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Lower Urinary Tract Symptoms May 2024This interim report presents the 12-week results of a post-marketing surveillance evaluating the safety of desmopressin orally disintegrating tablets 25 and 50 μg in...
Long-term safety of desmopressin orally disintegrating tablets in men with nocturia due to nocturnal polyuria: Interim results of a specified drug use-results survey in Japan.
OBJECTIVES
This interim report presents the 12-week results of a post-marketing surveillance evaluating the safety of desmopressin orally disintegrating tablets 25 and 50 μg in Japanese men with nocturia due to nocturnal polyuria.
METHODS
Of the planned study population of 1000 Japanese men receiving desmopressin for the first time for nocturia due to nocturnal polyuria, 971 cases were enrolled. In this interim analysis, 9 cases, including 6 registry violations and 3 cases of unconfirmed desmopressin dosing, were excluded from the 354 case report forms collected and fixed by the end of December 2021, and data up to 12 weeks after administration in 345 cases were defined as the safety analysis set.
RESULTS
The mean age was 74.5 ± 9.9 years and 88.7% of the survey participants were aged ≥65 years. Desmopressin was started at a dose of 25 μg in 153 cases (44.3%). There were 102 adverse drug reactions (ADRs) reported in 71 cases, including 6 serious ADRs in 3 cases (0.9%). The most common ADR was hyponatremia occurring in 29 cases (8.4%). Eight of the hyponatremic cases were asymptomatic. Symptoms were resolved or slightly improved within 4 weeks of onset in 13 of 29 cases of hyponatremia. In addition, hyponatremia occurred in 11 of 217 cases (5.1%), with a serum sodium level before the administration of desmopressin of ≥140 mmol/L, and in 13 of 87 cases (14.9%), with a level of 135-139 mmol/L, and was not measured in 5 hyponatremia cases. Patient characteristics that showed significant differences in the occurrence of hyponatremia included body weight, body mass index, renal function, and pretreatment serum sodium level. Regular monitoring of serum sodium is necessary for early detection of hyponatremia.
CONCLUSIONS
Hyponatremia was the most common ADR when desmopressin orally disintegrating tablets were used to treat nocturia due to nocturnal polyuria over a 12-week period.
Topics: Male; Humans; Middle Aged; Aged; Aged, 80 and over; Nocturia; Japan; Deamino Arginine Vasopressin; Hyponatremia; Polyuria; Drug-Related Side Effects and Adverse Reactions; Substance-Related Disorders; Tablets; Sodium
PubMed: 38616722
DOI: 10.1111/luts.12513 -
The Journal of Clinical Endocrinology... Apr 2024Current guidelines for distinguishing Cushing's disease (CD) from ectopic ACTH secretion (EAS) are questionable, as they use pituitary MRI as first-line investigation...
CONTEXT
Current guidelines for distinguishing Cushing's disease (CD) from ectopic ACTH secretion (EAS) are questionable, as they use pituitary MRI as first-line investigation for all patients, CRH testing is no longer available and they suggest performing inferior petrosal sinus sampling (BIPPS), an invasive and rarely available investigation, in many patients.
OBJECTIVE
To establish non-invasive personalized diagnostic strategies based on the probability of EAS estimated from simple baseline parameters.
DESIGN
Retrospective study.
SETTING
University hospitals.
PATIENTS
247 CD and 36 EAS patients evaluated between 2001 and 2023 in 2 French hospitals. A single-center cohort of 105 Belgian patients served for external validation.
RESULTS
24h-urinary free cortisol (UFC) had the highest area under ROC curve for discrimination of CD from EAS (0·96 [95% CI, 0·92-0·99] in the primary study and 0·99 [95% CI, 0·98-1·00] in the validation cohort). The addition of clinical, imaging and biochemical parameters did not improve EAS prediction over UFC alone, with only BIPPS showing a modest improvement (c-statistic index 0·99 [95% CI, 0·97-1·00]). 3 groups were defined based on baseline UFC: < 3 (group one), 3-10 (group 2) and > 10 x the upper limit of normal (group 3), and were associated with 0%, 6·1% and 66·7% prevalence of EAS, respectively. Diagnostic approaches performed in our cohort support the use of pituitary MRI alone in group one, MRI first followed by neck-to-pelvis CT-scan (npCT) when negative in group 2, and npCT first followed by pituitary MRI when negative in group 3. When not combined with the CRH test, the desmopressin test has limited diagnostic value.
CONCLUSION
UFC accurately predicts EAS and can serve to define personalized and non-invasive diagnostic algorithms.
PubMed: 38609171
DOI: 10.1210/clinem/dgae258 -
Journal of Internal Medicine Jul 2024Cushing's syndrome (CS) is a rare disorder, once exogenous causes have been excluded. However, when diagnosed, the majority of cases are adrenocorticotropic hormone... (Review)
Review
Cushing's syndrome (CS) is a rare disorder, once exogenous causes have been excluded. However, when diagnosed, the majority of cases are adrenocorticotropic hormone (ACTH)-dependent, of which a substantial minority are due to a source outside of the pituitary, ectopic ACTH syndrome (EAS). Differentiating among pituitary-dependent CS, Cushing's disease (CD) and an ectopic source can be problematic. Because non-invasive tests in the evaluation of CS patients often lack adequate sensitivity and specificity, bilateral inferior petrosal sinus sampling (BIPSS), a minimally invasive procedure performed during the investigation of ACTH-dependent CS, can be extremely helpful. BIPSS is considered to be the gold standard for differentiating CD from the EAS. Furthermore, although such differentiation may indeed be challenging, BIPSS is itself a complex investigation, especially in recent times due to the widespread withdrawal of corticotrophin-releasing hormone and its replacement by desmopressin. We review current published data on this investigation and, in the light of this and our own experience, discuss its appropriate use in diagnostic algorithms.
Topics: Humans; Petrosal Sinus Sampling; Diagnosis, Differential; Cushing Syndrome; ACTH Syndrome, Ectopic; Adrenocorticotropic Hormone; Pituitary ACTH Hypersecretion
PubMed: 38606956
DOI: 10.1111/joim.13789 -
Neurourology and Urodynamics Apr 2024To investigate changes in subjective and objective sleep quality after desmopressin administration in patients with nocturia due to nocturnal polyuria (NP) using...
Electroencephalography-based investigation of the effects of oral desmopressin on improving slow-wave sleep time in nocturnal polyuria patients (the DISTINCT study): A single-arm, open-label, single-assignment trial.
AIMS
To investigate changes in subjective and objective sleep quality after desmopressin administration in patients with nocturia due to nocturnal polyuria (NP) using electroencephalography (EEG) and the Pittsburgh sleep quality index (PSQI).
METHODS
Twenty male patients (≥65 years old) with NP participated in this study. The inclusion criteria were nocturnal frequency ≥ 2, NP index (NPi) ≥ 0.33, first uninterrupted sleep period (FUSP) ≤ 2.5 h, serum sodium concentration ≥ 135 mEq/L, and estimated glomerular filtration rate ≥ 50 mL/min/1.73 m. Participants were given 50 μg of desmopressin to be taken orally once daily before bed. The primary endpoint was the change in the duration of slow-wave sleep (nonrapid eye movement sleep stages 3 and 4), as evaluated by EEG 28 days from the baseline. The visual analog scale (VAS) was used as an additional indicator of sleep quality.
RESULTS
Analysis of data from 15 participants (median age: 74.0 [70.5, 76.0] years) revealed that from before to after desmopressin administration, significant decreases occurred in the median nocturnal frequency (3.0 [2.0, 4.0] to 1.5 [1.0, 2.0]) and NPi (0.445 [0.380, 0.475] to 0.360 [0.250, 0.430]). Furthermore, FUSP was significantly prolonged from 120.0 (94.0, 150.0) min to 210.0 (203.8, 311.3) min. Although the VAS scores improved, slow-wave sleep duration and the PSQI global score showed no significant differences (68.50 [47.50, 75.50] and 48.00 [38.00, 66.50]; 5.0 [5.0, 10.0] and 7.0 [5.0, 9.0] min, respectively).
CONCLUSION
Oral administration of 50 μg desmopressin improved nocturnal frequency and FUSP in older individuals with NP but did not significantly enhance sleep quality. In older adults, decreased nighttime urinary frequency may enhance quality of life; however, its influence on objective sleep quality may be limited.
PubMed: 38606623
DOI: 10.1002/nau.25476 -
Research and Practice in Thrombosis and... Feb 2024
PubMed: 38595335
DOI: 10.1016/j.rpth.2024.102369 -
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 -
Plastic and Reconstructive Surgery Apr 2024Persistent intraoperative bleeding, excessive post-operative ecchymosis, epistaxis, or blood collection in the supratip area increases the complexity of rhinoplasty,...
BACKGROUND
Persistent intraoperative bleeding, excessive post-operative ecchymosis, epistaxis, or blood collection in the supratip area increases the complexity of rhinoplasty, causing suboptimal outcomes. We present an intraoperative bleeding management algorithm developed by the senior author (B.G.) based on 43 years of experience and assess its efficacy in achieving hemostatic control through 103 consecutive cases.
METHODS
A retrospective chart review was conducted on 103 consecutive patients who had undergone septorhinoplasty by a single surgeon. Patient demographics, coagulopathies, medications, diet, intraoperative use of tranexamic acid (TXA), desmopressin (DDAVP), Vitamin K, and post-operative complications were reviewed.
RESULTS
Twenty-six (25.2%) patients did not receive intraoperative hemostatic agents. Twenty-six (25.2%) patients required TXA only, three (2.91%) patients were given DDAVP only, one (0.97%) patient received Vitamin K only, and forty-six (44.7%) patients required both TXA and DDAVP. One (0.97%) patient needed TXA, DDAVP, and vitamin K. Intraoperative bleeding was controlled in all patients. One patient with known factor 11 deficiency received both TXA and DDAVP intraoperatively but did not require fresh frozen plasma. Intraoperative bleeding was controlled by first administering 10 mg/kg of TXA intravenously, followed by DDAVP with a maximum dose of 0.3 mcg if needed, and 10 mg of Vitamin K if bleeding persisted. Patients with known type I or IIa Von Willebrand disease received DDAVP preoperatively. No patient experienced post-operative epistaxis, thromboembolism, or other associated complications.
CONCLUSION
The algorithm of TXA, DDAVP, and Vitamin K is effective in controlling excessive intraoperative bleeding, post-operative ecchymosis, and epistaxis.
LEVEL OF EVIDENCE
IV.
PubMed: 38589989
DOI: 10.1097/PRS.0000000000011462 -
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 -
Acta Neurochirurgica Apr 2024The ovine corticotropin-releasing hormone (oCRH) stimulation test has been routinely used in the diagnostic work-up of ACTH-dependent Cushing syndrome (CS). With oCRH...
PURPOSE
The ovine corticotropin-releasing hormone (oCRH) stimulation test has been routinely used in the diagnostic work-up of ACTH-dependent Cushing syndrome (CS). With oCRH currently being out-of-stock in Europe, we aimed at evaluating the diagnostic performance of inferior petrosal sinus sampling (IPSS) without oCRH stimulation.
METHODS
We compared the values of 40 patients with ACTH-dependent CS and negative MRI findings in whom ACTH was measured before and after oCRH stimulation.
RESULTS
The ratio of central-to-peripheral ACTH measurement (IPS:P) before the combined 3, 5, and 10 min of oCRH stimulation yielded diminished sensitivity (85% vs. 97%), alongside markedly decreased specificity (57% vs. 71%), as well as reduced positive and negative predictive values (90% vs. 94% and 44% vs. 83%), respectively.
CONCLUSIONS
With the current drug shortages in Europe, ACTH measurements without oCRH stimulation in IPSS cannot be recommended. Thus, we call for desmopressin or the commercially available human CRH as a potential alternative in the confirmation of ACTH excess by IPSS in equivocal MRI findings.
Topics: Humans; Sheep; Animals; Cushing Syndrome; Corticotropin-Releasing Hormone; Petrosal Sinus Sampling; Adrenocorticotropic Hormone; Predictive Value of Tests
PubMed: 38565838
DOI: 10.1007/s00701-024-06058-2 -
Scientific Reports Mar 2024This randomized controlled trial aimed to evaluate the safety and efficacy of proactive versus reactive desmopressin (DDAVP) strategies in treating severe symptomatic... (Randomized Controlled Trial)
Randomized Controlled Trial
This randomized controlled trial aimed to evaluate the safety and efficacy of proactive versus reactive desmopressin (DDAVP) strategies in treating severe symptomatic hyponatremia. Conducted from June 20, 2022, to February 20, 2023, it involved 49 patients with serum sodium levels below 125 mmol/L. Patients were assigned to either the proactive group, receiving DDAVP immediately upon diagnosis, or the reactive group, receiving DDAVP only if the serum sodium level tended to be overcorrected. The primary outcome was the incidence of overcorrection. The study revealed no significant difference in the overcorrection incidence between the proactive (16.7%) and reactive (28%) groups (p = 0.54). The change in serum sodium levels at 1, 6, 12, and 24 h were not different, however, at 48 h, the proactive group exhibited a higher but still safe change in serum sodium levels compared to the reactive group (10.3 ± 3.6 mmol/L vs. 7.7 ± 3.6 mmol/L, p = 0.013). Other parameters including time to symptom improvement, total intravenous fluid administered, DDAVP dose, urine volume, hospital stay duration, osmotic demyelination syndrome incidence, and 28-day mortality did not significantly differ between the groups. In conclusion, our findings suggest that there was no significant disparity in overcorrection rates between proactive and reactive DDAVP strategies for treating severe symptomatic hyponatremia. However, further large-scale studies are warranted to validate these results.
Topics: Humans; Hyponatremia; Deamino Arginine Vasopressin; Demyelinating Diseases; Hospitals; Sodium
PubMed: 38553491
DOI: 10.1038/s41598-024-57657-z