Evaluating fluticasone furoate + vilanterol for the treatment of chronic obstructive pulmonary disease (COPD)

Introduction: Inhaled corticosteroid/long-acting β-2 agonists (ICS/LABA) combination inhalers have been a lifeline for a generation of chronic obstructive pulmonary disease (COPD) and asthma patients. Fluticasone furoate and Vilanterol (FF/VI) as a once-daily ICS/LABA combination have an extensive clinical trial and real-world data to support its use in COPD patients.

Areas covered: The authors provide pharmacological profiles of fluticasone furoate, vilanterol and the FF/VI fixed dose combination. Salient clinical trials evaluating efficacy and safety of the FF/VI combination, and studies demonstrating the impact on COPD exacerbation risk and mortality are also discussed.

Expert opinion: ICS/LABA combinations provide bronchodilation and decrease the frequency of COPD exacerbations. Individualizing treatment of each COPD patient based on unique phenotypes will maximize chances of therapeutic responsiveness. Asthma-COPD overlap (ACO), patients with sputum and/or blood eosinophilia, patients with a brisk bronchodilator response, and patients with frequent exacerbations are more likely to show a therapeutic response to ICS than populations who have none of these features. FF/VI will likely remain a popular ICS/LBA combination to treat COPD, as a once-daily inhaled therapy delivered via the Ellipta device popular with COPD patients, with extensive clinical trial and real-world data to support its use.     

Gentiana scabra Bunge. Formula for Herpes Zoster: Biological Actions of Key Herbs and Systematic Review of Efficacy and Safety

This study reviewed the biological action of key herbs and evaluated systematically the efficacy and safety of oral Gentiana formula for herpes zoster (HZ). Experimental studies relevant to HZ were identified in PubMed. Randomized controlled trials using Gentiana formula for HZ were identified from nine English and Chinese databases. The primary outcome was evaluation of pain. Potential risk of bias was assessed. Meta‐analysis was conducted using mean difference or risk ratio with 95% confidence intervals. Key herbs Gentiana scabra Bunge, Gentiana triflora Pall, Scutellaria baicalensis Georgi, and Gardenia jasminoides Ellis have shown antiinflammatory actions through inhibition of inflammatory cytokines and pro‐inflammatory enzymes. Twenty‐six clinical studies, involving 2955 participants, were included. Modified Gentiana formula resolved pain earlier than pharmacotherapy when used alone or combined with topical Chinese herbal medicine. Incidence of postherpetic neuralgia was lower (risk ratio 0.14, 95% confidence interval 0.03 to 0.74) with modified Gentiana formula plus topical Chinese herbal medicine. Mild adverse events were reported. Antiinflammatory actions of key herbs of Gentiana formula may explain clinical benefit in hastening pain relief and decreasing postherpetic neuralgia. Few adverse events were reported. Findings were limited by study quality and diversity in intervention and comparator dosage. Copyright © 2017 John Wiley & Sons, Ltd.     

Development and initial validation of the Perceived Scarcity Scale

Though socio‐economic status (SES) partially explains the experience of stress and health outcomes, most research to date has relied on a small number of traditional indicators that fail to capture the full domain of socioeconomic factors. The recent reconceptualization of perceived scarcity is proposed as a subjective indicator of SES when attempting to predict both stress and health outcomes. Although a conceptualization of perceived scarcity has been advanced, a psychometrically sound scale is needed to assess the utility and scientific import of this concept. No such scale exists. Therefore, the current paper describes the development, psychometric properties, and initial validation of the Perceived Scarcity Scale (PScS). Four studies using traditional scale development processes were employed to develop (Studies 1 and 2) and provide an initial validation (Studies 3 and 4) for the PScS. Results support the existing model of perceived scarcity and indicate that the measure is valid. Moreover, the scale predicted concurrent perceived stress, as well as longitudinal ratings of perceived stress, global health, quality of life, and symptoms of depression and anxiety. The development of the new scale provides clinicians and researchers with a brief, validated measure that can assess the level of perceived scarcity individuals currently experience.     

Development and evolution of tooth renewal in neoselachian sharks as a model for transformation in chondrichthyan dentitions

A defining feature of dentitions in modern sharks and rays is the regulated pattern order that generates multiple replacement teeth. These are arranged in labio‐lingual files of replacement teeth that form in sequential time order both along the jaw and within successively initiated teeth in a deep dental lamina. Two distinct adult dentitions have been described: alternate, in which timing of new teeth alternates between two adjacent files, each erupting separately, and the other arranged as single files, where teeth of each file are timed to erupt together, in some taxa facilitating similarly timed teeth to join to form a cutting blade. Both are dependent on spatiotemporally regulated formation of new teeth. The adult Angel shark Squatina (Squalomorphii) exemplifies a single file dentition, but we obtained new data on the developmental order of teeth in the files of Squatina embryos, showing alternate timing of tooth initiation. This was based on micro‐CT scans revealing that the earliest mineralised teeth at the jaw margin and their replacements in file pairs (odd and even jaw positions) alternate in their initiation timing. Along with Squatina, new observations from other squalomorphs such as Hexanchus and Chlamydoselachus, together with representatives of the sister group Galeomorphii, have established that the alternate tooth pattern (initiation time and replacement order) characterises the embryonic dentition of extant sharks; however, this can change in adults. These character states were plotted onto a recent phylogeny, demonstrating that the Squalomorphii show considerable plasticity of dental development. We propose a developmental‐evolutionary model to allow change from the alternate to a single file alignment of replacement teeth. This establishes new dental morphologies in adult sharks from inherited alternate order.     

Triple therapy in type 2 diabetes: insulin glargine or rosiglitazone added to combination therapy of sulfonylurea plus metformin in insulin-naive patients

OBJECTIVE: To evaluate the efficacy and safety of add-on insulin glargine versus rosiglitazone in insulin-na?ve patients with type 2 diabetes inadequately controlled on dual oral therapy with sulfonylurea plus metformin. RESEARCH DESIGN AND METHODS: In this 24-week multicenter, randomized, open-label, parallel trial, 217 patients (HbA(1c) [A1C] 7.5-11%, BMI >25 kg/m(2)) on > or =50% of maximal-dose sulfonylurea and metformin received add-on insulin glargine 10 units/day or rosiglitazone 4 mg/day. Insulin glargine was forced-titrated to target fasting plasma glucose (FPG) < or =5.5-6.7 mmol/l (< or =100-120 mg/dl), and rosiglitazone was increased to 8 mg/day any time after 6 weeks if FPG was >5.5 mmol/l. RESULTS: A1C improvements from baseline were similar in both groups (-1.7 vs. -1.5% for insulin glargine vs. rosiglitazone, respectively); however, when baseline A1C was >9.5%, the reduction of A1C with insulin glargine was greater than with rosiglitazone (P < 0.05). Insulin glargine yielded better FPG values than rosiglitazone (-3.6 +/- 0.23 vs. -2.6 +/- 0.22 mmol/l; P = 0.001). Insulin glargine final dose per day was 38 +/- 26 IU vs. 7.1 +/- 2 mg for rosiglitazone. Confirmed hypoglycemic events at plasma glucose <3.9 mmol/l (<70 mg/dl) were slightly greater for the insulin glargine group (n = 57) than for the rosiglitazone group (n = 47) (P = 0.0528). The calculated average rate per patient-year of a confirmed hypoglycemic event (<70 mg/dl), after adjusting for BMI, was 7.7 (95% CI 5.4-10.8) and 3.4 (2.3-5.0) for the insulin glargine and rosiglitazone groups, respectively (P = 0.0073). More patients in the insulin glargine group had confirmed nocturnal hypoglycemia of <3.9 mmol/l (P = 0.02) and <2.8 mmol/l (P < 0.05) than in the rosiglitazone group. Effects on total cholesterol, LDL cholesterol, and triglyceride levels from baseline to end point with insulin glargine (-4.4, -1.4, and -19.0%, respectively) contrasted with those of rosiglitazone (+10.1, +13.1, and +4.6%, respectively; P < 0.002). HDL cholesterol was unchanged with insulin glargine but increased with rosiglitazone by 4.4% (P < 0.05). Insulin glargine had less weight gain than rosiglitazone (1.6 +/- 0.4 vs. 3.0 +/- 0.4 kg; P = 0.02), fewer adverse events (7 vs. 29%; P = 0.0001), and no peripheral edema (0 vs. 12.5%). Insulin glargine saved $235/patient over 24 weeks compared with rosiglitazone. CONCLUSIONS: Low-dose insulin glargine combined with a sulfonylurea and metformin resulted in similar A1C improvements except for greater reductions in A1C when baseline was > or =9.5% compared with add-on maximum-dose rosiglitazone. Further, insulin glargine was associated with more hypoglycemia but less weight gain, no edema, and salutary lipid changes at a lower cost of therapy.