-
In Vivo (Athens, Greece) 2023Effect predictors of desmopressin for nocturia associated with nocturnal polyuria are understudied. Herein, we investigated the effects of desmopressin on sleep and...
BACKGROUND/AIM
Effect predictors of desmopressin for nocturia associated with nocturnal polyuria are understudied. Herein, we investigated the effects of desmopressin on sleep and patient quality of life. We defined cases in which administration of desmopressin led to hours of undisturbed sleep (HUS) ≥3 hours as "marked response cases" and examined predictive factors of desmopressin treatment response.
PATIENTS AND METHODS
Our study included 129 patients who were administered desmopressin 50 μg for nocturia associated with nocturnal polyuria at our hospital. Efficacy and safety of desmopressin were examined using bladder diaries, International Prostate Symptom Score, Overactive Bladder Symptom Score, Athens Insomnia Scale, Patient Global Impression of Improvement (PGI-I) score, physical examinations, blood tests, and body composition analyzers, and the predictors of desmopressin efficacy were investigated.
RESULTS
Significant improvements in all endpoints were observed from the early stage onward after desmopressin treatment compared with before treatment. After treatment, HUS was significantly longer in patients with good PGI-I scores, which indicated patient satisfaction. Variation in nocturnal micturition frequency did not affect the improvement in patient satisfaction. Examination of cases defined as "marked response cases" showed that the mean night-time urine volume was an independent predictor of treatment response.
CONCLUSION
Desmopressin can improve patients' quality of life and sleep by extending HUS. This suggests that desmopressin may be effective in patients with high mean night-time urine volumes based on their bladder diary.
Topics: Male; Humans; Nocturia; Polyuria; Deamino Arginine Vasopressin; Antidiuretic Agents; Quality of Life
PubMed: 37905667
DOI: 10.21873/invivo.13383 -
Journal of Pediatric Urology Apr 2024The voiding chart is part of the initial evaluation of enuresis, since the data gathered this way are assumed to carry predictive information. However, there is little...
BACKGROUND
The voiding chart is part of the initial evaluation of enuresis, since the data gathered this way are assumed to carry predictive information. However, there is little evidence that the voiding chart actually does predict therapy response. Lundmark & Nevéus performed a pilot investigation in 2020 and found that anamnestic and voiding chart data did not predict response to second-line therapies. This study aims at evaluating whether these findings could be replicated.
PATIENTS AND METHODS
This is an evaluation of clinical practice. All patients in a tertiary outpatient clinic with enuresis resistant to first-line therapy (i.e. the enuresis alarm and desmopressin medication) during the evaluation period were included in the study. Baseline anamnestic data focused on bladder and bowel habits, were gathered and the families were instructed to complete a voiding chart including measurements of nocturnal urine production. The children were then treated in accordance with international guidelines, which are anticholinergics and antidepressants as second- and third-line treatment, respectively. Desmopressin was added if needed.
RESULTS
In total, 70 patients were included. At the end of the study 37 of these patients were dry, 11 patients were still wetting their beds and 22 patients were lost to follow-up. Of the dry patients 21 became dry on anticholinergics (and/or mirabegron, with or without desmopressin), five on tricyclic antidepressants (with or without desmopressin), seven after a new attempt with the alarm and five became dry spontaneously. The only statistically significant differences between responders and non-responders to the various treatments were that children responsive to anticholinergics had harder and more infrequent stools (p = 0.04 and p = 0.03, respectively).
CONCLUSION
This study found that anamnestic and voiding chart data do not predict response to treatment in children with therapy-resistant enuresis. Because of this and the fact that we lose some children who need our help by demanding that they complete a voiding chart before initiating treatment, we question the use of this instrument in the evaluation of therapy-resistant enuresis.
Topics: Child; Humans; Deamino Arginine Vasopressin; Enuresis; Nocturnal Enuresis; Urinary Bladder; Cholinergic Antagonists
PubMed: 37977907
DOI: 10.1016/j.jpurol.2023.10.036 -
Acta Bio-medica : Atenei Parmensis Dec 2023Nocturnal enuresis (NE) is a common condition in the pediatric age. NE is defined as an intermittent bedwetting with any frequency while sleeping in children. NE is...
Nocturnal enuresis (NE) is a common condition in the pediatric age. NE is defined as an intermittent bedwetting with any frequency while sleeping in children. NE is classified into primary form (patient never had achieved nocturnal urinary control) or secondary form (children with a period of 6 consecutive months of night-time urinary control before incontinence, which is generally associated with organic or psychological causes). Moreover, NE could be monosymptomatic (MNE) or non-monosymptomatic (NMNE), depending on the presence of daytime incontinence or any other lower urinary tract symptoms (LUTS). We report a 7-year- old female with a history of recent onset of sphincter troubles and recurrent low urinary tract infections. She presented urinary urgency associated to daytime incontinence, bedwetting almost every night in the previous 3 months and sometimes encopresis. The physical and neurological examination was silent, no psychological or social problem intercurred. As first approach, she was treated with deamino-delta-D-arginine vasopressin (dDAVP) 120 mcg associated with oxybutynin 5 mg and educational therapy, for 3 months without benefits. So, she underwent a magnetic resonance imaging (MRI) of the spinal cord, that highlighted the presence of hydrosyringomyelia from D6 to D10, lipoma of the terminal filum and the presence of synovial cyst between L5-S1. This case remarks that in secondary NMNE, any possible organic cause must be investigated.
Topics: Child; Humans; Female; Nocturnal Enuresis; Physical Examination
PubMed: 38054679
DOI: 10.23750/abm.v94i6.14931 -
Reviews in Endocrine & Metabolic... Jun 2024Arginine vasopressin deficiency (AVP-D) is one of the main entities of the polyuria-polydipsia syndrome. Its correct diagnosis and differentiation from the other two... (Review)
Review
Arginine vasopressin deficiency (AVP-D) is one of the main entities of the polyuria-polydipsia syndrome. Its correct diagnosis and differentiation from the other two causes - AVP resistance and primary polydipsia - is crucial as this determines the further management of these patients.Over the last years, several new diagnostic tests using copeptin, the stable surrogate marker of AVP, have been introduced. Among them, hypertonic saline stimulated copeptin was confirmed to reliably and safely improve the diagnostic accuracy to diagnose AVP-D. Due to its simplicity, arginine stimulated copeptin was put forward as alternative test procedure. Glucagon-stimulated copeptin also showed promising results, while the oral growth hormone secretagogue Macimorelin failed to provide a sufficient stimulus. Interestingly, an approach using machine learning techniques also showed promising results concerning diagnostic accuracy.Once AVP-D is diagnosed, further workup is needed to evaluate its etiology. This will partly define the further treatment and management. In general, treatment of AVP-D focuses on desmopressin substitution, with oral formulations currently showing the best tolerance and safety profile. However, in addition to desmopressin substitution, recent data also showed that psychopathological factors play an important role in managing AVP-D patients.
Topics: Humans; Arginine Vasopressin; Polyuria; Polydipsia; Deamino Arginine Vasopressin; Glycopeptides
PubMed: 38087160
DOI: 10.1007/s11154-023-09862-w -
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 -
Frontiers in Bioscience (Scholar... Dec 2023Diarrhea is the increase in the excretion of human water; meanwhile, fisetin, a bioactive flavonol molecule, is widely used in the treatment/prevention of...
BACKGROUND
Diarrhea is the increase in the excretion of human water; meanwhile, fisetin, a bioactive flavonol molecule, is widely used in the treatment/prevention of gastrointestinal disorders. The purpose of this study is to investigate the anti-diarrheal activity of fisetin by restoring kidney function, antioxidant activity, inflammatory markers, Na+/K+-ATPase level, apoptosis, and protein content in diarrheal rats.
METHODS
A total of 36 male rats were distributed into two groups (18 rats/group): normal and diarrheal. The normal group was further divided into three subgroups (6 rats/subgroup): Control, fisetin, and desmopressin drug subgroups, consisting of normal rats orally treated once a day for 4 weeks with 1 mL distilled water, 50 mg/kg fisetin, and 1 mg/kg desmopressin drug, respectively. A lactose diet containing 35% lactose was fed to the normal rats for a month. The diarrheal rats were also divided into three subgroups (6 rats/subgroup): diarrheal rats, diarrheal rats + fisetin, and diarrheal rats + desmopressin drug groups, whereby the diarrheal rats were orally treated once a day for 4 weeks with 1 mL distilled water, 50 mg/kg fisetin, and 1 mg/kg desmopressin drug, respectively.
RESULTS
Fisetin significantly decreased serum urea (41.20 ± 2.6-29.74 ± 2.65), creatinine (1.43 ± 0.05-0.79 ± 0.06), and urinary volume (1.30 ± 0.41-0.98 ± 0.20), while significantly increasing kidney weight (0.48 ± 0.03-0.67 ± 0.07), sodium, potassium, and chloride balance in both serum and urine. Fisetin significantly increased the antioxidant activity (superoxide dismutase (1170 ± 40-3230 ± 50), glutathione peroxidase (365 ± 18-775 ± 16), catalase (0.09 ± 0.03-0.14 ± 0.06), and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity (8.6 ± 1.31-10.5 ± 1.25), while significantly decreasing malondialdehyde (19.38 ± 0.54-9.54 ± 0.83), conjugated dienes (1.86 ± 0.24-1.64 ± 0.19), and oxidative index (0.62 ± 0.04-0.54 ± 0.05)), alongside the inflammatory markers (tumor necrosis factor-α (65.2 ± 2.59-45.3 ± 2.64), interleukin-1β, interleukin-6 (107 ± 4.5-56.1 ± 7.2), and interleukin-10) in the diarrheal rats to values approaching the control values. Fisetin also restored the Na+/K+-ATPase level, apoptosis, protein content, and kidney architecture in diarrheal rats to be near the control group.
CONCLUSIONS
Fisetin treated diarrhea in rats by restoring kidney function, antioxidant activity, inflammatory markers, apoptosis, proteome content, and histology.
Topics: Humans; Rats; Male; Animals; Antioxidants; Deamino Arginine Vasopressin; Lactose; Rats, Sprague-Dawley; Kidney; Oxidative Stress; Flavonols; Inflammation; Apoptosis; Diarrhea; Adenosine Triphosphatases; Water
PubMed: 38163954
DOI: 10.31083/j.fbs1504014 -
Frontiers in Pediatrics 2023The desmopressin combined with anticholinergic agents for the treatment of nocturnal enuresis (NE) remains controversial. This meta-analysis assesses the efficacy and... (Review)
Review
BACKGROUND
The desmopressin combined with anticholinergic agents for the treatment of nocturnal enuresis (NE) remains controversial. This meta-analysis assesses the efficacy and safety of desmopressin compared with desmopressin plus anticholinergic agents for the treatment of NE.
METHODS
We searched MEDLINE, Embase, and Cochrane Controlled Trials Register databases for RCTs published for the treatment of NE. Systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. This meta-analysis used RevMan v.5.1.0 to analyze data.
RESULTS
Eight studies involving 600 patients (293 in the combination group and 307 in the desmopressin group) contained meaningful data. The results were as follows: after one month of treatment, compared with the desmopressin monotherapy group, the combination group was significantly better in treating NE in FR (full responders, = 0.003), FR + PR (partial responders) ( < 0.0001), and the mean number of wet nights ( = 0.004); also, the combination group had a better effect in FR ( < 0.00001), FR + PR ( = 0.02) and the mean number of wet nights ( = 0.04) after 3 months' treatment. For side effects, combination therapy does not cause more adverse events in treating NE ( = 0.42).
CONCLUSIONS
This study elucidates that desmopressin combined with the anticholinergic agent was demonstrated to be more effective in treating NE than desmopressin monotherapy, and the anticholinergic agent does not increase the risk of adverse events (AEs).
PubMed: 37928358
DOI: 10.3389/fped.2023.1242777 -
Nature Reviews. Endocrinology May 2024Polyuria-polydipsia syndrome can be caused by central diabetes insipidus, nephrogenic diabetes insipidus or primary polydipsia. To avoid confusion with diabetes... (Review)
Review
Polyuria-polydipsia syndrome can be caused by central diabetes insipidus, nephrogenic diabetes insipidus or primary polydipsia. To avoid confusion with diabetes mellitus, the name 'central diabetes insipidus' was changed in 2022 to arginine vasopressin (AVP) deficiency and 'nephrogenic diabetes insipidus' was renamed as AVP resistance. To differentiate the three entities, various osmotic and non-osmotic copeptin-based stimulation tests have been introduced in the past decade. The hypertonic saline test plus plasma copeptin measurement emerged as the test with highest diagnostic accuracy, replacing the water deprivation test as the gold standard in differential diagnosis of the polyuria-polydipsia syndrome. The mainstay of treatment for AVP deficiency is AVP replacement with desmopressin, a synthetic analogue of AVP specific for AVP receptor 2 (AVPR2), which usually leads to rapid improvements in polyuria and polydipsia. The main adverse effect of desmopressin is dilutional hyponatraemia, which can be reduced by regularly performing the so-called desmopressin escape method. Evidence from the past few years suggests an additional oxytocin deficiency in patients with AVP deficiency. This potential deficiency should be further evaluated in future studies, including feasible provocation tests for clinical practice and interventional trials with oxytocin substitution.
PubMed: 38693275
DOI: 10.1038/s41574-024-00985-x -
International Journal of Molecular... Jan 2024Drugs based on peptides and proteins (PPs) have been widely used in medicine, beginning with insulin therapy in patients with diabetes mellitus over a century ago.... (Review)
Review
Drugs based on peptides and proteins (PPs) have been widely used in medicine, beginning with insulin therapy in patients with diabetes mellitus over a century ago. Although the oral route of drug administration is the preferred one by the vast majority of patients and improves compliance, medications of this kind due to their specific chemical structure are typically delivered parenterally, which ensures optimal bioavailability. In order to overcome issues connected with oral absorption of PPs such as their instability depending on digestive enzymes and pH changes in the gastrointestinal (GI) system on the one hand, but also their limited permeability across physiological barriers (mucus and epithelium) on the other hand, scientists have been strenuously searching for novel delivery methods enabling peptide and protein drugs (PPDs) to be administered enterally. These include utilization of different nanoparticles, transport channels, substances enhancing permeation, chemical modifications, hydrogels, microneedles, microemulsion, proteolytic enzyme inhibitors, and cell-penetrating peptides, all of which are extensively discussed in this review. Furthermore, this article highlights oral PP therapeutics both previously used in therapy and currently available on the medical market.
Topics: Humans; Gastrointestinal Agents; Insulin; Cell-Penetrating Peptides; Biological Availability; Hydrogels
PubMed: 38255888
DOI: 10.3390/ijms25020815 -
Frontiers in Endocrinology 2023The differential diagnosis between Cushing's disease (CD) and ectopic ACTH syndrome (EAS) is complex, and bilateral inferior petrosal sinus sampling (BIPSS) is...
INTRODUCTION
The differential diagnosis between Cushing's disease (CD) and ectopic ACTH syndrome (EAS) is complex, and bilateral inferior petrosal sinus sampling (BIPSS) is considered the gold-standard test. However, BIPSS with corticotropin-releasing hormone (CRH) stimulation is rarely available.
OBJECTIVE
This retrospective cohort study aimed to assess the accuracy of the inferior petrosal sinus to peripheral ACTH gradient (IPS:P) before and after desmopressin stimulation for the differential diagnosis of ACTH-dependent Cushing's syndrome (CS), applying different cutoff values.
METHODS
A total of 50 patients (48 with CD and 2 with EAS) who underwent BIPSS were included in this study. The sensitivity and specificity of IPS:P in BIPSS before and after desmopressin stimulation were evaluated. Various cutoff values for IPS:P were examined to determine their diagnostic accuracy.
RESULTS
Using the traditional IPS:P cutoff, the sensitivity was 85.1% before stimulation, 89.6% after stimulation, and a combined sensitivity of 91.7%. Applying cutoff values of IPS:P >1.4 before and >2.8 after stimulation, the sensitivity was 87.2% and 89.6%, respectively, with a combined sensitivity of 91.7%. Receiver operating characteristic (ROC) curve analysis determined optimal cutoff values of 1.2 before stimulation and 1.57 after stimulation, resulting in a sensitivity of 93.6% and 93.8%, respectively, with a combined sensitivity of 97.9%. Specificity remained at 100% throughout all analyses. Among the 43 patients who responded positively to stimulation, 42 (97.7%) did so within the first three minutes, and all 43 (100%) did so within the first five minutes. None of the assessed clinical variables predicted the ACTH response to stimulation in BIPSS with statistical significance.
DISCUSSION
ACTH stimulation with desmopressin during BIPSS improves the accuracy of IPS:P, making it a valuable tool for investigating ACTH-dependent Cushing's syndrome. Considering the low risk of complications, we recommend the use of desmopressin stimulation during BIPSS for the differential diagnosis of ACTH-dependent CS.
Topics: Humans; ACTH Syndrome, Ectopic; Adrenocorticotropic Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Petrosal Sinus Sampling; Pituitary ACTH Hypersecretion; Retrospective Studies
PubMed: 37600715
DOI: 10.3389/fendo.2023.1224001