Partially different? The importance of general equilibrium in health economic evaluations: An application to nocturia.

Both the human capital approach and the friction cost approach are frequently used to quantify the productivity costs associated with illness, disability or death in health economic evaluations. In this paper we argue that these approaches have one major, but common shortcoming: they only capture partial equilibrium (PE) effects and therefore underestimate the true potential productivity costs associated with health conditions. They neglect the sizable, indirect, ripple effects in the economy captured by general equilibrium (GE) models. To demonstrate our point, we compare a traditional PE with a GE approach for the application to nocturia, a condition characterized by the need to frequently wake up at night to urinate. Nocturia is associated with substantial impairment of daytime functioning and work productivity. We employ large-scale United Kingdom (UK) employer-employee survey data to estimate the prevalence and productivity loss. These estimates are then used as shared inputs to drive both approaches. We find that the traditional PE approach underestimates the annual productivity cost of clinically relevant nocturia by around 16%. We propose a generalized GE/PE multiplier to approximate the GE effect for other health conditions. Our findings stress the importance of accounting for sizable GE effects when conducting health economic evaluations.

A large survey of nocturia related to sleep quality and daytime quality of life in a young Japanese population: NOCTURNE study.

AIMS: Nocturia, due to nocturnal polyuria and other conditions associated with nocturnal voiding, affects sleep quality and daytime quality of life (QOL). We aimed to investigate the relationship among nocturia, sleep quality, and daytime QOL in a young Japanese population. METHODS: This epidemiological study analyzed data from a retrospective data set containing sleep data from wearable devices worn by 9446 Japanese users and a prospective data set containing answers to a 10-item questionnaire completed by a subset of 605 users in the retrospective dataset. We recorded the first uninterrupted sleep period (FUSP), total sleep time (TST), number of nocturnal voids, sleep quality, daytime QOL, bothering nocturnal voids, and early wake-ups in the morning. RESULTS: The subjects were 18-65 years old. The mean TST was 6.7 ± 0.9 h, and the mean number of wake-ups was 2.11 ± 1.1. FUSP and TST decreased (from 334 ± 114 to 173 ± 74 min and 5.9 ± 1.0 to 5.5 ± 1.0 h, respectively) with an increasing number of nocturnal voids, and the change was statistically significant. Logistic regression analysis showed a statistically significant relationship between nocturia and FUSP and the number of wake-ups. CONCLUSION: Nocturia has close relationships with FUSP and the number of wake-ups and can result in decreased daytime QOL in young Japanese people.

Night-time voids, level of bother and sleep characteristics in a non-patient population of wearable devices users.

INTRODUCTION: Nocturia is a highly prevalent and bothersome medical condition characterised mainly by the need to wake up to pass urine during the main sleep period. Using data from wearable devices, it is possible to examine the sleep of large cohorts in natural settings. This study seeks to use data from connected smartwatches combined with a one-time survey to explore the presence of nocturia and associated level of bother and sleep characteristics in a non-patient cohort of wearable device users representing a broad age range. METHODS: The data used come from a retrospective dataset containing sleep data from Withings watches of 250 000 users and a prospective dataset containing answers to a 10-item questionnaire completed by a subset of users in the retrospective dataset. RESULTS: The prospective dataset contained 6230 users. Overall, 6.0%, 15.3% and 38.9% of users in the age groups 18-44 years, 45-64 years and 65-90 years, respectively, reported 2 or more nocturnal voids as their customary voiding pattern, corresponding to levels of nocturia consistent with previous literature. The level of bother associated with nocturia was higher among younger users with 27.8% of users aged 18-44 years reporting that their daytime activity was highly affected versus just 14.1% among those aged 65-90 years. A higher number of reported voids per night was associated with watch-derived measures of a lower sleep efficiency, a longer awake duration at night and a shorter first uninterrupted sleep period. CONCLUSION: This study suggests not only that nocturia is present among the younger population but also that the younger are more bothered by this medical condition. Using data from wearables it was possible to establish that there is an association between the number of nocturnal voids and sleep characteristics.

A multitrait, multimethod matrix approach for a consumer-grade wrist-worn watch measuring sleep duration and continuity.

STUDY OBJECTIVES: We examined associations between self-reports about typical sleep patterns and sleep data derived from a wearable device worn on a nightly basis for a prolonged period (mean = 214 nights). We hypothesized that sleep characteristics would correlate better across different methods of assessment (self-report versus wearable) than they would correlate within the same method, a classic psychometric approach (multitrait, multimethod matrix). METHODS: A cross-national sample of 6,230 adult wearable users completed a brief sleep questionnaire collecting data on sleep duration and number of awakenings (NAW) and provided informed consent to link their responses to data from their wearable watches. The data collection for the wearable occurred over 12 months and the sleep questionnaire was completed subsequent to that. RESULTS: Results indicated a large (r = .615) correlation between sleep duration as assessed with the wearable and by self-report. A medium-to-large correlation (r = .406) was also seen for NAW. The multitrait, multimethod matrix suggested minimal method variance, i.e. similar "traits" (sleep duration and NAW) correlated across methods but within a given method, and such "traits" were generally unrelated. CONCLUSIONS: The results suggest that the longer period of data collection with the wearable generates more stable estimates of sleep than have been reported in most studies of actigraphy. Alternatively, the data might imply that individuals modify their self-reports about sleep via daily feedback to align their perceptions to the output of the wearable.

Assessing the burden of nocturia in the workplace: the associations between nocturnal voiding, subjective well-being, work engagement and productivity.

Aims: Nocturia (getting up at night to urinate, where each urination being followed by sleep or intention to sleep) is a bothersome symptom with potentially negative consequences for individual health and daytime functioning. This study assessed the burden of nocturia in the workplace by investigating associations between nocturia and subjective well-being (SWB), work engagement and productivity.Methods: Using large-scale international workplace survey data, the associations between nocturia, SWB, work engagement (Utrecht Work Engagement Scale, UWES-9) and productivity (Work Productivity and Activity Impairment, WPAI) were assessed. Bivariate and multivariate regression analysis was used with adjustment for a large set of confounding factors, including sleep duration and sleep quality.Results: Across a study sample of 92,129 observations, aged 18-70, an average of 10% of the survey population reported ≥2 nocturnal voids (generally considered clinically significant nocturia), with prevalence of nocturia increasing with age. Individuals with nocturia reported a 35.7% (p < .001) higher relative sleep disturbance score and were 10.5 percentage points (pp) (p < .001) more likely to report short sleep. Adjusted for covariates, nocturia was associated with a 3.5% (p < .001) lower relative SWB score and a 2% (p < .001) lower relative UWES-9 work engagement score. Nocturia was associated with a 3.9 pp (p < .001) higher work impairment due to absenteeism and presenteeism (WPAI). Adjusting additionally for sleep disturbance and sleep duration reduced the magnitude of the estimated effects, suggesting a key role for poor sleep in explaining the relationship between nocturia and the outcomes (SWB, UWES-9, WPAI) assessed.Conclusions: A key contribution of this study is the assessment of the association between nocturia and a range of work performance outcomes in a sizeable study using validated instruments to measure work engagement and productivity. The study highlights the importance of taking sleep into account when assessing the relationship between nocturia and associated outcomes.

Efficacy and safety of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder and recent methylphenidate use.

INTRODUCTION: Lisdexamfetamine dimesylate (LDX) is a long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). Post hoc subgroup analyses were performed from two studies in children with ADHD to compare the efficacy of LDX in participants who had received prior methylphenidate (MPH) treatment with that of the overall study populations. METHODS: Study 1 (7-week; open-label design) and study 2 (randomized, double-blind, placebo-controlled, crossover, laboratory school design) enrolled children aged 6-12 years with ADHD and baseline ADHD Rating Scale IV (ADHD-RS-IV) total score ≥28. Both studies excluded children whose prestudy ADHD treatment provided effective control of ADHD symptoms with an acceptable safety profile. Post hoc efficacy analyses were performed in children who had received MPH within 6 months of study enrollment. Efficacy measures included the following scales: ADHD-RS-IV, Clinical Global Impressions-Improvement (CGI-I), Expression and Emotion Scale for Children (EESC), Behavior Rating Inventory of Executive Function (BRIEF), Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP), and Permanent Product Measure of Performance (PERMP). RESULTS: In studies 1 and 2, 83/318 (26%) and 67/129 (52%) participants, respectively, had received MPH within 6 months and were not adequately controlled on current medication with acceptable tolerability; most of these participants had received long-acting MPH. In prior MPH participants, efficacy assessments demonstrated improvements from baseline (study 1) and versus placebo (study 2) that were comparable with those seen in the respective overall study population. Safety profiles were consistent with long-acting stimulant use. CONCLUSION: In two studies, children who had received prior MPH treatment improved during treatment with LDX and experienced similar improvements in their symptoms as the overall study populations. For children with ADHD who were previously treated with MPH, LDX may, therefore, be an efficacious treatment option.

Efficacy of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder previously treated with methylphenidate: a post hoc analysis.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral psychiatric disorder that afflicts children, with a reported prevalence of 2.4% to 19.8% worldwide. Stimulants (methylphenidate [MPH] and amphetamine) are considered first-line ADHD pharmacotherapy. MPH is a catecholamine reuptake inhibitor, whereas amphetamines have additional presynaptic activity. Although MPH and amphetamine can effectively manage ADHD symptoms in most pediatric patients, many still fail to respond optimally to either. After administration, the prodrug stimulant lisdexamfetamine dimesylate (LDX) is converted to l-lysine and therapeutically active d-amphetamine in the blood. The objective of this study was to evaluate the clinical efficacy of LDX in children with ADHD who remained symptomatic (ie, nonremitters; ADHD Rating Scale IV [ADHD-RS-IV] total score > 18) on MPH therapy prior to enrollment in a 4-week placebo-controlled LDX trial, compared with the overall population. METHODS: In this post hoc analysis of data from a multicenter, randomized, double-blind, forced-dose titration study, we evaluated the clinical efficacy of LDX in children aged 6-12 years with and without prior MPH treatment at screening. ADHD symptoms were assessed using the ADHD-RS-IV scale, Conners' Parent Rating Scale-Revised short form (CPRS-R), and Clinical Global Impressions-Improvement scale, at screening, baseline, and endpoint. ADHD-RS-IV total and CPRS-R ADHD Index scores were summarized as mean (SD). Clinical response for the subgroup analysis was defined as a ≥ 30% reduction from baseline in ADHD-RS-IV score and a CGI-I score of 1 or 2. Dunnett test was used to compare change from baseline in all groups. Number needed to treat to achieve one clinical responder or one symptomatic remitter was calculated as the reciprocal of the difference in their proportions on active treatment and placebo at endpoint. RESULTS: Of 290 randomized participants enrolled, 28 received MPH therapy at screening, of which 26 remained symptomatic (ADHD-RS-IV > 18). ADHD-RS-IV total scores, changes from baseline, clinical responsiveness, and rates of symptomatic remission in this subgroup were comparable to the overall population. The safety and tolerability profiles for LDX were comparable to other stimulants currently available. CONCLUSION: In this analysis, children with significant clinical ADHD symptoms despite MPH treatment improved during treatment with LDX and experienced similar improvements in their symptoms as the overall study population. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00556296.