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Nocturia: Time to wake up to the seriousness of the problem

Nocturia: Time to wake up to the seriousness of the problem. R. ROSEN 1 , V. KUPELIAN 1 , and T. HOLM-LARSEN 2 1 New England Research Institutes, Watertown, Massachusetts, USA; 2 University of Copenhagen, Denmark and The Right Value Story, Copenhagen, Denmark. Absolutely!

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Nocturia: Time to wake up to the seriousness of the problem

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  1. Nocturia: Time to wake up to the seriousness of the problem R. ROSEN1, V. KUPELIAN1, and T. HOLM-LARSEN2 1New England Research Institutes, Watertown, Massachusetts, USA; 2University of Copenhagen, Denmark and The Right Value Story, Copenhagen, Denmark

  2. Absolutely! Because it is linked with: Increased mortality and morbidity Increased falls and fractures Reduced productivity Sleep disruption Reduced QoL AND It is highly prevalent – in young and old, men and women Is nocturia a serious health issue? QoL, quality of life

  3. Nocturia and Mortality – U.S. Data NHANES III - Kupelian et al. J Urol 2011;185:571–7 Kupelian et al. J Urol 2011;185:571–7

  4. Nocturia and Mortality – Hazard Ratios (HR)NHANES III: Kupelian et al. J Urol 2011;185:571–7 *Adjusted for baseline age, BMI, marital status, education, smoking, CVD, diabetes, hypertension, medications use (diuretics, antihypertensives, lipid lowering, antidepressants) Kupelian et al. J Urol 2011;185:571–7

  5. Similar findings in a recent study in Japan (Nakagawa et al., 2009) 100.0 ≤1 97.5 n=788, mean age 75 years Log rank testp<0.0002 95.0 Percentage survival ≥2 92.5 90.0 0 5 10 15 20 25 30 35 40 Months ≥2 voids/night are associated with increased mortality in the elderly, even after adjusting for age, gender, BMI, comorbidities and medications (HR: 2.68 [1.12–6.43]) BMI, body mass index; HR, hazard ratio Nakagawa et al. J Urol 2009;181(Suppl):8

  6. Increased risk of falls in elderly patients with nocturia 5872 community-dwelling men aged ≥65 years Primary outcome: 1-year cumulative incidence of falls with moderate/severe vs mild LUTS at baseline Nocturia was among the LUTS most strongly associated with falls LUTS, lower urinary tract symptom; RR, relative risk; CI, confidence interval Parsons et al. BJU Int 2009;104:63–68

  7. Nocturia is a risk factor for hip fractures, regardless of age 1820 Austrian men aged 40–80 years completed the IPSS1 The IPSS was not correlated with the occurrence of hip fractures Nocturia (≥2 voids/night) was an age-independent risk factor for hip fractures (OR 1.36; 95% CI 1.03–1.80, p=0.03) Hip fracture, age and nocturia1 An overall in-hospital mortality rate of 5.3% following hip fracture has been reported2 IPSS, International Prostate Symptom Score; OR, odds ratio 1. Temml et al. Neurourol Urodyn 2009;28:949–952; 2. Alvarez-Nebreda et al. Bone 2008;42:278–285

  8. Nocturia affects daytime activity and work productivity Productivity, vitality and QoL were assessed in 203 professionally active adults in Sweden with ≥1 void/night Compared with controls, nocturia patients had significantly (p<0.001): Increased work impairment, due to greater impairment while working (not hours missed; assessed using WPAI) Increased impairment in non-work activities (WPAI) Reduced vitality (SF-36) Reduced overall QoL (utility; EQ-5D) Work impairment increased with nocturia severity (p<0.05) Vitality decreased with nocturia severity (p<0.01) WPAI, work productivity and activity impairment questionnaire; SF-36, Short-Form 36; EQ-5D, EuroQol questionnaire Kobelt et al. BJU Int 2003;91:190–195

  9. Reduced QoL is specifically associated with nocturia in LUTS patients Amongst a sample of 502 Spanish men ≥60 years with LUTS, proportion who rate QoL as good/very good is more than halved if nocturia is present1 Of all IPSS symptoms, nocturia correlates most strongly with HRQoL at baseline and after treatment2 Nocturia is a key factor driving QoL in LUTS patients Reducing nocturia to <2 voids/night may reduce QoL burden Percentage of patients with LUTS rating QoL as good or very good1 100 90.6 80 60 Percentage 42.9 40 20 0 Without nocturia With noctura HRQoL, health-related quality of life • Hernández et al. Curr Med Res Opin 2008;24:1033–1038; 2. Van Dijk et al. BJU Int [Epub ahead of print]

  10. Nocturia associated with similar reductions in QoL as local advanced prostate cancer Nocturia PCa 1 0.9 0.8 0.7 0.6 0.5 Utility score of HRQoL 0.4 0.3 0.2 0.1 0 Local Localadvanced Terminal 1 void/night 2 voids/night 3 voids/night 4 voids/night PCa, prostate cancer Kobelt et al. BJU Int 2003;91:190–195; Tengs & Wallace. Med Care 2000;38:583–637

  11. Burden of nocturia increases with severity QoL in 663 Taiwanese community-dwelling adults aged 40–79 years with nocturia 100 Voids/night 90 1 80 2 70 60 3 NQoL score* 50 4+ 40 30 20 10 0 Sleep/energysubscale Bother/concernsubscale NQoL total *Lower score indicates worse QoL NQoL, nocturia-specific quality of life Yu et al. Urology 2006;67:713–718

  12. Nocturia associated with significant decreases in 14/15 dimensions of HRQoL 1.0 No nocturia * 1 void/night 0.9 2 voids/night ** ** 15D instrument (level value) ** ≥3 voids/night ** 0.8 ** ** ** ** ** 0.7 ** ** ** ** Eating Seeing Moving Vitality Speech Hearing Distress Sleeping Breathing Depression Discomfort Eliminating Sexual activity Usual activities Mental function n=1888 Finnish women (similar results in males) *p <0.05; **p <0.001 (test for trend) Tikkinen et al. Eur Urol 2010;57:488–496

  13. What level of severity of nocturia is important? Results from multiple studies of mortality, fractures and QoL all show ≥2 voids/night is a ‘threshold’ for significant negative impact from nocturia One void/night is less likely to have serious consequences If treatment can reduce nocturia frequency to <2 voids/night on average, risks to patients may be significantly reduced

  14. Nocturia usually considered a male condition1BUT it is just as prevalent in women2 Nocturia increases with age2 Over a third of younger people (<40 years of age) are affected 13–17% in this age group have ≥2 voids/night2 Nocturia affects both sexes equally EPIC study: survey of 19,165 adults in Europe and Canada 80 Males Females 70 60 ≥1 void/night♀: 54.5%♂: 48.6% 50 Prevalence of nocturia (%) 40 30 ≥2 voids/night♀: 24.0%♂: 20.9% 20 10 0 ≤39 years 40–59 years ≥60 years 1. Wein et al. BJU Int 2002;90(suppl 3):28–31;2. Irwin et al. Eur Urol 2006;50:1306–1314

  15. Could sleep disruption be a prime mediator of subsequent effects of nocturia? Prevalence of poor sleep in 3669 Swedish women aged 40–64 years according to nocturia severity 80 Age (years) 40–44 45–49 50–54 55–59 60–64 60 Percentage (%) 40 20 0 None One Two Three or more Nocturia episodes/night Asplund & Aberg. Maturitas 1996:24:73–81

  16. Nocturia is the leading cause of sleep disturbance in older adults How often do the following disturb your sleep? 90 80 n=1424; aged 55–84 years Nocturia Headache 70 Physical pain Money problems 60 Caregiving Family problems Prevalence (%) of self-reported causes of disturbed sleep Health concerns Uncomfortable bed 50 Cough Night-time heartburn 40 30 20 10 0 Every night/almost every night Few nights/week Few nights/month Rarely Never Bliwise et al. Sleep Med 2009;10:540–548

  17. Reduced sleep efficiency associated with increased mortality in the elderly Survival as a function of sleep efficiency 1.0 n=185 healthy older adults 0.8 0.6 Cumulative survival Efficiency ≥80% 0.4 Controlling for age, gender and baseline medical burden, those with sleep efficiency <80% are at 1.93 times greater risk of mortality (p=0.014; CI 1.14–3.25) Efficiency <80% 0.2 0.0 0 100 200 300 400 500 600 700 800 900 1000 Weeks Dew et al. Psychosom Med 2003;65:67–73

  18. Sleep efficiency is reduced in nocturia 2 3 4 ≥5.0 2.0 Voids per night 1.8 *** 1.6 *** 1.4 1.2 Score Increasing difficulty ** 1.0 0.8 * 0.6 0.4 0.2 0.0 Subjective sleep quality Sleep latency Sleep duration Habitual sleep efficiency Sleep disturbance Sleep medication Daytimedysfunction Domain PSQI domain scores for all patients by increasing voiding frequency *p=0.0012, **p=0.0003, ***p<0.0001 Score range: 0 (no difficulty) to 3 (severe difficulty). PSQI domain scores are standardised versions of areas routinely assessed during clinical interviews of patients with sleep/wake complaints PSQI, Pittsburgh Sleep Quality Index Ancoli-Israel et al. Neurourol Urodyn 2009;28:635. Abstract 54; Chartier-Kastler et al. Prog Urol 2009;19:333–340

  19. Nocturnal awakening due to nocturia as a cardiovascular stressor Awaking from sleep is associated with increased heart rate and blood pressure (major determinants of cardiac oxygen consumption and vascular stress, endocrine and clotting activation) Contributes to clustering of cardiovascular events during morning hours Nocturia causes additional awakening during the night and is associated with non-dipping hypertension1 12-year survival is 10% lower for CHD patients with nocturia vs without (61% vs 72%, p=0.02)2 No nocturiaNocturia 1.0 0.8 0.6 Survival distribution function 0.4 0.2 0.0 0 2 4 6 8 10 12 Years of follow-up Nocturia 54 50 47 39 33 28 24 No nocturia 65 61 57 53 48 46 43 12-year survival in 70-year-old subjects with ischaemic heart disease for 54 who reported nocturia versus 65 who did not (p=0.0206, log-rank test) 1. Perk et al. Hypertension 2001;37(2 Part 2):749–752; 2. Bursztyn et al. Am J Cardiol 2006;98:1311–1315

  20. Conclusions Like other asymptomatic conditions (hypertension, type 2 diabetes, hypercholesterolaemia), nocturia is associated with serious consequences for mortality, morbidity and QoL – but is most often considered a ‘lifestyle condition’ and ignored, BUT… Nocturia (≥2 voids) is potentially a harbinger of multiple negative outcomes High risks to patient QoL, functioning, health, possibly mortality Large proportion of men and women are affected by nocturia1,2 Increasing evidence that older andyounger people are:3–6 Widely affected by nocturia Experience major QoL and health impact Public health attention to nocturia, its aetiology and treatment is urgently needed 1. Wein et al. BJU Int 2002;90(Suppl 3):28–31; 2. Irwin et al. Eur Urol 2006;50:1306–1314; 3. Asplund & Aberg. Maturitas 1996;24:73–81; 4. Hunskaar. BJU Int 2005;96(suppl 1):4–7; 5. Fitzgerald et al. J Urol 2007;177:1385–1389; 6. Bosch & Weiss. J Urol: in press

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