The cost of lifelong LUTS-A systematic literature review.

BACKGROUND: Lower urinary tract symptoms (LUTS) are highly prevalent and very bothersome. To support the best possible allocation of health care resources and to avoid unnecessary expenditures, it is important to understand and quantify the wide-ranging health care costs affecting people suffering from LUTS. We aimed at creating a foundation for exploring the cost of LUTS. METHOD: In this systematic literature review, we explored the costs of illness of the LUTS umbrella. We used the online literature review tool Silvi.ai for transparent decision-making and literature management. RESULTS: A total of 1821 original articles were screened. Forty had explored the cost of illness of a LUTS disease since 2013. The studies were conducted in 18 countries. A number of different study designs were applied, including both retrospective and prospective studies. In total, seven LUTS indications were explored. None of them focused on lifelong LUTS. None of them were conducted in infants or children. Eighty-two percent were conducted in adults and 18% in frail elderly. Most cost of illness studies focused on the cost of hospitalization and use of medicine. CONCLUSION: We have created the groundwork for understanding the cost of LUTS illness. To fully understand the cost of illness of lifelong LUTS, the main gap in research is to investigate the cost of LUTS in infants and children.

OAB supraspinal control network, transition with age, and effect of treatment: A systematic review.

OBJECTIVE: In light of a better understanding of supraspinal control of nonneurogenic overactive bladder (OAB), the prevalence of which increases with age, functional imaging has gained significant momentum. The objective of this study was to perform a systematic review on the transition of supraspinal control of OAB with age, the effect of therapeutic modalities, and a coordinate-based meta-analysis of all neuroimaging evidence on supraspinal OAB control in response to bladder filling. METHODOLOGY: We performed a systematic literature search of all relevant libraries in November 2021. The coordinates of brain activity were extracted from eligible neuroimaging studies to perform an activation likelihood estimation (ALE) meta-analysis. RESULTS: A total of 16 studies out of 241 were selected for our systematic review. Coordinates were extracted from five experiments involving 70 patients. ALE meta-analysis showed activation of the insula, supplementary motor area, dorsolateral prefrontal cortex, anterior cingulate gyrus, and temporal gyrus with a transition of activation patterns with age, using a threshold of uncorrected p < 0.001. Among young patients, neuroplasticity allows the activation of accessory circuits to maintain continence, as in the cerebellum and temporoparietal lobes. Anticholinergics, pelvic floor muscle training, sacral neuromodulation, and hypnotherapy are correlated with supraspinal changes attributed to adaptability and possibly a substratum of an intrinsic supraspinal component. The latter is better demonstrated by a resting-state functional connectivity analysis, a promising tool to phenotype OAB with recent successful models of predicting severity and response to behavioral treatments. CONCLUSION: Future neuroimaging studies are necessary to better define an OAB neurosignature to allocate patients to successful treatments.

Validation of the Self-Reported Psoriasis Treatment Convenience Scale (PTCS).

INTRODUCTION: Adherence to topical treatments for psoriasis is reported to be poor. One key contributing factor is the inconvenience associated with formulations that may be greasy, time consuming to apply, and slow to absorb. There is a paucity of patient-reported outcome measures that evaluate psoriasis patients' perceptions of treatment convenience. The Psoriasis Treatment Convenience Scale (PTCS) was therefore developed and validated. METHODS: Following a literature review of issues relating to convenience of topical treatments, important items were identified and a draft version of the PTCS was developed and underwent content validity testing (n = 20). The revised scale was included in a clinical trial of topical therapy (n = 794; NCT03308799), and psychometric testing was performed. RESULTS: The final questionnaire included five core items and one overall satisfaction question. In psychometric testing, the scale demonstrated stability across trial population, and good validity, reliability, and sensitivity. CONCLUSION: The PTCS is a new, reliable, sensitive, validated tool for the assessment of patient-reported treatment convenience. Use of the PTCS will facilitate evaluation of convenience as part of the clinical development of topical therapies, and thus may help to improve patient adherence and, therefore, treatment outcomes.

Nocturia is more bothersome than daytime LUTS: Results from an Observational, Real-life Practice Database including 8659 European and American LUTS patients.

PURPOSE: Lower urinary tract symptoms (LUTS) encompass several diagnoses, including overactive bladder (OAB) and benign prostatic hyperplasia (BPH). Nocturia is a standalone symptom, but also included in OAB and BPH. Current discussion addresses whether the overlap of the diagnoses is too broad, leading to misdiagnosis. This study explored the differences in level, causes and consequences for patients with a diagnosis of daytime LUTS compared with a diagnosis of nocturia, and discussed whether people are being treated for the symptoms that truly bother them the most. PATIENTS AND METHODS: Data were drawn from a survey of physicians and patients in France, Germany, Spain, UK and USA. Physicians filled out patient record forms (PRFs) for patients with LUTS diagnosis. The patients completed the patient self-completion form (PSC). Three PRO questionnaires were included; the OAB-q SF, NI-Diary and WPAI. Patients were grouped based on the diagnoses assigned to them by their physicians in a real-life setting. RESULTS: Eight thousand seven hundred and thirty eight patients had a LUTS diagnosis and 5335 completed a PSC. Patients diagnosed with night-time symptoms were significantly more bothered by their LUTS than only daytime LUTS patients (all questionnaires P < .0001). Patients with nocturia reported being tired "always" or "usually" more often than patients with daytime problems only (P < .0001). Only 13% of patients with nocturia had an initial sleep period of more than 2-3 hours. CONCLUSION: In this population of real-life patients, those with a diagnosis of nocturia reported significantly higher impact on their quality of life than patients with a diagnosis of daytime LUTS only. The underlying causes of bother were related to sleep problems. It is essential that nocturia is understood, treated and monitored as a distinct problem from OAB and BPH, to ensure that patients are treated for their main symptom.

Risk-Sharing Agreements in the EU: A Systematic Review of Major Trends.

OBJECTIVE: Our objectives were to explore the changes in the level of interest in risk-sharing agreements (RSAs) in the EU during the last 15 years and the underlying reasons for these changes. METHODS: A systematic literature review was conducted using PubMed, Scopus, Web of Science, and Embase. Articles identified were divided into 'quantitative articles' used to establish the level of interest and 'qualitative articles' used to identify the underlying trends in RSAs. RESULTS: The literature search retrieved 2144 scientific articles. Data were extracted from 238 articles. Of these, 100 contained quantitative data and 138 contained qualitative data. The pace of articles being published about RSAs grew significantly in 2015, which related to the increase in interest in and knowledge about RSAs. The underlying reasons for the fluctuations were condensed into four overall themes: (1) push for value-based pricing, (2) economic crisis and further push to contain costs, (3) criticism of RSAs in the real world, and (4) diversification of RSAs to fit the purpose. CONCLUSION: The overall level of interest in RSAs in the EU has been increasing since 2000; therefore, articles reporting the number of RSAs implemented and case studies have been steadily growing as evidence is becoming more readily available. The number of qualitative articles reporting and discussing the underlying reasons for these changes in interest has largely fluctuated over the last 15 years. Despite these fluctuations, interest in RSAs remains high.

Validation of a Simple Stool Diary Used by Caregivers to Document Diarrhea Among Young Children in a Low-Income Country.

OBJECTIVES: The aim of the study was the development and validation of a simple stool diary for caretakers collecting data on stool frequency and consistency among young children in a low-income country. METHODS: Focus group studies evaluated how diarrhea was understood by caregivers (content validity). The sensitivity, reliability, and correlations between dehydration and diary scores (construct validity) were tested in a clinical trial. RESULTS: Caregivers recognized and understood the concept and severity of diarrhea. Stool frequency and liquid consistency decreased in children admitted with diarrhea (P < 0.0001 for both), confirming good sensitivity of the diary. High reliability was obtained after a few days of training. The caregiver intracorrelation coefficients were 0.66 (0.55-0.77) and 0.75 (0.66-0.84) after 2 and 7 days of training, respectively, and subjective staff evaluation of caregiver scores showed that ≤6% of caregivers had low scoring abilities after 3 days. The degree of dehydration (4-point score) was correlated with both increasing stool frequency and liquid stool consistency (+0.2 points [0.07-0.3], P = 0.0018 for 6 or more diarrheal stools, compared to 3 or more diarrheal stools per day, and +0.5 points (0.3-0.6), P < 0.0001 for diarrheal episodes with 3 or more watery stools/day compared with episodes with 3 or more "watery + abnormally loose + loose" stools per day). CONCLUSIONS: The diary showed high validity, good reliability, and high sensitivity. After 3 days of training, caregivers with mainly no or limited education could report stool consistency with good reliability. Stool consistency, which correlated strongly with dehydration, may be considered an important marker of diarrhea severity in future research.

Nocturia is often inadequately assessed, diagnosed and treated by physicians: results of an observational, real-life practice database containing 8659 European and US-American patients.

AIMS: The aim of this study was to investigate the quality and timing of the diagnosis and treatment of nocturia in real-life practice in European and US-American patients to obtain better insights into the management of nocturia in different Western healthcare systems. METHODS: Data were drawn from the "LUTS Disease Specific Programme," a real-life survey of physicians and patients in France, Germany, Spain, UK and the USA. Physicians completed a patient record form for lower urinary tract symptoms (LUTS) patients. Patients filled out a self-completion form, indicating - among other items - information on the mean number of day- and night-time voids during the last 7 days, and questions on the management of LUTS in daily practice. RESULTS: In total, 8659 patients were analysed. The majority of patients initially consulted a physician because of worsening of LUTS frequency (43%-58%) or severity (44%-55%). Only 37% of all LUTS diagnoses, regardless of the appearance or severity of nocturia, were based on bladder diaries. Patients took approximately 1 year to consult a medical professional following the onset of LUTS. At the initial visit, most patients received advice on behavioural strategies. Regardless the type of LUTS and physician, 59% of men received α-blockers and 76% of women antimuscarinics. CONCLUSIONS: Data show that patients with nocturia and LUTS accept their symptoms for a considerable period before they seek help or ultimately receive treatment. They may therefore be enduring significant negative impact on their quality-of-life which could be avoided. Physicians rarely use bladder diaries and primarily use antimuscarinics (women) or α-blockers (men). Improved awareness of nocturia among patients and physicians could improve the management of nocturia.

Assessing the impact of nocturia on health-related quality-of-life and utility: results of an observational survey in adults.

BACKGROUND AND AIM: The impact of nocturia (getting up at night to void) on health-related quality-of-life (HRQoL) is often under-estimated. This study investigated the relative burden in terms of HRQoL and utilities of nocturia in a real-world setting. METHODS: Patient data were collected from two surveys: a nocturia-specific, cross-sectional survey of physicians and their patients (DSP), and a general UK population health survey (HSFE). Utilities (EQ-5D-5L), productivity (Work Productivity and Activity Index), and the impact of nocturia symptoms (Nocturia Impact Diary and Overactive Bladder Questionnaires) were assessed against the number of voids. A robust linear regression model with propensity score weights was used to control for confounding factors in estimating utilities. RESULTS: Physician-recorded data were available from 8,738 patients across the US, Germany, Spain, France, and the UK; of these, 5,335 (61%) included patient-reported outcomes. In total, 6,302 controls were drawn from the two surveys and compared to 1,104 nocturia patients. Deterioration of HRQoL was associated with increasing number of night-time voids (p < 0.0001). In particular, significant differences were observed between 0-1 and ≥2 voids (p < 0.001). The regression model demonstrated that nocturia (≥2 per night) is associated with a modest but significant deterioration in utility of 0.0134 (p < 0.05). LIMITATIONS: The cause of nocturia is multifactorial and the mostly elderly patients may have several concomitant diseases. The authors tried to adjust for the most common ones, but there may be diseases or unknown relationships not included. CONCLUSIONS: Nocturia negatively affected HRQoL and patient utility. A clear effect is seen already at two voids per night. Every effort should, therefore, be made to reduce nocturia below the bother threshold of two voids per night.

Delay of first voiding episode is associated with longer reported sleep duration.

OBJECTIVES: Time to first void is a common outcome in nocturia clinical trials, but its relationship to other conventional self-reported sleep measures is uncertain. We examined associations between change in time to first void and change in sleep duration over the course of such a trial. METHODS: Secondary data analyses were based on a previously published study of a medication treating nocturia in 757 adult patients studied for periods up to 5 months. We used repeated-measures logistic regression models with generalized estimating equations (GEE) to examine the odds ratios (ORs) for achieving 6.0, 6.5, or 7.0 hours of total sleep duration based on increases of time to first void of 1, 2, or 3 hours. RESULTS: Increases in time to first void were associated with longer sleep durations from beginning to end of study. A 1-hour increment in time to first void was associated with a higher likelihood of obtaining a total sleep duration of e6 (OR = 1.43; 95% confidence interval [CI], 1.19-1.73), e6.5 (OR = 1.30; 95% CI, 1.16-1.47), or e7 (OR = 1.24; 95% CI, 1.12-1.37) hours, after controlling for baseline time to first void, baseline sleep duration, time, and age (all Ps < .0001). Similar results were seen for 2- and 3-hour increments in time to first void. CONCLUSIONS: Time to first void may be an important supplementary variable about which to inquire in population-based studies.

Short time to first void is associated with lower whole-night sleep quality in nocturia patients.

STUDY OBJECTIVE: To examine associations between diary-based reports of the time to first void and a commonly used measure of sleep across the entire night, the Pittsburgh Sleep Quality Index (PSQI). DESIGN AND SETTING: Data from the Baseline phase of a large, multi-site, US-based, randomized clinical trial of a nocturia medication were analyzed. We examined age-adjusted associations between time to first void as reported in a 3-day diary and PSQI Global and individual subscale scores. PATIENTS: 757 patients with nocturia completing Baseline measurements. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Using quartile analysis, higher scores indicating poorer sleep on all PSQI scales were associated (p's ≤ 0.05) with short time to first void durations. Among individuals in the lowest quartile of time to first void (< 1.17 hours), the odds ratio (OR) of a PSQI Global score > 5 was nearly 3 times (2.96; 95% CI 1.75-5.01) that of those in the highest quartile (> 2.50 h). Shorter time to first void was associated with lower sleep quality, shorter sleep duration, poorer sleep efficiency, and greater daytime dysfunction. CONCLUSIONS: Time to first void may serve as a valuable adjunctive, self-report measure for characterizing poor sleep among populations with nocturia.

The Nocturia Impact Diary: a self-reported impact measure to complement the voiding diary.

BACKGROUND: Nocturia is a chronic, fluctuating disease that disrupts sleep and has a wide-ranging impact on quality of life. Valid tools to measure the patient-reported impact of nocturia are essential for evaluating the value of treatment, but the available tools are suboptimal. OBJECTIVES: This study reports the development and validation of the Nocturia Impact Diary-an augmented form of the Nocturia Quality of Life questionnaire designed to be completed in conjunction with the widely used 3-day voiding diary. METHODS: The process comprised three steps: Step 1: Development of a concept pool using the Nocturia Quality of Life questionnaire and data from relevant studies; Step 2: Content validity study; Step 3: Psychometric testing of construct validity, reliability, and sensitivity of the diary in a randomized, placebo-controlled study in patients with nocturia. RESULTS: Step 1: Fourteen items and 4 domains were included in the first draft of the diary. Step 2: Twenty-three patients with nocturia participated in the cognitive debriefing study. Items were adjusted accordingly, and the content validity was high. Step 3: Fifty-six patients were randomized to desmopressin orally disintegrating tablet or placebo. The diary demonstrated high construct validity, with good sensitivity and a good fit to Rasch model, as well as high internal consistency, discriminatory ability, and acceptable sensitivity to change. Results indicated that the diary was unidimensional. CONCLUSIONS: The Nocturia Impact Diary is a convenient, validated patient-reported outcome measure. It should be used in conjunction with a voiding diary to capture the real-life consequences of nocturia and its treatment.

Increases in duration of first uninterrupted sleep period are associated with improvements in PSQI-measured sleep quality.

OBJECTIVE: Urology clinical trials assessing bladder function have relied on the self-reported duration of the first uninterrupted sleep period (FUSP) as a proxy outcome for sleep, but the relationship between this measure and more conventional self-reported measures of sleep is unknown. In this study, we examined the association between changes in FUSP and a widely used self-reported measure of sleep, the Pittsburgh Sleep Quality Index (PSQI). METHODS: We conducted post hoc (secondary) analyses of unpublished data from a previously published randomized clinical trial (NCT00477490) of desmopressin (a medication used to treat nocturia) and examined relationships between baseline and 4-week change in FUSP and PSQI global and subscale scores for participants (N = 580 to N = 606) having complete data. RESULTS: Data indicated strong associations between change in PSQI global score and FUSP change in six of seven subscale scores. A reduction of 1.8 points in the PSQI global score was associated with a 72-min lengthening of FUSP. CONCLUSIONS: Results suggest that FUSP is a potentially valuable metric that correlates with changes in perceived sleep duration, depth, quality for the entire night, efficiency, latency, and daytime function. An increase in FUSP was related to improvement in nearly all PSQI subscales. The validity of this measure in the general population remains to be determined.

The economic impact of nocturia.

Sleep disturbances associated with nocturia cause direct, indirect, and intangible costs. Direct costs are primarily associated with injuries from falling. Indirect costs are associated with loss of work productivity. Intangible costs include emotional distress, behavioral modifications, feelings of loss of control, poor mood, and cancellation of planned activities. A study that compared the number of falls for patients with varying numbers of voids per night demonstrated that the incremental risk (population attributable risk [PAR]) of falling as a result of nocturia (≥ 2 voids compared with ≤ 1 void) was 16.2%. Using the 16.2% PAR, the annual direct cost of nocturia in the USA was estimated at $1.5 billion. An analysis in the EU-15 countries estimated the total annual cost of hospitalizations for hip fracture due to severe nocturia to be approximately € 1 billion. Studies have shown that periods of sick leave are significantly greater in both men and women who have more nocturnal voids, with an estimated annual indirect cost of nocturia of $61 billion in the USA. A similar European analysis showed an estimated annual cost of lost work productivity due to nocturia of € 29 billion in the EU-15. The intangible personal costs of nocturia are related to diminished quality of life and overall health status. High-quality articles on the cost of illness associated with nocturia, as well as cost-benefit analyses of nocturia treatment, are generally lacking.