METHODS: Pharmaceutical emulsion holds a significant place as a primary choice of oral drug delivery system for lipophilic drugs used in pediatric and geriatric patients. Pharmacokinetic studies on nanoemulsion mediated drugs delivery approach indicates practical feasibility in regards to their clinical translation and commercialization.
RESULTS: This review article is to provide an updated understanding on pharmacokinetic and pharmacodynamic features of nanoemulsion delivered via oral, intravenous, topical and nasal route.
CONCLUSION: The article is of huge interest to formulation scientists working on range of lipophilic drug molecules intended to be administered through oral, intravenous, topical and nasal routes for vivid medical benefits.
AIM: To perform a systematic review with network meta-analysis to resolve this uncertainty.
METHODS: We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities.
RESULTS: We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58-0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36-0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo.
CONCLUSIONS: TCAs, histamine-2 receptor antagonists, standard- and low-dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.
MATERIAL AND METHODS: A literature search was conducted for the period from January 2000 to December 2019 by using a number of medical literature data bases including Scopus, PubMed and Embase. The following search words were used either individually or in combination: drug-induced sleep endoscopy, sleep endoscopy directed surgery, paediatrics sleep apnoea. The search was conducted over a month period (December 2019). Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions were followed when possible.
RESULTS: Seven clinical research articles were selected based on our objective and selection criteria. Seven studies were of level III evidence: retrospective, case-control and prospective series. Altogether, there were 996 patients with male predominance; 61%. Over 10% of patients (133 patients) were found to have comorbidities or were syndromic. The mean age of patient was 6 years and majority (87.6%) of our patients were found to be surgically naïve, that is, no previous surgical procedures were performed for OSA. Surgical decision was changed in 295 patients (30%) following DISE. Post intervention outcomes were objectively revealed in 4 studies. Most of our patients underwent a multilevel surgery based on DISE (86%). Complications were documented in 3 studies.
CONCLUSIONS: Analysis of the results indicated that DISE directed surgery was an effective, safe therapeutic approach to treating paediatrics obstructive sleep apnoea. DISE directed surgery has shown to have changed surgical management in most studies.
METHODS: review of thirty-nine public opinion surveys on the death penalty carried out in five Asian countries which retain the death penalty for drugs or are considering re-introducing it. The review was conducted by analysing and comparing design, methodology, findings, and the relationship between these elements.
RESULTS: all but two surveys recorded a majoritarian support for the death penalty, driven by beliefs in (a) deterrent effect of the death penalty, and (b) perfect justice - both disproven. Complex surveys found a low intensity of support, and a limited interest and knowledge by the public in capital punishment. Support for capital punishment is lower for drug offences specifically, and it decreases significantly when expressed with reference to real-life cases. Limited data suggest that the public in the focus countries has reservations on the effectiveness of the death penalty to reduce drug offences, and prefers a discretionary system of punishment. The analysis also revealed correlations between the framing of survey questions and their findings.
CONCLUSION: Public opinion surveys conducted in China, Malaysia, the Philippines, Singapore, and Thailand suggest that the public knows little and has little interest in the death penalty. Although majoritarian, its support is based on a faulty understanding of key facts related to capital punishment, and an increase in knowledge is correlated to a decrease in support. More rigorous polling exercises demonstrate that public support for capital punishment - both in general and for drug offences specifically - is instinctive, abstract, elastic, and contextual.
METHODS: Over 30,000 pages of documents have been accessed through the National Archives of Australia in Canberra. These have been photographed, scanned and converted to OCR. The most relevant folders have then been analysed through NVivo 12 to look for relevant mentions of the research question: capital punishment and Malaysia. All probative data is then presented in the article.
RESULTS: The data from National Archives suggests that the UN, Australia, and other western countries were happy to continue supporting Malaysia's drug policy and to elect it to high positions at UN meetings despite their public proclamations that they were opposed to the death penalty.
CONCLUSION: Applying a critical juncture approach, the article concludes that the 1980s was a critical juncture in the movement to abolish the death penalty but abolitionist countries allowed capital punishment to continue for drug offences. This may have set back the abolition movement by decades.
METHODS: Data were pooled from 2 multicenter, double-blind, placebo-controlled, parallel-group, 14-week treatment studies of mirogabalin conducted at ∼350 study sites (Japan, South Korea, Taiwan, Singapore, Malaysia, and Thailand). Eligible patients in both studies were randomized in a 2:1:1:1 ratio, stratified according to a baseline average daily pain score (ADPS) of <6 or ≥6, to placebo, mirogabalin 15-mg once daily (QD), mirogabalin 10-mg twice daily (BID), or mirogabalin 15-mg BID treatment groups. Safety was assessed based on treatment-emergent adverse events identified from the adverse events collected throughout both studies. The primary efficacy end point of both studies was the change from baseline in ADPS at week 14.
FINDINGS: In total, 1587 patients (824 with diabetic peripheral neuropathic pain; 763 with post-herpetic neuralgia) who received at least 1 dose of study drug were analyzed (633 received placebo, 954 treated with mirogabalin). Treatment-emergent adverse events included somnolence (3.8%, 10.8%, 14.5%, and 19.1%) and dizziness (2.7%, 5.7%, 9.1%, and 13.1%) in patients receiving placebo, mirogabalin 15 mg QD, mirogabalin 10 mg BID, and mirogabalin 15 mg BID, respectively. In patients treated with mirogabalin 15 mg QD, 2 (0.6%) of 316 patients discontinued due to somnolence. In the mirogabalin 10-mg BID group, somnolence, edema, and peripheral edema each resulted in 3 (0.9%) of 318 patient discontinuations. In the mirogabalin 15-mg BID group, 6 (1.9%) of 320 patients discontinued due to dizziness and 3 (0.9%) due to somnolence. At week 14, mirogabalin 10 mg BID and 15 mg BID statistically significantly improved ADPS versus placebo, with least squares mean changes (95% CI) of -0.31 (-0.55, -0.08) and -0.63 (-0.86, -0.40). Post hoc analysis showed a statistically significant difference 2 days after administration in the mirogabalin 10-mg and 15-mg BID groups compared with placebo. Female sex, age ≥65 years, and baseline weight <60 kg may influence the safety of mirogabalin, particularly regarding the incidence of somnolence and dizziness, but had no notable impact on efficacy. ClinicalTrials.gov identifiers: NCT02318706 and NCT02318719.
IMPLICATIONS: This pooled analysis showed that mirogabalin was efficacious and well-tolerated by Asian patients with peripheral neuropathic pain.