Biomarkers of potential harm in people switching from smoking tobacco to exclusive e-cigarette use, dual use or abstinence: secondary analysis of Cochrane systematic review of trials of e-cigarettes for smoking cessation

Aims This study aims to compare biomarkers of potential harm between people switching from smoking combustible cigarettes (CC) completely to electronic cigarettes (EC), continuing to smoke CC, using both EC and CC (dual users) and using neither (abstainers), based on behaviour during EC intervention studies. Design Secondary analysis following systematic review, incorporating inverse variance random-effects meta-analysis and effect direction plots. Setting This study was conducted in Greece, Italy, Poland, the United Kingdom and the United States. Participants A total of 1299 adults smoking CC (nine studies) and provided EC. Measurements Measurements were conducted using carbon monoxide (CO) and 26 other biomarkers. Findings In pooled analyses, exhaled CO (eCO) was lower in EC versus EC + CC [mean difference (MD) = −4.40 parts per million (p.p.m.), 95% confidence interval (CI) = −12.04 to 3.24, two studies] and CC (MD = −9.57 p.p.m., 95% CI = −17.30 to −1.83, three studies). eCO was lower in dual users versus CC only (MD = −1.91 p.p.m., 95% CI = −3.38 to −0.45, two studies). Magnitude rather than direction of effect drove substantial statistical heterogeneity. Effect direction plots were used for other biomarkers. Comparing EC with CC, 12 of 13 biomarkers were significantly lower in EC users, with no difference for the 13th. Comparing EC with dual users, 12 of the 25 biomarkers were lower for EC, and five were lower for dual use. For the remaining eight measures, single studies did not detect statistically significant differences, or the multiple studies contributing to the outcome had inconsistent results. Only one study provided data comparing dual use with CC; of the 13 biomarkers measured, 12 were significantly lower in the dual use group, with no statistically significant difference detected for the 13th. Only one study provided data on abstainers. Conclusions Switching from smoking to vaping or dual use appears to reduce levels of biomarkers of potential harm significantly

Characteristics of clinical trials in rare vs. common diseases : A register-based Latvian study

Publisher Copyright: © 2018 Logviss et al. This is an open ccess article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and eproduction in any medium, provided the original author and source are credited.Background Conducting clinical studies in small populations may be very challenging; therefore quality of clinical evidence may differ between rare and non-rare disease therapies. Objective This register-based study aims to evaluate the characteristics of clinical trials in rare diseases conducted in Latvia and compare them with clinical trials in more common conditions. Methods The EU Clinical Trials Register (clinicaltrialsregister.eu) was used to identify interventional clinical trials related to rare diseases (n = 51) and to compose a control group of clinical trials in non-rare diseases (n = 102) for further comparison of the trial characteristics. Results We found no significant difference in the use of overall survival as a primary endpoint in clinical trials between rare and non-rare diseases (9.8% vs. 13.7%, respectively). However, clinical trials in rare diseases were less likely to be randomized controlled trials (62.7% vs. 83.3%). Rare and non-rare disease clinical trials varied in masking, with rare disease trials less likely to be double blind (45.1% vs. 63.7%). Active comparators were less frequently used in rare disease trials (36.4% vs. 58.8% of controlled trials). Clinical trials in rare diseases enrolled fewer participants than those in non-rare diseases: In Latvia (mean 18.3 vs. 40.2 subjects, respectively), in the European Economic Area (mean 181.0 vs. 626.9 subjects), and in the whole clinical trial (mean 335.8 vs. 1406.3 subjects). Although, we found no significant difference in trial duration between the groups (mean 38.3 vs. 36.4 months). Conclusions The current study confirms that clinical trials in rare diseases vary from those in non-rare conditions, with notable differences in enrollment, randomization, masking, and the use of active comparators. However, we found no significant difference in trial duration and the use of overall survival as a primary endpoint.publishersversionPeer reviewe

Community pharmacists’ knowledge and perspectives of reporting adverse drug reactions in Australia: a cross-sectional survey

Background Under-reporting of adverse drug reactions (ADRs) by healthcare professionals is prevalent worldwide. Community pharmacists are the most frequently visited healthcare professional and are well placed to document ADRs as a part of their routine practice. Objective To measure community pharmacists’ knowledge and perspectives towards ADR reporting and their reporting practices. Setting Community pharmacists in the New South Wales, Queensland, Victoria and Tasmania, Australia. Method A survey tool consisting of 28 items was developed, piloted and validated by a panel of expert reviewers. The final anonymised survey was distributed online to community pharmacists. Exploratory factor analysis and Cronbach’s alpha were used to measure the validity and reliability of the tool, respectively. Non-parametric statistical tests were used to analyse knowledge, perspectives and ADR reporting practices. Main outcome measures: Knowledge, perceived importance, enablers and barriers to reporting ADRs. Results The survey tool showed acceptable validity and reliability. A total of 232 respondents completed the survey. The median knowledge score was 5 out of 10 (interquartile range, 2). Less than a third of respondents (31.0%) reported sufficient knowledge and training on ADR reporting. Only 35.3% of pharmacists reported at least one ADR in the previous 12 months. Non-reporting pharmacists were more likely to report lack of time as a barrier (P < 0.001), conversely they were more likely to report if the practice was remunerated (P = 0.007). Conclusion Under-reporting of ADRs by community pharmacists is highly prevalent. Initiatives to educate and train them on ADR reporting and simplifying the reporting process may improve reporting practices

Antihelminthic drugs

The Side Effects of Drugs Annuals form a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: the International Encyclopedia of Adverse Drug Reactions and Interactions. This review of the 2011 publications on antihelminthic drugs covers the benzimidazoles albendazole and benznidazole, ivermectin, levamisole, and praziquantel. Levamisole has become a very common adulterant of street cocaine and can cause a wide range of adverse reactions, such as neutropenia and agranulocytosis, vasculitis and/or vasculopathy, with a particular predilection for the ears, causing necrosis of the pinnae, skin necrosis, purpuric eruptions, often retiform, antiphospholipid antibody syndrome, and microvascular thrombosis; in some cases combinations of two or more of these reactions occur. © 2014 Elsevier B.V

Effect of the natural sweetener, steviol glycoside, on cardiovascular risk factors: A systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Many different dietary supplements are currently marketed for the management of hypertension and diabetes, but the evidence for effectiveness is mixed. The objective of this systematic review was to critically appraise and evaluate the evidence for effectiveness of steviol glycosides (stevioside and rebaudioside A) on cardiovascular risk factors, using data from randomised clinical trials (RCTs). METHODS: Electronic searches were conducted in Medline, Embase, Amed, Cinahl and The Cochrane Library. We also searched Google Scholar, and hand searched the bibliography of retrieved full texts. The reporting quality of included studies was assessed using the Cochrane criteria. Two reviewers independently determined the eligibility, assessed the reporting quality, and extracted the data. RESULTS: Nine studies with a total of 756 participants were included. There was a variation in the reporting quality of included studies. Meta-analysis revealed a non-significant difference in systolic blood pressure between steviol glycoside and placebo, mean difference (MD): -2.98 mm Hg (-6.23 to 0.27). Significant reductions in diastolic blood pressure and fasting blood glucose were observed. There was no significant effect on blood lipid profile. Heterogeneity was significant. Adverse events included abdominal fullness, epigastric pain, and dizziness. CONCLUSION: The evidence from published RCTs suggests that stevioside may generate reductions in blood pressure and fasting blood glucose. The sizes of the effects are small, and the substantial heterogeneity limits the robustness of any conclusions. Rebaudioside A does not appear to have any significant effects on blood pressure or cardiovascular risk factors. Available clinical trials vary in design and reporting quality, and some are characterised by inadequate sample sizes. In addition, the participants in most of the trials have high cardiovascular risk. Further clinical trials and regulatory assessments are warranted

Effect of the natural sweetener, steviol glycoside, on cardiovascular risk factors: A systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Many different dietary supplements are currently marketed for the management of hypertension and diabetes, but the evidence for effectiveness is mixed. The objective of this systematic review was to critically appraise and evaluate the evidence for effectiveness of steviol glycosides (stevioside and rebaudioside A) on cardiovascular risk factors, using data from randomised clinical trials (RCTs). METHODS: Electronic searches were conducted in Medline, Embase, Amed, Cinahl and The Cochrane Library. We also searched Google Scholar, and hand searched the bibliography of retrieved full texts. The reporting quality of included studies was assessed using the Cochrane criteria. Two reviewers independently determined the eligibility, assessed the reporting quality, and extracted the data. RESULTS: Nine studies with a total of 756 participants were included. There was a variation in the reporting quality of included studies. Meta-analysis revealed a non-significant difference in systolic blood pressure between steviol glycoside and placebo, mean difference (MD): -2.98 mm Hg (-6.23 to 0.27). Significant reductions in diastolic blood pressure and fasting blood glucose were observed. There was no significant effect on blood lipid profile. Heterogeneity was significant. Adverse events included abdominal fullness, epigastric pain, and dizziness. CONCLUSION: The evidence from published RCTs suggests that stevioside may generate reductions in blood pressure and fasting blood glucose. The sizes of the effects are small, and the substantial heterogeneity limits the robustness of any conclusions. Rebaudioside A does not appear to have any significant effects on blood pressure or cardiovascular risk factors. Available clinical trials vary in design and reporting quality, and some are characterised by inadequate sample sizes. In addition, the participants in most of the trials have high cardiovascular risk. Further clinical trials and regulatory assessments are warranted