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Goran Medic,1,2 Micheline Wille,1 Michiel EH Hemels1 1Market Access, Horizon Pharma B.V., Utrecht, 2Unit of Pharmacoepidemiology & Pharmacoeconomics, Department of Pharmacy, University of Groningen, Groningen, The Netherlands Abstract: Sleep plays a vital role in brain function and systemic physiology across many body systems. Problems with sleep are widely prevalent and include deficits in quantity and quality of sleep; sleep problems that impact the continuity of sleep are collectively referred to as sleep disruptions. Numerous factors contribute to sleep disruption, ranging from lifestyle and environmental factors to sleep disorders and other medical conditions. Sleep disruptions have substantial adverse short- and long-term health consequences. A literature search was conducted to provide a nonsystematic review of these health consequences (this review was designed to be nonsystematic to better focus on the topics of interest due to the myriad parameters affected by sleep). Sleep disruption is associated with increased activity of the sympathetic nervous system and hypothalamic–pituitary–adrenal axis, metabolic effects, changes in circadian rhythms, and proinflammatory responses. In otherwise healthy adults, short-term consequences of sleep disruption include increased stress responsivity, somatic pain, reduced quality of life, emotional distress and mood disorders, and cognitive, memory, and performance deficits. For adolescents, psychosocial health, school performance, and risk-taking behaviors are impacted by sleep disruption. Behavioral problems and cognitive functioning are associated with sleep disruption in children. Long-term consequences of sleep disruption in otherwise healthy individuals include hypertension, dyslipidemia, cardiovascular disease, weight-related issues, metabolic syndrome, type 2 diabetes mellitus, and colorectal cancer. All-cause mortality is also increased in men with sleep disturbances. For those with underlying medical conditions, sleep disruption may diminish the health-related quality of life of children and adolescents and may worsen the severity of common gastrointestinal disorders. As a result of the potential consequences of sleep disruption, health care professionals should be cognizant of how managing underlying medical conditions may help to optimize sleep continuity and consider prescribing interventions that minimize sleep disruption. Keywords: sleep, sleep disorders, children, adolescents, adults, health status

Tim Kinnaird,1 Goran Medic,2 Gianni Casella,3 Francois Schiele,4 Upendra Kaul,5 Peter W Radke,6 Indra Eijgelshoven,2 Gert Bergman,2 Derek P Chew71Cardiff and Vale University Health Board, Cardiff, UK; 2Mapi-Health Economics Outcomes Research and Strategic Market Access, Houten, the Netherlands; 3Ospedale Maggiore, Unità Operativa di Cardiologia, Bologna, Italy; 4Hôpital Jean Minjoz, Besançon Cedex, France; 5Fortis Escorts Heart Institute and Research Centre, Okhla Road, New Delhi, India; 6Schön Klinik Neustadt, Neustadt, Germany; 7Flinders University; Department of Cardiovascular Medicine, Southern Adelaide Health Service, Bedford Park, SA, AustraliaAbstract: In the absence of head-to-head clinical data, the objective of this study was to indirectly compare the efficacy and safety of a bivalirudin-based anticoagulation strategy with that of heparin monotherapy in patients with ST-elevation myocardial infarction (STEMI) intended for primary percutaneous coronary intervention. A systematic literature review was performed to identify randomized controlled trials to build a network of bivalirudin and heparin monotherapy strategies in STEMI patients using heparin, with glycoprotein IIb/IIIa inhibitor as a common reference strategy. At 30 days, the bivalirudin-based strategy was expected to result in lower mortality rates than heparin monotherapy (odds ratio [OR], 0.55; credible limit [CrL], 0.32–0.95). This relationship was sustained at 1 year. At 30 days, the risk for stroke (OR, 0.88; CrL, 0.37–2.13), myocardial infarction (OR, 0.79; CrL, 0.40–1.55), and thrombolysis in myocardial infarction major and minor bleedings (OR, 0.66; CrL, 0.45–0.98) tended to be numerically reduced with bivalirudin in comparison with heparin monotherapy. For patients with STEMI intended for primary percutaneous coronary intervention, bivalirudin is associated with lower mortality rates in comparison with heparin monotherapy. This study suggests that bivalirudin is more effective and safer than heparin monotherapy and should therefore be preferred over heparin monotherapy.Keywords: primary angioplasty, STEMI, pharmacology

Goran Medic,1 Kyoko Higashi,1 Kavi J Littlewood,1 Teresa Diez,2 Ola Granström,3 René S Kahn41MAPI Consultancy, Houten, The Netherlands; 2AstraZeneca, Zaventem, Belgium; 3AstraZeneca, Södertälje, Sweden; 4Division of Neuroscience at the Utrecht University Medical Center, Utrecht, The NetherlandsBackground: The purpose of this study was to investigate the impact of dosing frequency on adherence in severe chronic psychiatric and neurological diseases.Methods: A systematic literature review was conducted for articles in English from medical databases. Diseases were schizophrenia, psychosis, epilepsy, bipolar disorder, and major depressive disorder.Results: Of 1420 abstracts screened, 12 studies were included. Adherence measures included Medication Event Monitoring System (MEMS®), medication possession ratio, medication persistence, and refill adherence. Three schizophrenia and one epilepsy study used MEMS, and all showed a trend towards higher adherence rates with less frequent dosing regimens. Three depression and one schizophrenia study used the medication possession ratio; the pooled odds ratio of being adherent was 89% higher (ie, 1.89, 95% credibility limits 1.71–2.09) on once-daily versus twice-daily dosing. Two studies in depression and one in all bupropion patients assessed medication persistence and refill adherence. The pooled odds ratio for the two depression studies using medication persistence was 2.10 (95% credibility limits 1.86–2.37) for once-daily versus twice-daily dosing. For refill adherence after 9 months, 65%–75% of patients on once-daily versus 56% on twice-daily dosing had at least one refill. In all but one of the studies using other measures of adherence, adherence rates were higher with once-daily dosing compared with more frequent dosing regimens. No relevant studies were identified for bipolar disorder or psychosis.Conclusion: Differences in study design and adherence measures used across the studies were too large to allow pooling of all results. Despite these differences, there was a consistent trend of better adherence with less frequent dosing.Keywords: adherence, dosing frequency, schizophrenia, epilepsy, depression