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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 -
BMC Urology Oct 2023Patients with benign prostatic hyperplasia (BPH) receive α-blockers as first-line therapy to treat lower urinary tract symptoms; however, some individuals still... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with benign prostatic hyperplasia (BPH) receive α-blockers as first-line therapy to treat lower urinary tract symptoms; however, some individuals still experience residual storage symptoms. Antimuscarinics, β3-agonists, and desmopressin are effective add-on medications. Nevertheless, there is currently no evidence for the appropriate choice of the first add-on medication. This systematic review aimed to investigate the clinical benefits of antimuscarinics, β3-agonists, and desmopressin, in addition to α-blockers, for persistent storage symptoms in BPH patients.
METHODS
A comprehensive literature search of randomized controlled trials (RCTs) comparing the efficacy of different add-on medications in BPH patients with persistent storage symptoms despite α-blocker treatment was conducted. Clinical outcomes included the International Prostate Symptom Score (IPSS), IPSS storage subscore, nocturia, micturition, and urgency. A network meta-analysis was performed to estimate the effect size. Surface under cumulative ranking curves (SUCRAs) were used to rank the included treatments for each outcome.
RESULTS
A total of 15 RCTs were identified. Add-on imidafenacin and mirabegron resulted in significant improvement in all outcomes assessed. Other add-on medications such as desmopressin, tolterodine, solifenacin, fesoterodine, and propiverine showed positive benefits for most, but not all, outcomes. Based on the SUCRA rankings, add-on desmopressin was the best-ranked treatment for IPSS and nocturia, and add-on imidafenacin was the best for the IPSS storage subscore and micturition.
CONCLUSIONS
BPH patients presenting with persistent storage symptoms despite α-blocker administration are recommended to include additional treatment. Desmopressin and imidafenacin may be considered high-priority add-on treatments because of their superior efficacy compared with other medications.
Topics: Male; Humans; Muscarinic Antagonists; Prostatic Hyperplasia; Nocturia; Network Meta-Analysis; Deamino Arginine Vasopressin; Treatment Outcome; Drug Therapy, Combination; Lower Urinary Tract Symptoms; Adrenergic alpha-Antagonists
PubMed: 37789333
DOI: 10.1186/s12894-023-01327-1 -
Pediatrics Jul 2016A high relapse rate after discontinuation of desmopressin treatment of pediatric enuresis is consistently reported. Structured withdrawal strategies have been used to... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
A high relapse rate after discontinuation of desmopressin treatment of pediatric enuresis is consistently reported. Structured withdrawal strategies have been used to prevent relapse.
OBJECTIVE
To assess the efficacy of a structured withdrawal strategy of desmopressin on the relapse-free rate for desmopressin responder pediatric enuresis.
DATA SOURCES
Systematic literature search up to November 2015 on Medline, Embase, Ovid, Science Direct, Google Scholar, Wiley Online Library databases, and related references without language restriction.
STUDY SELECTION
Related clinical trials were summarized for systematic review. Randomized controlled trials on the efficacy of structured versus abrupt withdrawal of desmopressin in sustaining relapse-free status in pediatric enuresis were included for meta-analysis.
DATA EXTRACTION
Eligible studies were evaluated according to Cochrane Collaboration recommendations. Relapse-free rate was extracted for relative risk (RR) and 95% confidence interval (CI). Effect estimates were pooled via the Mantel-Haenszel method with random effect model.
RESULTS
Six hundred one abstracts were reviewed. Four randomized controlled trials (total 500 subjects) of adequate methodological quality were included for meta-analysis. Pooled effect estimates compared with the abrupt withdrawal, structured withdrawal results to a significantly better relapse-free rate (pooled RR: 1.38; 95% CI, 1.17-1.63; P = .0001). Subgroup analysis for a dose-dependent structured withdrawal regimen showed a significantly better relapse-free rate (pooled RR: 1.48; 95% CI, 1.21-1.80; P = .0001).
LIMITATIONS
The small number of studies included in meta-analysis represents a major limitation.
CONCLUSIONS
Structured withdrawal of desmopressin results in better relapse-free rates. Specifically, the dose-dependent structured withdrawal regimen showed significantly better outcomes.
Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Enuresis; Humans; Recurrence; Withholding Treatment
PubMed: 27343233
DOI: 10.1542/peds.2016-0495 -
European Urology Focus Jan 2022Neurological disease can affect the rate of urine production and bladder storage function, increasing nocturia severity, with additional risks if mobility or cognition... (Review)
Review
CONTEXT
Neurological disease can affect the rate of urine production and bladder storage function, increasing nocturia severity, with additional risks if mobility or cognition is impaired.
OBJECTIVE
To conduct a systematic review (SR) of nocturia in neurological diseases and achieve expert consensus for management in clinics without neurologist input.
EVIDENCE ACQUISITION
Four databases were searched from January 2000 to April 2020. A total of 6262 titles and abstracts were screened and 43 studies were included for full-text screening. Eleven of these met the inclusion criteria and two studies were identified through other sources. The nominal group technique (NGT) was used to develop consensus in panel comprising experts and public representation.
EVIDENCE SYNTHESIS
Thirteen studies (seven in Parkinson's disease, five in multiple sclerosis) were included, all undertaken in secondary care. Neurological disease severity was incompletely described, and nocturia severity was generally measured subjectively. NGT consensus supported basic neurological assessment, and the use of bladder diaries where neurological impairment permits. Treatments include pelvic-floor muscle training, review of medications, risk mitigation, improving bowel function, therapy for overactive bladder syndrome (if urgency is reported in association with nocturia episodes), treatment of postvoid residual and desmopressin according to licence. Measures to improve mobility and mitigate risk when using the toilet overnight should be considered. Multifactorial issues such as obstructive sleep apnoea and hypoventilation must be considered.
CONCLUSIONS
Nocturia in neurological disease is complex and lacks a robust evidence base, with very little research done in the primary care context. Guidance should be pragmatic, with reduction of risk a key requirement, until a multidisciplinary evidence base can be developed.
PATIENT SUMMARY
People with a neurological disease can suffer severe sleep disturbance because of the need to pass urine several times overnight (called nocturia). We looked at published research and found very little information to help general practitioners in managing this condition. We assembled a group of experts to develop practical approaches for assessing and treating nocturia in neurological disease.
Topics: Consensus; Humans; Nervous System Diseases; Nocturia; Primary Health Care; Severity of Illness Index
PubMed: 35031351
DOI: 10.1016/j.euf.2021.12.012 -
The Cochrane Database of Systematic... Sep 2015Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug... (Review)
Review
BACKGROUND
Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated.This is an update of a Cochrane review first published in 2013.
OBJECTIVES
To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 18 June 2015.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible.
DATA COLLECTION AND ANALYSIS
No trials matching the selection criteria were eligible for inclusion.
MAIN RESULTS
No trials matching the selection criteria were eligible for inclusion.
AUTHORS' CONCLUSIONS
The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.
Topics: Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Pregnancy; Pregnancy Complications, Hematologic
PubMed: 26350784
DOI: 10.1002/14651858.CD009824.pub3 -
CNS Spectrums Jan 2022Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis... (Review)
Review
BACKGROUND
Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis and urinary incontinence. This side effect can be burdensome and lead to medication nonadherence and psychotic relapse. Evidence to guide treatment of clozapine-induced nocturnal enuresis and urinary incontinence is sparse. We therefore aimed to synthesize the evidence base to guide management for clinicians, patients, and their carers.
METHODS
We systematically searched PubMed, Embase, PsycInfo, CINAHL, and the Cochrane Trial Registry databases from inception to May 2021 for publications on management of clozapine-induced nocturnal enuresis and urinary incontinence using a PROSPERO preregistered search strategy.
RESULTS
We identified 22 case reports and case series describing 74 patients. Interventions included clozapine dose reduction, nonpharmacological treatment, and pharmacological treatments. Among pharmacological treatments, desmopressin, oxybutynin, trihexyphenidyl, tolterodine, imipramine, amitriptyline, ephedrine, pseudoephedrine, aripiprazole, and verapamil were associated with complete resolution of nocturnal enuresis and urinary incontinence. Balancing evidence for effectiveness against risk of adverse effects, we developed a management framework for clozapine-induced nocturnal enuresis and urinary incontinence.
CONCLUSIONS
Following assessment of urological, psychiatric, pharmacological, and common comorbid medical issues, first-line treatments should be nonpharmacological, including bathroom alarms, voiding before bedtime, and nocturnal fluid restriction. If these interventions do not provide adequate relief, aripiprazole should be trialed. Desmopressin may be considered for severe refractory cases, but monitoring for hyponatremia is essential.
PubMed: 35086595
DOI: 10.1017/S1092852922000050 -
International Urology and Nephrology Nov 2019To evaluate the efficacy and safety of desmopressin treatment in women with nocturia. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the efficacy and safety of desmopressin treatment in women with nocturia.
METHODS
The PubMed, EMBASE, ISI web of knowledge, and the Cochrane Controlled Trial Register of Controlled Trials were searched from their inception date till April, 2019. The meta-analysis was performed by Revman 5.3. This review also stratified each outcome by dose (< 25 μg, 25 μg versus > 25 μg) to explore the differences in the dose response for orally disintegrating tablet (ODT).
RESULTS
Seven publications with seven trials were included in this review. The methodological quality of these trials was fair, and four studies had low risk of bias. The number of nocturnal voids per night was significantly decreased by desmopressin when compared to the control [6 trials, Weighted Mean Difference (WMD) = 0.41, P < 0.00001], and the difference between < 25, 25 and > 25 μg dose ODT groups was also significant (P = 0.03). The duration of first sleep period was significantly increased by desmopressin [4 trials, WMD = 66.64, P < 0.00001], and the difference between these three doses ODT was not significant (P = 0.15). Overall, the risk ratios (RR) for 33% responder rate showed significance when compared with desmopressin to controls [3 trials, RR = 1.30, P = 0.0003]. The number of total adverse events was similar in both desmopressin and control groups [5 trials, RR = 0.95, P = 0.59], otherwise, showed no significant difference between different ODT dose groups (P = 0.82).
CONCLUSIONS
Desmopressin had certain efficacy and adequate safety in women with nocturia. The exploration of appropriate dose for female patients, and other influential factors, such as age should be conducted and considered in future.
Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Female; Humans; Nocturia; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31352583
DOI: 10.1007/s11255-019-02242-x -
Clinical Otolaryngology : Official... Mar 2023To examine the efficacy of prophylactic desmopressin versus placebo among patients undergoing functional endoscopic sinus surgery (FESS). (Meta-Analysis)
Meta-Analysis Review
Efficacy of prophylactic pre-operative desmopressin administration during functional endoscopic sinus surgery for chronic rhinosinusitis: A systematic review and meta-analysis of randomised placebo-controlled trials.
OBJECTIVES
To examine the efficacy of prophylactic desmopressin versus placebo among patients undergoing functional endoscopic sinus surgery (FESS).
DESIGN
Systematic review and meta-analysis of randomised controlled trials (RCTs).
SETTING
The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Scopus, and Web of Science databases were screened from inception until 18 March 2022.
PARTICIPANTS
Patients undergoing FESS.
MAIN OUTCOME MEASURES
Primary efficacy endpoints comprised intraoperative blood loss, visual clarity, and operation time. Secondary endpoints comprised side effects. The efficacy endpoints were summarised as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI).
RESULTS
Five RCTs comprising 380 patients (desmopressin = 191 patients and placebo = 189 patients) were included. Collectively, the included RCTs had an overall low risk of bias. The pooled results showed that the mean intraoperative blood loss (n = 5 RCTs, MD = -37.97 ml, 95% CI [-56.97, -18.96], p < .001), 5-point Boezaart scores (n = 2 RCTs, MD = -.97, 95% CI [-1.21, -.74], p < .001), and 10-point Boezaart scores (n = 2 RCTs, MD = -3.00, 95% CI [-3.61, -2.40], p < .001) were significantly reduced in favour of the desmopressin group compared with the placebo group. Operation time did not significantly differ between both groups (n = 5 RCTs, MD = -3.73 min, 95% CI [-14.65, 7.18], p = .50). No patient in both groups developed symptomatic hyponatremia (n = 3 RCTs, 194 patients) or thromboembolic events (n = 2 RCTs, 150 patients).
CONCLUSIONS
Among patients undergoing FESS, prophylactic administration of desmopressin does not correlate with significant clinical benefits. Data on safety is limited. Future research may explore the synergistic antihaemorrhagic efficacy and safety of tranexamic acid (TXA) plus desmopressin versus TXA alone among patients undergoing FESS.
Topics: Humans; Deamino Arginine Vasopressin; Blood Loss, Surgical; Hemostatics; Tranexamic Acid; Randomized Controlled Trials as Topic
PubMed: 36536598
DOI: 10.1111/coa.14020 -
Blood Advances Jun 2022von Willebrand Disease (VWD) is associated with significant morbidity because of excessive bleeding. Early diagnosis and treatment are important to prevent and treat... (Meta-Analysis)
Meta-Analysis
von Willebrand Disease (VWD) is associated with significant morbidity because of excessive bleeding. Early diagnosis and treatment are important to prevent and treat these symptoms. We systematically reviewed the accuracy of any von Willebrand factor (VWF) activity assay in the diagnosis and classification of patients for VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 and the certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. The review included 77 studies that evaluated the use of newer tests of VWF platelet binding activity (VWF:GPIbR, VWF:GPIbM) and VWF:RCo for the diagnosis of VWD (13 studies), VWF propeptide to VWF:Ag ratio, and desmopressin trial for the diagnosis of type 1C VWD (5 studies), VWF multimer analysis and VWF:CB/VWF:Ag ratio for the classification of type 2 VWD (11 studies), genetic testing and ristocetin-induced platelet aggregation to diagnose type 2B VWD (14 studies), genetic testing and FVIII:VWF binding to diagnose type 2N VWD (17 studies). Based on available diagnostic test accuracy, there appear to be comparable test accuracy results between newer tests of platelet binding activity of VWF function and VWF:RCo. The findings of these reviews support VWF multimer analysis or VWF:CB/VWF:Ag to diagnose type 2 VWD. The desmopressin trial test with 1- and 4-hour postinfusion blood work is the test of choice to confirm increased VWF clearance in patients with suspected VWD type 1C. Additionally, genetic testing is most useful in diagnosing type 2B VWD and has a role in the diagnostic algorithm of suspected type 2N VWD.
Topics: Blood Coagulation Tests; Deamino Arginine Vasopressin; Humans; von Willebrand Disease, Type 2; von Willebrand Diseases; von Willebrand Factor
PubMed: 35192687
DOI: 10.1182/bloodadvances.2021005431 -
Autonomic Neuroscience : Basic &... Jan 2023Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic health condition affecting mostly women of childbearing age, and significantly impacting their health and... (Review)
Review
BACKGROUND AND OBJECTIVE
Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic health condition affecting mostly women of childbearing age, and significantly impacting their health and quality of life. It is currently poorly understood with no approved licensed treatments. The aim of this systematic review was to contextualize the symptom burden of POTS, and review factors associated with this burden that may guide future treatments. The specific questions were (1) How does symptom burden in POTS compare to the burden in other long term conditions (LTCs), (2) Which factors are associated with POTS symptom burden, and (3) Which interventions show promise in reducing symptom burden in POTS.
DATABASES AND DATA TREATMENT
Electronic databases (CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, APA PsycArticles, OpenGrey) were searched from inception to January 2022 for observational studies reporting on the association between any biological, psychological or social factors and symptom burden, and randomized controlled trials reporting on interventions for symptom burden in adults with POTS. Two reviewers independently conducted eligibility screening, data extraction and quality assessment. A narrative synthesis was undertaken.
RESULTS/CONCLUSION
5159 entries were screened for eligibility. Twenty-nine studies were included (1372 participants with POTS of a total sample size of 2314, 17 High-, 12 Medium-quality), seventeen were observational and twelve were randomized controlled experimental and intervention trials. Overall methodological quality of the evidence was medium-high but heterogeneity was high and sample sizes modest, allowing moderately robust conclusions. Orthostatic symptom burden was higher in POTS than other LTCs. Serum activity against adrenergic α1 receptors, physical functioning, depression, catastrophizing, prolonged cognitive stress testing and anxiety were significantly associated with symptom burden in medium-high quality studies. Preliminary medium-high quality evidence from predominantly proof-of-concept (n = 11) studies and one 3-month 2 × 2 factorial design trial suggest that compression garments, propranolol, pyridostigmine, desmopressin, and bisoprolol may hold promise in reducing symptom burden. Directions for future research include investigating associated factors over time, the development of complex interventions which address both biological and psychosocial factors associated with symptom burden, and effectiveness trials of these interventions.
SIGNIFICANCE
POTS symptom burden is high, particularly in relation to orthostatic intolerance when compared to other long-term conditions (LTCs). Despite this burden, there are no effectiveness randomized controlled trials of treatment to reduce symptoms in POTS. This review provides a starting point to understanding researched biological and psychosocial factors associated with this burden. There was however inconsistency in the measurement of symptom burden, lowering the confidence of cross-study inferences. A coherent definition of POTS symptom range, severity and impact along with a validated and reliable POTS-specific instrument is currently lacking. A standardized questionnaire to assess POTS symptom burden as a core outcome measure will help clarify future research and clinical practice.
Topics: Adult; Humans; Female; Male; Postural Orthostatic Tachycardia Syndrome; Quality of Life; Self Report; Anxiety; Orthostatic Intolerance; Chronic Disease; Randomized Controlled Trials as Topic
PubMed: 36525900
DOI: 10.1016/j.autneu.2022.103052