strategies for desmopressin administration are described in the literature. Limitations in study design and sample size prevent definitive conclusions about the optimal strategy for desmopressin administration to correct hyponatremia. There is a pressing need for better quality research to guide clinicians in managing severe hyponatremia.
Topics: Acute Disease; Antidiuretic Agents; Deamino Arginine Vasopressin; Humans; Hyponatremia; Sodium
PubMed: 26031887
DOI: 10.1016/j.amjmed.2015.04.040 -
Seminars in Thrombosis and Hemostasis Apr 2022Mortality after aneurysmal subarachnoid hemorrhage (aSAH) is augmented by rebleeding and delayed cerebral ischemia (DCI). A range of assays evaluating the dynamic...
Mortality after aneurysmal subarachnoid hemorrhage (aSAH) is augmented by rebleeding and delayed cerebral ischemia (DCI). A range of assays evaluating the dynamic process of blood coagulation, from activation of clotting factors to fibrinolysis, has emerged and a comprehensive review of hemostasis and fibrinolysis following aSAH may reveal targets of treatment. We conducted a systematic review of existing literature assessing coagulation and fibrinolysis following aSAH, but prior to treatment. PubMed, Embase, and Web of Science were searched on November 18, 2020, without time boundaries. In total, 45 original studies were eventually incorporated into this systematic review, divided into studies presenting data only from conventional or quantitative assays ( = 22) and studies employing dynamic assays ( = 23). Data from conventional or quantitative assays indicated increased platelet activation, whereas dynamic assays detected platelet dysfunction possibly related to an increased risk of rebleeding. Secondary hemostasis was activated in conventional, quantitative, and dynamic assays and this was related to poor neurological outcome and mortality. Studies systematically investigating fibrinolysis were sparse. Measurements from conventional or quantitative assays, as well as dynamic fibrinolysis assays, revealed conflicting results with normal or increased lysis and changes were not associated with outcome. In conclusion, dynamic assays were able to detect reduced platelet function, not revealed by conventional or quantitative assays. Activation of secondary hemostasis was found in both dynamic and nondynamic assays, while changes in fibrinolysis were not convincingly demonstrable in either dynamic or conventional or quantitative assays. Hence, from a mechanistic point of view, desmopressin to prevent rebleeding and heparin to prevent DCI may hold potential as therapeutic options. As changes in fibrinolysis were not convincingly demonstrated and not related to outcome, the use of tranexamic acid prior to aneurysm closure is not supported by this review.
Topics: Brain Ischemia; Fibrin Clot Lysis Time; Fibrinolysis; Hemostasis; Humans; Subarachnoid Hemorrhage
PubMed: 34261149
DOI: 10.1055/s-0041-1730346 -
Journal of Clinical Neuroscience :... Apr 2021The purpose of this study was to perform a systematic review and meta-analysis on the effect of desmopressin on hematoma expansion (HE) in antiplatelet-associated... (Meta-Analysis)
Meta-Analysis
The purpose of this study was to perform a systematic review and meta-analysis on the effect of desmopressin on hematoma expansion (HE) in antiplatelet-associated intracerebral hemorrhage (AA-ICH). Secondary outcomes examined were the rate of thrombotic complications and neurologic outcome. Three databases were searched (Pubmed, Scopus, and Cochrane) for randomized clinical trials and controlled studies comparing desmopressin versus controls in adult patients with AA-ICH. The Mantel-Haenszel method was applied to calculate an overall effect estimate for each outcome by combining stratum-specific risk ratio (RR). Risk of bias was computed using the Newcastle-Ottawa Scale. The protocol was registered in PROSPERO (42020190234). Three retrospective controlled studies involving 263 patients were included in the meta-analysis. Compared to controls, desmopressin was associated with a non-significant reduction in HE (19.1% vs. 30%; RR:0.61; 95%CI, 0.27-1.39; P = 0.24), a similar rate of thrombotic events (5.5% vs. 9.9%; RR:0.47; 95%CI, 0.17-1.31; P = 0.15), and significantly worse neurologic outcome (mRS ≥ 4) (66.3% vs. 50%; RR:1.36; 95%CI, 1.08-1.7; P = 0.008). Qualitative analysis of included studies for each outcome revealed low to moderate risk of bias. The available literature does not support the routine use of desmopressin in the setting of AA-ICH. Until larger prospective trials are performed, the administration of desmopressin should be judiciously considered on a case-by-case basis.
Topics: Cerebral Hemorrhage; Deamino Arginine Vasopressin; Hematoma; Hemostatics; Humans; Platelet Aggregation Inhibitors; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome
PubMed: 33775314
DOI: 10.1016/j.jocn.2021.01.017 -
Thrombosis Research May 2022Desmopressin (DDAVP) is a proven therapy for bleeding disorders; however, the therapeutic efficacy of different parenteral formulations has never been systematically... (Review)
Review
INTRODUCTION
Desmopressin (DDAVP) is a proven therapy for bleeding disorders; however, the therapeutic efficacy of different parenteral formulations has never been systematically analyzed. This study investigated whether subcutaneous (SC) DDAVP provides equivalent hemostatic efficacy to intravenous (IV) desmopressin, particularly in patients with mild to moderate bleeding tendencies from hemophilia A (HA) or von Willebrand disease (vWD).
MATERIALS AND METHODS
We searched PubMed, EMBASE, MEDLINE, Cochrane, and CINAHL databases for observational studies and randomized controlled trials which compared the hemostatic efficacy of parenteral formulations of DDAVP in healthy patients and those with bleeding disorders. Two reviewers independently performed screening and data extraction. Extracted data included Factor VIII (FVIII) levels, von Willebrand factor (vWF) antigen levels, and vWF activity.
RESULTS
The search strategy yielded a total of 5519 studies. Twelve studies met the inclusion criteria and were included in the review. Seven out of eight studies conducted in patients with bleeding disorders and all four studies conducted in healthy subjects found no difference in hemostatic efficacy between parenteral formulations. A meta-analysis was not performed due to disparities between study design and outcomes of interest.
CONCLUSIONS
Our study showed that IV and SC administration of DDAVP appeared to result in near equivalent hemostatic efficacy; however, the strength of these findings is limited by the small number and lack of comparability in the primary studies. A sizable contemporary study powered to detect differences in coagulation factor levels would be required to confirm our findings.
Topics: Deamino Arginine Vasopressin; Factor VIII; Hemophilia A; Hemostatics; Humans; von Willebrand Diseases; von Willebrand Factor
PubMed: 35278886
DOI: 10.1016/j.thromres.2022.02.019 -
The Cochrane Database of Systematic... Nov 2014Heavy menstrual bleeding without an organic lesion is mainly due to an imbalance of the various hormones which have a regulatory effect on the menstrual cycle. Another... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heavy menstrual bleeding without an organic lesion is mainly due to an imbalance of the various hormones which have a regulatory effect on the menstrual cycle. Another cause of heavy menstrual bleeding with no pelvic pathology, is the presence of an acquired or inherited bleeding disorder. The haemostatic system has a central role in controlling the amount and the duration of menstrual bleeding, thus abnormally prolonged or profuse bleeding does occur in most women affected by bleeding disorders. Whereas irregular, pre-menarchal or post-menopausal uterine bleeding is unusual in inherited or acquired haemorrhagic disorders, severe acute bleeding and heavy menstrual bleeding at menarche and chronic heavy menstrual bleeding during the entire reproductive life are common.
OBJECTIVES
To determine the efficacy and safety of non-surgical interventions versus each other, placebo or no treatment for reducing menstrual blood loss in women with bleeding disorders.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Haemoglobinopathies Trials Register (13 March 2014), Embase (May 2013), LILACS (February 2013) and the WHO International Clinical Trial registry (February 2013).
SELECTION CRITERIA
Randomised controlled studies of non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women of reproductive age suffering from a congenital or acquired bleeding disorder.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion, extracted data and assessed the risk of bias.
MAIN RESULTS
Three cross-over studies, with 175 participants were included in the review. All three studies had an unclear risk of bias with regards to trial design and overall, the quality of evidence generated was judged to be poor.Two of the studies (n = 59) compared desmopressin (1-deamino-8-D-arginine vasopressin) with placebo. Menstrual blood loss was the primary outcome for both of these studies. Neither study found clear evidence of a difference between groups. The first of these reported a mean difference in menstrual blood loss in the desmopressin versus placebo group of 21.20 mL (95% confidence interval -19.00 to 61.50)The second study reported that even though there was an improvement of pictorial bleeding assessment chart scores with desmopressin and placebo when compared to pretreatment assessment, there was no clear evidence of difference in these scores when the two were compared to each other (results presented graphically, P = 0.51). The data from these studies could not be combined.The third study (n = 116) compared desmopressin with tranexamic acid (n = 116). This study found a decrease in pictorial bleeding assessment chart scores after both treatments as compared to baseline. The decrease in these scores was greater for tranexamic acid than for desmopressin, with a mean difference of 41.6 mL (95% confidence interval 19.6 to 63) (P < 0.0002).In relation to adverse events, across two studies, there was no clear evidence of a difference when placebo was compared to desmopressin, risk ratio 1.17 (95% confidence interval 0.41 to 3.34) . The same was also true when desmopressin was compared to tranexamic acid, risk ratio 1.17 (95% confidence interval 0.41 to 3.34).Only the study that compared desmopressin to tranexamic acid assessed quality of life. However, we are unable to present any data from this study, since no differences in this outcome between the two intervention groups were reported.
AUTHORS' CONCLUSIONS
Evidence from randomised controlled studies on the effect of desmopressin when compared to placebo in reducing menstrual blood loss is very limited and inconclusive. Two studies, each with a very limited number of participants, have shown uncertain effects in menstrual blood loss and adverse effects. A non-randomised comparison in one of the studies points to the value of combining desmopressin and tranexamic acid, which needs to be tested in a formal randomised controlled study comparison.When tranexamic acid was compared to desmopressin, a single study showed a reduction in menstrual blood loss with tranexamic acid use compared to desmopressin.There is a need to evaluate non-surgical methods for treating of menorrhagia in women with bleeding disorders through randomised controlled studies. Such methods would be more acceptable than surgery for women wishing to retain their fertility. Given that women may need to use these treatments throughout their entire reproductive life, long-term side-effects should be evaluated.
Topics: Adult; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Menorrhagia; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 25426776
DOI: 10.1002/14651858.CD010338.pub2