Understanding the unmet needs in insomnia treatment: a systematic literature review of real-world evidence.

STUDY OBJECTIVE: The objective of this study was to define and characterize the unmet needs in the pharmacological management of insomnia. METHODS: A systematic literature review was conducted to identify relevant literature reporting real-world evidence in insomnia, published from January 2009 to April 2020. Pharmacological treatments - both prescription (benzodiazepines, 'Z-drugs' and suvorexant) and off-label (antidepressants, antipsychotics, and antihistamines) - were considered. RESULTS: Overall, 108 publications describing the humanistic (n = 59) and economic burden (n = 20) of insomnia, off-label treatment patterns (n = 28) and factors influencing treatment adherence or persistence (n = 8) were identified. A high prevalence of comorbid conditions was reported in patients with insomnia resulting in significantly lower health-related QoL compared to those with insomnia or a comorbidity alone. Current treatment options were associated with adverse events, including reduced sleep quality and next-day somnolence. An increased risk of accidents/injuries was also associated with insomnia and its treatment. Furthermore, safety concerns and perceived lack of efficacy for approved treatments have led to frequent off-label prescribing, despite a lack of clinical evidence of risk/benefit ratios. Safety concerns associated with benzodiazepines include risk of dependence, leading to prolonged treatment persistence and exacerbated adverse events, making them unsuitable for use in patients with chronic insomnia. Finally, the substantial economic burden of insomnia was evident, with reduced work productivity demonstrated in patients with insomnia compared to the general population. CONCLUSIONS: This review highlights a clear unmet need for insomnia therapies that improve sleep quality without resulting in next-day impairment and/or dependence.

Evaluation of Patients with Insufficient Efficacy and/or Tolerability to Triptans for the Acute Treatment of Migraine: A Systematic Literature Review.

INTRODUCTION: Use of triptans for acute treatment of migraine is associated with insufficient efficacy and/or tolerability in approximately 30-40% of people. We conducted a systematic literature review (SLR) to synthesize definitions, terminology, subsequent treatment outcomes, and characteristics associated with this subpopulation. METHODS: A comprehensive SLR was conducted to identify studies, published from Jan 1995 to May 2019, which focused on insufficient efficacy and/or tolerability to triptans. RESULTS: Thirty-five publications were identified, of which 22 described randomized controlled trials and open-label studies, and 13 described observational studies. Across studies, multiple objectives and a high amount of variability in methodologies and outcomes were noted. The most commonly applied measures of efficacy were headache pain freedom and pain relief at 2 h. Ten studies assessed efficacy of switching or optimizing treatment in patients with historical insufficient efficacy or tolerability to previous triptan treatment and demonstrated varying levels of success. Factors associated with increased risk of triptan insufficient efficacy included severe baseline headache severity, photophobia, phonophobia, nausea, and depression. CONCLUSIONS: Irrespective of the methodology or definition used to identify people with insufficient efficacy and/or tolerability to triptans, study results support the assertion that a high unmet need remains for effective acute treatment of migraine.

Cost-Effectiveness Analysis of a HMGA2 Prognostic Test for Acute Myeloid Leukemia in a Canadian Setting.

BACKGROUND: Current strategies for risk stratification of patients with acute myeloid leukemia assign approximately 40% of patients to the intermediate-risk group, where uncertainty about optimal therapy still persists. OBJECTIVE: The objective of this study was to assess the cost effectiveness of a HMGA2 prognostic test based on HMGA2+/HMGA2- expression, which improves genetic risk stratification in acute myeloid leukemia, and compare this test with the current standard of care in Canada. METHODS: A cost-effectiveness model was developed from the Canadian National Healthcare Service and societal perspective using data from the Quebec Leukemia Cell Bank, published literature, and physician surveys. The model includes a lifetime horizon assessing the HMGA2 test vs. standard of care. RESULTS: The HMGA2 test outperformed the standard of care at all time horizons culminating with estimated improvements of 1.92 and 3.12 months in leukemia-free survival and overall survival, respectively. Costs associated with the HMGA2 test were consistently lower, except diagnostic costs, routine medical costs, and costs related to infections and false positives. From a societal perspective, total lifetime costs were $161,358 CAD and $151,908 CAD with the standard of care and the HMGA2 test, respectively. The incremental quality-adjusted life-year gain was 0.138, which led to dominance over the standard of care. Deterministic sensitivity analyses confirmed the results of the base-case scenario. Probabilistic sensitivity analyses revealed that for a willingness-to-pay threshold of $100,000 CAD, the probability of cost effectiveness was 87.19%. CONCLUSIONS: The HMGA2 test is estimated to improve leukemia-free survival and overall survival outcomes, and yield costs savings from a healthcare system and societal perspective.

Nausea and vomiting of pregnancy and resource implications: the NVP Impact Study.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) is the most prevalent medical condition associated with pregnancy. The Royal College of Obstetricians and Gynaecologists published its first guidelines for management of NVP in 2016, although many current treatments are off label, with only one recently licensed treatment for NVP in the UK. AIM: To identify the current practices for NVP management across the patient pathway, and estimate the economic burden to NHS services. DESIGN AND SETTING: This was an observational, retrospective research study conducted in the Newcastle Gateshead Clinical Commissioning Group (CCG) health economy area in England. METHOD: Data were collected from GP practices, local hospital datasets, ambulance services (April 2013-March 2016), and the Hospital Episode Statistics dataset (2006-2016). RESULTS: Eight GP practices participated in the study. In all, 15.2% of the total pregnant population presented with NVP. Treatment varied significantly between GP practices, and 33.6% of women re-presented to their GP. There was an annual increase in women admitted to hospital for NVP symptoms, with increasing length of stay per admission. Almost half (44.6%) of the calls to 999/111 from women experiencing NVP symptoms resulted in an ambulance dispatch. The annual cost of NVP to this health economy was estimated to be £199 804, which crudely extrapolates to £25 758 731 at UK level. Due to underestimations of costs, the impact to the UK NHS could be up to £62 373 961. CONCLUSION: There is considerable variation in current management practices for NVP outside of recently published guidelines, and this may result in substantial resource use and avoidable financial impact to the NHS.

A cross-sectional developmental examination of the SNARC effect in a visually-guided grasping task.

The present study documents the influence of numerical processing on hand and space use during a reach-to-grasp task. Three questions regarding the SNARC (spatial-numerical association of response codes) effect were asked: (1) would the SNARC effect influence hand and/or space preference for grasping?; (2) would the SNARC effect be demonstrated during the processing of one-digit numbers, two-digit numbers, or both?; and (3) would developmental age influence the strength of the SNARC effect? A total of 84 participants in three age/school level groups (Primary, Secondary, and Post-secondary) took part in the study. Two identical sets of small wooden blocks numbered from 0 to 19 were used. Each set was presented to the right and to the left of each participant. A number was called and participants were asked to find and grasp a block with the corresponding number as fast and accurately as possible. Hand and space used (L/R) was recorded for each grasp. Number magnitude was shown to influence the selection of hand and hemi-space in accordance with the SNARC effect. In the small percentage of trials where the left hand was used, it was more commonly recruited to grasp blocks displaying low numbers than high numbers. Participants grasped blocks from left and right space with equal frequency, but respectively left/right space was accessed more often for blocks displaying low/high numbers. Regression analyses revealed that developmental age is a powerful predictor of the SNARC effect on hand and space selection for grasping. This study provides the first description of the SNARC effect on hand and space preference for the reach-to-grasp action. Results are discussed with relevant literature of numerical processing in the human brain.