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.

First uninterrupted sleep period in children and adolescents with nocturnal enuresis: Added value in diagnosis and follow-up during therapy.

BACKGROUND: The first uninterrupted sleep period (FUSP, time up to the first episode of enuresis/nocturia after falling asleep) is a frequently investigated parameter in adults with nocturia, as it correlates with quality of life. However, it has not been included in pediatric enuresis studies. AIM: Investigate FUSP, circadian renal water and sodium handling, as well as sleep quality before and after desmopressin therapy in enuresis. MATERIALS AND METHODS: We conducted a post hoc analysis of a prospective study in 30 treatment-naïve children with enuresis who underwent a video-polysomnography and a 24-h urine concentration profile before and after 6 months of desmopressin therapy. We analyzed FUSP, periodic limb movements in sleep (PLMS), and arousal indexes and their correlations with the urinary parameters. RESULTS: Sixteen children with a mean age of 10.9 ± 3.1 years had full registrations and were included in this subanalysis. After therapy, FUSP was significantly longer (p < 0.001), and the PLMS index was lower (p = 0.023). Significant differences in the circadian rhythm of diuresis (night/day diuresis, p = 0.041), nocturnal urinary osmolality (p = 0.009), and creatinine (p = 0.001) were found, demonstrating the increase of urinary concentration overnight by desmopressin, as well as a significant antidiuretic effect (diuresis [p = 0.013] and diuresis rate (p = 0.008). There was no correlation between the difference of FUSP, PLMS index, and urinary parameters. Nevertheless, despite this study being underpowered, there are indications of a correlation between nocturnal diuresis and diuresis rate. RESULTS: Our results support the need for further research regarding FUSP in children with enuresis, in accordance with nocturia studies in adults, as this parameter could be valuable in the follow-up and evaluation of therapeutic strategies for enuresis.

Effect of Treadmill Perturbation-Based Balance Training on Fall Rates in Community-Dwelling Older Adults: A Randomized Clinical Trial.

Importance: Falls are common and the leading cause of injuries among older adults, but falls may be attenuated by the promising and time-efficient intervention called perturbation-based balance training (PBT). Objective: To evaluate the effects of a 4-session treadmill PBT intervention compared with regular treadmill walking on daily-life fall rates among community-dwelling older adults. Design, Setting, and Participants: This 12-month, assessor-blinded randomized clinical trial was conducted from March 2021 through December 2022 in Aalborg University in Denmark. Participants were community-dwelling adults 65 years or older and were able to walk without a walking aid. Participants were randomized to either PBT (intervention group) or treadmill walking (control group). Data analyses were based on the intention-to-treat principle. Interventions: Participants who were randomized to the intervention group underwent four 20-minute sessions of PBT, including 40 slip, trip, or mixed slip and trip perturbations. Participants who were randomized to the control group performed four 20-minute sessions of treadmill walking at their preferred speed. The 3 initial training sessions were completed within the first week, whereas the fourth session was performed after 6 months. Main Outcomes and Measures: Primary outcome was the daily-life fall rates that were collected from fall calendars for the 12 months after the third training session. Secondary outcomes were the proportion of participants with at least 1 fall and recurrent falls, time to first fall, fall-related fractures, fall-related injuries, fall-related health care contacts, and daily-life slip and trip falls. Results: A total of 140 highly functioning, community-dwelling older adults (mean [SD] age, 72 [5] years; 79 females [56%]), 57 (41%) of whom had a fall in the past 12 months, were included in this trial. Perturbation training had no significant effect on daily-life fall rate (incidence rate ratio [IRR]: 0.78; 95% CI, 0.48-1.27) or other fall-related metrics. However, there was a significant reduction in laboratory fall rates at the posttraining assessment (IRR, 0.20; 95% CI, 0.10-0.41), 6-month follow-up (IRR, 0.47; 95% CI, 0.26-0.86), and 12-month follow-up (IRR, 0.37; 95% CI, 0.19-0.72). Conclusions and Relevance: Results of this trial showed that participants who received an 80-minute PBT intervention experienced a statistically nonsignificant 22% reduction in daily-life fall rates. There was no significant effect on other daily-life fall-related metrics; however, a statistically significant decrease in falls was found in the laboratory setting. Trial Registration: ClinicalTrials.gov Identifier: NCT04733222.

Validity and intrarater reliability of a novel device for assessing Plantar flexor strength.

INTRODUCTION: Plantar flexor weakness is an identified prospective factor for developing Achilles tendinopathy. Various authors have reported relationships between symptoms and weakness of this muscle group. Despite this relationship, many clinicians and researchers fail to examine Plantar flexor strength due to the cumbersome, stationary and expensive nature of an isokinetic dynamometer (IKD), known as the "Gold Standard". This study examined the validity and reliability of a fast, easy and portable device for assessing plantarflexion. METHODS: Validity between the Cybex NORM® by Humac and the C-Station by Fysiometer was explored using Pearson correlation coefficient. Participants were randomly selected to start in the Cybex NORM® or the FysioMeter C-Station. Intra-rater reliability on the C-station was investigated by test-retest two days apart using Intraclass Correlation Coefficient (ICC). All testing involved isometric maximal force of the soleus muscle with the knee at 90 degrees flexion. RESULTS: 40 healthy university students were recruited for the validity part, while 65 healthy university students were recruited for the reliability part of the study. The mean peak torque on the IKD was 198.55Nm (SD 94.45) versus 1443.88 (412.82)N on the C-Station. The results of the Pearson correlation revealed an r-value of r = 0.72 with a 95%CI 0.52-0.84. The test re-test reliability was calculated as an ICC of 0.91 with a (95%CI 0.86-0.94). CONCLUSIONS: The C-Station by Fysiometer appears to provide valid measures and have excellent reliability for Plantar flexor isometric strength. It would appear suitable for both clinical and research work.

Impact of Antibiotic Treatment on the Gut Microbiome and its Resistome in Hematopoietic Stem Cell Transplant Recipients.

Antibiotic-resistant bacterial infections are increasingly an issue in allogenic hematopoietic stem cell transplant patients. How antibiotic treatment impacts antibiotic resistance in the human gut microbiome remains poorly understood in vivo. Here, a total of 577 fecal samples from 233 heavily antibiotic-treated transplant patients were examined using high-resolution prescription data and shotgun metagenomics. The 13 most frequently used antibiotics were significantly associated with 154 (40% of tested associations) microbiome features. Use of broad-spectrum ß-lactam antibiotics was most markedly associated with microbial disruption and increase in resistome features. The enterococcal vanA gene was positively associated with 8 of the 13 antibiotics, and in particular piperacillin/tazobactam and vancomycin. Here, we highlight the need for a high-resolution approach in understanding the development of antibiotic resistance in the gut microbiome. Our findings can be used to inform antibiotic stewardship and combat the increasing threat of antibiotic resistance.

Chest x-ray imaging score is associated with severity of COVID-19 pneumonia: the MBrixia score.

Spatial resolution in existing chest x-ray (CXR)-based scoring systems for coronavirus disease 2019 (COVID-19) pneumonia is low, and should be increased for better representation of anatomy, and severity of lung involvement. An existing CXR-based system, the Brixia score, was modified to increase the spatial resolution, creating the MBrixia score. The MBrixia score is the sum, of a rule-based quantification of CXR severity on a scale of 0 to 3 in 12 anatomical zones in the lungs. The MBrixia score was applied to CXR images from COVID-19 patients at a single tertiary hospital in the period May 4th-June 5th, 2020. The relationship between MBrixia score, and level of respiratory support at the time of performed CXR imaging was investigated. 37 hospitalized COVID-19 patients with 290 CXRs were identified, 22 (59.5%) were admitted to the intensive care unit and 10 (27%) died during follow-up. In a Poisson regression using all 290 MBrixia scored CXRs, a higher MBrixia score was associated with a higher level of respiratory support at the time of performed CXR. The MBrixia score could potentially be valuable as a quantitative surrogate measurement of COVID-19 pneumonia severity, and future studies should investigate the score's validity and capabilities of predicting clinical outcomes.

Pre-Transplant Prediction of Acute Graft-versus-Host Disease Using the Gut Microbiome.

Gut microbiota is thought to influence host responses to allogeneic hematopoietic stem cell transplantation (aHSCT). Recent evidence points to this post-transplant for acute graft-versus-host disease (aGvHD). We asked whether any such association might be found pre-transplant and conducted a metagenome-wide association study (MWAS) to explore. Microbial abundance profiles were estimated using ensembles of Kaiju, Kraken2, and DeepMicrobes calls followed by dimensionality reduction. The area under the curve (AUC) was used to evaluate classification of the samples (aGvHD vs. none) using an elastic net to test the relevance of metagenomic data. Clinical data included the underlying disease (leukemia vs. other hematological malignancies), recipient age, and sex. Among 172 aHSCT patients of whom 42 developed aGVHD post transplantation, a total of 181 pre-transplant tool samples were analyzed. The top performing model predicting risk of aGVHD included a reduced species profile (AUC = 0.672). Beta diversity (37% in Jaccard's Nestedness by mean fold change, p < 0.05) was lower in those developing aGvHD. Ten bacterial species including Prevotella and Eggerthella genera were consistently found to associate with aGvHD in indicator species analysis, as well as relief and impurity-based algorithms. The findings support the hypothesis on potential associations between gut microbiota and aGvHD based on a data-driven approach to MWAS. This highlights the need and relevance of routine stool collection for the discovery of novel biomarkers.

Metabolic Potential of the Gut Microbiome Is Significantly Impacted by Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Allogeneic hematopoietic stem cell transplantation (aHSCT) is a putative curative treatment for malignant hematologic disorders. During transplantation, the immune system is suppressed/eradicated through a conditioning regimen (non-myeloablative or myeloablative) and replaced with a donor immune system. In our previous study, we showed changes in gut taxonomic profiles and a decrease in bacterial diversity post-transplant. In this study, we expand the cohort with 114 patients and focus on the impact of the conditioning regimens on taxonomic features and the metabolic functions of the gut bacteria. This is, to our knowledge, the first study to examine the metabolic potential of the gut microbiome in this patient group. Adult aHSCT recipients with shotgun sequenced stool samples collected day -30 to +28 relative to aHSCT were included. One sample was selected per patient per period: pre-aHSCT (day -30-0) and post-aHSCT (day 1-28). In total, 254 patients and 365 samples were included. Species richness, alpha diversity, gene richness and metabolic richness were all lower post-aHSCT than pre-aHSCT and the decline was more pronounced for the myeloablative group. The myeloablative group showed a decline in 36 genera and an increase in 15 genera. For the non-myeloablative group, 30 genera decreased and 16 increased with lower fold changes than observed in the myeloablative group. For the myeloablative group, 32 bacterial metabolic functions decreased, and one function increased. For the non-myeloablative group, three functions decreased, and two functions increased. Hence, the changes in taxonomy post-aHSCT caused a profound decline in bacterial metabolic functions especially in the myeloablative group, thus providing new evidence for associations of myeloablative conditioning and gut dysbiosis from a functional perspective.

Effects of treadmill slip and trip perturbation-based balance training on falls in community-dwelling older adults (STABILITY): study protocol for a randomised controlled trial.

INTRODUCTION: Falls among older adults are most frequently caused by slips and trips and can have devastating consequences. Perturbation-based balance training (PBT) have recently shown promising fall preventive effects after even small training dosages. However, the fall preventive effects of PBT delivered on a treadmill are still unknown. Therefore, this parallel-group randomised controlled trial aims to quantify the effects of a four-session treadmill-PBT training intervention on falls compared with treadmill walking among community-dwelling older adults aged 65 years or more. METHODS AND ANALYSIS: 140 community-dwelling older adults will be recruited and randomised into either the treadmill-PBT or the treadmill walking group. Each group will undergo three initial training sessions within a week and an additional 'booster' session after 26 weeks. Participants in the treadmill-PBT group will receive 40 slip and/or trip perturbations induced by accurately timed treadmill belt accelerations at each training session. The primary outcome of interest is daily life fall rates collected using fall calendars for a follow-up period of 52 weeks. Secondary outcomes include physical, cognitive and social-psychological fall-related risk factors and will be collected at the pre-training and post-training test and the 26-week and 52-week follow-up tests. All outcomes will be analysed using the intention-to-treat approach by an external statistician. A Poisson's regressions with bootstrapping, to account for overdispersion, will be used to compare group differences in fall rates. ETHICS AND DISSEMINATION: The study protocol has been approved by the North Denmark Region Committee on Health Research Ethics (N-20200089). The results will be disseminated in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: NCT04733222.

The Effect of Anodal Transcranial Direct Current Stimulation on Quadriceps Maximal Voluntary Contraction, Corticospinal Excitability, and Voluntary Activation Levels.

ABSTRACT: Kristiansen, M, Thomsen, MJ, Nørgaard, J, Aaes, J, Knudsen, D, and Voigt, M. The effect of anodal transcranial direct current stimulation on quadriceps maximal voluntary contraction, corticospinal excitability, and voluntary activation levels. J Strength Cond Res 36(6): 1540-1547, 2022-Anodal transcranial direct current stimulation (a-tDCS) has previously been shown to improve maximal isometric voluntary contraction (MVIC), possibly through an upregulation of corticospinal excitability. Because muscle strength is an essential part of the performance of many sports, any ergogenic effect of a-tDCS on this parameter could potentially increase performance outcomes. The purpose of this study was to investigate the effect of a-tDCS on MVIC, voluntary activation levels (VALs), and corticospinal excitability, assessed by eliciting motor-evoked potentials (MEPs), in untrained subjects. Thirteen subjects completed 2 test sessions in which they received either a-tDCS or sham stimulation for 3 consecutive intervals of 10 minutes, separated by 5-minute breaks. Before and after each stimulation session, transcranial magnetic stimulation was used to elicit MEPs, and femoral nerve stimulation was used to assess VAL by measuring twitch torque during an MVIC test and in a relaxed state. Two-way analyses of variance with statistical significance set at p ≤ 0.05 were used to test for differences. A significant main effect was identified, as the MVIC pre-test (271.2 ± 56.6 Nm) was on average 4.1% higher compared to the post-test (260.6 ± 61.4 Nm) (p = 0.05). No significant differences were found in MEP, MVIC, or VAL as a result of stimulation type or time. In healthy subjects, the potential for improvement in corticospinal excitability may be negligible, which may in turn explain the lack of improvements in MEP, MVIC, and VAL after a-tDCS. The small decrease in MVIC for both conditions and nonsignificant changes in MEP and VAL do not justify the use of a-tDCS in combination with sporting performance in which the intent is to increase maximal isometric strength performance in the quadriceps muscle of healthy subjects.

Anodal transcranial direct current stimulation increases corticospinal excitability, while performance is unchanged.

Anodal transcranial direct current stimulation (a-tDCS) has been shown to improve bicycle time to fatigue (TTF) tasks at 70-80% of VO2max and downregulate rate of perceived exertion (RPE). This study aimed to investigate the effect of a-tDCS on a RPE-clamp test, a 250-kJ time trial (TT) and motor evoked potentials (MEP). Twenty participants volunteered for three trials; control, sham stimulation and a-tDCS. Transcranial magnetic stimulation was used to determine the corticospinal excitability for 12 participants pre and post sham stimulation and a-tDCS. The a-tDCS protocol consisted of 13 minutes of stimulation (2 mA) with the anode placed above the Cz. The RPE-clamp test consisted of 5 minutes ergometer bicycling at an RPE of 13 on the Borg scale, and the TT consisted of a 250 kJ (∼10 km) long bicycle ergometer test. During each test, power output, heart rate and oxygen consumption was measured, while RPE was evaluated. MEPs increased significantly by 36% (±36%) post a-tDCS, with 8.8% (±31%) post sham stimulation (p = 0.037). No significant changes were found for any parameter at the RPE-clamp or TT. The lack of improvement may be due to RPE being more controlled by afferent feedback during TT tests than during TTF tests. Based on the results of the present study, it is concluded that a-tDCS applied over Cz, does not enhance self-paced cycling performance.

Effects of gait adaptability training on falls and fall-related fractures in older adults: a systematic review and meta-analysis.

OBJECTIVE: falls among older adults are common and can have devastating consequences. A novel task-specific exercise modality, gait adaptability training (GAT), has shown promising preventive effects. This systematic review and meta-analysis synthesise the evidence regarding GATs effect on falls and fall-related fractures in community-dwelling older adults. METHODS: electronic databases (PubMed, EMBASE, CINAHL, CENTRAL) were systematically searched from inception to 18 June 2020. Additional sources include searches of trial registrations, manual screening of reference lists and requests to experts. We included randomised controlled trials (RCTs) evaluating the effect of GAT on falls with at least 6-month follow-up among community-dwelling people aged 60+ years. Two reviewers independently screened studies against eligibility criteria, extracted relevant information and appraised studies for bias. Random-effects meta-analytic models were employed to pool effect estimates. RESULTS: eleven studies with 1,131 participants were included. A meta-analysis in which an outlier study was excluded showed that GAT reduces fall rates by 42% (incidence rate ratio 0.58, 95% confidence interval [CI] 0.39-0.81, I2 = 0.00%; moderate certainty; seven RCTs). Moreover, proportion with fall-related fractures and proportion of fallers was reduced by 81% (risk ratio [RR] 0.19, 95% CI 0.06-0.56, I2 = 0.00%; very low certainty; two RCTs) and 43% (RR 0.57, 95% CI 0.4-to 0.8, I2 = 47.08%; low certainty; 11 RCTs), respectively. CONCLUSIONS: our results show that GAT significantly reduces the number of falls and prevents fall-related fractures in older community dwellers. GAT is a promising and feasible exercise modality; however, studies of high quality should be conducted to support a robust conclusion. PROTOCOL REGISTRATION: PROSPERO; CRD42020191051.

Associations of the gut microbiome and clinical factors with acute GVHD in allogeneic HSCT recipients.

Acute graft-versus-host disease (aGVHD) is a leading cause of transplantation-related mortality after allogeneic hematopoietic stem cell transplantation (aHSCT). 16S ribosomal RNA (16S rRNA) gene-based studies have reported that lower gut bacterial diversity and the relative abundance of certain bacteria after aHSCT are associated with aGVHD. Using shotgun metagenomic sequencing and a large cohort, we aimed to confirm and extend these observations. Adult aHSCT recipients with stool samples collected from day -30 to day 100 relative to aHSCT were included. One sample was selected per patient per period (pre-aHSCT (day -30 to day 0), early post-aHSCT (day 1 to day 28), and late post-aHSCT (day 29 to day 100)), resulting in 150 aHSCT recipients and 259 samples. Microbial and clinical factors were tested for differences between time periods and an association with subsequent aGVHD. Patients showed a decline in gut bacterial diversity posttransplant, with several patients developing a dominance of Enterococcus. A total of 36 recipients developed aGVHD at a median of 34 days (interquartile range, 26-50 days) post-aHSCT. Lower microbial gene richness (P = .02), a lower abundance of the genus Blautia (P = .05), and a lower abundance of Akkermansia muciniphila (P = .01) early post-aHSCT was observed in those who developed aGVHD. Myeloablative conditioning was associated with aGVHD along with a reduction in gene richness and abundance of Blautia and A muciniphila. These results confirm low diversity and Blautia being associated with aGVHD. Crucially, we add that pretransplant conditioning is associated with changes in gut microbiota. Investigations are warranted to determine the interplay of gut microbiota and conditioning in the development of aGVHD.

Pediatric Pharmacology of Desmopressin in Children with Enuresis: A Comprehensive Review.

Desmopressin is a synthetic analogue of the natural antidiuretic hormone arginine vasopressin. Over the years, it has been clinically used to manage nocturnal polyuria in children with enuresis. Various pharmaceutical formulations of desmopressin have been commercialized for this indication-nasal spray, nasal drops, oral tablet and oral lyophilizate. Despite the fact that desmopressin is a frequently prescribed drug in children, its use and posology is based on limited pediatric data. This review provides an overview of the current pediatric pharmacological data related to the different desmopressin formulations, including their pharmacokinetics, pharmacodynamics and adverse events. Regarding the pharmacokinetics, a profound food effect on the oral bioavailability was demonstrated as well as different plasma concentration-time profiles (double absorption peak) of the desmopressin lyophilizate between adults and children. Literature about maturational differences in distribution, metabolism and excretion of desmopressin is rather limited. Regarding the pharmacodynamics, formulation/dose/food effect and predictors of response were evaluated. The lyophilizate is the preferred formulation, but the claimed bioequivalence in adults (200 µg tablet and 120 µg lyophilizate), could not be readily extrapolated to children. Prescribing the standard flat-dose regimen to the entire pediatric population might be insufficient to attain response to desmopressin treatment, whereby dosing schemes based on age and weight were proposed. Moreover, response to desmopressin is variable, whereby complete-, partial- and non-responders are reported. Different reasons were enumerated that might explain the difference in response rate to desmopressin observed: different pathophysiological mechanisms, bladder capacity and other predictive factors (i.e. breast feeding, familial history, compliance, sex, etc.). Also, the relapse rate of desmopressin treatment was high, rendering it necessary to use a pragmatic approach for the treatment of enuresis, whereby careful consideration of the position of desmopressin within this treatment is required. Regarding the safety of the different desmopressin formulations, the use of desmopressin was generally considered safe, but additional measures should be taken to prevent severe hyponatremia. To conclude the review, to date, major knowledge gaps in pediatric pharmacological aspects of the different desmopressin formulations still remain. Additional information should be collected about the clinical relevance of the double absorption peak, the food effect, the bioequivalence/therapeutic equivalence, the pediatric adapted dosing regimens, the study endpoints and the difference between performing studies at daytime or at nighttime. To fill in these gaps, additional well designed pharmacokinetic and pharmacodynamic studies in children should be performed.

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.

Questions to ask a patient with nocturia.

BACKGROUND: Patients may not raise nocturia as a concern as they mistakenly consider the symptom to be a normal part of ageing. Nocturia is associated with significant morbidity and is likely to be a marker of poor health. OBJECTIVE: This paper provides questions to guide diagnosis, evaluation and individualised treatment of nocturia. DISCUSSION: Nocturia results from the interplay between nocturnal polyuria, reduced bladder storage and sleep disruption. Changes in the function of the urinary bladder, kidneys, brain and cardiovascular system, and hormone status underlie the development and progression of nocturia. Medications commonly prescribed to older people can affect development or resolution of nocturia. The bother caused to a patient by waking to void relates to disturbance of slow-wave sleep, the physical act of getting out of bed and resulting chronic fatigue. An assessment process that identifies relevant and co-existing causes of an individual's nocturia will facilitate a targeted approach to treatment.

Nationwide citizen access to their health data: analysing and comparing experiences in Denmark, Estonia and Australia.

BACKGROUND: Most countries face an ageing population, increasing chronic diseased, and constrictions on budget for providing health services. Involving patients in their own care by allowing them access to their patient data is a trend seen in many places. METHODS: Data on the type and level of access citizens have to their own health data in three countries was gathered from public sources. RESULTS: Data from each individual country is presented and the experiences of Denmark, Estonia and Australia are examined whilst similarities and differences explored. The discussion adopts a citizen-centred perspective to consider how the different e-portal systems support, protect and structure citizen interactions with their own health data in three key areas: Security, privacy and data protection; User support; and Citizen adoption and use. CONCLUSIONS: The paper highlights the impact of opt-in/opt-out approaches on citizen access and the lack of a structured approach to addressing differences in citizen health and e-health literacy. This research also confirms while current data provides detail on the availability and use of personal health data by citizens, questions still remain over the ultimate impact on patient outcomes of these initiatives. It is anticipated the insights generated from the three countries experiences, supporting citizen access to their health data will be useful to improve these initiatives and guide other countries aspiring to support similar initiatives.

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.

Pitfalls and opportunities in multidisciplinary research about nocturia in adults.

OBJECTIVES: Describe current shortcomings in clinical research on the treatment of nocturia in adults, and suggest new directions for future studies in this field. METHODS: A literature search was conducted using the keywords 'nocturia,' 'nocturnal polyuria,' 'sleep,' and 'hypertension.' RESULTS: Nocturia, or waking up at night to void, is a highly prevalent and bothersome lower urinary tract symptom (LUTS) affecting up to 40% of adults. Since the majority of patients are diagnosed with nocturnal polyuria (NP) as one of the underlying causes, it is not surprising that the effect of treatments for overactive bladder (OAB) and bladder outlet obstruction (BOO) are disappointing with regard to nocturia. Therefore, we suggest to conduct studies in which nocturic patients are treated according to the underlying pathophysiology: (1) antimuscarinics or ß3-agonists for OAB symptoms, (2) α-blockers or 5α-reductase inhibitors in men with BOO caused by enlarged prostates, (3) desmopressin or diuretics for NP, (4) continuous positive airway pressure in nocturic patients with obstructive sleep apnea, and (5) all its combinations in case of combined pathophysiology. Not only the effect on treatment efficacy or side effects needs to be assessed, but also the impact on related comorbidities such as sleep disorders, hypertension, and endocrine functions such as blood glucose regulation. CONCLUSION: Future research needs to subtype nocturic patients in order to adapt treatment according to the underlying cause.