Tove Holm-Larsen

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 METHODS We conducted post hoc (secondary) analyses of unpublished data from a previously published randomized clinical trial (NCT00477490) of desmopressin (a medication used to treat nocturia) and examined relationships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

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

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

The Nocturia Impact Diary: A Self-Reported Impact Measure to Complement the Voiding Diary

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. Neurourol. Urodynam. 33:S10–S14, 2014.

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

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 (ps ≤ 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.

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

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.

Consequences of nocturia.

Abstract 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

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.

2 ECONOMIC BURDEN OF NOCTURIA IN THE US ADULT POPULATION

Abstract Nocturia is defined as waking at night ≥ 1 time to void. The traditional view of nocturia, as a medically nonsignificant lifestyle problem not deserving of further attention by physicians or health care providers, is contradicted strongly by a growing body of evidence. Increasingly, nocturia is viewed as a significant health risk or comorbidity that may result from various underlying disorders not exclusively related to lower urinary tract symptoms. Nocturia is common in men and women of all ages, and is a major cause of sleep disruption in the general population. Poor sleep, in turn, is associated with profound effects on quality of life and normal daytime function in patients with nocturia, particularly in younger patients. Despite the patient bother associated with the condition and the potential adverse health and quality of life effects, common misconceptions limit help-seeking by patients for the problem. In contrast, recent studies indicate that regularly waking ≥ 2 times to void per night leads to significant reductions in the quantity and quality of sleep, which likely contribute to the association between nocturia and increased morbidity and mortality. This finding of waking ≥ 2 times to void as a threshold for serious consequences of nocturia has been shown consistently in studies by different investigators, and in different research settings and populations. Future research is required to determine whether reducing nocturnal voids to < 2 per night results in clinically meaningful outcomes for patients with nocturia.

CORRELATION BETWEEN VOIDING/SLEEP DIARIES, AND NOCTURIA AND SLEEP QUALITY OF LIFE QUESTIONNAIRES

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.