75 results on '"Thom S"'
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2. Loneliness, Not Social Support, Is Associated with Cognitive Decline and Dementia Across Two Longitudinal Population-Based Cohorts
- Author
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Freak-Poli, Rosanne, Wagemaker, Nina, Wang, Rui, Lysen, Thom S., Ikram, M. Arfan, Vernooij, Meike W., Dintica, Christina S., Vernooij-Dassen, Myrra, Melis, Rene J. F., Laukka, Erika J., Fratiglioni, Laura, Xu, Weili, Tiemeier, Henning, Freak-Poli, Rosanne, Wagemaker, Nina, Wang, Rui, Lysen, Thom S., Ikram, M. Arfan, Vernooij, Meike W., Dintica, Christina S., Vernooij-Dassen, Myrra, Melis, Rene J. F., Laukka, Erika J., Fratiglioni, Laura, Xu, Weili, and Tiemeier, Henning
- Abstract
Background: Poor social health is likely associated with cognitive decline and risk of dementia; however, studies show inconsistent results. Additionally, few studies separate social health components or control for mental health. Objective: To investigate whether loneliness and social support are independently associated with cognitive decline and risk of dementia, and whether depressive symptoms confound the association. Methods: We included 4,514 participants from the population-based Rotterdam Study (RS; aged 71 +/- 7SD years) followed up to 14 years (median 10.8, interquartile range 7.4-11.6), and 2,112 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; aged 72 +/- 10SD years) followed up to 10 years (mean 5.9 +/- 1.6SD). At baseline, participants were free of major depression and scored on the Mini-Mental State Examination (MMSE) >= 26 for RS and >= 25 for SNAC-K. We investigated loneliness, perceived social support, and structural social support (specifically marital status and number of children). In both cohorts, dementia was diagnosed and cognitive function was repeatedly assessed with MMSE and a global cognitive factor (g-factor). Results: Loneliness was prospectively associated with a decline in the MMSE in both cohorts. Consistently, persons who were lonely had an increased risk of developing dementia (RS: HR 1.34, 95% CI 1.08-1.67; SNAC-K: HR 2.16, 95% CI 1.12-4.17). Adjustment for depressive symptoms and exclusion of the first 5 years of follow-up did not alter results. Neither perceived or structural social support was associated with cognitive decline or dementia risk. Conclusion: Loneliness, not social support, predicted cognitive decline and incident dementia independently of depressive symptoms.
- Published
- 2022
- Full Text
- View/download PDF
3. Loneliness, Not Social Support, Is Associated with Cognitive Decline and Dementia Across Two Longitudinal Population-Based Cohorts
- Author
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Freak-Poli, Rosanne, Wagemaker, Nina, Wang, Rui, Lysen, Thom S., Arfan Ikram, M., Vernooij, Meike W., Vernooij-Dassen, M.J.F.J., Melis, R.J.F., Xu, Weili, Tiemeier, Henning, Freak-Poli, Rosanne, Wagemaker, Nina, Wang, Rui, Lysen, Thom S., Arfan Ikram, M., Vernooij, Meike W., Vernooij-Dassen, M.J.F.J., Melis, R.J.F., Xu, Weili, and Tiemeier, Henning
- Abstract
Contains fulltext : 247188.pdf (Publisher’s version ) (Open Access)
- Published
- 2022
4. Loneliness, Not Social Support, Is Associated with Cognitive Decline and Dementia Across Two Longitudinal Population-Based Cohorts
- Author
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Freak-Poli, Rosanne, Wagemaker, Nina, Wang, Rui, Lysen, Thom S., Arfan Ikram, M., Vernooij, Meike W., Vernooij-Dassen, M.J.F.J., Melis, R.J.F., Xu, Weili, Tiemeier, Henning, Freak-Poli, Rosanne, Wagemaker, Nina, Wang, Rui, Lysen, Thom S., Arfan Ikram, M., Vernooij, Meike W., Vernooij-Dassen, M.J.F.J., Melis, R.J.F., Xu, Weili, and Tiemeier, Henning
- Abstract
Contains fulltext : 247188.pdf (Publisher’s version ) (Open Access)
- Published
- 2022
5. Association of Low-Dose Triple Combination Therapy vs Usual Care With Time at Target Blood Pressure: A Secondary Analysis of the TRIUMPH Randomized Clinical Trial
- Author
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Gnanenthiran, SR, Wang, N, DiTanna, GL, Salam, A, Webster, R, DeSilva, HA, Guggilla, R, Jan, S, Maulik, PK, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Schutte, AE, Patel, A, Rodgers, A, Gnanenthiran, SR, Wang, N, DiTanna, GL, Salam, A, Webster, R, DeSilva, HA, Guggilla, R, Jan, S, Maulik, PK, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Schutte, AE, Patel, A, and Rodgers, A
- Abstract
Importance Cumulative exposure to high blood pressure BP is an adverse prognostic marker Assessments of BP control over time such as time at target have been developed but assessments of the effects of BP lowering interventions on such measures are lacking Objective To evaluate whether low dose triple combination antihypertensive therapy was associated with greater rates of time at target compared with usual care Design Setting and Participants The Triple Pill vs Usual Care Management for Patients With Mild to Moderate Hypertension TRIUMPH trial was a open label randomized clinical trial of low dose triple BP therapy vs usual care conducted in urban hospital clinics in Sri Lanka from February 2016 to May 2017 Adults with hypertension systolic BP 140 mm Hg and or diastolic BP 90 mm Hg or in patients with diabetes or chronic kidney disease systolic BP 130 mm Hg and or diastolic BP 80 mm Hg requiring initiation untreated patients or escalation patients receiving monotherapy of antihypertensive therapy were included Patients were excluded if they were currently taking 2 or more blood pressure lowering drugs or had severe or uncontrolled blood pressure accelerated hypertension or physician determined need for slower titration of treatment a contraindication to the triple combination pill therapy an unstable medical condition or clinically significant laboratory values deemed by researchers to be unsuitable for the study All 700 individuals in the original trial were included in the secondary analysis This post hoc analysis was conducted from December 2020 to December 2021 Intervention Once daily fixed dose triple combination pill telmisartan 20 mg amlodipine 2 5 mg and chlorthalidone 12 5 mg therapy vs usual care Main Outcomes and Measures Between group differences in time at target were compared over 24 weeks of follow up with time at target defined as percentage of time at target BP Results There were a total of 700 randomized patients mean SD age 56 11 years 403 57 6
- Published
- 2022
6. Loneliness, Not Social Support, Is Associated with Cognitive Decline and Dementia Across Two Longitudinal Population-Based Cohorts.
- Author
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Freak-Poli, Rosanne, Freak-Poli, Rosanne, Wagemaker, Nina, Wang, Rui, Lysen, Thom S, Ikram, M Arfan, Vernooij, Meike W, Dintica, Christina S, Vernooij-Dassen, Myrra, Melis, Rene JF, Laukka, Erika J, Fratiglioni, Laura, Xu, Weili, Tiemeier, Henning, Freak-Poli, Rosanne, Freak-Poli, Rosanne, Wagemaker, Nina, Wang, Rui, Lysen, Thom S, Ikram, M Arfan, Vernooij, Meike W, Dintica, Christina S, Vernooij-Dassen, Myrra, Melis, Rene JF, Laukka, Erika J, Fratiglioni, Laura, Xu, Weili, and Tiemeier, Henning
- Abstract
BackgroundPoor social health is likely associated with cognitive decline and risk of dementia; however, studies show inconsistent results. Additionally, few studies separate social health components or control for mental health.ObjectiveTo investigate whether loneliness and social support are independently associated with cognitive decline and risk of dementia, and whether depressive symptoms confound the association.MethodsWe included 4,514 participants from the population-based Rotterdam Study (RS; aged 71±7SD years) followed up to 14 years (median 10.8, interquartile range 7.4-11.6), and 2,112 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; aged 72±10SD years) followed up to 10 years (mean 5.9±1.6SD). At baseline, participants were free of major depression and scored on the Mini-Mental State Examination (MMSE) ≥26 for RS and ≥25 for SNAC-K. We investigated loneliness, perceived social support, and structural social support (specifically marital status and number of children). In both cohorts, dementia was diagnosed and cognitive function was repeatedly assessed with MMSE and a global cognitive factor (g-factor).ResultsLoneliness was prospectively associated with a decline in the MMSE in both cohorts. Consistently, persons who were lonely had an increased risk of developing dementia (RS: HR 1.34, 95%CI 1.08-1.67; SNAC-K: HR 2.16, 95%CI 1.12-4.17). Adjustment for depressive symptoms and exclusion of the first 5 years of follow-up did not alter results. Neither perceived or structural social support was associated with cognitive decline or dementia risk.ConclusionLoneliness, not social support, predicted cognitive decline and incident dementia independently of depressive symptoms.
- Published
- 2022
7. Association of Low-Dose Triple Combination Therapy vs Usual Care With Time at Target Blood Pressure: A Secondary Analysis of the TRIUMPH Randomized Clinical Trial
- Author
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Gnanenthiran, SR, Wang, N, DiTanna, GL, Salam, A, Webster, R, DeSilva, HA, Guggilla, R, Jan, S, Maulik, PK, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Schutte, AE, Patel, A, Rodgers, A, Gnanenthiran, SR, Wang, N, DiTanna, GL, Salam, A, Webster, R, DeSilva, HA, Guggilla, R, Jan, S, Maulik, PK, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Schutte, AE, Patel, A, and Rodgers, A
- Abstract
Importance Cumulative exposure to high blood pressure BP is an adverse prognostic marker Assessments of BP control over time such as time at target have been developed but assessments of the effects of BP lowering interventions on such measures are lacking Objective To evaluate whether low dose triple combination antihypertensive therapy was associated with greater rates of time at target compared with usual care Design Setting and Participants The Triple Pill vs Usual Care Management for Patients With Mild to Moderate Hypertension TRIUMPH trial was a open label randomized clinical trial of low dose triple BP therapy vs usual care conducted in urban hospital clinics in Sri Lanka from February 2016 to May 2017 Adults with hypertension systolic BP 140 mm Hg and or diastolic BP 90 mm Hg or in patients with diabetes or chronic kidney disease systolic BP 130 mm Hg and or diastolic BP 80 mm Hg requiring initiation untreated patients or escalation patients receiving monotherapy of antihypertensive therapy were included Patients were excluded if they were currently taking 2 or more blood pressure lowering drugs or had severe or uncontrolled blood pressure accelerated hypertension or physician determined need for slower titration of treatment a contraindication to the triple combination pill therapy an unstable medical condition or clinically significant laboratory values deemed by researchers to be unsuitable for the study All 700 individuals in the original trial were included in the secondary analysis This post hoc analysis was conducted from December 2020 to December 2021 Intervention Once daily fixed dose triple combination pill telmisartan 20 mg amlodipine 2 5 mg and chlorthalidone 12 5 mg therapy vs usual care Main Outcomes and Measures Between group differences in time at target were compared over 24 weeks of follow up with time at target defined as percentage of time at target BP Results There were a total of 700 randomized patients mean SD age 56 11 years 403 57 6
- Published
- 2022
8. Loneliness, Not Social Support, Is Associated with Cognitive Decline and Dementia Across Two Longitudinal Population-Based Cohorts
- Author
-
Freak-Poli, Rosanne, Wagemaker, Nina, Wang, Rui, Lysen, Thom S., Ikram, M. Arfan, Vernooij, Meike W., Dintica, Christina S., Vernooij-Dassen, Myrra, Melis, Rene J.F., Laukka, Erika J., Fratiglioni, Laura, Xu, Weili, Tiemeier, Henning, Freak-Poli, Rosanne, Wagemaker, Nina, Wang, Rui, Lysen, Thom S., Ikram, M. Arfan, Vernooij, Meike W., Dintica, Christina S., Vernooij-Dassen, Myrra, Melis, Rene J.F., Laukka, Erika J., Fratiglioni, Laura, Xu, Weili, and Tiemeier, Henning
- Abstract
Background: Poor social health is likely associated with cognitive decline and risk of dementia; however, studies show inconsistent results. Additionally, few studies separate social health components or control for mental health. Objective: To investigate whether loneliness and social support are independently associated with cognitive decline and risk of dementia, and whether depressive symptoms confound the association. Methods: We included 4,514 participants from the population-based Rotterdam Study (RS; aged 71±7SD years) followed up to 14 years (median 10.8, interquartile range 7.4-11.6), and 2,112 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; aged 72±10SD years) followed up to 10 years (mean 5.9±1.6SD). At baseline, participants were free of major depression and scored on the Mini-Mental State Examination (MMSE) ≥26 for RS and ≥25 for SNAC-K. We investigated loneliness, perceived social support, and structural social support (specifically marital status and number of children). In both cohorts, dementia was diagnosed and cognitive function was repeatedly assessed with MMSE and a global cognitive factor (g-factor). Results: Loneliness was prospectively associated with a decline in the MMSE in both cohorts. Consistently, persons who were lonely had an increased risk of developing dementia (RS: HR 1.34, 95%CI 1.08-1.67; SNAC-K: HR 2.16, 95%CI 1.12-4.17). Adjustment for depressive symptoms and exclusion of the first 5 years of follow-up did not alter results. Neither perceived or structural social support was associated with cognitive decline or dementia risk. Conclusion: Loneliness, not social support, predicted cognitive decline and incident dementia independently of depressive symptoms.
- Published
- 2022
9. Association of Low-Dose Triple Combination Therapy vs Usual Care With Time at Target Blood Pressure: A Secondary Analysis of the TRIUMPH Randomized Clinical Trial
- Author
-
Gnanenthiran, SR, Wang, N, DiTanna, GL, Salam, A, Webster, R, DeSilva, HA, Guggilla, R, Jan, S, Maulik, PK, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Schutte, AE, Patel, A, Rodgers, A, Gnanenthiran, SR, Wang, N, DiTanna, GL, Salam, A, Webster, R, DeSilva, HA, Guggilla, R, Jan, S, Maulik, PK, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Schutte, AE, Patel, A, and Rodgers, A
- Abstract
Importance Cumulative exposure to high blood pressure BP is an adverse prognostic marker Assessments of BP control over time such as time at target have been developed but assessments of the effects of BP lowering interventions on such measures are lacking Objective To evaluate whether low dose triple combination antihypertensive therapy was associated with greater rates of time at target compared with usual care Design Setting and Participants The Triple Pill vs Usual Care Management for Patients With Mild to Moderate Hypertension TRIUMPH trial was a open label randomized clinical trial of low dose triple BP therapy vs usual care conducted in urban hospital clinics in Sri Lanka from February 2016 to May 2017 Adults with hypertension systolic BP 140 mm Hg and or diastolic BP 90 mm Hg or in patients with diabetes or chronic kidney disease systolic BP 130 mm Hg and or diastolic BP 80 mm Hg requiring initiation untreated patients or escalation patients receiving monotherapy of antihypertensive therapy were included Patients were excluded if they were currently taking 2 or more blood pressure lowering drugs or had severe or uncontrolled blood pressure accelerated hypertension or physician determined need for slower titration of treatment a contraindication to the triple combination pill therapy an unstable medical condition or clinically significant laboratory values deemed by researchers to be unsuitable for the study All 700 individuals in the original trial were included in the secondary analysis This post hoc analysis was conducted from December 2020 to December 2021 Intervention Once daily fixed dose triple combination pill telmisartan 20 mg amlodipine 2 5 mg and chlorthalidone 12 5 mg therapy vs usual care Main Outcomes and Measures Between group differences in time at target were compared over 24 weeks of follow up with time at target defined as percentage of time at target BP Results There were a total of 700 randomized patients mean SD age 56 11 years 403 57 6
- Published
- 2022
10. Sleep and perivascular spaces in the middle-aged and elderly population
- Author
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Lysen, Thom S., Yilmaz, Pinar, Dubost, Florian, Ikram, M. Arfan, de Bruijne, Marleen, Vernooij, Meike W., Luik, Annemarie I., Lysen, Thom S., Yilmaz, Pinar, Dubost, Florian, Ikram, M. Arfan, de Bruijne, Marleen, Vernooij, Meike W., and Luik, Annemarie I.
- Abstract
Sleep has been hypothesised to facilitate waste clearance from the brain. We aimed to determine whether sleep is associated with perivascular spaces on brain magnetic resonance imaging (MRI), a potential marker of impaired brain waste clearance, in a population-based cohort of middle-aged and elderly people. In 559 participants (mean [SD] age 62 [6] years, 52% women) from the population-based Rotterdam Study, we measured total sleep time, sleep onset latency, wake after sleep onset and sleep efficiency with actigraphy and polysomnography. Perivascular space load was determined with brain MRI in four regions (centrum semiovale, basal ganglia, hippocampus, and midbrain) via a validated machine learning algorithm using T2-weighted MR images. Associations between sleep characteristics and perivascular space load were analysed with zero-inflated negative binomial regression models adjusted for various confounders. We found that higher actigraphy-estimated sleep efficiency was associated with a higher perivascular space load in the centrum semiovale (odds ratio 1.10, 95% confidence interval 1.04–1.16, p = 0.0008). No other actigraphic or polysomnographic sleep characteristics were associated with perivascular space load in other brain regions. We conclude that, contrary to our hypothesis, associations of sleep with perivascular space load in this middle-aged and elderly population remained limited to an association of a high actigraphy-estimated sleep efficiency with a higher perivascular space load in the centrum semiovale.
- Published
- 2022
11. Sampling-Based Verification of CTMCs with Uncertain Rates
- Author
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Badings, Thom S., Jansen, Nils, Junges, Sebastian, Stoelinga, Marielle, Volk, Matthias, Badings, Thom S., Jansen, Nils, Junges, Sebastian, Stoelinga, Marielle, and Volk, Matthias
- Abstract
We employ uncertain parametric CTMCs with parametric transition rates and a prior on the parameter values. The prior encodes uncertainty about the actual transition rates, while the parameters allow dependencies between transition rates. Sampling the parameter values from the prior distribution then yields a standard CTMC, for which we may compute relevant reachability probabilities. We provide a principled solution, based on a technique called scenario-optimization, to the following problem: From a finite set of parameter samples and a user-specified confidence level, compute prediction regions on the reachability probabilities. The prediction regions should (with high probability) contain the reachability probabilities of a CTMC induced by any additional sample. To boost the scalability of the approach, we employ standard abstraction techniques and adapt our methodology to support approximate reachability probabilities. Experiments with various well-known benchmarks show the applicability of the approach.
- Published
- 2022
- Full Text
- View/download PDF
12. Sleep and perivascular spaces in the middle-aged and elderly population
- Author
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Lysen, Thom S., Yilmaz, Pinar, Dubost, Florian, Ikram, M. Arfan, de Bruijne, Marleen, Vernooij, Meike W., Luik, Annemarie I., Lysen, Thom S., Yilmaz, Pinar, Dubost, Florian, Ikram, M. Arfan, de Bruijne, Marleen, Vernooij, Meike W., and Luik, Annemarie I.
- Abstract
Sleep has been hypothesised to facilitate waste clearance from the brain. We aimed to determine whether sleep is associated with perivascular spaces on brain magnetic resonance imaging (MRI), a potential marker of impaired brain waste clearance, in a population-based cohort of middle-aged and elderly people. In 559 participants (mean [SD] age 62 [6] years, 52% women) from the population-based Rotterdam Study, we measured total sleep time, sleep onset latency, wake after sleep onset and sleep efficiency with actigraphy and polysomnography. Perivascular space load was determined with brain MRI in four regions (centrum semiovale, basal ganglia, hippocampus, and midbrain) via a validated machine learning algorithm using T2-weighted MR images. Associations between sleep characteristics and perivascular space load were analysed with zero-inflated negative binomial regression models adjusted for various confounders. We found that higher actigraphy-estimated sleep efficiency was associated with a higher perivascular space load in the centrum semiovale (odds ratio 1.10, 95% confidence interval 1.04–1.16, p = 0.0008). No other actigraphic or polysomnographic sleep characteristics were associated with perivascular space load in other brain regions. We conclude that, contrary to our hypothesis, associations of sleep with perivascular space load in this middle-aged and elderly population remained limited to an association of a high actigraphy-estimated sleep efficiency with a higher perivascular space load in the centrum semiovale.
- Published
- 2022
13. Sleep and perivascular spaces in the middle-aged and elderly population
- Author
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Lysen, Thom S., Yilmaz, Pinar, Dubost, Florian, Ikram, M. Arfan, de Bruijne, Marleen, Vernooij, Meike W., Luik, Annemarie I., Lysen, Thom S., Yilmaz, Pinar, Dubost, Florian, Ikram, M. Arfan, de Bruijne, Marleen, Vernooij, Meike W., and Luik, Annemarie I.
- Abstract
Sleep has been hypothesised to facilitate waste clearance from the brain. We aimed to determine whether sleep is associated with perivascular spaces on brain magnetic resonance imaging (MRI), a potential marker of impaired brain waste clearance, in a population-based cohort of middle-aged and elderly people. In 559 participants (mean [SD] age 62 [6] years, 52% women) from the population-based Rotterdam Study, we measured total sleep time, sleep onset latency, wake after sleep onset and sleep efficiency with actigraphy and polysomnography. Perivascular space load was determined with brain MRI in four regions (centrum semiovale, basal ganglia, hippocampus, and midbrain) via a validated machine learning algorithm using T2-weighted MR images. Associations between sleep characteristics and perivascular space load were analysed with zero-inflated negative binomial regression models adjusted for various confounders. We found that higher actigraphy-estimated sleep efficiency was associated with a higher perivascular space load in the centrum semiovale (odds ratio 1.10, 95% confidence interval 1.04–1.16, p = 0.0008). No other actigraphic or polysomnographic sleep characteristics were associated with perivascular space load in other brain regions. We conclude that, contrary to our hypothesis, associations of sleep with perivascular space load in this middle-aged and elderly population remained limited to an association of a high actigraphy-estimated sleep efficiency with a higher perivascular space load in the centrum semiovale.
- Published
- 2022
14. Loneliness, Not Social Support, Is Associated with Cognitive Decline and Dementia Across Two Longitudinal Population-Based Cohorts
- Author
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Freak-Poli, Rosanne, Wagemaker, Nina, Wang, Rui, Lysen, Thom S., Ikram, M. Arfan, Vernooij, Meike W., Dintica, Christina S., Vernooij-Dassen, Myrra, Melis, Rene J.M., Laukka, Erica J., Fratiglioni, Laura, Xu, Weili, Tiemeier, Henning, Freak-Poli, Rosanne, Wagemaker, Nina, Wang, Rui, Lysen, Thom S., Ikram, M. Arfan, Vernooij, Meike W., Dintica, Christina S., Vernooij-Dassen, Myrra, Melis, Rene J.M., Laukka, Erica J., Fratiglioni, Laura, Xu, Weili, and Tiemeier, Henning
- Abstract
Background: Poor social health is likely associated with cognitive decline and risk of dementia; however, studies show inconsistent results. Additionally, few studies separate social health components or control for mental health. Objective: To investigate whether loneliness and social support are independently associated with cognitive decline and risk of dementia, and whether depressive symptoms confound the association. Methods: We included 4,514 participants from the population-based Rotterdam Study (RS; aged 71±7SD years) followed up to 14 years (median 10.8, interquartile range 7.4-11.6), and 2,112 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; aged 72±10SD years) followed up to 10 years (mean 5.9±1.6SD). At baseline, participants were free of major depression and scored on the Mini-Mental State Examination (MMSE) ≥26 for RS and ≥25 for SNAC-K. We investigated loneliness, perceived social support, and structural social support (specifically marital status and number of children). In both cohorts, dementia was diagnosed and cognitive function was repeatedly assessed with MMSE and a global cognitive factor (g-factor). Results: Loneliness was prospectively associated with a decline in the MMSE in both cohorts. Consistently, persons who were lonely had an increased risk of developing dementia (RS: HR 1.34, 95%CI 1.08-1.67; SNAC-K: HR 2.16, 95%CI 1.12-4.17). Adjustment for depressive symptoms and exclusion of the first 5 years of follow-up did not alter results. Neither perceived or structural social support was associated with cognitive decline or dementia risk. Conclusion: Loneliness, not social support, predicted cognitive decline and incident dementia independently of depressive symptoms.
- Published
- 2022
- Full Text
- View/download PDF
15. Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis
- Author
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Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-verhoeff, M. Elisabeth, Luijk, Maartje P. C. M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., De Bruin, Eduard J., De Graaf, Ron, Derks, Ivonne P. M., Dewald-kaufmann, Julia F., Elders, Petra J. M., Gemke, Reinoldus J. B. J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W. J. H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, Ten Have, Margreet, Twisk, Jos W. R., Van De Mheen, Dike, Van Der Ende, Jan, Van Der Heijden, Kristiaan B., Van Der Velden, Peter G., Van Lenthe, Frank J., Van Litsenburg, Raphaële R. L., Van Oostrom, Sandra H., Van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C. M., Vermeulen, Roel C. H., Verschuren, W. M. Monique, Vrijkotte, Tanja G. M., Wijga, Alet H., Willemen, Agnes M., Ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J. W., Tiemeier, Henning, Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-verhoeff, M. Elisabeth, Luijk, Maartje P. C. M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., De Bruin, Eduard J., De Graaf, Ron, Derks, Ivonne P. M., Dewald-kaufmann, Julia F., Elders, Petra J. M., Gemke, Reinoldus J. B. J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W. J. H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, Ten Have, Margreet, Twisk, Jos W. R., Van De Mheen, Dike, Van Der Ende, Jan, Van Der Heijden, Kristiaan B., Van Der Velden, Peter G., Van Lenthe, Frank J., Van Litsenburg, Raphaële R. L., Van Oostrom, Sandra H., Van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C. M., Vermeulen, Roel C. H., Verschuren, W. M. Monique, Vrijkotte, Tanja G. M., Wijga, Alet H., Willemen, Agnes M., Ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J. W., and Tiemeier, Henning
- Abstract
We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1–100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40–69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the ‘acceptable’ sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8–10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6–19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending <6 h in bed. TST was similar across countries, but insomnia symptoms were 1.5–2.9 times higher in the United States. Women (≥41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.
- Published
- 2021
16. Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis
- Author
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IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Leerstoel Dekovic, Development and Treatment of Psychosocial Problems, Sub KGP, Urban Accessibility and Social Inclusion, LS IRAS EEPI ME (Milieu epidemiologie), Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-verhoeff, M. Elisabeth, Luijk, Maartje P. C. M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., De Bruin, Eduard J., De Graaf, Ron, Derks, Ivonne P. M., Dewald-kaufmann, Julia F., Elders, Petra J. M., Gemke, Reinoldus J. B. J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W. J. H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, Ten Have, Margreet, Twisk, Jos W. R., Van De Mheen, Dike, Van Der Ende, Jan, Van Der Heijden, Kristiaan B., Van Der Velden, Peter G., Van Lenthe, Frank J., Van Litsenburg, Raphaële R. L., Van Oostrom, Sandra H., Van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C. M., Vermeulen, Roel C. H., Verschuren, W. M. Monique, Vrijkotte, Tanja G. M., Wijga, Alet H., Willemen, Agnes M., Ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J. W., Tiemeier, Henning, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Leerstoel Dekovic, Development and Treatment of Psychosocial Problems, Sub KGP, Urban Accessibility and Social Inclusion, LS IRAS EEPI ME (Milieu epidemiologie), Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-verhoeff, M. Elisabeth, Luijk, Maartje P. C. M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., De Bruin, Eduard J., De Graaf, Ron, Derks, Ivonne P. M., Dewald-kaufmann, Julia F., Elders, Petra J. M., Gemke, Reinoldus J. B. J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W. J. H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, Ten Have, Margreet, Twisk, Jos W. R., Van De Mheen, Dike, Van Der Ende, Jan, Van Der Heijden, Kristiaan B., Van Der Velden, Peter G., Van Lenthe, Frank J., Van Litsenburg, Raphaële R. L., Van Oostrom, Sandra H., Van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C. M., Vermeulen, Roel C. H., Verschuren, W. M. Monique, Vrijkotte, Tanja G. M., Wijga, Alet H., Willemen, Agnes M., Ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J. W., and Tiemeier, Henning
- Published
- 2021
17. Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis
- Author
-
Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-Verhoeff, M. Elisabeth, Luijk, Maartje P.C.M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., de Bruin, Eduard J., de Graaf, Ron, Derks, Ivonne P.M., Dewald-Kaufmann, Julia F., Elders, Petra J.M., Gemke, Reinoldus J.B.J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W.J.H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, ten Have, Margreet, Twisk, Jos W.R., Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B., van der Velden, Peter G., van Lenthe, Frank J., van Litsenburg, Raphaële R.L., van Oostrom, Sandra H., van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C.M., Vermeulen, Roel C.H., Verschuren, W. M.Monique, Vrijkotte, Tanja G.M., Wijga, Alet H., Willemen, Agnes M., ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J.W., Tiemeier, Henning, Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-Verhoeff, M. Elisabeth, Luijk, Maartje P.C.M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., de Bruin, Eduard J., de Graaf, Ron, Derks, Ivonne P.M., Dewald-Kaufmann, Julia F., Elders, Petra J.M., Gemke, Reinoldus J.B.J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W.J.H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, ten Have, Margreet, Twisk, Jos W.R., Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B., van der Velden, Peter G., van Lenthe, Frank J., van Litsenburg, Raphaële R.L., van Oostrom, Sandra H., van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C.M., Vermeulen, Roel C.H., Verschuren, W. M.Monique, Vrijkotte, Tanja G.M., Wijga, Alet H., Willemen, Agnes M., ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J.W., and Tiemeier, Henning
- Abstract
We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1–100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40–69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the ‘acceptable’ sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8–10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6–19.4%) were more prevalent than short sleep duration (6.5% with TST <6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending
- Published
- 2021
- Full Text
- View/download PDF
18. Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis
- Author
-
Kocevska, Desana, Lysen, Thom S, Dotinga, Aafje, Koopman-Verhoeff, M Elisabeth, Luijk, Maartje P C M, Antypa, Niki, Biermasz, Nienke R, Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J, Comijs, Hannie C, Corpeleijn, Eva, Dashti, Hassan S, de Bruin, Eduard J, de Graaf, Ron, Derks, Ivonne P M, Dewald-Kaufmann, Julia F, Elders, Petra J M, Gemke, Reinoldus J B J, Grievink, Linda, Hale, Lauren, Hartman, Catharina A, Heijnen, Cobi J, Huisman, Martijn, Huss, Anke, Ikram, M Arfan, Jones, Samuel E, Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J, Groeniger, Joost Oude, Penninx, Brenda W J H, Picavet, H Susan J, Pieters, Sara, Reijneveld, Sijmen A, Reitz, Ellen, Renders, Carry M, Rodenburg, Gerda, Rutters, Femke, Smith, Matt C, Singh, Amika S, Snijder, Marieke B, Stronks, Karien, Ten Have, Margreet, Twisk, Jos W R, Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B, van der Velden, Peter G, van Lenthe, Frank J, van Litsenburg, Raphaële R L, van Oostrom, Sandra H, van Schalkwijk, Frank J, Sheehan, Connor M, Verheij, Robert A, Verhulst, Frank C, Vermeulen, Marije C M, Vermeulen, Roel C H, Verschuren, W M Monique, Vrijkotte, Tanja G M, Wijga, Alet H, Willemen, Agnes M, Ter Wolbeek, Maike, Wood, Andrew R, Xerxa, Yllza, Bramer, Wichor M, Franco, Oscar H, Luik, Annemarie I, Van Someren, Eus J W, Tiemeier, Henning, Kocevska, Desana, Lysen, Thom S, Dotinga, Aafje, Koopman-Verhoeff, M Elisabeth, Luijk, Maartje P C M, Antypa, Niki, Biermasz, Nienke R, Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J, Comijs, Hannie C, Corpeleijn, Eva, Dashti, Hassan S, de Bruin, Eduard J, de Graaf, Ron, Derks, Ivonne P M, Dewald-Kaufmann, Julia F, Elders, Petra J M, Gemke, Reinoldus J B J, Grievink, Linda, Hale, Lauren, Hartman, Catharina A, Heijnen, Cobi J, Huisman, Martijn, Huss, Anke, Ikram, M Arfan, Jones, Samuel E, Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J, Groeniger, Joost Oude, Penninx, Brenda W J H, Picavet, H Susan J, Pieters, Sara, Reijneveld, Sijmen A, Reitz, Ellen, Renders, Carry M, Rodenburg, Gerda, Rutters, Femke, Smith, Matt C, Singh, Amika S, Snijder, Marieke B, Stronks, Karien, Ten Have, Margreet, Twisk, Jos W R, Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B, van der Velden, Peter G, van Lenthe, Frank J, van Litsenburg, Raphaële R L, van Oostrom, Sandra H, van Schalkwijk, Frank J, Sheehan, Connor M, Verheij, Robert A, Verhulst, Frank C, Vermeulen, Marije C M, Vermeulen, Roel C H, Verschuren, W M Monique, Vrijkotte, Tanja G M, Wijga, Alet H, Willemen, Agnes M, Ter Wolbeek, Maike, Wood, Andrew R, Xerxa, Yllza, Bramer, Wichor M, Franco, Oscar H, Luik, Annemarie I, Van Someren, Eus J W, and Tiemeier, Henning
- Abstract
We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending <6 h in bed. TST was similar across countries, but insomnia symptoms were 1.5-2.9 times higher in the United States. Women (≥41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.
- Published
- 2021
19. Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis
- Author
-
IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Leerstoel Dekovic, Development and Treatment of Psychosocial Problems, Sub KGP, Urban Accessibility and Social Inclusion, LS IRAS EEPI ME (Milieu epidemiologie), Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-verhoeff, M. Elisabeth, Luijk, Maartje P. C. M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., De Bruin, Eduard J., De Graaf, Ron, Derks, Ivonne P. M., Dewald-kaufmann, Julia F., Elders, Petra J. M., Gemke, Reinoldus J. B. J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W. J. H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, Ten Have, Margreet, Twisk, Jos W. R., Van De Mheen, Dike, Van Der Ende, Jan, Van Der Heijden, Kristiaan B., Van Der Velden, Peter G., Van Lenthe, Frank J., Van Litsenburg, Raphaële R. L., Van Oostrom, Sandra H., Van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C. M., Vermeulen, Roel C. H., Verschuren, W. M. Monique, Vrijkotte, Tanja G. M., Wijga, Alet H., Willemen, Agnes M., Ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J. W., Tiemeier, Henning, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Leerstoel Dekovic, Development and Treatment of Psychosocial Problems, Sub KGP, Urban Accessibility and Social Inclusion, LS IRAS EEPI ME (Milieu epidemiologie), Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-verhoeff, M. Elisabeth, Luijk, Maartje P. C. M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., De Bruin, Eduard J., De Graaf, Ron, Derks, Ivonne P. M., Dewald-kaufmann, Julia F., Elders, Petra J. M., Gemke, Reinoldus J. B. J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W. J. H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, Ten Have, Margreet, Twisk, Jos W. R., Van De Mheen, Dike, Van Der Ende, Jan, Van Der Heijden, Kristiaan B., Van Der Velden, Peter G., Van Lenthe, Frank J., Van Litsenburg, Raphaële R. L., Van Oostrom, Sandra H., Van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C. M., Vermeulen, Roel C. H., Verschuren, W. M. Monique, Vrijkotte, Tanja G. M., Wijga, Alet H., Willemen, Agnes M., Ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J. W., and Tiemeier, Henning
- Published
- 2021
20. Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis
- Author
-
IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Leerstoel Dekovic, Development and Treatment of Psychosocial Problems, Sub KGP, Urban Accessibility and Social Inclusion, LS IRAS EEPI ME (Milieu epidemiologie), Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-verhoeff, M. Elisabeth, Luijk, Maartje P. C. M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., De Bruin, Eduard J., De Graaf, Ron, Derks, Ivonne P. M., Dewald-kaufmann, Julia F., Elders, Petra J. M., Gemke, Reinoldus J. B. J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W. J. H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, Ten Have, Margreet, Twisk, Jos W. R., Van De Mheen, Dike, Van Der Ende, Jan, Van Der Heijden, Kristiaan B., Van Der Velden, Peter G., Van Lenthe, Frank J., Van Litsenburg, Raphaële R. L., Van Oostrom, Sandra H., Van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C. M., Vermeulen, Roel C. H., Verschuren, W. M. Monique, Vrijkotte, Tanja G. M., Wijga, Alet H., Willemen, Agnes M., Ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J. W., Tiemeier, Henning, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Leerstoel Dekovic, Development and Treatment of Psychosocial Problems, Sub KGP, Urban Accessibility and Social Inclusion, LS IRAS EEPI ME (Milieu epidemiologie), Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-verhoeff, M. Elisabeth, Luijk, Maartje P. C. M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., De Bruin, Eduard J., De Graaf, Ron, Derks, Ivonne P. M., Dewald-kaufmann, Julia F., Elders, Petra J. M., Gemke, Reinoldus J. B. J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W. J. H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, Ten Have, Margreet, Twisk, Jos W. R., Van De Mheen, Dike, Van Der Ende, Jan, Van Der Heijden, Kristiaan B., Van Der Velden, Peter G., Van Lenthe, Frank J., Van Litsenburg, Raphaële R. L., Van Oostrom, Sandra H., Van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C. M., Vermeulen, Roel C. H., Verschuren, W. M. Monique, Vrijkotte, Tanja G. M., Wijga, Alet H., Willemen, Agnes M., Ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J. W., and Tiemeier, Henning
- Published
- 2021
21. Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis
- Author
-
Kocevska, Desana, Lysen, Thom S, Dotinga, Aafje, Koopman-Verhoeff, M Elisabeth, Luijk, Maartje P C M, Antypa, Niki, Biermasz, Nienke R, Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J, Comijs, Hannie C, Corpeleijn, Eva, Dashti, Hassan S, de Bruin, Eduard J, de Graaf, Ron, Derks, Ivonne P M, Dewald-Kaufmann, Julia F, Elders, Petra J M, Gemke, Reinoldus J B J, Grievink, Linda, Hale, Lauren, Hartman, Catharina A, Heijnen, Cobi J, Huisman, Martijn, Huss, Anke, Ikram, M Arfan, Jones, Samuel E, Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J, Groeniger, Joost Oude, Penninx, Brenda W J H, Picavet, H Susan J, Pieters, Sara, Reijneveld, Sijmen A, Reitz, Ellen, Renders, Carry M, Rodenburg, Gerda, Rutters, Femke, Smith, Matt C, Singh, Amika S, Snijder, Marieke B, Stronks, Karien, Ten Have, Margreet, Twisk, Jos W R, Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B, van der Velden, Peter G, van Lenthe, Frank J, van Litsenburg, Raphaële R L, van Oostrom, Sandra H, van Schalkwijk, Frank J, Sheehan, Connor M, Verheij, Robert A, Verhulst, Frank C, Vermeulen, Marije C M, Vermeulen, Roel C H, Verschuren, W M Monique, Vrijkotte, Tanja G M, Wijga, Alet H, Willemen, Agnes M, Ter Wolbeek, Maike, Wood, Andrew R, Xerxa, Yllza, Bramer, Wichor M, Franco, Oscar H, Luik, Annemarie I, Van Someren, Eus J W, Tiemeier, Henning, Kocevska, Desana, Lysen, Thom S, Dotinga, Aafje, Koopman-Verhoeff, M Elisabeth, Luijk, Maartje P C M, Antypa, Niki, Biermasz, Nienke R, Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J, Comijs, Hannie C, Corpeleijn, Eva, Dashti, Hassan S, de Bruin, Eduard J, de Graaf, Ron, Derks, Ivonne P M, Dewald-Kaufmann, Julia F, Elders, Petra J M, Gemke, Reinoldus J B J, Grievink, Linda, Hale, Lauren, Hartman, Catharina A, Heijnen, Cobi J, Huisman, Martijn, Huss, Anke, Ikram, M Arfan, Jones, Samuel E, Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J, Groeniger, Joost Oude, Penninx, Brenda W J H, Picavet, H Susan J, Pieters, Sara, Reijneveld, Sijmen A, Reitz, Ellen, Renders, Carry M, Rodenburg, Gerda, Rutters, Femke, Smith, Matt C, Singh, Amika S, Snijder, Marieke B, Stronks, Karien, Ten Have, Margreet, Twisk, Jos W R, Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B, van der Velden, Peter G, van Lenthe, Frank J, van Litsenburg, Raphaële R L, van Oostrom, Sandra H, van Schalkwijk, Frank J, Sheehan, Connor M, Verheij, Robert A, Verhulst, Frank C, Vermeulen, Marije C M, Vermeulen, Roel C H, Verschuren, W M Monique, Vrijkotte, Tanja G M, Wijga, Alet H, Willemen, Agnes M, Ter Wolbeek, Maike, Wood, Andrew R, Xerxa, Yllza, Bramer, Wichor M, Franco, Oscar H, Luik, Annemarie I, Van Someren, Eus J W, and Tiemeier, Henning
- Abstract
We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending <6 h in bed. TST was similar across countries, but insomnia symptoms were 1.5-2.9 times higher in the United States. Women (≥41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.
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- 2021
22. Sampling-Based Robust Control of Autonomous Systems with Non-Gaussian Noise
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Badings, Thom S., Abate, Alessandro, Jansen, Nils, Parker, David, Poonawala, Hasan A., Stoelinga, Marielle, Badings, Thom S., Abate, Alessandro, Jansen, Nils, Parker, David, Poonawala, Hasan A., and Stoelinga, Marielle
- Abstract
Controllers for autonomous systems that operate in safety-critical settings must account for stochastic disturbances. Such disturbances are often modelled as process noise, and common assumptions are that the underlying distributions are known and/or Gaussian. In practice, however, these assumptions may be unrealistic and can lead to poor approximations of the true noise distribution. We present a novel planning method that does not rely on any explicit representation of the noise distributions. In particular, we address the problem of computing a controller that provides probabilistic guarantees on safely reaching a target. First, we abstract the continuous system into a discrete-state model that captures noise by probabilistic transitions between states. As a key contribution, we adapt tools from the scenario approach to compute probably approximately correct (PAC) bounds on these transition probabilities, based on a finite number of samples of the noise. We capture these bounds in the transition probability intervals of a so-called interval Markov decision process (iMDP). This iMDP is robust against uncertainty in the transition probabilities, and the tightness of the probability intervals can be controlled through the number of samples. We use state-of-the-art verification techniques to provide guarantees on the iMDP, and compute a controller for which these guarantees carry over to the autonomous system. Realistic benchmarks show the practical applicability of our method, even when the iMDP has millions of states or transitions.
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- 2021
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23. Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis
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Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-Verhoeff, M. Elisabeth, Luijk, Maartje P.C.M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., de Bruin, Eduard J., de Graaf, Ron, Derks, Ivonne P.M., Dewald-Kaufmann, Julia F., Elders, Petra J.M., Gemke, Reinoldus J.B.J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W.J.H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, ten Have, Margreet, Twisk, Jos W.R., Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B., van der Velden, Peter G., van Lenthe, Frank J., van Litsenburg, Raphaële R.L., van Oostrom, Sandra H., van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C.M., Vermeulen, Roel C.H., Verschuren, W. M.Monique, Vrijkotte, Tanja G.M., Wijga, Alet H., Willemen, Agnes M., ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J.W., Tiemeier, Henning, Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-Verhoeff, M. Elisabeth, Luijk, Maartje P.C.M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., de Bruin, Eduard J., de Graaf, Ron, Derks, Ivonne P.M., Dewald-Kaufmann, Julia F., Elders, Petra J.M., Gemke, Reinoldus J.B.J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W.J.H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, ten Have, Margreet, Twisk, Jos W.R., Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B., van der Velden, Peter G., van Lenthe, Frank J., van Litsenburg, Raphaële R.L., van Oostrom, Sandra H., van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C.M., Vermeulen, Roel C.H., Verschuren, W. M.Monique, Vrijkotte, Tanja G.M., Wijga, Alet H., Willemen, Agnes M., ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J.W., and Tiemeier, Henning
- Abstract
We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1–100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40–69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the ‘acceptable’ sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8–10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6–19.4%) were more prevalent than short sleep duration (6.5% with TST <6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending
- Published
- 2021
- Full Text
- View/download PDF
24. Balancing Wind and Batteries: Towards Predictive Verification of Smart Grids
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Badings, Thom S., Hartmanns, Arnd, Jansen, Nils, Suilen, Marnix, Badings, Thom S., Hartmanns, Arnd, Jansen, Nils, and Suilen, Marnix
- Abstract
We study a smart grid with wind power and battery storage. Traditionally, day-ahead planning aims to balance demand and wind power, yet actual wind conditions often deviate from forecasts. Short-term flexibility in storage and generation fills potential gaps, planned on a minutes time scale for 30-60 minute horizons. Finding the optimal flexibility deployment requires solving a semi-infinite non-convex stochastic program, which is generally intractable to do exactly. Previous approaches rely on sampling, yet such critical problems call for rigorous approaches with stronger guarantees. Our method employs probabilistic model checking techniques. First, we cast the problem as a continuous-space Markov decision process with discretized control, for which an optimal deployment strategy minimizes the expected grid frequency deviation. To mitigate state space explosion, we exploit specific structural properties of the model to implement an iterative exploration method that reuses pre-computed values as wind data is updated. Our experiments show the method's feasibility and versatility across grid configurations and time scales.
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- 2021
- Full Text
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25. Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis
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Planetary Health & Exposoom, Circulatory Health, Public Health Epidemiologie, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cluster Onderzoek, Kocevska, Desana, Lysen, Thom S, Dotinga, Aafje, Koopman-Verhoeff, M Elisabeth, Luijk, Maartje P C M, Antypa, Niki, Biermasz, Nienke R, Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J, Comijs, Hannie C, Corpeleijn, Eva, Dashti, Hassan S, de Bruin, Eduard J, de Graaf, Ron, Derks, Ivonne P M, Dewald-Kaufmann, Julia F, Elders, Petra J M, Gemke, Reinoldus J B J, Grievink, Linda, Hale, Lauren, Hartman, Catharina A, Heijnen, Cobi J, Huisman, Martijn, Huss, Anke, Ikram, M Arfan, Jones, Samuel E, Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J, Groeniger, Joost Oude, Penninx, Brenda W J H, Picavet, H Susan J, Pieters, Sara, Reijneveld, Sijmen A, Reitz, Ellen, Renders, Carry M, Rodenburg, Gerda, Rutters, Femke, Smith, Matt C, Singh, Amika S, Snijder, Marieke B, Stronks, Karien, Ten Have, Margreet, Twisk, Jos W R, Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B, van der Velden, Peter G, van Lenthe, Frank J, van Litsenburg, Raphaële R L, van Oostrom, Sandra H, van Schalkwijk, Frank J, Sheehan, Connor M, Verheij, Robert A, Verhulst, Frank C, Vermeulen, Marije C M, Vermeulen, Roel C H, Verschuren, W M Monique, Vrijkotte, Tanja G M, Wijga, Alet H, Willemen, Agnes M, Ter Wolbeek, Maike, Wood, Andrew R, Xerxa, Yllza, Bramer, Wichor M, Franco, Oscar H, Luik, Annemarie I, Van Someren, Eus J W, Tiemeier, Henning, Planetary Health & Exposoom, Circulatory Health, Public Health Epidemiologie, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cluster Onderzoek, Kocevska, Desana, Lysen, Thom S, Dotinga, Aafje, Koopman-Verhoeff, M Elisabeth, Luijk, Maartje P C M, Antypa, Niki, Biermasz, Nienke R, Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J, Comijs, Hannie C, Corpeleijn, Eva, Dashti, Hassan S, de Bruin, Eduard J, de Graaf, Ron, Derks, Ivonne P M, Dewald-Kaufmann, Julia F, Elders, Petra J M, Gemke, Reinoldus J B J, Grievink, Linda, Hale, Lauren, Hartman, Catharina A, Heijnen, Cobi J, Huisman, Martijn, Huss, Anke, Ikram, M Arfan, Jones, Samuel E, Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J, Groeniger, Joost Oude, Penninx, Brenda W J H, Picavet, H Susan J, Pieters, Sara, Reijneveld, Sijmen A, Reitz, Ellen, Renders, Carry M, Rodenburg, Gerda, Rutters, Femke, Smith, Matt C, Singh, Amika S, Snijder, Marieke B, Stronks, Karien, Ten Have, Margreet, Twisk, Jos W R, Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B, van der Velden, Peter G, van Lenthe, Frank J, van Litsenburg, Raphaële R L, van Oostrom, Sandra H, van Schalkwijk, Frank J, Sheehan, Connor M, Verheij, Robert A, Verhulst, Frank C, Vermeulen, Marije C M, Vermeulen, Roel C H, Verschuren, W M Monique, Vrijkotte, Tanja G M, Wijga, Alet H, Willemen, Agnes M, Ter Wolbeek, Maike, Wood, Andrew R, Xerxa, Yllza, Bramer, Wichor M, Franco, Oscar H, Luik, Annemarie I, Van Someren, Eus J W, and Tiemeier, Henning
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- 2021
26. 021 Effects of Low-dose Triple Combination Therapy on Therapeutic Inertia and Prescribing Patterns in Hypertension – Results from the TRIUMPH Trial
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Wang, N ; https://orcid.org/0000-0002-8197-5090, Salam, A, Webster, R ; https://orcid.org/0000-0002-5136-1098, De Silva, A, Guggilla, R, Stepien, S, Mysore, J, Billot, L ; https://orcid.org/0000-0002-4975-9793, Jan, S ; https://orcid.org/0000-0003-2839-1405, Maulik, P ; https://orcid.org/0000-0001-6835-6175, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Patel, A ; https://orcid.org/0000-0003-3825-4092, Rodgers, A ; https://orcid.org/0000-0003-1282-1896, Wang, N ; https://orcid.org/0000-0002-8197-5090, Salam, A, Webster, R ; https://orcid.org/0000-0002-5136-1098, De Silva, A, Guggilla, R, Stepien, S, Mysore, J, Billot, L ; https://orcid.org/0000-0002-4975-9793, Jan, S ; https://orcid.org/0000-0003-2839-1405, Maulik, P ; https://orcid.org/0000-0001-6835-6175, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Patel, A ; https://orcid.org/0000-0003-3825-4092, and Rodgers, A ; https://orcid.org/0000-0003-1282-1896
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- 2020
27. Association of Low-Dose Triple Combination Therapy with Therapeutic Inertia and Prescribing Patterns in Patients with Hypertension: A Secondary Analysis of the TRIUMPH Trial
- Author
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Wang, N ; https://orcid.org/0000-0002-8197-5090, Salam, A, Webster, R ; https://orcid.org/0000-0002-5136-1098, De Silva, A, Guggilla, R, Stepien, S, Mysore, J, Billot, L ; https://orcid.org/0000-0002-4975-9793, Jan, S ; https://orcid.org/0000-0003-2839-1405, Maulik, PK ; https://orcid.org/0000-0001-6835-6175, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Patel, A ; https://orcid.org/0000-0003-3825-4092, Rodgers, A ; https://orcid.org/0000-0003-1282-1896, Mohammad, Mohammad ; https://orcid.org/0000-0002-5870-7936, Wang, N ; https://orcid.org/0000-0002-8197-5090, Salam, A, Webster, R ; https://orcid.org/0000-0002-5136-1098, De Silva, A, Guggilla, R, Stepien, S, Mysore, J, Billot, L ; https://orcid.org/0000-0002-4975-9793, Jan, S ; https://orcid.org/0000-0003-2839-1405, Maulik, PK ; https://orcid.org/0000-0001-6835-6175, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Patel, A ; https://orcid.org/0000-0003-3825-4092, Rodgers, A ; https://orcid.org/0000-0003-1282-1896, and Mohammad, Mohammad ; https://orcid.org/0000-0002-5870-7936
- Abstract
Importance: Fixed-dose combination (FDC) therapies are being increasingly recommended for initial or early management of patients with hypertension, as they reduce treatment complexity and potentially reduce therapeutic inertia. Objective: To investigate the association of antihypertensive triple drug FDC therapy with therapeutic inertia and prescribing patterns compared with usual care. Design, Setting, and Participants: A post hoc analysis of the Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) study, a randomized clinical trial of 700 patients with hypertension, was conducted. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. Data were analyzed from September to November 2019. Interventions: Once-daily FDC antihypertensive pill (telmisartan, 20 mg; amlodipine, 2.5 mg; and chlorthalidone, 12.5 mg) or usual care. Main Outcomes and Measures: Therapeutic inertia, defined as not intensifying therapy in those with blood pressure (BP) above target, was assessed at baseline and during follow-up visits. Prescribing patterns were characterized by BP-lowering drug class and treatment regimen potency. Predictors of therapeutic inertia were assessed with binomial logistic regression. Results: Of the 700 included patients, 403 (57.6%) were female, and the mean (SD) age was 56 (11) years. Among patients who did not reach the BP target, therapeutic inertia was more common in the triple pill group compared with the usual care group at the week 6 visit (92 of 106 [86.8%] vs 124 of 194 [63.9%]; P <.001) and week 12 visit (81 of 90 [90%] vs 116 of 179 [64.8%]; P <.001). At the end of the study, 221 of 318 patients in the triple pill group (69.5%) and 182 of 329 patients in the usual care group (55.3%) reached BP targets. Among those who received treatment intensification, the increase in estimated regimen potency was greater in the triple pill group compare
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- 2020
28. Sleep and resting-state functional magnetic resonance imaging connectivity in middle-aged adults and the elderly: A population-based study
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Lysen, T.S. (Thom S.), Zonneveld, H.I. (Hazel), Muetzel, R.L. (Ryan), Ikram, M.A. (Arfan), Luik, A.I. (Annemarie), Vernooij, M.W. (Meike), Tiemeier, H.W. (Henning), Lysen, T.S. (Thom S.), Zonneveld, H.I. (Hazel), Muetzel, R.L. (Ryan), Ikram, M.A. (Arfan), Luik, A.I. (Annemarie), Vernooij, M.W. (Meike), and Tiemeier, H.W. (Henning)
- Abstract
Sleep problems increase with ageing. Increasing evidence suggests that sleep problems are not only a consequence of age-related processes, but may independently contribute to developing vascular or neurodegenerative brain disease. Yet, it remains unclear what mechanisms underlie the impact sleep problems may have on brain health in the general middle-aged and elderly population. Here, we studied sleep's relation to brain functioning in 621 participants (median age 62 years, 55% women) from the population-based Rotterdam Study. We investigated cross-sectional associations of polysomnographic and subjectively measured aspects of sleep with intrinsic neural activity measured with resting-state functional magnetic resonance imaging on a different day. We investigated both functional connectivity between regions and brain activity (blood-oxygen-level-dependent signal amplitude) within regions, hierarchically towards smaller topographical levels. We found that longer polysomnographic total sleep time is associated with lower blood-oxygen-level-dependent signal amplitude in (pre)frontal regions. No objective or subjective sleep parameters were associated with functional connectivity between or within resting-state networks. The findings may indicate a pathway through which sleep, in a ‘real-life’ population setting, impacts brain activity or regional brain activity determines to
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- 2020
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29. Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States:a systematic review and meta-analysis
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Kocevska, Desana, Lysen, Thom S, Dotinga, Aafje, Koopman-Verhoeff, M Elisabeth, Luijk, Maartje P C M, Antypa, Niki, Biermasz, Nienke R, Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J, Comijs, Hannie C, Corpeleijn, Eva, Dashti, Hassan S, de Bruin, Eduard J, de Graaf, Ron, Derks, Ivonne P M, Dewald-Kaufmann, Julia F, Elders, Petra J M, Gemke, Reinoldus J B J, Grievink, Linda, Hale, Lauren, Hartman, Catharina A, Heijnen, Cobi J, Huisman, Martijn, Huss, Anke, Ikram, M Arfan, Jones, Samuel E, Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J, Groeniger, Joost Oude, Penninx, Brenda W J H, Picavet, H Susan J, Pieters, Sara, Reijneveld, Sijmen A, Reitz, Ellen, Renders, Carry M, Rodenburg, Gerda, Rutters, Femke, Smith, Matt C, Singh, Amika S, Snijder, Marieke B, Stronks, Karien, Ten Have, Margreet, Twisk, Jos W R, Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B, van der Velden, Peter G, van Lenthe, Frank J, van Litsenburg, Raphaële R L, van Oostrom, Sandra H, van Schalkwijk, Frank J, Sheehan, Connor M, Verheij, Robert A, Verhulst, Frank C, Vermeulen, Marije C M, Vermeulen, Roel C H, Verschuren, W M Monique, Vrijkotte, Tanja G M, Wijga, Alet H, Willemen, Agnes M, Ter Wolbeek, Maike, Wood, Andrew R, Xerxa, Yllza, Bramer, Wichor M, Franco, Oscar H, Luik, Annemarie I, Van Someren, Eus J W, Tiemeier, Henning, Kocevska, Desana, Lysen, Thom S, Dotinga, Aafje, Koopman-Verhoeff, M Elisabeth, Luijk, Maartje P C M, Antypa, Niki, Biermasz, Nienke R, Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J, Comijs, Hannie C, Corpeleijn, Eva, Dashti, Hassan S, de Bruin, Eduard J, de Graaf, Ron, Derks, Ivonne P M, Dewald-Kaufmann, Julia F, Elders, Petra J M, Gemke, Reinoldus J B J, Grievink, Linda, Hale, Lauren, Hartman, Catharina A, Heijnen, Cobi J, Huisman, Martijn, Huss, Anke, Ikram, M Arfan, Jones, Samuel E, Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J, Groeniger, Joost Oude, Penninx, Brenda W J H, Picavet, H Susan J, Pieters, Sara, Reijneveld, Sijmen A, Reitz, Ellen, Renders, Carry M, Rodenburg, Gerda, Rutters, Femke, Smith, Matt C, Singh, Amika S, Snijder, Marieke B, Stronks, Karien, Ten Have, Margreet, Twisk, Jos W R, Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B, van der Velden, Peter G, van Lenthe, Frank J, van Litsenburg, Raphaële R L, van Oostrom, Sandra H, van Schalkwijk, Frank J, Sheehan, Connor M, Verheij, Robert A, Verhulst, Frank C, Vermeulen, Marije C M, Vermeulen, Roel C H, Verschuren, W M Monique, Vrijkotte, Tanja G M, Wijga, Alet H, Willemen, Agnes M, Ter Wolbeek, Maike, Wood, Andrew R, Xerxa, Yllza, Bramer, Wichor M, Franco, Oscar H, Luik, Annemarie I, Van Someren, Eus J W, and Tiemeier, Henning
- Abstract
We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending <6 h in bed. TST was similar across countries, but insomnia symptoms were 1.5-2.9 times higher in the United States. Women (≥41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.
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- 2020
30. Association of Low-Dose Triple Combination Therapy With Therapeutic Inertia and Prescribing Patterns in Patients With Hypertension: A Secondary Analysis of the TRIUMPH Trial.
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Wang, N, Salam, A, Webster, R, de Silva, A, Guggilla, R, Stepien, S, Mysore, J, Billot, L, Jan, S, Maulik, PK, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Patel, A, Rodgers, A, TRIUMPH Study Group, Wang, N, Salam, A, Webster, R, de Silva, A, Guggilla, R, Stepien, S, Mysore, J, Billot, L, Jan, S, Maulik, PK, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Patel, A, Rodgers, A, and TRIUMPH Study Group
- Abstract
Importance:Fixed-dose combination (FDC) therapies are being increasingly recommended for initial or early management of patients with hypertension, as they reduce treatment complexity and potentially reduce therapeutic inertia. Objective:To investigate the association of antihypertensive triple drug FDC therapy with therapeutic inertia and prescribing patterns compared with usual care. Design, Setting, and Participants:A post hoc analysis of the Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) study, a randomized clinical trial of 700 patients with hypertension, was conducted. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. Data were analyzed from September to November 2019. Interventions:Once-daily FDC antihypertensive pill (telmisartan, 20 mg; amlodipine, 2.5 mg; and chlorthalidone, 12.5 mg) or usual care. Main Outcomes and Measures:Therapeutic inertia, defined as not intensifying therapy in those with blood pressure (BP) above target, was assessed at baseline and during follow-up visits. Prescribing patterns were characterized by BP-lowering drug class and treatment regimen potency. Predictors of therapeutic inertia were assessed with binomial logistic regression. Results:Of the 700 included patients, 403 (57.6%) were female, and the mean (SD) age was 56 (11) years. Among patients who did not reach the BP target, therapeutic inertia was more common in the triple pill group compared with the usual care group at the week 6 visit (92 of 106 [86.8%] vs 124 of 194 [63.9%]; P < .001) and week 12 visit (81 of 90 [90%] vs 116 of 179 [64.8%]; P < .001). At the end of the study, 221 of 318 patients in the triple pill group (69.5%) and 182 of 329 patients in the usual care group (55.3%) reached BP targets. Among those who received treatment intensification, the increase in estimated regimen potency was greater in the triple pill group compared wi
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- 2020
31. Association of Low-Dose Triple Combination Therapy With Therapeutic Inertia and Prescribing Patterns in Patients With Hypertension: A Secondary Analysis of the TRIUMPH Trial.
- Author
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Wang, N, Salam, A, Webster, R, de Silva, A, Guggilla, R, Stepien, S, Mysore, J, Billot, L, Jan, S, Maulik, PK, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Patel, A, Rodgers, A, TRIUMPH Study Group, Wang, N, Salam, A, Webster, R, de Silva, A, Guggilla, R, Stepien, S, Mysore, J, Billot, L, Jan, S, Maulik, PK, Naik, N, Selak, V, Thom, S, Prabhakaran, D, Patel, A, Rodgers, A, and TRIUMPH Study Group
- Abstract
Importance:Fixed-dose combination (FDC) therapies are being increasingly recommended for initial or early management of patients with hypertension, as they reduce treatment complexity and potentially reduce therapeutic inertia. Objective:To investigate the association of antihypertensive triple drug FDC therapy with therapeutic inertia and prescribing patterns compared with usual care. Design, Setting, and Participants:A post hoc analysis of the Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) study, a randomized clinical trial of 700 patients with hypertension, was conducted. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. Data were analyzed from September to November 2019. Interventions:Once-daily FDC antihypertensive pill (telmisartan, 20 mg; amlodipine, 2.5 mg; and chlorthalidone, 12.5 mg) or usual care. Main Outcomes and Measures:Therapeutic inertia, defined as not intensifying therapy in those with blood pressure (BP) above target, was assessed at baseline and during follow-up visits. Prescribing patterns were characterized by BP-lowering drug class and treatment regimen potency. Predictors of therapeutic inertia were assessed with binomial logistic regression. Results:Of the 700 included patients, 403 (57.6%) were female, and the mean (SD) age was 56 (11) years. Among patients who did not reach the BP target, therapeutic inertia was more common in the triple pill group compared with the usual care group at the week 6 visit (92 of 106 [86.8%] vs 124 of 194 [63.9%]; P < .001) and week 12 visit (81 of 90 [90%] vs 116 of 179 [64.8%]; P < .001). At the end of the study, 221 of 318 patients in the triple pill group (69.5%) and 182 of 329 patients in the usual care group (55.3%) reached BP targets. Among those who received treatment intensification, the increase in estimated regimen potency was greater in the triple pill group compared wi
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- 2020
32. The prospective association of objectively measured sleep and cerebral white matter microstructure in middle-aged and older persons
- Author
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Kocevska, D, Tiemeier, Henning, Lysen, Thom S, de Groot, Marius, Muetzel, Ryan L, Van Someren, Eus J W, Ikram, M Arfan, Vernooij, Meike W, Luik, Annemarie I, Kocevska, D, Tiemeier, Henning, Lysen, Thom S, de Groot, Marius, Muetzel, Ryan L, Van Someren, Eus J W, Ikram, M Arfan, Vernooij, Meike W, and Luik, Annemarie I
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- 2019
33. Reaching cardiovascular prevention guideline targets with a polypill-based approach: A meta-Analysis of randomised clinical trials
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Selak, V, Webster, R ; https://orcid.org/0000-0002-5136-1098, Stepien, S, Bullen, C, Patel, A ; https://orcid.org/0000-0003-3825-4092, Thom, S, Arroll, B, Bots, ML, Brown, A, Crengle, S, Dorairaj, P, Elley, CR, Grobbee, DE, Harwood, M, Hillis, GS, Laba, TL, Neal, B ; https://orcid.org/0000-0002-0490-7465, Peiris, D ; https://orcid.org/0000-0002-6898-3870, Rafter, N, Reid, C, Stanton, A, Tonkin, A, Usherwood, T, Wadham, A, Rodgers, A ; https://orcid.org/0000-0003-1282-1896, Selak, V, Webster, R ; https://orcid.org/0000-0002-5136-1098, Stepien, S, Bullen, C, Patel, A ; https://orcid.org/0000-0003-3825-4092, Thom, S, Arroll, B, Bots, ML, Brown, A, Crengle, S, Dorairaj, P, Elley, CR, Grobbee, DE, Harwood, M, Hillis, GS, Laba, TL, Neal, B ; https://orcid.org/0000-0002-0490-7465, Peiris, D ; https://orcid.org/0000-0002-6898-3870, Rafter, N, Reid, C, Stanton, A, Tonkin, A, Usherwood, T, Wadham, A, and Rodgers, A ; https://orcid.org/0000-0003-1282-1896
- Abstract
Objective The aim of this study was to determine the effect of polypill-based care on the achievement of 2016 European Society of Cardiology (ESC) guideline targets for blood pressure (BP), low-density lipoprotein (LDL) cholesterol and antiplatelet therapy. Methods We conducted an individual participant data meta-Analysis of three randomised clinical trials that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior cardiovascular disease (CVD) event or who were at high risk of their first event. Overall, the trials included 3140 patients from Australia, England, India, Ireland, the Netherlands and New Zealand (75% male, mean age 62 years and 76% with a prior CVD event). The primary outcome for this study was the proportion of people achieving ESC guideline targets for BP, LDL and antiplatelet therapy. Results Those randomised to polypill-based care were more likely than those receiving usual care to achieve recommended targets for BP (62% vs 58%, risk ratio (RR) 1.08, 95% CI 1.02 to 1.15), LDL (39% vs 34%, RR 1.13, 95% CI 1.02 to 1.25) and all three targets for BP, LDL and adherence to antiplatelet therapy (the latter only applicable to those with a prior CVD event) simultaneously (24% vs 19%, RR 1.27, 95% CI 1.10 to 1.47) at 12 months. There was no difference between groups in antiplatelet adherence (96% vs 96%, RR 1.00, 95% CI 0.98 to 1.01). There was heterogeneity by baseline treatment intensity such that treatment effects increased with the fewer the number of treatments being taken at baseline: for patients taking 3, 2 and 0-1 treatment modalities the RRs for reaching all three guideline goals simultaneously were 1.10 (95% CI 0.94 to 1.30, 22% vs 20%), 1.62 (95% CI 1.09 to 2.42, 27% vs 17%) and 3.07 (95% CI 1.77 to 5.33, 35% vs 11%), respectively. Conclusions Polypill-based therapy significantly improved the achievement of all three ESC targets for BP, LDL and antiplatelet therapy c
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- 2019
34. Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial
- Author
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Lung, T ; https://orcid.org/0000-0001-9978-6311, Jan, S ; https://orcid.org/0000-0003-2839-1405, de Silva, HA, Guggilla, R, Maulik, PK ; https://orcid.org/0000-0001-6835-6175, Naik, N, Patel, A ; https://orcid.org/0000-0003-3825-4092, de Silva, AP, Rajapakse, S, Ranasinghe, G, Prabhakaran, D, Rodgers, A ; https://orcid.org/0000-0003-1282-1896, Salam, A, Selak, V, Stepien, S, Thom, S, Webster, R ; https://orcid.org/0000-0002-5136-1098, Lea-Laba, T, Mohammad, Mohammad ; https://orcid.org/0000-0002-5870-7936, Lung, T ; https://orcid.org/0000-0001-9978-6311, Jan, S ; https://orcid.org/0000-0003-2839-1405, de Silva, HA, Guggilla, R, Maulik, PK ; https://orcid.org/0000-0001-6835-6175, Naik, N, Patel, A ; https://orcid.org/0000-0003-3825-4092, de Silva, AP, Rajapakse, S, Ranasinghe, G, Prabhakaran, D, Rodgers, A ; https://orcid.org/0000-0003-1282-1896, Salam, A, Selak, V, Stepien, S, Thom, S, Webster, R ; https://orcid.org/0000-0002-5136-1098, Lea-Laba, T, and Mohammad, Mohammad ; https://orcid.org/0000-0002-5870-7936
- Abstract
Background: Elevated blood pressure incurs a major health and economic burden, particularly in low-income and middle-income countries. The Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial showed a greater reduction in blood pressure in patients using fixed-combination, low-dose, triple-pill antihypertensive therapy (consisting of amlodipine, telmisartan, and chlorthalidone) than in those receiving usual care in Sri Lanka. We aimed to assess the cost-effectiveness of the triple-pill strategy. Methods: We did a within-trial (6-month) and modelled (10-year) economic evaluation of the TRIUMPH trial, using the health system perspective. Health-care costs, reported in 2017 US dollars, were determined from trial records and published literature. A discrete-time simulation model was developed, extrapolating trial findings of reduced systolic blood pressure to 10-year health-care costs, cardiovascular disease events, and mortality. The primary outcomes were the proportion of people reaching blood pressure targets (at 6 months from baseline) and disability-adjusted life-years (DALYs) averted (at 10 years from baseline). Incremental cost-effectiveness ratios were calculated to estimate the cost per additional participant achieving target blood pressure at 6 months and cost per DALY averted over 10 years. Findings: The triple-pill strategy, compared with usual care, cost an additional US$9·63 (95% CI 5·29 to 13·97) per person in the within-trial analysis and $347·75 (285·55 to 412·54) per person in the modelled analysis. Incremental cost-effectiveness ratios were estimated at $7·93 (95% CI 6·59 to 11·84) per participant reaching blood pressure targets at 6 months and $2842·79 (−28·67 to 5714·24) per DALY averted over a 10-year period. Interpretation: Compared with usual care, the triple-pill strategy is cost-effective for patients with mild-to-moderate hypertension. Scaled up investment in the triple pill for hypertension
- Published
- 2019
35. Reaching cardiovascular prevention guideline targets with a polypill-based approach: A meta-Analysis of randomised clinical trials
- Author
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Selak, V, Webster, R, Stepien, S, Bullen, C, Patel, A, Thom, S, Arroll, B, Bots, ML, Brown, A, Crengle, S, Dorairaj, P, Elley, CR, Grobbee, DE, Harwood, M, Hillis, GS, Laba, TL, Neal, B, Peiris, D, Rafter, N, Reid, C, Stanton, A, Tonkin, A, Usherwood, T, Wadham, A, Rodgers, A, Selak, V, Webster, R, Stepien, S, Bullen, C, Patel, A, Thom, S, Arroll, B, Bots, ML, Brown, A, Crengle, S, Dorairaj, P, Elley, CR, Grobbee, DE, Harwood, M, Hillis, GS, Laba, TL, Neal, B, Peiris, D, Rafter, N, Reid, C, Stanton, A, Tonkin, A, Usherwood, T, Wadham, A, and Rodgers, A
- Abstract
© © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Objective The aim of this study was to determine the effect of polypill-based care on the achievement of 2016 European Society of Cardiology (ESC) guideline targets for blood pressure (BP), low-density lipoprotein (LDL) cholesterol and antiplatelet therapy. Methods We conducted an individual participant data meta-Analysis of three randomised clinical trials that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior cardiovascular disease (CVD) event or who were at high risk of their first event. Overall, the trials included 3140 patients from Australia, England, India, Ireland, the Netherlands and New Zealand (75% male, mean age 62 years and 76% with a prior CVD event). The primary outcome for this study was the proportion of people achieving ESC guideline targets for BP, LDL and antiplatelet therapy. Results Those randomised to polypill-based care were more likely than those receiving usual care to achieve recommended targets for BP (62% vs 58%, risk ratio (RR) 1.08, 95% CI 1.02 to 1.15), LDL (39% vs 34%, RR 1.13, 95% CI 1.02 to 1.25) and all three targets for BP, LDL and adherence to antiplatelet therapy (the latter only applicable to those with a prior CVD event) simultaneously (24% vs 19%, RR 1.27, 95% CI 1.10 to 1.47) at 12 months. There was no difference between groups in antiplatelet adherence (96% vs 96%, RR 1.00, 95% CI 0.98 to 1.01). There was heterogeneity by baseline treatment intensity such that treatment effects increased with the fewer the number of treatments being taken at baseline: for patients taking 3, 2 and 0-1 treatment modalities the RRs for reaching all three guideline goals simultaneously were 1.10 (95% CI 0.94 to 1.30, 22% vs 20%), 1.62 (95% CI 1.09 to 2.42, 27% vs 17%) and 3
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- 2019
36. Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial
- Author
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Lung, T, Jan, S, de Silva, HA, Guggilla, R, Maulik, PK, Naik, N, Patel, A, de Silva, AP, Rajapakse, S, Ranasinghe, G, Prabhakaran, D, Rodgers, A, Salam, A, Selak, V, Stepien, S, Thom, S, Webster, R, Lea-Laba, T, Lung, T, Jan, S, de Silva, HA, Guggilla, R, Maulik, PK, Naik, N, Patel, A, de Silva, AP, Rajapakse, S, Ranasinghe, G, Prabhakaran, D, Rodgers, A, Salam, A, Selak, V, Stepien, S, Thom, S, Webster, R, and Lea-Laba, T
- Abstract
© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license Background: Elevated blood pressure incurs a major health and economic burden, particularly in low-income and middle-income countries. The Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial showed a greater reduction in blood pressure in patients using fixed-combination, low-dose, triple-pill antihypertensive therapy (consisting of amlodipine, telmisartan, and chlorthalidone) than in those receiving usual care in Sri Lanka. We aimed to assess the cost-effectiveness of the triple-pill strategy. Methods: We did a within-trial (6-month) and modelled (10-year) economic evaluation of the TRIUMPH trial, using the health system perspective. Health-care costs, reported in 2017 US dollars, were determined from trial records and published literature. A discrete-time simulation model was developed, extrapolating trial findings of reduced systolic blood pressure to 10-year health-care costs, cardiovascular disease events, and mortality. The primary outcomes were the proportion of people reaching blood pressure targets (at 6 months from baseline) and disability-adjusted life-years (DALYs) averted (at 10 years from baseline). Incremental cost-effectiveness ratios were calculated to estimate the cost per additional participant achieving target blood pressure at 6 months and cost per DALY averted over 10 years. Findings: The triple-pill strategy, compared with usual care, cost an additional US$9·63 (95% CI 5·29 to 13·97) per person in the within-trial analysis and $347·75 (285·55 to 412·54) per person in the modelled analysis. Incremental cost-effectiveness ratios were estimated at $7·93 (95% CI 6·59 to 11·84) per participant reaching blood pressure targets at 6 months and $2842·79 (−28·67 to 5714·24) per DALY averted over a 10-year period. Interpretation: Compared with usual care, the triple-pill strategy is cost-ef
- Published
- 2019
37. Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial
- Author
-
Lung, T, Jan, S, de Silva, HA, Guggilla, R, Maulik, PK, Naik, N, Patel, A, de Silva, AP, Rajapakse, S, Ranasinghe, G, Prabhakaran, D, Rodgers, A, Salam, A, Selak, V, Stepien, S, Thom, S, Webster, R, Lea-Laba, T, Lung, T, Jan, S, de Silva, HA, Guggilla, R, Maulik, PK, Naik, N, Patel, A, de Silva, AP, Rajapakse, S, Ranasinghe, G, Prabhakaran, D, Rodgers, A, Salam, A, Selak, V, Stepien, S, Thom, S, Webster, R, and Lea-Laba, T
- Abstract
© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license Background: Elevated blood pressure incurs a major health and economic burden, particularly in low-income and middle-income countries. The Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial showed a greater reduction in blood pressure in patients using fixed-combination, low-dose, triple-pill antihypertensive therapy (consisting of amlodipine, telmisartan, and chlorthalidone) than in those receiving usual care in Sri Lanka. We aimed to assess the cost-effectiveness of the triple-pill strategy. Methods: We did a within-trial (6-month) and modelled (10-year) economic evaluation of the TRIUMPH trial, using the health system perspective. Health-care costs, reported in 2017 US dollars, were determined from trial records and published literature. A discrete-time simulation model was developed, extrapolating trial findings of reduced systolic blood pressure to 10-year health-care costs, cardiovascular disease events, and mortality. The primary outcomes were the proportion of people reaching blood pressure targets (at 6 months from baseline) and disability-adjusted life-years (DALYs) averted (at 10 years from baseline). Incremental cost-effectiveness ratios were calculated to estimate the cost per additional participant achieving target blood pressure at 6 months and cost per DALY averted over 10 years. Findings: The triple-pill strategy, compared with usual care, cost an additional US$9·63 (95% CI 5·29 to 13·97) per person in the within-trial analysis and $347·75 (285·55 to 412·54) per person in the modelled analysis. Incremental cost-effectiveness ratios were estimated at $7·93 (95% CI 6·59 to 11·84) per participant reaching blood pressure targets at 6 months and $2842·79 (−28·67 to 5714·24) per DALY averted over a 10-year period. Interpretation: Compared with usual care, the triple-pill strategy is cost-ef
- Published
- 2019
38. Reaching cardiovascular prevention guideline targets with a polypill-based approach: A meta-Analysis of randomised clinical trials
- Author
-
Selak, V, Webster, R, Stepien, S, Bullen, C, Patel, A, Thom, S, Arroll, B, Bots, ML, Brown, A, Crengle, S, Dorairaj, P, Elley, CR, Grobbee, DE, Harwood, M, Hillis, GS, Laba, TL, Neal, B, Peiris, D, Rafter, N, Reid, C, Stanton, A, Tonkin, A, Usherwood, T, Wadham, A, Rodgers, A, Selak, V, Webster, R, Stepien, S, Bullen, C, Patel, A, Thom, S, Arroll, B, Bots, ML, Brown, A, Crengle, S, Dorairaj, P, Elley, CR, Grobbee, DE, Harwood, M, Hillis, GS, Laba, TL, Neal, B, Peiris, D, Rafter, N, Reid, C, Stanton, A, Tonkin, A, Usherwood, T, Wadham, A, and Rodgers, A
- Abstract
© © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Objective The aim of this study was to determine the effect of polypill-based care on the achievement of 2016 European Society of Cardiology (ESC) guideline targets for blood pressure (BP), low-density lipoprotein (LDL) cholesterol and antiplatelet therapy. Methods We conducted an individual participant data meta-Analysis of three randomised clinical trials that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior cardiovascular disease (CVD) event or who were at high risk of their first event. Overall, the trials included 3140 patients from Australia, England, India, Ireland, the Netherlands and New Zealand (75% male, mean age 62 years and 76% with a prior CVD event). The primary outcome for this study was the proportion of people achieving ESC guideline targets for BP, LDL and antiplatelet therapy. Results Those randomised to polypill-based care were more likely than those receiving usual care to achieve recommended targets for BP (62% vs 58%, risk ratio (RR) 1.08, 95% CI 1.02 to 1.15), LDL (39% vs 34%, RR 1.13, 95% CI 1.02 to 1.25) and all three targets for BP, LDL and adherence to antiplatelet therapy (the latter only applicable to those with a prior CVD event) simultaneously (24% vs 19%, RR 1.27, 95% CI 1.10 to 1.47) at 12 months. There was no difference between groups in antiplatelet adherence (96% vs 96%, RR 1.00, 95% CI 0.98 to 1.01). There was heterogeneity by baseline treatment intensity such that treatment effects increased with the fewer the number of treatments being taken at baseline: for patients taking 3, 2 and 0-1 treatment modalities the RRs for reaching all three guideline goals simultaneously were 1.10 (95% CI 0.94 to 1.30, 22% vs 20%), 1.62 (95% CI 1.09 to 2.42, 27% vs 17%) and 3
- Published
- 2019
39. Reaching cardiovascular prevention guideline targets with a polypill-based approach: A meta-Analysis of randomised clinical trials
- Author
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Selak, V., Webster, R., Stepien, S., Bullen, C., Patel, A., Thom, S., Arroll, B., Bots, M., Brown, A., Crengle, S., Dorairaj, P., Elley, C., Grobbee, D., Harwood, M., Hillis, G., Laba, T., Neal, B., Peiris, D., Rafter, N., Reid, Christopher, Stanton, A., Tonkin, A., Usherwood, T., Wadham, A., Rodgers, A., Selak, V., Webster, R., Stepien, S., Bullen, C., Patel, A., Thom, S., Arroll, B., Bots, M., Brown, A., Crengle, S., Dorairaj, P., Elley, C., Grobbee, D., Harwood, M., Hillis, G., Laba, T., Neal, B., Peiris, D., Rafter, N., Reid, Christopher, Stanton, A., Tonkin, A., Usherwood, T., Wadham, A., and Rodgers, A.
- Abstract
Objective: The aim of this study was to determine the effect of polypill-based care on the achievement of 2016 European Society of Cardiology (ESC) guideline targets for blood pressure (BP), low-density lipoprotein (LDL) cholesterol and antiplatelet therapy. Methods: We conducted an individual participant data meta-Analysis of three randomised clinical trials that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior cardiovascular disease (CVD) event or who were at high risk of their first event. Overall, the trials included 3140 patients from Australia, England, India, Ireland, the Netherlands and New Zealand (75% male, mean age 62 years and 76% with a prior CVD event). The primary outcome for this study was the proportion of people achieving ESC guideline targets for BP, LDL and antiplatelet therapy. Results: Those randomised to polypill-based care were more likely than those receiving usual care to achieve recommended targets for BP (62% vs 58%, risk ratio (RR) 1.08, 95% CI 1.02 to 1.15), LDL (39% vs 34%, RR 1.13, 95% CI 1.02 to 1.25) and all three targets for BP, LDL and adherence to antiplatelet therapy (the latter only applicable to those with a prior CVD event) simultaneously (24% vs 19%, RR 1.27, 95% CI 1.10 to 1.47) at 12 months. There was no difference between groups in antiplatelet adherence (96% vs 96%, RR 1.00, 95% CI 0.98 to 1.01). There was heterogeneity by baseline treatment intensity such that treatment effects increased with the fewer the number of treatments being taken at baseline: for patients taking 3, 2 and 0-1 treatment modalities the RRs for reaching all three guideline goals simultaneously were 1.10 (95% CI 0.94 to 1.30, 22% vs 20%), 1.62 (95% CI 1.09 to 2.42, 27% vs 17%) and 3.07 (95% CI 1.77 to 5.33, 35% vs 11%), respectively. Conclusions: Polypill-based therapy significantly improved the achievement of all three ESC targets for BP, LDL and antiplatelet thera
- Published
- 2019
40. A protocol for an economic evaluation of a polypill in patients with established or at high risk of cardiovascular disease in a UK NHS setting: RUPEE (NHS) study
- Author
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Crossan, C, Dehbi, HM, Williams, H, Poulter, N, Rodgers, A ; https://orcid.org/0000-0003-1282-1896, Jan, S ; https://orcid.org/0000-0003-2839-1405, Thom, S, Lord, J, Crossan, C, Dehbi, HM, Williams, H, Poulter, N, Rodgers, A ; https://orcid.org/0000-0003-1282-1896, Jan, S ; https://orcid.org/0000-0003-2839-1405, Thom, S, and Lord, J
- Abstract
Introduction The Use of a Multi-drug Pill in Reducing cardiovascular Events' (UMPIRE) trial was a randomised controlled clinical trial evaluating the impact of a polypill strategy on adherence to indicated medication in a population with established cardiovascular disease (CVD) of or at high risk thereof. The aim of Researching the UMPIRE Processes for Economic Evaluation in the National Health Service (RUPEE NHS) is to estimate the potential health economic impact of a polypill strategy for CVD prevention within the NHS using UMPIRE trial and other relevant data. This paper describes the design of a modelled economic evaluation of the impact of increased adherence to the polypill versus usual care among the UK UMPIRE participants. Methods and analysis As recommended by the International Society for Pharmacoeconomics and Outcomes Research and the Society for Medical Decision Making modelling guidelines, a review of published CVD models was undertaken to identify the most appropriate modelling approach and structure. The review was carried out in the electronic databases, MEDLINE and EMBASE. 40 CVD models were identified from 57 studies, the majority of economic models were health state transition cohort models and individual-level simulation models. The findings were discussed with clinical experts to confirm the approach and structure. An individual simulation approach was identified as the most suitable method to capture the heterogeneity in the population at CVD risk. RUPEE-NHS will use UMPIRE trial data on adherence to estimate the long-term cost-effectiveness of the polypill strategy. Dissemination The evaluation findings will be presented in open-access scientific and healthcare policy journals and at national and international conferences. We will also present findings to NHS policy makers and pharmaceutical companies.
- Published
- 2018
41. Validity of the Maudsley Staging Method in Predicting Treatment-Resistant Depression Outcome Using the Netherlands Study of Depression and Anxiety
- Author
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van Belkum, Sjoerd M., van Belkum, Sjoerd M., Geugies, Hanneke, Lysen, Thom S., Cleare, Anthony J., Peeters, Frenk P. M. L., Penninx, Brenda W. J. H., Schoevers, Robert A., Ruhe, Henricus G., van Belkum, Sjoerd M., van Belkum, Sjoerd M., Geugies, Hanneke, Lysen, Thom S., Cleare, Anthony J., Peeters, Frenk P. M. L., Penninx, Brenda W. J. H., Schoevers, Robert A., and Ruhe, Henricus G.
- Abstract
Objective: We investigated if the degree of treatment resistance of depression, as measured by the Maudsley Staging Method (MSM), is predictive of a worse depression outcome by using a large naturalistic cohort of depressed patients. Methods: 643 subjects from the general population, primary care, and secondary care who suffered from current depressive disorder were included from the Netherlands Study of Depression and Anxiety baseline assessment. The diagnostic criterion was major depressive disorder (MDD) in the last month, based on the Composite Interview Diagnostic Instrument (CIDI), or a CIDI diagnosis of MDD in the past 6 months with an Inventory of Depressive Symptomatology Self-Report score > 24 at baseline. In these subjects, composite scores of the MSM, based on duration, severity, and treatment history of current episode, were determined retrospectively. We then determined if the MSM score prospectively predicted the 2-year course of depression after baseline. The primary outcomes were percentage of follow-up time spent in a depressive episode and being "mostly depressed" (>= 50% of the follow-up) between baseline and 2-year follow-up. Results: The MSM predicted "percentage of follow-up time with depression" (P < .001) and was associated with being "mostly depressed" (OR = 1.40; 95% CI, 1.23-1.60; P < .001). These effects were not modified by having received treatment. Conclusions: The current study shows that the MSM is a promising tool to predict worse depression outcomes in depressed patients. In this study that adds to previous work, we show the applicability of MSM in a wider range of primary and secondary care patients with depression.
- Published
- 2018
42. Cost-effectiveness of a fixed dose combination (polypill) in secondary prevention of cardiovascular diseases in India: Within-trial cost-effectiveness analysis of the UMPIRE trial.
- Author
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Singh, K, Crossan, C, Laba, T-L, Roy, A, Hayes, A, Salam, A, Jan, S, Lord, J, Tandon, N, Rodgers, A, Patel, A, Thom, S, Prabhakaran, D, Singh, K, Crossan, C, Laba, T-L, Roy, A, Hayes, A, Salam, A, Jan, S, Lord, J, Tandon, N, Rodgers, A, Patel, A, Thom, S, and Prabhakaran, D
- Abstract
BACKGROUND: The Use of Multidrug Pill In Reducing cardiovascular Events (UMPIRE) trial, showed that access to a cardiovascular polypill (aspirin, statin and two blood pressure lowering drugs) significantly improved adherence, lowered systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDLc) in patients with or at high risk of cardiovascular disease (CVD). We aimed to analyze the within-trial cost-effectiveness of the polypill strategy versus usual care in India. METHODS: Relative effectiveness and costs of polypill versus usual care groups in UMPIRE were estimated from the health sector perspective. Only direct medical costs were considered. The effectiveness of the polypill was reported as a percentage increase in adherence and mean reductions in SBP, and LDL-c, over the 15-month trial period. Healthcare resource utilization and costs were collected for each patient during the trial. Polypill price was constructed using a range of scenarios: $0.06-$0.94/day. The cost-effectiveness of the polypill was measured as the additional cost for 10% increase in adherence, and per unit reduction in SBP and LDL-c. RESULTS: Overall, the mean cost per patient was significantly lower with the polypill strategy (-$203 per person, (95% CI: -286, -119, p < 0.01). In scenario analyses that varied polypill price assumptions, incremental cost-effectiveness ratios for a polypill strategy ranged between cost-saving to $75 per 10% increase in adherence for polypill price of $0.94 per day. CONCLUSIONS: The polypill strategy was cost-saving compared to usual care among patients with or at high risk of CVD in India.
- Published
- 2018
43. Validity of the Maudsley Staging Method in Predicting Treatment-Resistant Depression Outcome Using the Netherlands Study of Depression and Anxiety
- Author
-
van Belkum, Sjoerd M., Geugies, Hanneke, Lysen, Thom S., Cleare, Anthony J., Peeters, Frenk P. M. L., Penninx, Brenda W. J. H., Schoevers, Robert A., Ruhe, Henricus G., van Belkum, Sjoerd M., Geugies, Hanneke, Lysen, Thom S., Cleare, Anthony J., Peeters, Frenk P. M. L., Penninx, Brenda W. J. H., Schoevers, Robert A., and Ruhe, Henricus G.
- Abstract
Objective: We investigated if the degree of treatment resistance of depression, as measured by the Maudsley Staging Method (MSM), is predictive of a worse depression outcome by using a large naturalistic cohort of depressed patients. Methods: 643 subjects from the general population, primary care, and secondary care who suffered from current depressive disorder were included from the Netherlands Study of Depression and Anxiety baseline assessment. The diagnostic criterion was major depressive disorder (MDD) in the last month, based on the Composite Interview Diagnostic Instrument (CIDI), or a CIDI diagnosis of MDD in the past 6 months with an Inventory of Depressive Symptomatology Self-Report score > 24 at baseline. In these subjects, composite scores of the MSM, based on duration, severity, and treatment history of current episode, were determined retrospectively. We then determined if the MSM score prospectively predicted the 2-year course of depression after baseline. The primary outcomes were percentage of follow-up time spent in a depressive episode and being "mostly depressed" (>= 50% of the follow-up) between baseline and 2-year follow-up. Results: The MSM predicted "percentage of follow-up time with depression" (P < .001) and was associated with being "mostly depressed" (OR = 1.40; 95% CI, 1.23-1.60; P < .001). These effects were not modified by having received treatment. Conclusions: The current study shows that the MSM is a promising tool to predict worse depression outcomes in depressed patients. In this study that adds to previous work, we show the applicability of MSM in a wider range of primary and secondary care patients with depression.
- Published
- 2018
44. Cost-effectiveness of a fixed dose combination (polypill) in secondary prevention of cardiovascular diseases in India: Within-trial cost-effectiveness analysis of the UMPIRE trial.
- Author
-
Singh, K, Crossan, C, Laba, T-L, Roy, A, Hayes, A, Salam, A, Jan, S, Lord, J, Tandon, N, Rodgers, A, Patel, A, Thom, S, Prabhakaran, D, Singh, K, Crossan, C, Laba, T-L, Roy, A, Hayes, A, Salam, A, Jan, S, Lord, J, Tandon, N, Rodgers, A, Patel, A, Thom, S, and Prabhakaran, D
- Abstract
BACKGROUND: The Use of Multidrug Pill In Reducing cardiovascular Events (UMPIRE) trial, showed that access to a cardiovascular polypill (aspirin, statin and two blood pressure lowering drugs) significantly improved adherence, lowered systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDLc) in patients with or at high risk of cardiovascular disease (CVD). We aimed to analyze the within-trial cost-effectiveness of the polypill strategy versus usual care in India. METHODS: Relative effectiveness and costs of polypill versus usual care groups in UMPIRE were estimated from the health sector perspective. Only direct medical costs were considered. The effectiveness of the polypill was reported as a percentage increase in adherence and mean reductions in SBP, and LDL-c, over the 15-month trial period. Healthcare resource utilization and costs were collected for each patient during the trial. Polypill price was constructed using a range of scenarios: $0.06-$0.94/day. The cost-effectiveness of the polypill was measured as the additional cost for 10% increase in adherence, and per unit reduction in SBP and LDL-c. RESULTS: Overall, the mean cost per patient was significantly lower with the polypill strategy (-$203 per person, (95% CI: -286, -119, p < 0.01). In scenario analyses that varied polypill price assumptions, incremental cost-effectiveness ratios for a polypill strategy ranged between cost-saving to $75 per 10% increase in adherence for polypill price of $0.94 per day. CONCLUSIONS: The polypill strategy was cost-saving compared to usual care among patients with or at high risk of CVD in India.
- Published
- 2018
45. Evolocumab and clinical outcomes in patients with cardiovascular disease
- Author
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Sabatine, M. S., Giugliano, R. P., Keech, A. C., Honarpour, N., Wiviott, S. D., Murphy, S. A., Kuder, J. F., Wang, H., Liu, T., Wasserman, S. M., Sever, P. S., Pedersen, T. R., Fish, M. P., Abrahamsen, T. E., Im, K., Kanevsky, E., Bonaca, M. P., Lira Pineda, A., Hanlon, K., Knusel, B., Somaratne, R., Kurtz, C., Scott, R., Accini Mendoza, J. L., Amerena, J., Badariene, J., Burgess, L., Ceska, R., Charng, M. J., Choi, D., Cobos, J. L., Dan, G. A., De Ferrari, G. M., Deedwania, P. C., Chopra, V. K., Erglis, A., Ezhov, M. V., Ferreira, J., Filipova, S., Gaciong, Z. A., Pasierski, T., Georgiev, B. G., Gonzalez-Galvez, G., Gouni-Berthold, I., Schaufele, T., Hirayama, A., Huber, K., Rammer, M., Kjaerulf Jensen, H., Wermuth, S., Jiang, L., Jukema, J. W., Kraydashenko, O., Leiter, L. A., Lewis, B. S., Lopez-Miranda, J., Lorenzatti, A. J., Mach, F., Mcadam, B., Nilsson, L., Olsson, A., Rallidis, L., Rogelio, G. G., Kerr Saraiva, J. F., Scheen, A., Schiele, F., Connolly, D., Siu, C. W., Tay, L., Thorgeirsson, G., Tikkanen, M. J., Tokgozoglu, S. L., Toth, K., Viigimaa, M., Wan Ahmad, W. A., Hennekens, C. H., Andreotti, F., Baigent, C., Brown, W. V., Davis, B. R., Newcomer, J. W., Wood, S. K., Larosa, J., Ansell, B., Lowe, C., Zahn, L., Awtry, E., Berger, C., Croce, K., Desai, A., Gelfand, E., Ho, C., Leeman, D., Link, M., Norden, A., Pande, A., Rost, N., Ruberg, F., Silverman, S., Singhal, A., Vita, J., Mackinnon, I., Vogel, D. R., Leon de la Fuente, R., Perna, E., Amuchastegui, M., Pacora, F., Hershson, A., Blumberg, E., Glenny, J. A., Colombo, H., Cuadrado, J. A., Nicolosi, L., Rojas, C. G., Ulla, M. R., Hasbani, E. G., Cuneo, C., Lopez Santi, R. G., Sanabria, H. D., Hrabar, A., Lozada, A., Begg, A., Lehman, S., Wittert, G., Juergens, C., Kostner, K., Beltrame, J., Simpson, R., Sinhal, A., Adams, M., Kritharides, L., Roberts Thomson, P., Cross, D., Thompson, P., Van Gaal, W., Cox, N., Farshid, A., Hammett, C., Garrahy, P., Prasan, A., Horrigan, M., Ebenbichler, C., Hanusch, U., Prager, R., Schernthaner, G., Luger, A., Siostrzonek, P., Toplak, H., Bergler-Klein, J., Paulweber, B., Sinzinger, H., Buysschaert, I., Thoeng, J., Vandekerckhove, H., Catez, E., Verheye, S., Descamps, O., Hoffer, E., Wollaert, B., Chenu, P., van de Borne, P., De Meulemeester, M., Friart, A., Charlier, F., De Raedt, H., Rietzschel, E., Roelandt, R., Lalmand, J., Tavares Russo, L. A., Reis, G., Duarte Barbosa, E. C., Vidotti, M. H., Fernandes Manenti, E. R., Dutra, O., Leaes, P. E., Rech, R. L., Bertolim Precoma, D., Nicolau, J. C., Amoedo, R., Eliaschewitz, F. G., Pereira, A., Kurtz Lisboa, H. R., Soares Piegas, L., Cunha Borges, J. L., Ferreira Rossi, P. R., Pimentel Filho, P., Bodanese, L. C., de Sa Cunha, R., Moura Jorge, J. C., Ardito, W. R., Barroso de Souza, W. K., Hissa, M., Izar, M. C., Manolova, A., Kitova, L., Kinova, E., Tzekova, M., Velchev, V., Tarnovska-Kadreva, R., Gotchev, D., Petrov, I., Raev, D., Trendafilova-Lazarova, D., Yotov, Y., Lazov, P., Rahimi, S., St Amour, E., Constance, C., Pesant, Y., Hess, A., Anderson, T., Sussex, B., Henein, S., Tsoukas, G., Pandey, A. S., Bergeron, J., Hart, R., Gosselin, G., Chehayeb, R., Hamet, P., Hartleib, M., Mukherjee, A., Halperin, F., Petrella, R., Bhargava, R., Lonn, E., Sabbah, E., Bata, I., Cha, J., Gaudet, D., Chapman, K., Murthy, D., Nigro, F., Rupka, D., Gossard, D., Gupta, M., Dowell, A., Mansour, S., Baass, A., Geadah, C., Huynh, T., Peterson, S., Poirier, P., Sabe-Affaki, G., Vertes, G., Crowley, D., Duchesne, L., Pincetti Jofre, C. P., Potthoff Cardenas, S., Conejeros Kindel, C., Saavedra Gajardo, V. A., Lanas Zanetti, F., Sepulveda Varela, P. A., Stockins Fernandez, B. A., Li, W., Li, D., Zhao, S., Li, Z., Wang, J., Yang, Y., Zhang, L., Yang, P., Zhang, X., Huang, H., Xue, L., Zheng, Z., Huang, W., Dai, H., Su, H., Zeng, X., Zheng, Y., Tang, Y., Yao, Z., Sun, Y., Du, Y., Ge, Z., Yan, J., Chen, X., Liu, F., Pei, H., Yang, X., Cui, H., Gu, Y., Yang, Z., Li, J., Lian, Y., Cui, Y., Wang, D., Jiang, J., Li, X., Chen, J., Mo, Z., Xu, P., He, Y., Zhou, C., Qu, P., Zhu, Y., Liu, Y., Shen, X., Gao, X., Terront Lozano, M. A., Moncada Corredor, M. A., Hernandez Triana, E., Botero Lopez, R., Coronel Arroyo, J. A., Quintero Baiz, A. E., Sanchez Vallejo, G., Arana Londono, C., Molina de Salazar, D. I., Castellanos Bueno, R., Manzur Jattin, F., Cure Cure, C. A., Sotomayor Herazo, A., Spinar, J., Hala, T., Machkova, M., Klimsa, Z., Polasek, R., Jerabek, O., Kazdera, P., Pozdisek, Z., Vaclavik, J., Frana, P., Elbl, L., Kucera, D., Kryza, R., Malecha, J., Reichert, P., Sochor, K., Ludka, O., Kellnerova, I., Peterka, K., Zidkova, E., Cech, V., Brabec, T., Fiserova, N., Kvasnicka, J., Rosolova, H., Nemecek, E., Adamkova, V., Dunaj, M., Pojsl, S., Cepelak, M., Podpera, I., Kuchar, L., Rysava, D., Burianova, H., Spinarova, L., Skrobakova, J., Charvat, J., Homza, M., Zemanek, J., Koleckar, P., Karen, I., Krupicka, J., Blaha, V., Matuska, J., Brotanek, J., Cifkova, R., Kuchar, R., Vomacka, Z., Kosek, Z., Hulinsky, V., Krejcova, H., Kuchar, J., Jelinek, Z., Jelinek, P., Markdanner Lindgren, L., Saetre Lihn, A., Korsgaard Thomsen, K., Bronnum-Schou, J., Nielsen, H., Nielsen, T., Egstrup, K., Klausen, I. C., Mickley, H., Hove, J., Jeppesen, J., Melchior, T., Schmidt, E. B., Valter, I., Rosenthal, A., Kaik, J., Kork, A., Alt, I., Strand, J., Nieminen, S., Kahri, J., Suomi, J., Nyman, K., Strandberg, T. E., Piippo, T., Savolainen, M., Vikman, S., Pucheu, Y., Cariou, B., Henry, P., Ferrari, E., Montalescot, G., Ferrieres, J., Roubille, F., Bonnet, B., Angoulvant, D., Range, G., Bammert, A., Delarche, N., Mariat, C., Cayla, G., Durlach, V., Coisne, D., Paillard, F., Rouzier, R., Goralski, M., Khanoyan, P., Cottin, Y., Ziegler, O., Khalife, K., Le Corvoisier, P., Motreff, P., Spaulding, C., Vanbelle, E., Bourhaial, H., Opitz, C., Kahrmann, G., Contzen, C., Appel, K., Schenkenberger, I., Rinke, A., Trenk, D., Maus, O., Karakas, M., Hanefeld, M., Darius, H., Hetzel, G., Munzel, T., Wohrle, J., Stawowy, P., Marten, I., Isermann, B., Kast, P., Vorpahl, M., Bosiljanoff, P., Hengstenberg, C., Kassner, U., Salbach, P., Fischer, M., Steiner, S., Wagner, S., Kraatz, U., von Hodenberg, E., Weyland, K., Mantas, I., Tziakas, D., Bousboulas, S., Patsilinakos, S., Mertzanos, G., Panagoulis, C., Bilianou, H., Skoumas, I., Elisaf, M., Manolis, A., Moschos, N., Kochiadakis, G., Ntaios, G., Richter, D., Athyros, V., Kolovou, G., Danias, P., Melidonis, A., Fan, K. Y. Y., Siu, S. C., Hornyik, A., Lakatos, F., Zilahi, Z., Nagy, K., Laszlo, Z., Peterfai, E., Lupkovics, G., Andreka, P., Merkely, B., Herczeg, B., Piros, G. A., Salamon, C., Mark, L., Papp, A., Szakal, I., Edes, I., Mohacsi, A., Tomcsanyi, J., Hajko, E., Nagy, A., Papp, E., Kiss, R., Karadi, I., Sigurdsson, A., Jain, A., Pai, R., Kothiwale, V., Kulkarni, G., Mahajan, A., Aggarwal, S., Mehta, V., Rajadhyaksha, G., Joshi, A., Khandait, V., Parmar, M., Tyagi, S., Airody Govinda, R., Dwivedi, S. K., Parikh, K., Pothineni, R. B., Solanki, B., O'Donnell, M., Crean, P., Barton, J., Shechter, M., Shotan, A., Klutstein, M., Chorin, E., Gavish, D., Kracoff, O., Atar, S., Rigler, S., Hasin, Y., Schiff, E., Merlini, P., Rapezzi, C., Pirro, M., Gonnelli, S., Floresta, A. M., Mennuni, M., Ardissino, D., Senni, M., Marenzi, G., Marcucci, R., Sampietro, T., Cosmi, F., Perrone Filardi, P., De Caterina, R., Fedele, F., Moretti, L., Biasucci, Luigi Marzio, Ferri, C., Go, Y., Kiyosue, A., Higashi, Y., Tokunaga, T., Kawasaki, T., Sakagami, S., Namba, S., Saku, K., Oku, K., Arakawa, T., Iida, H., Nakamura, Y., Yamamoto, K., Hata, Y., Katsuda, Y., Koga, Y., Shimizu, M., Uehara, H., Kajiyama, S., Okamoto, H., Shinozaki, T., Fujino, Y., Funazaki, T., Higa, N., Kaigawa, K., Koike, A., Nakane, H., Sato, K., Satoh, Y., Shirasawa, K., Sugino, H., Tanabe, J., Uemura, O., Yoshimichi, G., Akai, A., Himeno, H., Inage, T., Inoko, M., Kadokami, T., Noguchi, Y., Yamashita, K., Yasumura, Y., Yuge, M., Hosokawa, S., Kawamitsu, K., Kozuma, K., Matsuo, H., Nakashima, E., Okada, M., Wada, A., Yokoya, K., Iwade, K., Kawabata, K., Tanno, H., Ako, J., Fujita, H., Izumiya, Y., Kanno, M., Nunohiro, T., Ohmura, H., Ueno, T., Kakurina, N., Jasinkevica, I., Stukena, I., Veze, I., Eglite, R., Teterovska, D., Sime, I., Strazdiene, V., Venceviciene, L., Gustiene, O., Radzeviciene-Jurgute, R., Kucinskiene, A., Maskon, O., Lee, C. Y., Erng, T., Gan, H. W., Mohamed Yusof, A. K., Ramanathan, G. L., Liew, H., Lopez Alvarado, A., Nevarez Ruiz, L. A., De los Rios Ibarra, M. O., Bazzoni Ruiz, A. E., Ramos Lopez, G. A., Llamas Esperon, G. A., De la Pena Topete, G. D. J., Violante Ortiz, R. M., Illescas Diaz, J. J., Leon Gonzalez, S., Sanchez Diaz, C. J., Mendez Machado, G. F., Venegas Carrillo, L. A., Aldrete Velasco, J. A., Cardona Munoz, E. G., Leiva Pons, J. L., Perez Alva, J. C., van der Zwaan, C., Oomen, A., van de Wal, R., Magro, M., Boswijk, D., Janus, C., Groutars, R., Tonino, W., Cornel, J. H., Oude Ophuis, A., Troquay, R., Liem, A., Westendorp, I., Van Hessen, M., Lok, D., De Nooijer, C., Den Hartog, F., Van Beek, E., Bendermacher, P., Jansen, R., Romer, T., Rensing, B., Hersbach, F., Herrman, J., Ladyjanskaia, G., Karalis, I., Linssen, G., Bokern, M., Visman, A., Kooij, A., Monajemi, H., Lieverse, A., Baker, J., Tie, S., Risberg, K., Hysing, J., Hoivik, H. O., Norheim, P., Solnor, L., Hovland, A., Kjaernli, T., Jocson, G., Coching, R. M., Batalla, E., Go, A., Habaluyas, R., Barcinas, R., Sy, R. A., Estepar, R. A., Germar, A., Trebacz, J., Szymkowiak, K., Wnetrzak-Michalska, R., Kopaczewski, J., Przekwas-Jaruchowska, M., Kania, G., Zabowka, M., Mirek-Bryniarska, E., Dabrowska, M., Napora, P., Konieczny, M., Spyra, J., Lysek, R., Pijanowski, Z., Grzegorzewski, B., Bednarkiewicz, Z., Kinasz, L., Antkowiak-Piatyszek, K., Stania, K., Szpajer, M., Staneta, P., Skonieczny, G., Ksiezycka-Majczynska, E., Blicharski, T., Piepiorka, M., Wozakowska-Kaplon, B., Zechowicz, T., Ilkowski, J., Lubiszewska, B., Hiczkiewicz, J., Wierzbicka, K., Kosior, D., Garbocz, P., Kubica, J., Raczak, G., Wozniak, I., Cygler, J., Kramarczuk, E., Bystryk, L., Pentela-Nowicka, J., Dabrowski, M., Podolec, P., Zieba, B., Mosiewicz, J., Dubaniewicz, W., Banach, M., Tyszecka, G., Lepich, T., Rychlewska-Hanczewska, A., Guzik, T., Monteiro, P., Pereira, H., Oliveira, L., Matos, P., Soares Goncalves, S., Leitao, A., Vasco Salgado, A., Timoteo, A. 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O., Norheim, P., Solnor, L., Hovland, A., Kjaernli, T., Jocson, G., Coching, R. M., Batalla, E., Go, A., Habaluyas, R., Barcinas, R., Sy, R. A., Estepar, R. A., Germar, A., Trebacz, J., Szymkowiak, K., Wnetrzak-Michalska, R., Kopaczewski, J., Przekwas-Jaruchowska, M., Kania, G., Zabowka, M., Mirek-Bryniarska, E., Dabrowska, M., Napora, P., Konieczny, M., Spyra, J., Lysek, R., Pijanowski, Z., Grzegorzewski, B., Bednarkiewicz, Z., Kinasz, L., Antkowiak-Piatyszek, K., Stania, K., Szpajer, M., Staneta, P., Skonieczny, G., Ksiezycka-Majczynska, E., Blicharski, T., Piepiorka, M., Wozakowska-Kaplon, B., Zechowicz, T., Ilkowski, J., Lubiszewska, B., Hiczkiewicz, J., Wierzbicka, K., Kosior, D., Garbocz, P., Kubica, J., Raczak, G., Wozniak, I., Cygler, J., Kramarczuk, E., Bystryk, L., Pentela-Nowicka, J., Dabrowski, M., Podolec, P., Zieba, B., Mosiewicz, J., Dubaniewicz, W., Banach, M., Tyszecka, G., Lepich, T., Rychlewska-Hanczewska, A., Guzik, T., Monteiro, P., Pereira, H., Oliveira, L., Matos, P., Soares Goncalves, S., Leitao, A., Vasco Salgado, A., Timoteo, A. T., Pintilei, E., Badila, E., Militaru, C., Tudoran, M., Arsenescu-Georgescu, C., Mitu, F., Zdrenghea, D., Lighezan, D., Teodorescu, I., Popescu, M. I., Coman, I., Vintila, M. M., Vishnevsky, A., Lukyanov, Y., Blokhin, A., Kostenko, V., Shvarts, Y., Markov, V., Motylev, I., Dronov, D., Sherenkov, A., Barbarash, O., Shutemova, E., Bolshakova, O., Kobalava, Z., Voevoda, M., Treshkur, T., Zrazhevskiy, K., Pimenov, L., Solovev, O., Tarasov, N., Arkhipov, M., Freidlin, M., Shalaev, S., Yakhontova, P., Shustov, S., Goloshchekin, B., Panov, A., Bart, B., Bubnova, M., Gordeev, I., Osipova, I., Tereshenko, S., Solovieva, E., Meshkov, A., Zateyshchikov, D., Tan, J. L., Subramaniam, T., Pella, D., Fulop, P., Antalik, L., Dzupina, A., Banikova, A., Sosovec, D., Urgeova, L., Mazur, J., Hranai, M., Banik, M., Vinanska, D., Lennerova, J., Kovar, F., Pastrnakova, E., Uhliar, R., Blasko, P., Gonsorcik, J., Lukacova, J., Oriesek, R., Hatalova, K., du Toit, M., Ebrahim, I., Vawda, G., Lipschitz, S., Blignaut, S., Engelbrecht, J., Coetzer, T. F., Pretorius, M., Urbach, D., Badat, A., Pillay, S., Van Zyl, L., Abelson, M., van der Walt, E., Moodley, R., Jacovides, A., Oosthuysen, W. M., Klug, E., Lottering, H., Kok, J., Saaiman, J., Dawood, S., De Jong, D. M., Kapp, C., Makotoko, E., Bayat, J., Sarvan, M., Vally, T., Stapelberg, A., Kim, M., Bae, J., Cho, Y., Kim, S., Han, K. H., Her, S., Kim, B., Lee, S., Hong, B., Kim, W., Rha, S., Jeong, M., Shin, G. J., Vida Gutierrez, M., Valdes Chavarri, M., Pinto Sala, X., Gonzalez Juanatey, J. R., Civeira Murillo, F., Zamorano Gomez, J. L., Lekuona Goya, I., Iniguez Romo, A., Cordero Fort, A., Ascaso Gimilio, J. F., Millan Nunez-Cortes, J., Lindholm, C., Soderberg, S., Suutari, A., Berglund, S., Mooe, T., Kusiak, D., Bandh, S., Dahlen, G., Olsson, S., Witt, N., Tyden, P., Johansson, P., Cizinsky, S., Falck, G., Pettersson, S. I., Rasmanis, G., Ostergren, J., Moccetti, T., Beer, H. J., Eberli, F., Krahenbuhl, S., Linka, A., Ackermann, D., Michel, P., Yeh, H., Tsai, C. F., Wu, C., Hsia, C., Juang, J., Hsieh, I., Lai, W., Huang, C., Hsieh, Y., Sahin, T., Duzenli, M., Yigit, Z., Demir, M., Yilmaz, M. B., Muderrisoglu, I. H., Kirma, C., Ercan, E., Kayikcioglu, L., Balbay, Y., Lymar, I., Kulynych, O., Prokhorov, O., Karpenko, O., Vakaliuk, I., Stanislavchuk, M., Korzh, O., Rudyk, I., Zhurba, S., Svishchenko, Y., Tseluyko, V., Gyrina, O., Reshotko, D., Kopytsya, M., Volkov, V., Myshanych, G., Rebrov, B., Rishko, M., Rudenko, L., Shatylo, V., Parkhomenko, O., Yena, L., Golovchenko, O., Sorokina, I., Malynovsky, Y., Ivan, P., Blagden, M., Dear, H., Mathew, A., Lagocki, S., Kondagunta, V., Ahsan, A., Mckinnon, C., Douglas, F., Thom, S., Fiore, G., Caulfield, M., Lynch, M., Thomas, H., Bain, S., Hall, A., Mcnally, D., Fisher, M., Keeling, P., Al-Bahrani, A., Lip, G., Ellery, A., Purohit, J., Travill, C., Cappuccio, F., Davis, G., Gaunt, R., Adlam, D., Asamoah, N., Jaafar, F., Mccormack, T., Jupp, B., Pye, M., Ainsworth, P., Chauhan, A., Paul, N., Fairlie, H., Fox, C., Muzulu, S., Trevelyan, J., Aggarwal, R., Issa, B., Saravanan, P., Cruickshank, K., Gorog, D., Heller, S., Newby, D., Nicolson, A., Hare, P. O., Donnelly, P., Rutherfurd, S., de Belder, M., Finlayson, J., Harvey, J., Hoye, A., Kingston, D., Sarkar, D., Negahban, A., Webster, J., Wyatt, N., Muir, S., Cummings, M., Mackenzie, I., Senior, R., Capps, N., Fotherby, K., Mcintyre, H., Aldegather, J., Dixon, L., Saksena, R., Butler, R., Ramstad, D., Pierpont, B., Levinson, D., Mohammed, A., Haddad, T., Goel, A., Dave, K., Haught, W. H., Desire, A., Hershon, K., Napoli, M., Tami, L., Rothschild, R., Khurana, S., Gupta, D., Cheung, D., Hearne, S., Grubb, S., Miller, A., Baird, I., Marcus, A., Srivastava, S., Forgosh, L., Fritz, R., Mays, M., Bertolet, B., Reddy, J., Khan, M., Nakhle, S., Dill, S., Fishbein, G., Khan, B., Marais, H., Reschak, M., Malone, M., Nadar, V., Whitney, R., Reichman, A., Reyes, H., El Shahawy, M., Rabinowitz, A., Weinstein, D., Farhat, N., Onyema, D., Potu, R., Runquist, L., Barnum, O., Crater, T., Fialkow, J., Shah, A., Thompson, C., Wiseman, A., Doyle, T., Henderson, D., Herzog, W., Schnitzler, R., Carr, K., Davis, M., Nagajothi, N., Olsen, S., Rogers, W., Rubino, J., Singh, I., Tarleton, G., Bhagwat, R., Clardy, D., Jardula, M., Robinson, J., Torres, M., Vijay, N., Farris, N., Lillo, J., Moriarty, P., Recknor, C., Berlacher, P., Christensen, T., Gabra, N., Issa, M., Janik, M., Lawless, A., Molter, D., Stout, E., Brezina, B., Claxton, E., Linsky, R., Poock, J., Remler, R., Roseman, H., Schramm, E., Al-Joundi, T., Amin, J., Hitchcock, J., Isserman, S., Kirstein, J., Rider, J., Shalek, M., Sherman, H., Bernstein, M., Chandra, L., Hatharasinghe, R., Ibrahim, H., Iteld, B., Linzmeyer, K., Seaton, B., Zeig, S., Christofides, E., Dunbar, R., Griffin, S., Kohli, N., Koren, M., Pharr, W., Purdy, D., Spencer, R., Yeoman, G., Banerjee, S., Cheek, H. B., Engel, E., Hamroff, G., Huling, R., Kozlowski, L., Levin, P., Makam, S., Meengs, M., Bhushan, R., Erickson, B., Herman, L., Lo, E., Mcdowell, E., Mcgrew, F., Miller, M., Ord, J., Webel, R., Wilhoit, G., Wise, J., Yang, E., Budoff, M., Collins, J., Dauber, I., Dobkin, L., Focil, A., Gandy, W., Pasquini, J., Ramos, M., Rodriguez, D., Rosenson, R., Sanford, K., Schlau, A., Snyder, B., Stonesifer, L., Tang, A., De Souza, J., Elam, M., French, J., Guyton, J., Hage Korban, E., Kereiakes, D., King, M., Loh, I., Navarro, J., Simons, R., Tobin, T., Younis, L., Aboufakher, R., Baldari, D., Ballantyne, C., Broughton, R., Eaton, C., Johnston, J., Simon, W., Thomson, S., Vora, K., Youngman, D., Alzohaili, O., Auerbach, E., Brown, C., Burrough, B., Chen, Y., Gilpatrick, M., Landzberg, J., Mitchell, C., Rice, L., Rubenfire, M., Sofley, C. W., Strobl, D., Atassi, K., Davila, W., Diogo, J., Fagan, T., Joffe, I., Krishna, J., Osea, E., Penny, W., Rowe, W., Shapiro, M., Welker, J., Benton, R., Dobratz, D., Fortuin, F., Graham, J., Henry, B., Kusnick, B., Lutskiy, M., Mcrae, A., Saway, W., Scott, J., Shah, M., Weinberg, B., Zarich, S., Acheatel, R., Case, C., Earl, J., Fernandez, S., Giugliano, G., Handelsman, Y., Hermany, P., Holder, S., Kashyap, M., Khan, A., Lader, E., Peniston, J., Raoof, T., Sacco, J., Shore, K., Spriggs, D., Stringam, S., Tahirkheli, N., Delgado, E., Derian, W., Greenwald, J., Harris, M., Jackson, R., Marhefka, G., Mcelveen, W., Mooss, A., Morris, P., Murray, J., Pearlstein, P., Raisinghani, A., Rezkalla, S., Sakhrani, L., Schreibman, D., Shaoulian, E., Steinsapir, J., Yataco, A., De La Cruz, A., Fredrick, M., Goldenberg, E., Lee, D., Mccullum, K., Mclellan, B., Stephens, L., Wilson, S., Alfieri, A., Mandviwala, M., Orourke, D., Samal, A., Schmedtje, J., Waxman, F., Carhart, R., Clements, B., Dyke, C., Ghali, J., Gruberg, L., Hack, T., Jehle, A., Pogue, B., Schooley, C., Shifrin, G., and Biasucci L. M. (ORCID:0000-0002-6921-6497)
- Abstract
BACKGROUND Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. METHODS We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. RESULTS At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reacti
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- 2017
46. Impact of switching from different treatment regimens to a fixed-dose combination pill (polypill) in patients with cardiovascular disease or similarly high risk
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Lafeber, M, Spiering, W, Visseren, FLJ, Grobbee, DE, Bots, ML, Stanton, A, Patel, A ; https://orcid.org/0000-0003-3825-4092, Prabhakaran, D, Webster, R ; https://orcid.org/0000-0002-5136-1098, Thom, S, Rodgers, A ; https://orcid.org/0000-0003-1282-1896, Lafeber, M, Spiering, W, Visseren, FLJ, Grobbee, DE, Bots, ML, Stanton, A, Patel, A ; https://orcid.org/0000-0003-3825-4092, Prabhakaran, D, Webster, R ; https://orcid.org/0000-0002-5136-1098, Thom, S, and Rodgers, A ; https://orcid.org/0000-0003-1282-1896
- Abstract
Aims Cardiovascular fixed-dose combination pills, or polypills, may help address the widespread lack of access and adherence to proven medicines. Initiation of polypill-based care typically entails switching from current separately taken medications. Given the heterogeneity in usual care, there is interest in the impact of polypill treatment across different patterns of prior medication regimen. Methods A total of 2004 participants with established cardiovascular disease or estimated 5-year cardiovascular risk of over 15% were randomised to polypill-based treatment (aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg) or usual care. Baseline medications were classified by potency relative to polypill components. Estimated cardiovascular risk reduction was calculated by combining risk factor changes with results seen in meta-analyses of previous randomised trials. Results For cholesterol reduction conferred by polypills, there was a dose response across baseline statin groups, with mean low-density lipoprotein (LDL)-cholesterol differences of 0.37, 0.22, 0.14 and 0.07 mmol/L among patients taking no statin, less potent, equipotent and more potent statin at baseline, respectively. Similarly there were differences in mean systolic BP of 5.4, 6.2, 3.3 and 1.8 mmHg among patients taking 0, 1, 2 or 3 BP-lowering agents. Among patients taking more potent statins at baseline, there was no significant difference in LDL-cholesterol but there were benefits for BP and aspirin adherence. Similar results were seen among patients taking 3 BP-lowering agents at baseline. Switching to a polypill-based strategy resulted in estimated cardiovascular relative risk reductions across a wide range of usual care patterns of antiplatelet, statin and BP-lowering therapy prescribing. Conclusion Adherence benefits from switching to a polypill resulted in risk factor changes that were at least as good as usual care across a wide variety of
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- 2017
47. Efficacy and Safety of Quarter-Dose Blood Pressure-Lowering Agents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
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Bennett, A, Chow, CK, Chou, M, Dehbi, HM, Webster, R ; https://orcid.org/0000-0002-5136-1098, Salam, A, Patel, A ; https://orcid.org/0000-0003-3825-4092, Neal, B ; https://orcid.org/0000-0002-0490-7465, Peiris, D ; https://orcid.org/0000-0002-6898-3870, Thakkar, J, Chalmers, J ; https://orcid.org/0000-0002-9931-0580, Nelson, M, Reid, C, Hillis, GS, Woodward, M ; https://orcid.org/0000-0001-9800-5296, Hilmer, S, Usherwood, T, Thom, S, Rodgers, A ; https://orcid.org/0000-0003-1282-1896, Mohammad, Mohammad ; https://orcid.org/0000-0002-5870-7936, Bennett, A, Chow, CK, Chou, M, Dehbi, HM, Webster, R ; https://orcid.org/0000-0002-5136-1098, Salam, A, Patel, A ; https://orcid.org/0000-0003-3825-4092, Neal, B ; https://orcid.org/0000-0002-0490-7465, Peiris, D ; https://orcid.org/0000-0002-6898-3870, Thakkar, J, Chalmers, J ; https://orcid.org/0000-0002-9931-0580, Nelson, M, Reid, C, Hillis, GS, Woodward, M ; https://orcid.org/0000-0001-9800-5296, Hilmer, S, Usherwood, T, Thom, S, Rodgers, A ; https://orcid.org/0000-0003-1282-1896, and Mohammad, Mohammad ; https://orcid.org/0000-0002-5870-7936
- Abstract
There is a critical need for blood pressure-lowering strategies that have greater efficacy and minimal side effects. Low-dose combinations hold promise in this regard, but there are few data on very-low-dose therapy. We, therefore, conducted a systematic review and meta-analysis of randomized controlled trials with at least one quarter-dose and one placebo and standard-dose monotherapy arm. A search was conducted of Medline, Embase, Cochrane Registry, Food and Drug Administration, and European Medicinal Agency websites. Data on blood pressure and adverse events were pooled using a fixed-effect model, and bias was assessed using Cochrane risk of bias. The review included 42 trials involving 20 284 participants. Thirty-six comparisons evaluated quarter-dose with placebo and indicated a blood pressure reduction of -4.7/-2.4 mm Hg (P<0.001). Six comparisons were of dual quarter-dose therapy versus placebo, observing a -6.7/ -4.4 mm Hg (P<0.001) blood pressure reduction. There were no trials of triple quarter-dose combination versus placebo, but one quadruple quarter-dose study observed a blood pressure reduction of -22.4/-13.1 mm Hg versus placebo (P<0.001). Compared with standard-dose monotherapy, the blood pressure differences achieved by single (37 comparisons), dual (7 comparisons), and quadruple (1 trial) quarter-dose combinations were +3.7/+2.6 (P<0.001), +1.3/-0.3 (NS), and -13.1/-7.9 (P<0.001) mm Hg, respectively. In terms of adverse events, single and dual quarter-dose therapy was not significantly different from placebo and had significantly fewer adverse events compared with standard-dose monotherapy. Quarter-dose combinations could provide improvements in efficacy and tolerability of blood pressure-lowering therapy.
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- 2017
48. Developing consensus measures for global programs: Lessons from the Global Alliance for Chronic Diseases Hypertension research program.
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Li X., Oldenburg B., Riddell M., Srikanth V., Heritier S., Kalyanram K., Kartik K., Suresh O., Maulik P., Salam A., Sudhir T., Thankappan K., Thirunavukkarasu S., Varma R., Thomas N., Clifford G., Prabhakaran D., Thom S., Shivashankar R., Mohan S., Reddy K.S., Krishnan A., Faletoese S., Ieremia M., Ulberg C., Viali S., Pillay A., Sukhu A., Schultz J., Siitia J., Snowdon W., Antonio Bernabe-Ortiz, Cardenas M.K., Gilman R.H., Miranda J.J., Diez-Canseco F., Ponce-Lucero V., Sacksteder K., Gyamfi J., Ogedegbe O., Apusiga K., Cooper R., Ntim M., Plange-Rhule J., Rotich J., Binanay C., Finkelstein E., Bloomfield G., DeLong A., Hogan J., Inui T., Naanyu V., Fuster V., Horowitz C., Kimaiyo S., Kofler C., Menya D., Kamano J.H., Vedanthan R., Velazquez E., Were M., Dolan J., Irazola V., Krousel-Wood M., Augustovski F., Beratarrechea A., Chen J., He J., Mills K., Poggio R., Rubinstein A., Shi L., Webber L., Akinyemi R., Arulogun O., Hurst S., Waddy S., Warth S., Gebregziabher M., Uvere E., Riddell M.A., Edwards N., Thompson S.R., Bernabe-Ortiz A., Praveen D., Johnson C., Kengne A.P., Liu P., McCready T., Ng E., Nieuwlaat R., Ovbiagele B., Owolabi M., Peiris D., Thrift A.G., Tobe S., Yusoff K., de Villiers A., He F., MacGregor G., Jan S., Neal B., Chow C., Joshi R., MacMahon S., Patel A., Rodgers A., Webster R., Keat N.K., Attaran A., Mills E., Muldoon K., Yaya S., Featherstone A., Mukasa B., Forrest J., Kalyesubula R., Kamwesiga J., Lopez P.C., Tayari J.-C., Lopez P., Casas J.L., McKee M., Zainal A.O., Yusuf S., Campbell N., Kilonzo K., Marr M., Yeates K., Feng X., Yuan J., Lin C.-P., Yan L., Zhang J., Wu Y., Ma J., Wang H., Ma Y., Nowson C., Moodie M., Goudge J., Kabudula C., Limbani F., Masilela N., Myakayaka N., Gomez-Olive F.X., Thorogood M., Arabshahi S., Evans R., Mahal A., Li X., Oldenburg B., Riddell M., Srikanth V., Heritier S., Kalyanram K., Kartik K., Suresh O., Maulik P., Salam A., Sudhir T., Thankappan K., Thirunavukkarasu S., Varma R., Thomas N., Clifford G., Prabhakaran D., Thom S., Shivashankar R., Mohan S., Reddy K.S., Krishnan A., Faletoese S., Ieremia M., Ulberg C., Viali S., Pillay A., Sukhu A., Schultz J., Siitia J., Snowdon W., Antonio Bernabe-Ortiz, Cardenas M.K., Gilman R.H., Miranda J.J., Diez-Canseco F., Ponce-Lucero V., Sacksteder K., Gyamfi J., Ogedegbe O., Apusiga K., Cooper R., Ntim M., Plange-Rhule J., Rotich J., Binanay C., Finkelstein E., Bloomfield G., DeLong A., Hogan J., Inui T., Naanyu V., Fuster V., Horowitz C., Kimaiyo S., Kofler C., Menya D., Kamano J.H., Vedanthan R., Velazquez E., Were M., Dolan J., Irazola V., Krousel-Wood M., Augustovski F., Beratarrechea A., Chen J., He J., Mills K., Poggio R., Rubinstein A., Shi L., Webber L., Akinyemi R., Arulogun O., Hurst S., Waddy S., Warth S., Gebregziabher M., Uvere E., Riddell M.A., Edwards N., Thompson S.R., Bernabe-Ortiz A., Praveen D., Johnson C., Kengne A.P., Liu P., McCready T., Ng E., Nieuwlaat R., Ovbiagele B., Owolabi M., Peiris D., Thrift A.G., Tobe S., Yusoff K., de Villiers A., He F., MacGregor G., Jan S., Neal B., Chow C., Joshi R., MacMahon S., Patel A., Rodgers A., Webster R., Keat N.K., Attaran A., Mills E., Muldoon K., Yaya S., Featherstone A., Mukasa B., Forrest J., Kalyesubula R., Kamwesiga J., Lopez P.C., Tayari J.-C., Lopez P., Casas J.L., McKee M., Zainal A.O., Yusuf S., Campbell N., Kilonzo K., Marr M., Yeates K., Feng X., Yuan J., Lin C.-P., Yan L., Zhang J., Wu Y., Ma J., Wang H., Ma Y., Nowson C., Moodie M., Goudge J., Kabudula C., Limbani F., Masilela N., Myakayaka N., Gomez-Olive F.X., Thorogood M., Arabshahi S., Evans R., and Mahal A.
- Abstract
Background: The imperative to improve global health has prompted transnational research partnerships to investigate common health issues on a larger scale. The Global Alliance for Chronic Diseases (GACD) is an alliance of national research funding agencies. To enhance research funded by GACD members, this study aimed to standardise data collection methods across the 15 GACD hypertension research teams and evaluate the uptake of these standardised measurements. Furthermore we describe concerns and difficulties associated with the data harmonisation process highlighted and debated during annual meetings of the GACD funded investigators. With these concerns and issues in mind, a working group comprising representatives from the 15 studies iteratively identified and proposed a set of common measures for inclusion in each of the teams' data collection plans. One year later all teams were asked which consensus measures had been implemented. Result(s): Important issues were identified during the data harmonisation process relating to data ownership, sharing methodologies and ethical concerns. Measures were assessed across eight domains; demographic; dietary; clinical and anthropometric; medical history; hypertension knowledge; physical activity; behavioural (smoking and alcohol); and biochemical domains. Identifying validated measures relevant across a variety of settings presented some difficulties. The resulting GACD hypertension data dictionary comprises 67 consensus measures. Of the 14 responding teams, only two teams were including more than 50 consensus variables, five teams were including between 25 and 50 consensus variables and four teams were including between 6 and 24 consensus variables, one team did not provide details of the variables collected and two teams did not include any of the consensus variables as the project had already commenced or the measures were not relevant to their study. Conclusion(s): Deriving consensus measures across diverse research pro
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- 2017
49. Developing consensus measures for global programs: Lessons from the Global Alliance for Chronic Diseases Hypertension research program.
- Author
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Li X., Oldenburg B., Riddell M., Srikanth V., Heritier S., Kalyanram K., Kartik K., Suresh O., Maulik P., Salam A., Sudhir T., Thankappan K., Thirunavukkarasu S., Varma R., Thomas N., Clifford G., Prabhakaran D., Thom S., Shivashankar R., Mohan S., Reddy K.S., Krishnan A., Faletoese S., Ieremia M., Ulberg C., Viali S., Pillay A., Sukhu A., Schultz J., Siitia J., Snowdon W., Antonio Bernabe-Ortiz, Cardenas M.K., Gilman R.H., Miranda J.J., Diez-Canseco F., Ponce-Lucero V., Sacksteder K., Gyamfi J., Ogedegbe O., Apusiga K., Cooper R., Ntim M., Plange-Rhule J., Rotich J., Binanay C., Finkelstein E., Bloomfield G., DeLong A., Hogan J., Inui T., Naanyu V., Fuster V., Horowitz C., Kimaiyo S., Kofler C., Menya D., Kamano J.H., Vedanthan R., Velazquez E., Were M., Dolan J., Irazola V., Krousel-Wood M., Augustovski F., Beratarrechea A., Chen J., He J., Mills K., Poggio R., Rubinstein A., Shi L., Webber L., Akinyemi R., Arulogun O., Hurst S., Waddy S., Warth S., Gebregziabher M., Uvere E., Riddell M.A., Edwards N., Thompson S.R., Bernabe-Ortiz A., Praveen D., Johnson C., Kengne A.P., Liu P., McCready T., Ng E., Nieuwlaat R., Ovbiagele B., Owolabi M., Peiris D., Thrift A.G., Tobe S., Yusoff K., de Villiers A., He F., MacGregor G., Jan S., Neal B., Chow C., Joshi R., MacMahon S., Patel A., Rodgers A., Webster R., Keat N.K., Attaran A., Mills E., Muldoon K., Yaya S., Featherstone A., Mukasa B., Forrest J., Kalyesubula R., Kamwesiga J., Lopez P.C., Tayari J.-C., Lopez P., Casas J.L., McKee M., Zainal A.O., Yusuf S., Campbell N., Kilonzo K., Marr M., Yeates K., Feng X., Yuan J., Lin C.-P., Yan L., Zhang J., Wu Y., Ma J., Wang H., Ma Y., Nowson C., Moodie M., Goudge J., Kabudula C., Limbani F., Masilela N., Myakayaka N., Gomez-Olive F.X., Thorogood M., Arabshahi S., Evans R., Mahal A., Li X., Oldenburg B., Riddell M., Srikanth V., Heritier S., Kalyanram K., Kartik K., Suresh O., Maulik P., Salam A., Sudhir T., Thankappan K., Thirunavukkarasu S., Varma R., Thomas N., Clifford G., Prabhakaran D., Thom S., Shivashankar R., Mohan S., Reddy K.S., Krishnan A., Faletoese S., Ieremia M., Ulberg C., Viali S., Pillay A., Sukhu A., Schultz J., Siitia J., Snowdon W., Antonio Bernabe-Ortiz, Cardenas M.K., Gilman R.H., Miranda J.J., Diez-Canseco F., Ponce-Lucero V., Sacksteder K., Gyamfi J., Ogedegbe O., Apusiga K., Cooper R., Ntim M., Plange-Rhule J., Rotich J., Binanay C., Finkelstein E., Bloomfield G., DeLong A., Hogan J., Inui T., Naanyu V., Fuster V., Horowitz C., Kimaiyo S., Kofler C., Menya D., Kamano J.H., Vedanthan R., Velazquez E., Were M., Dolan J., Irazola V., Krousel-Wood M., Augustovski F., Beratarrechea A., Chen J., He J., Mills K., Poggio R., Rubinstein A., Shi L., Webber L., Akinyemi R., Arulogun O., Hurst S., Waddy S., Warth S., Gebregziabher M., Uvere E., Riddell M.A., Edwards N., Thompson S.R., Bernabe-Ortiz A., Praveen D., Johnson C., Kengne A.P., Liu P., McCready T., Ng E., Nieuwlaat R., Ovbiagele B., Owolabi M., Peiris D., Thrift A.G., Tobe S., Yusoff K., de Villiers A., He F., MacGregor G., Jan S., Neal B., Chow C., Joshi R., MacMahon S., Patel A., Rodgers A., Webster R., Keat N.K., Attaran A., Mills E., Muldoon K., Yaya S., Featherstone A., Mukasa B., Forrest J., Kalyesubula R., Kamwesiga J., Lopez P.C., Tayari J.-C., Lopez P., Casas J.L., McKee M., Zainal A.O., Yusuf S., Campbell N., Kilonzo K., Marr M., Yeates K., Feng X., Yuan J., Lin C.-P., Yan L., Zhang J., Wu Y., Ma J., Wang H., Ma Y., Nowson C., Moodie M., Goudge J., Kabudula C., Limbani F., Masilela N., Myakayaka N., Gomez-Olive F.X., Thorogood M., Arabshahi S., Evans R., and Mahal A.
- Abstract
Background: The imperative to improve global health has prompted transnational research partnerships to investigate common health issues on a larger scale. The Global Alliance for Chronic Diseases (GACD) is an alliance of national research funding agencies. To enhance research funded by GACD members, this study aimed to standardise data collection methods across the 15 GACD hypertension research teams and evaluate the uptake of these standardised measurements. Furthermore we describe concerns and difficulties associated with the data harmonisation process highlighted and debated during annual meetings of the GACD funded investigators. With these concerns and issues in mind, a working group comprising representatives from the 15 studies iteratively identified and proposed a set of common measures for inclusion in each of the teams' data collection plans. One year later all teams were asked which consensus measures had been implemented. Result(s): Important issues were identified during the data harmonisation process relating to data ownership, sharing methodologies and ethical concerns. Measures were assessed across eight domains; demographic; dietary; clinical and anthropometric; medical history; hypertension knowledge; physical activity; behavioural (smoking and alcohol); and biochemical domains. Identifying validated measures relevant across a variety of settings presented some difficulties. The resulting GACD hypertension data dictionary comprises 67 consensus measures. Of the 14 responding teams, only two teams were including more than 50 consensus variables, five teams were including between 25 and 50 consensus variables and four teams were including between 6 and 24 consensus variables, one team did not provide details of the variables collected and two teams did not include any of the consensus variables as the project had already commenced or the measures were not relevant to their study. Conclusion(s): Deriving consensus measures across diverse research pro
- Published
- 2017
50. Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review.
- Author
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Chow, CK, Thakkar, J, Bennett, A, Hillis, G, Burke, M, Usherwood, T, Vo, K, Rogers, K, Atkins, E, Webster, R, Chou, M, Dehbi, H-M, Salam, A, Patel, A, Neal, B, Peiris, D, Krum, H, Chalmers, J, Nelson, M, Reid, CM, Woodward, M, Hilmer, S, Thom, S, Rodgers, A, Chow, CK, Thakkar, J, Bennett, A, Hillis, G, Burke, M, Usherwood, T, Vo, K, Rogers, K, Atkins, E, Webster, R, Chou, M, Dehbi, H-M, Salam, A, Patel, A, Neal, B, Peiris, D, Krum, H, Chalmers, J, Nelson, M, Reid, CM, Woodward, M, Hilmer, S, Thom, S, and Rodgers, A
- Abstract
BACKGROUND: Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs. METHODS: We did a randomised, placebo-controlled, double-blind, crossover trial of a quadpill-a single capsule containing four blood pressure-lowering drugs each at quarter-dose (irbesartan 37·5 mg, amlodipine 1·25 mg, hydrochlorothiazide 6·25 mg, and atenolol 12·5 mg). Participants with untreated hypertension were enrolled from four centres in the community of western Sydney, NSW, Australia, mainly by general practitioners. Participants were randomly allocated by computer to either the quadpill or matching placebo for 4 weeks; this treatment was followed by a 2-week washout, then the other study treatment was administered for 4 weeks. Study staff and participants were unaware of treatment allocations, and masking was achieved by use of identical opaque capsules. The primary outcome was placebo-corrected 24-h systolic ambulatory blood pressure reduction after 4 weeks and analysis was by intention to treat. We also did a systematic review of trials evaluating the efficacy and safety of quarter-standard-dose blood pressure-lowering therapy against placebo. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614001057673. The trial ended after 1 year and this report presents the final analysis. FINDINGS: Between November, 2014, and December, 2015, 55 patients were screened for our randomised trial, of whom 21 underwent randomisation. Mean age of participants was 58 years (SD 11) and mean baseline office and 24-h systolic and diastolic blood pressure levels were 154 (14)/90 (11) mm Hg and 140 (9)/87 (8) mm Hg, respectively. One individual declined part
- Published
- 2017
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