Potential clinical applications of current and future oral forms of desmopressin (Review).

Desmopressin is a synthetic analogue of vasopressin and a selective vasopressin receptor 2 agonist. It was first synthesised in 1967 and utilised for its antidiuretic properties. It is also used in bleeding disorders to enhance clotting. Other potential uses of the drug have been reported. The present review aims to provide a broad overview of the literature on potential further uses of oral forms of desmopressin. Key therapeutic areas of interest were identified based on known physiological activities/targets of desmopressin or reports of an effect of desmopressin in the literature. The feasibility of adequate dosing with oral forms of the drug was also considered. Systematic literature searches were carried out using the silvi.ai software for the identified areas, and summaries of available papers were included in tables and discussed. The results of the searches showed that desmopressin has been investigated for its efficacy in a number of areas, including bleeding control, renal colic, the central nervous system and oncology. Evidence suggests that oral desmopressin may have the potential to be of clinical benefit for renal colic and bleeding control in particular. However, further research is needed to clarify its effect in these areas, including randomised controlled studies and studies specifically of oral formulations (and doses). Further research may also yield findings for cancer, cognition and overactive bladder.

Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Nocturnal polyuria in women: results from the EpiNP study.

INTRODUCTION AND HYPOTHESIS: Data from a large US population-based, cross-sectional, epidemiological study (the EpiNP Study) were used to assess the symptoms and bother experienced by women with nocturnal polyuria (NP). METHODS: Consenting participants recruited from an online panel completed the baseline EpiNP survey online (Lower Urinary Tract Symptoms Tool and urological comorbidities). All reporting ≥2 voids/night and a random sample of 100 respondents, each reporting 0 or 1 void/night were asked to complete a 3-day web-based bladder diary recording time, volume, and urgency rating of each void. NP was calculated by the proportion of urine production that occurred during nocturnal hours using a Nocturnal Polyuria Index (NPI33) threshold of >0.33 or nocturnal urine production of >90 ml/h (NUP90). The frequency of participants reporting LUTS and bother was determined by age and NP: idiopathic NP, NP associated with overactive bladder (NPOAB), NP associated with comorbidities (NPCom), and no NP (did not meet NP criteria). RESULTS: A total of 5,290 women completed the baseline survey. Mean age (range) was 54.9 (30-95) years; 1,841 (34.8%) reported ≥2 nocturnal voids. The prevalence of LUTS increased across the lifespan; however, bother associated with each LUTS decreased with increasing age. The percentage of women rating bother by nocturia episodes ≥2 "> somewhat" ranged from 40.3% to 68.3%, with bother ratings highest in the NPOAB and No NP groups. CONCLUSIONS: NP is prevalent in women with considerable bother and is often associated with other urinary symptoms. Multifactorial causes and potential treatments of NP should be considered, particularly at a later age.

The patient burden of nocturnal polyuria in the United States: Results from the epidemiology of nocturnal polyuria (EpiNP) study.

OBJECTIVES: To explore the impact of nocturnal polyuria (NP) on health-related quality of life (HRQoL), work productivity, mental health, fatigue, bother, and daytime sleepiness. MATERIALS AND METHODS: This large-scale, US population-representative epidemiologic study was conducted in two parts: a web-based survey and 3-day bladder diary. Consenting participants completed the baseline Epidemiology of NP (EpiNP) survey online (Lower Urinary Tract Symptoms [LUTS] Tool, comorbidities, burden, and multiple HRQoL measures). Participants who reported ≥2 voids/night, and a random sample of 100 respondents each reporting 0 or 1 void/night, were sent urine measurement containers and asked to complete the 3-day bladder diary. NP was defined as Nocturnal Polyuria Index >0.33 (NPI33) or nocturnal urine production >90 ml/h (NUP90). Five subgroups were created: Idiopathic NP (NP with no underlying cause), NP associated with symptoms of overactive bladder (NPOAB) or bladder outlet obstruction (NPBOO; men only), NP associated with other comorbidities (NPCOM; e.g., diabetes, hypertension, heart disease, sleep apnea), and no NP (did not meet NP criteria). RESULTS: A total of 4893 men and 5297 women completed the EpiNP survey; mean age was 54.4 (SD = 14.7). Significantly greater patient burden (p < 0.0001) was evidenced in the nocturia group (≥2 voids/night) versus no nocturia group (0-1 void/night) on daily impact of nocturia, LUTS Bother, prostate symptoms (men only), work productivity, physical and mental health component scores, depression, fatigue, and daytime sleepiness. NP subgroup analyses showed men in the NPBOO group and women in the NPOAB group reported the greatest impact on LUTS bother, fatigue, physical health, work productivity impairment, daytime sleepiness, and depression (women only). CONCLUSION: This was the first large-scale, epidemiologic study to explore the impact of different forms of NP on patients' HRQoL. Findings demonstrate that NP associated with other urologic or comorbid conditions appears to have greater patient burden than idiopathic NP, in particular for women.

Differences in the Prevalence of Nocturnal Polyuria in the U.S. by Definition: Results from the Epidemiology of Nocturnal Polyuria Study.

PURPOSE: Prevalence data on nocturnal polyuria (NP), nocturia caused by overproduction of urine during sleep, is primarily limited to men and varies by NP definition. This U.S.-representative epidemiological study of men and women ≥30 years old assessed the prevalence of NP. MATERIALS AND METHODS: Consenting participants completed the baseline EpiNP (Epidemiology of Nocturnal Polyuria) survey (eg Lower Urinary Tract Symptoms Tool, comorbidities). All reporting ≥2 voids/night and a target of 100 random respondents reporting 0 or 1 void/night were asked to complete 3-day bladder diaries. NP was defined as nocturnal polyuria index (NPI) >0.33 (NPI33) and nocturnal urine production >90 ml/hour (NUP90). Extrapolated prevalence was stratified by sex and subgroups: idiopathic (without underlying causes), associated with overactive bladder (NPOAB), bladder outlet obstruction (NPBOO; men) and comorbidities. Voided volumes and timing, including first uninterrupted sleep period, were assessed by subgroup. RESULTS: A total of 10,190 individuals completed the baseline survey; mean age (range) was 54.4 (30-95). A total of 3,938 individuals were invited to complete the diary; 1,763 (49.3%) completed 3-day bladder diaries. Urine production (maximum nighttime volume, total volume, nocturnal urine production, nocturia index) was higher in both men and women with idiopathic NP and comorbidities. The median number of nighttime voids was greatest for NPBOO in men and NPOAB in women. Bother associated with nighttime voiding differed by NP subgroup but was highest in NPBOO for men (NPI33: 69.6%; NUP90: 71.1%) and NPOAB for women (NPI33: 67.5%; NUP90: 66.0%). CONCLUSIONS: This population-based NP prevalence study including men and women characterizes NP subgroups and provides insights into nocturia treatment by emphasizing factors influencing urine production versus factors influencing bladder capacity.

The Prevalence of Nocturnal Polyuria in the United States: Results from the Epidemiology of Nocturnal Polyuria Study.

BACKGROUND: The prevalence of nocturnal polyuria (NP), which is passing large volumes of urine during the main sleep period, has been investigated primarily in middle-aged to older men. There is thus a gap in the NP evidence base for women and for younger individuals. OBJECTIVE: To estimate the prevalence of nocturia due to NP in the USA. DESIGN, SETTING, AND PARTICIPANTS: This large epidemiologic study used a US population-representative sample of men and women aged ≥30 yr to assess the prevalence of NP (NCT04125186). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consenting participants completed an online survey (Lower Urinary Tract Symptoms Tool and comorbidities). All who reported two or more voids per night and 100 random respondents each reporting no or one void per night were asked to complete a 3-d bladder diary. Two NP definitions were used: nocturnal urine production >90 ml/h (NUP90) and Nocturnal Polyuria Index >0.33 (NPI33). Crude and population-adjusted prevalence results were calculated from completed diaries for the following subgroups by sex and age: idiopathic NP; NP with overactive bladder (NP-OAB) or bladder outlet obstruction (NP-BOO; men only); NP associated with other comorbidities; and no NP (did not meet the NPI33 or NUP90 definition). RESULTS AND LIMITATIONS: Among the 10,190 respondents who completed the survey, the mean age was 54.4 yr (range 30-95); 3,339 reported two or more nocturnal voids and 1,763 completed the 3-d diary (response rate 49.3%). The adjusted overall NP prevalence was 31.5% among men and 38.5% among women using the NPI33 definition, and 23.8% among men and 18.1% among women using NUP90. The adjusted idiopathic NP prevalence was lower among men (NPI33: 5.2%; NUP90: 1.4%) than among women (NPI33: 9.8%; NUP90: 4.0%). The prevalence of idiopathic NP decreased with age as NP associated with other possible causes increased with age in men (most common, BOO) and women (most common, OAB). CONCLUSIONS: This is the first population-based study of NP prevalence to include men, women, and young adults. NP is common; a multifactorial etiology should be considered, particularly as age increases. PATIENT SUMMARY: In this population-based US study, we examined the frequency of nighttime urination among men and women aged ≥30 y and older. We found that nighttime urination is common among men and women. Many conditions can lead to increased nighttime urination as people age.

Achieving clinically meaningful quality of life benefits in nocturia takes time: Results from a long-term, multicenter phase 3 study of desmopressin in Japanese patients.

OBJECTIVES: To investigate the long-term efficacy, quality of life (QoL), and safety of desmopressin orally disintegrating tablets (ODTs) in Japanese patients with nocturia. METHODS: A long-term, multicenter phase 3 study was conducted that enrolled Japanese male and female patients with nocturia (NCT03051009). Male patients received desmopressin 25- or 50-µg ODTs, and female patients received desmopressin 25-µg ODTs for up to 1 year. The primary endpoint was safety. Secondary endpoints included change from baseline in number of nocturnal voids, time to first awakening to void, and QoL assessments (nocturia-specific zQoL [N-QoL], Insomnia Severity Index [ISI], and Hsu bother score). RESULTS: Overall, 503 patients were enrolled. Reductions from baseline in mean number of nocturnal voids were observed in all treatment groups from week 1 (-0.62 to -1.00), with improvements continuing through week 52 (-1.39 to -1.71). Changes from baseline above or approximating a clinically meaningful improvement were seen by week 52 in the disease-specific N-QoL total score (improved by 11.5-22.6), ISI (improved by -3.9 to -7.1), and Hsu bother scores (improved by -1.5 to -2.0). Adverse events (AEs) were reported in 54.9% of desmopressin-treated patients. Most AEs were mild or moderate in severity. CONCLUSIONS: Desmopressin ODTs (25 and 50 µg) demonstrated long-term efficacy, improved QoL, and were well tolerated in Japanese male and female patients with nocturia treated for up to 1 year. Clinically meaningful improvements in patients' QoL, assessed by N-QoL, sleep quality, and bother, occur later than objective symptom improvements, such as voids.

Psychometric evaluation of the Nocturia Sleep Quality Scale based on data from a prospective observational study.

STUDY OBJECTIVES: The Nocturia Sleep Quality Scale (NSQS), a novel patient-reported outcomes measure, was developed to assess the impact of sleep disturbance from nocturia. The objective of this study was to assess the psychometric properties of the NSQS, including its structure, reliability, and validity. METHODS: Data were collected in the context of a web-based, prospective, longitudinal, observational study. Participants with nocturia were randomized 1:1 to either a group that received sleep hygiene instructions, including instructions to limit liquids at nighttime and empty bladder prior to bedtime, or one that did not receive sleep instructions. All participants were asked to provide responses to the web-based questionnaires from day 1 to day 10. Psychometric analyses, aligned with current regulatory guidance, were conducted to evaluate the daily scores and 3-day average scores of NSQS items and potential composites. Item-level analyses were conducted first, followed by composite-level analyses. RESULTS: The NSQS items and supporting measures demonstrated very slight improvement in patient-perceived sleep disturbance from nocturia over the course of the study. NSQS test-retest reliabilities were generally satisfactory. Correlations between NSQS items and related patient-reported measures tended to support the construct validity of the NSQS, and the known-groups analyses supplied evidence of its discriminating ability. NSQS responsiveness statistics were small. CONCLUSIONS: The NSQS is a reliable and valid measure of the impact of nocturia on patients' sleep. The present analyses lay the psychometric groundwork for the use of the NSQS in future clinical trials to support product approval and labeling claims.

Efficacy and safety of 25 and 50 µg desmopressin orally disintegrating tablets in Japanese patients with nocturia due to nocturnal polyuria: Results from two phase 3 studies of a multicenter randomized double-blind placebo-controlled parallel-group development program.

This study assessed the efficacy and safety of desmopressin orally disintegrating tablets (ODTs) in Japanese males (50 and 25 µg) and females (25 µg) with nocturia due to nocturnal polyuria (NP). Two Phase 3 randomized double-blind placebo-controlled studies of 342 males and 190 females with nocturia due to NP were conducted. The primary endpoint was change from baseline in mean number of nocturnal voids. In addition, time to first awakening to void, nocturnal urine volume, NP index (NPI), and quality of life were assessed during a 12-week treatment period. In males, 50 and 25 µg desmopressin ODTs significantly reduced the number of nocturnal voids by -1.21 (P < .0001) and - 0.96 (P = .0143), respectively, and significantly prolonged the time to first awakening to void by 117.60 minutes (P < .0001) and 93.37 minute (P = .0009), respectively, with no safety concerns. In females, 25 µg desmopressin ODT significantly prolonged the time to first awakening to void by 116.11 minutes (P = .0257), with no safety concerns. The reduction in the number of nocturnal voids (-1.11) was not significantly different compared with placebo (P = .0975). Desmopressin ODTs (50 and 25 µg) were an effective and well-tolerated treatment for nocturia due to NP in Japanese males, and desmopressin ODT 50 µg is an appropriate dose in these patients. For patients who are likely to experience hyponatremia, such as elderly males, starting with 25 µg desmopressin ODT should be considered.

Low-dose Desmopressin Orally Disintegrating Tablet: Suggested Clinically Meaningful Benefit in Patients with Nocturia Due to Nocturnal Polyuria.

BACKGROUND: Clinical benefit has not been evaluated much in patients with nocturia. OBJECTIVE: To assess the clinical benefit of desmopressin orally disintegrating tablet (ODT) in women (25µg) and men (50µg) with nocturia due to nocturnal polyuria (NP). DESIGN, SETTING, AND PATIENTS: Patients with NP from two randomised, placebo-controlled trials in men (CS41) and women (CS40) with two or more nocturnal voids per night were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Change from baseline in nocturnal voids, 33% and 50% responder status (average reduction of ≤33% and ≤50%, respectively, in the mean number of nocturnal voids vs baseline), and percentage of nights with at most one void or no voids (ie, complete response) during 3-mo treatment period were assessed for clinical benefit. Two-sided test (5% significance level) was used for all endpoints. RESULTS AND LIMITATIONS: Demographics and baseline characteristics of patients in CS41 (N=230) and CS40 (N=232) were similar. A greater reduction in the mean number of nocturnal voids was seen with desmopressin ODT in men (treatment difference [TD]: -0.37 voids) compared with women (TD: -0.29 voids). For 33% and 50% responder status, TD with ODT versus placebo were 21% and 12%, respectively, in men, and 12% and 17%, respectively, in women. For the number of nights with at most one void, TDs were 11% and 13% (p<0.009 for both) for men and women, respectively. For complete response, TD was significant in men (TD: 9%, p<0.001). Limitations inherent in this analysis were evident as the data for cotreatments (baseline) and quality of life were not collected. CONCLUSIONS: A stronger treatment effect with desmopressin ODT versus placebo and the magnitude of differences are indicative of clinical benefit in patients with NP. PATIENT SUMMARY: We looked at the clinical benefit of desmopressin ODT in patients with nocturnal polyuria. We conclude that clinical benefit was observed with desmopressin ODT in these patients.

An exploratory pilot study with copeptin as a biomarker for individualizing treatment for nocturnal polyuria.

OBJECTIVE: The aim of the present study was to investigate the use of random copeptin concentrations as possible biomarkers for the differential diagnosis of nocturnal polyuria (NP). METHODS: In all, 111 patients with and without nocturia were enrolled in the study. Patients with a neurogenic bladder and/or those who had undergone bladder or urethral surgery were excluded from the study. All patients completed a 72-hour frequency-volume chart and a renal function profile. A random blood sample was obtained during the day for measurement of plasma copeptin concentrations, osmolality, and serum sodium and creatinine concentrations. The effect of the use of different definitions for NP was evaluated. RESULTS: The median age of the study participants was 61 years, and 48% were female. Copeptin was significantly correlated with urinary and plasma osmolality, as well as free water clearance (r=0.43, 0.56 and -0.38 respectively; P < .001 for all). Study participants were divided into 3 groups: controls (n = 51), those with NP (n = 41), and those with global polyuria (n = 19). Copeptin concentrations were significantly lower in subjects with global polyuria than in those with NP and the control group (2.96 vs 3.97 and 3.94 pM, respectively; P = .008 and .005). There was no significant difference in random daytime copeptin concentrations between the NP and control groups (P = .972). The results differed when other definitions for NP were used (e.g. NPi33 or NUP10). CONCLUSIONS: We could not confirm our hypothesis that patients with NP have lower copeptin concentrations, although random blood sampling is not ideal. Further research is required to determine the use of copeptin in NP, perhaps in the identification of the desmopressin response.

A Danish population-based cohort study of desmopressin use in adults with nocturia or nocturnal enuresis.

OBJECTIVE: This study investigated how desmopressin is prescribed to adults in Denmark. METHODS: All adult users of desmopressin over an 8-year period were identified from the Danish National Prescription Registry. Adult patients with nocturia or nocturnal enuresis (NE) were identified by indication codes for "frequent nocturnal voiding" or "involuntary nocturnal voiding", respectively. Patient demographics, desmopressin formulation and dose, and concomitant medication were investigated. RESULTS: In all, 13 871 adults with nocturia and 2872 adults with chronic (i.e. >10 prescriptions) NE were given 102 547 and 43 712 desmopressin prescriptions, respectively. Across the entire patient cohort, 57% were women and mean patient age was 62 years. Over 40% of prescriptions were to elderly patients (≥65 years), and desmopressin use for adult enuresis increased with age. Orally disintegrating tablets were the most frequently used formulation (57%-65% of prescriptions), and a greater proportion of women than men used low-dose desmopressin (60 µg). Concomitant use of painkillers (opioids: 18%-26.7% of prescriptions; non-steroidal anti-inflammatory drugs: 14.2%-16.4% of prescriptions) and antidepressants (14.4%-18.1% of prescriptions) was common in both conditions, and 5.4%-9.2% of concomitant prescriptions were for overactive bladder medications. CONCLUSIONS: This study provides insights into desmopressin use among Danish adults. Nearly half the prescriptions were to patients aged ≥65 years, despite historical manufacturer recommendations that desmopressin be restricted to patients <65 years of age. NE is considered a childhood condition, but desmopressin use for adult NE increased with age. A greater proportion of desmopressin prescriptions to women than men were for the lowest dose, consistent with greater sensitivity to desmopressin in women.

Low-dose Desmopressin and Tolterodine Combination Therapy for Treating Nocturia in Women with Overactive Bladder: A Double-blind, Randomized, Controlled Study.

OBJECTIVE: Evaluation of safety and efficacy of desmopressin/tolterodine combination therapy in women. METHODS: This double-blind, randomized, proof-of-concept study enrolled 106 patients (≥18 years), with overactive bladder (OAB) and nocturia, with ≥2 nocturnal voids, receiving a 3-month once-daily combination (desmopressin 25 µg, orally-disintegrating tablets [ODT]/tolterodine 4 mg [Detrol® LA]; n = 49) or monotherapy (tolterodine 4 mg/placebo ODT; n = 57). Primary endpoint was change from baseline in mean number of nocturnal voids. Secondary endpoints were change from baseline in nocturnal voided volume, time to first nocturnal void, and quality-of-life. Post-hoc exploratory analysis were performed for patients with and without baseline nocturnal polyuria (NP, n = 47 each). RESULTS: Overall population showed a non-significant reduction in mean number of nocturnal voids with combination versus monotherapy (full analysis set: adjusted treatment contrast [TC], -0.34; P = 0.112). Change in mean nocturnal void volume (TC, -64.16 mL; P = 0.103), mean time to first nocturnal void (TC, 18.00 min; P = 0.385) and Nocturia Impact (NI) Diary© scores were comparable. In post-hoc analysis, NP patients showed a benefit with combination versus monotherapy for nocturnal void volume (P = 0.034) and time to first nocturnal void (P = 0.045), and a non-significant improvement in NI Diary© scores. Safety profile was comparable between treatments. A single transient event of asymptomatic clinically significant hyponatremia in combination group resolved subsequently. CONCLUSION: Low-dose desmopressin could be safely combined with tolterodine for treating nocturia in women with OAB, with a significant benefit in women with NP. Further, prospective validation studies of combination therapy are warranted in mixed NP/OAB population, based on this favorable proof-of-concept finding.

Recent advances in managing and understanding enuresis.

Enuresis, particularly in children during sleep, can be a debilitating condition, affecting the quality of life of the child and his or her family. The pathophysiology of nocturnal enuresis, though not clear, revolves around the inter-related mechanisms of overactive bladder, excessive nocturnal urine production, and sleep fragmentation. The first mechanism is more related to isolated nocturnal voiding, whereas the latter two are more related to nocturnal enuresis, in which circadian variations in arginine vasopressin hormone play a key role. A successful treatment would depend upon appropriately addressing the key factors precipitating nocturnal enuresis, necessitating an accurate diagnosis. Thus, advancements in diagnostic tools and treatment options play a key role in achieving overall success. This review summarizes recent advances in understanding the pathophysiology of nocturnal enuresis, diagnostic tools, and treatment options which can be explored in the future.

The analgesic action of desmopressin in renal colic.

Urolithiasis is a frequent problem causing a significant clinical, psychological and socio-economic burden. Analgesia remains the most important element in the medical treatment of renal colic. Nonetheless, both NSAIDs and opiates have a side effect profile which can cause further complications. As such, the use of desmopressin for renal colic has received increased attention in the last two decades. This paper provides an overview of current evidence on the use of desmopressin as an analgesic strategy in renal colic.

Low-dose desmopressin combined with serum sodium monitoring can prevent clinically significant hyponatraemia in patients treated for nocturia.

OBJECTIVE: To explore risk factors for desmopressin-induced hyponatraemia and evaluate the impact of a serum sodium monitoring plan. SUBJECTS AND METHODS: This was a meta-analysis of data from three clinical trials of desmopressin in nocturia. Patients received placebo or desmopressin orally disintegrating tablet (ODT; 10-100 µg). The incidence of serum sodium <130 mmol/L was recorded by age, sex and dose. Potential predictors of clinically significant hyponatraemia were identified using multivariate analysis in a Cox proportional hazards model. RESULTS: Dose, age, baseline serum sodium level and kidney function, according to estimated GFR clearance, were significant risk factors for hyponatraemia in both sexes; similar to the known risk factors associated with hyponatraemia in the general population. In men, arthritis and use of drugs for bone disease were also predictive of hyponatraemia, while in women, raised monocytes and absence of lipid-modifying drugs increased the risk of hyponatraemia. Use of the proposed monitoring scheme and the minimum effective dose would have omitted all patients with clinically significant hyponatraemia from further treatment. CONCLUSIONS: The incidence of hyponatraemia can be reduced by using minimum effective gender-specific dosing with the ODT formulation of desmopressin (25 µg in women, 50 µg in men). A sodium monitoring plan is proposed whereby baseline sodium must be ≥135 mmol/L (especially important in the elderly), with additional monitoring at week 1 and month 1 for those at elevated risk because they are aged ≥65 years or receiving concomitant medication associated with hyponatraemia. This monitoring plan would help to prevent some at-risk patients developing hyponatraemia; retrospective application of the monitoring plan showed that, once at-risk patients were appropriately screened out, only mild, non-clinically significant hyponatraemia was observed, within ranges of other drugs associated with hyponatraemia and similar to the background prevalence in the treatment population.

Delaying time to first nocturnal void may have beneficial effects on reducing blood glucose levels.

Experimental studies disrupting sleep and epidemiologic studies of short sleep durations indicate the importance of deeper and longer sleep for cardiometabolic health. We examined the potential beneficial effects of lengthening the first uninterrupted sleep period (FUSP) on blood glucose. Long-term data (≥3 months of treatment) were derived from three clinical trials, testing low-dose (10-100 µg) melt formulations of desmopressin in 841 male and female nocturia patients (90 % of which had nocturnal polyuria). We performed post hoc multiple regression with non-fasting blood glucose as dependent variable and the following potential covariates/factors: time-averaged change of FUSP since baseline, age, gender, race, ethnicity, baseline glucose, baseline weight, change in weight, patient metabolic status (normal, metabolic syndrome, type II diabetes), dose, follow-up interval, and time of random glucose sampling. Increases in FUSP resulted in statistically significant reductions in blood glucose (p = 0.0131), even after controlling for all remaining covariates. Per hour increase in time to first void was associated with glucose decreases of 1.6 mg/dL. This association was more pronounced in patients with increased baseline glucose levels (test of baseline glucose by FUSP change interaction: p < 0.0001). Next to FUSP change, other statistically significant confounding factors/covariates also associated with glucose changes were gender, ethnicity, metabolic subgroup, and baseline glucose. These analyses indicate that delaying time to first void may have beneficial effects on reducing blood glucose in nocturia patients. These data are among the first to suggest that improving sleep may have salutary effects on a cardiometabolic measure.

Desmopressin as an adjuvant to opioids or NSAIDs in treatment of renal colic: a nationwide register-based study.

AIMS: Desmopressin has been reported to be effective as an adjuvant to opioids or NSAIDs in management of pain in renal colic; however real-life data are lacking on the utilisation of desmopressin in this patient segment. METHODS: The Danish National Prescription Registry data-linked with Danish National Patient Registry during a 3-year period from 2009 to 2011 was used to study prescriptions for desmopressin in renal colic. RESULTS: We identified 888 desmopressin prescriptions for renal colic, dispensed to 95 patients. The mean treatment period was 159 days, with a large variation up to a maximum of 924 days. Approximately two thirds of patients received dosing instructions to administer the drug 4 times daily to provide 24-h antidiuretic coverage. Among concomitant opioids and NSAIDs, tramadol and ibuprofen were prescribed most frequently. Antidepressants and diuretics were also widely used. A clear sex difference was seen, with female renal colic patients having three times more prescriptions overall than males, and in particular receiving more antidepressants and psychotropic drugs. A total of 4 (4.2%) of the patients experienced hospital admissions because of hyponatraemia or polydipsia during the 3-year period. We confirmed a previous case report that nephrolithiasis could be at least an occasional complication of successful therapy of Central Diabetes Insipidus (CDI) with desmopressin, identifying 12 CDI patients in total, or 2.4% of all Danish CDI patients in that period, who were also treated for renal colic. CONCLUSION: In summary, these real-life prescription data provide exact epidemiological measures on desmopressin utilisation in renal colic.