Real-world evidence of the safety and efficacy profile of suvorexant in elderly patients with insomnia: a sub-analysis of the post-marketing drug-use results survey in Japan

Abstract

Objective: Global Phase III trials of suvorexant showed no obvious differences in the safety and efficacy profile of suvorexant between elderly and non-elderly patients. However, the clinical profile of suvorexant in elderly patients with comorbidities in a real-world setting was not evaluated. To further understand the safety and efficacy profile of suvorexant in elderly patients with insomnia in a daily clinical practice setting, we conducted a sub-group analysis of the post-marketing drug-use results survey.

Methods: Patients with insomnia who were treated with suvorexant for the first time were divided into three groups: group-1 (<65?years, N?=?1490), group-2 (≥65?years and <75?years, N?=?730), and group-3 (≥75?years, N?=?1028).

Results: The incidence of overall adverse drug reactions (ADRs) were 11.28% (N?=?168), 8.63% (N?=?63), and 8.17% (N?=?84) in group-1, -2, and -3, respectively. The ADRs most commonly observed in this survey were somnolence, insomnia, and dizziness, with no new safety concerns or differences in safety issues found. The numbers of patients in group-1, -2, and -3 who visited internal medicine departments were: 690 patients (46.3%), 521 patients (71.4%), and 793 patients (77.1%), respectively. The percentage of patients who were deemed to have “improved”, based on the patient’s self-assessment and their physician’s assessment, was 70–75% of patients in all groups.

Conclusion: These results reveal the safety and efficacy profile of suvorexant in elderly patients who often have various and multiple comorbidities and were treated in a daily clinical practice setting.     

Efficacy and safety of treatment with dupilumab for severe asthma: A systematic review of the EAACI guidelines—Recommendations on the use of biologicals in severe asthma

Dupilumab, a fully human monoclonal antibody against interleukin-4 receptor α, is approved as add-on maintenance treatment for inadequately controlled type 2 severe asthma. This systematic review evaluated the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled severe asthma. PubMed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. Three RCTs including 2735 subjects >12 years old and 24-52 weeks of follow-up were included. Dupilumab reduced with high certainty severe asthma exacerbations (Incidence rate ratio 0.51; 95% CI 0.45-0.59) and the percentage use of oral corticosteroid use (mean difference (MD) −28.2 mg/d; 95% CI −40.7 to −15.7). Asthma control (ACQ-5), quality of life (AQLQ) and rescue medication use [puffs/d] improved, without reaching the minimal important clinical difference: ACQ-5 MD −0.28 (95% CI −0.39 to −0.17); AQLQ MD +0.28 (95% CI 0.20-0.37); and rescue medication MD −0.35 (95% CI −0.73 to +0.02). FEV₁ increased (MD +0.15; 95% CI +0.11 to +0.18) (moderate certainty). There was an increased rate of dupilumab-related adverse events (AEs) (moderate certainty) and of drug-related serious AEs (low certainty). The incremental cost-effectiveness ratio of dupilumab versus standard therapy was 464 000$/QALY (moderate certainty). More data on long-term safety are needed both for children and for adults, together with more efficacy data in the paediatric population.     

Necklace‐embedded electrocardiogram for the detection and diagnosis of atrial fibrillation

BackgroundAtrial fibrillation (AF) is the major cause of stroke since approximately 25% of all strokes are of cardioembolic‐origin. The detection and diagnosis of AF are often challenging due to the asymptomatic and intermittent nature of AF.HypothesisA wearable electrocardiogram (ECG)‐device could increase the likelihood of AF detection. The aim of this study was to evaluate the feasibility and reliability of a novel, consumer‐grade, single‐lead ECG recording device (Necklace‐ECG) for screening, identifying and diagnosing of AF both by a cardiologist and automated AF‐detection algorithms.MethodsA thirty‐second ECG was recorded with the Necklace‐ECG device from two positions; between the palms (palm) and between the palm and the chest (chest). Simultaneously registered 3‐lead ECGs (Holter) served as a golden standard for the final rhythm diagnosis. Two cardiologists interpreted independently in a blinded fashion the Necklace‐ECG recordings from 145 patients (66 AF and 79 sinus rhythm, SR). In addition, the Necklace‐ECG recordings were analyzed with an automatic AF detection algorithm.ResultsTwo cardiologists diagnosed the correct rhythm of the interpretable Necklace‐ECG with a mean sensitivity of 97.2% and 99.1% (palm and chest, respectively) and specificity of 100% and 98.5%. The automatic arrhythmia algorithm detected the correct rhythm with a sensitivity of 94.7% and 98.3% (palm and chest) and specificity of 100% of the interpretable measurements.ConclusionsThe novel Necklace‐ECG device is able to detect AF with high sensitivity and specificity as evaluated both by cardiologists and an automated AF‐detection algorithm. Thus, the wearable Necklace‐ECG is a new, promising method for AF screening. Clinical trial registration: Study was registered in the ClinicalTrials.gov database ({"type":"clinical-trial","attrs":{"text":"NCT03753139","term_id":"NCT03753139"}}NCT03753139).     

Gamification improves melanoma visual identification among high school students: Results from a randomized study

Identification of melanoma or worrisome moles is often taught as an important part of routine skin checks. We sought to evaluate the efficacy of gamified education vs. traditional ABCDEs education on melanoma identification and self-confidence in identifying worrisome moles. We report that in our cohort (n = 271), participants randomized to the gamified intervention were more likely to correctly identify melanoma and non-melanoma skin lesions than those randomized to the ABCDE control cohort (74.2% vs 63.5% correct, P < .0001) and perceived confidence in self-identifying worrisome lesions was slightly higher in the gamified group than the traditional group, though the trend was not significant. These novel findings have significant implications on improved ways to educate young patients on the visual identification of melanoma and worrisome moles.     

Sports injuries in elderly athletes: a three-year prospective, controlled study

A 3-year prospective, controlled study of sports injuries in elderly athletes (over 60 years of age) treated at an outpatient sports clinic was carried out in order to determine the number, profile, and specific features of these injuries compared with those of young athletes (between 21 and 25 years). During the study period, 57 elderly and 457 young adult athletes visited the clinic. The majority of the patients in both groups were male (83% of the veterans and 85% of the young). Forty-eight veterans (84%) were endurance sportsmen, while only 115 of the young patients (25%) went in for endurance sports. In both groups the knee joint was most frequently affected, in the young athletes (36%) more frequently than in the elderly (21%). In the elderly athletes shoulder (18%) as well as Achilles tendon and calf (20%) complaints were significantly more common than among young athletes (7% and 5%, respectively). Most (70%) of the injuries in the elderly were overuse injuries, but these comprised only 41% in the young.     

Predictive clinical and laboratory parameters for serum zinc and copper in rheumatoid arthritis.

Zinc and copper have important effects on T cell mediated immunity and on neutrophil function, but it is not known how the causes or effects, of low serum zinc and high serum copper relate to the clinical picture of rheumatoid arthritis (RA). In this study serum zinc and copper determined by flame atomic absorption spectrometry and 30 other clinical, immunological, and laboratory parameters in 60 patients with RA were analysed by stepwise multiple linear regression analysis. Joint score index, rheumatoid factor titre, seropositivity, haemoglobin, and C reactive protein (CRP) were among the nine independent variables which together predicted 73% of the serum zinc variation. This suggests that there is an association between the immune-inflammatory rheumatoid process and the serum zinc concentration. CRP alone had only a 3% independent predicting value for serum zinc, however. This suggests that metallothionein mediated sequestration in the liver, induced by interleukin 1, is not an important explanatory factor in a cross sectional study of chronic inflammation. Furthermore, serum zinc did not have any predictive value at all for serum copper concentration. This does not support the hypothesis suggesting that serum zinc deficiency leads to high serum copper by inducing gastrointestinal metallothionein and high caeruloplasmin.     

Comparison of the Effects of Intravenously Bolus-administered Endothelin-1 and Infused Angiotensin II on the Subcutaneous Tumor Blood Flow in Anesthetized Rats

To evaluate the effects of endothelin-1 (ET-1) on tumor blood flow, the authors measured the mean arterial blood pressure (MABP) of enflurane-anesthetized male Donryu rats and the tissue blood flow of subcutaneously implanted tumor (Yoshida rat ascites hepatoma LY-80) by using a hydrogen clearance method. The tumor blood flow was evaluated in terms of the ratio to the maximum blood flow, which was defined as the largest flow in the same position during successive measurements. After bolus intravenous administration of ET-1 (1.0 nmol/kg), MABP reached approximately 140 mmHg (at 5 30 min), diminishing gradually to the baseline level over 2 h. The tumor blood flow increased from 36.7 ± 20.6 to 59.5 ± 30.2% (n = 32, P <0.001, at 2 min), returning to the baseline level at 10 min. On the other hand, at 2 min after the beginning of continuous intravenous infusion of [Asp¹, Ile⁵]-angiotensin II (AII; the dose was determined by a blood pressure control system for keeping MABP at approximately 150 mmHg, consequently 0.26 μg/kg/min on the average), the tumor blood flow increased from 42.3 ±21.6 to 76.4±22.6% (n = 32, P < 0.001), which was significantly larger than the flow after ET-1. The results indicate that hypertension induced by systemic ET-1 injection is less effective than hypertension induced by continuous systemic AII infusion in increasing tumor blood flow; AII is probably a suitable agent as a safe and effective enhancer of tumor blood flow. Moreover, ET-1 appears to constrict arterial vessels in the microcirculation time-dependently, while AII constricts probably only normal peripheral arterioles.