RESUMO
Patients with advanced non-small cell lung cancer (NSCLC) who harbor susceptible epidermal growth factor receptor (EGFR) mutations and are treated with EGFR tyrosine kinase inhibitors (TKIs) show longer progression-free survival (PFS) than those treated with chemotherapy. However, developed EGFR-TKI resistance limits PFS improvements. Currently, combination treatment with EGFR-TKIs and anti-angiogenic agents is considered a beneficial regimen for advanced-stage NSCLC harboring susceptible EGFR mutations. However, several trials reported osimertinib plus bevacizumab failed to show superior efficacy over osimertinib alone. However, subgroup analysis showed significantly longer PFS among patients with a history of smoking over those who never smoked. We performed a comprehensive systematic review and meta-analysis to evaluate the smoking status impact. At the end of the process, a total of 2068 patients from 11 randomized controlled trials (RCTs) were included in our meta-analysis. Overall, combination EGFR-TKI plus anti-angiogenic agent treatment showed significantly better PFS among patients with a smoking history (Hazard Ratio (HR) = 0.59, 95% confidence interval (CI) = 0.48-0.73). Erlotinib-based combination therapy showed positive PFS benefits regardless of smoking status (HR = 0.54, 95%CI = 0.41-0.71 for ever smoker, HR = 0.69, 95%CI = 0.54-0.87 for never smoker). Combination therapy prolonged PFS significantly regardless of ethnicity (HR: 0.64, 95% CI: 0.44-0.93 for Asian RCTs, HR: 0.55, 95% CI: 0.41-0.74 for global and non-Asian RCTs). PROSPERO registration number is CRD42022304198).
RESUMO
Gemifloxacin is a common oral antibiotic for lower respiratory tract infection worldwide. We noticed an uncommon delayed onset skin rash in patients who received Gemifloxacin. Therefore, we retrospectively reviewed all patients who received Gemifloxacin from 1 January 2011 to 31 May 2016 in a university-affiliated hospital in Taiwan. A total of 1358 patients were enrolled, of whom 36 (2.65%) had skin eruptions. The female patients had a significantly higher odds ratio (OR) 2.24 (95% confidence interval (CI) 1.11-4.53, p = 0.021) of having skin eruptions. A history of asthma was also a significant risk factor (OR 2.04, 95% CI = 1.01-4.14, p = 0.043). Female asthmatic patients had the highest risk of skin eruptions (10/129, 7.2%) with an adjusted OR up to 4.45 (95% CI = 1.81-10.93, p < 0.001) compared to male and non-asthmatic patients. Of note, up to 58.3% (21/36) of the patients experienced a skin rash after they had completed and stopped Gemifloxacin. The median onset time was on the second day (ranging one to five days) after completing treatment. We reported that female asthmatic patients have the highest risk of Gemifloxacin-associated skin eruptions in Asia and that they highlighted a unique delayed onset skin rash.
RESUMO
PURPOSE: Mirabegron, a ß3-adrenoceptor agonist, was approved for overactive bladder (OAB), but worsened hypertension was a potential risk based on its mechanism of action. Besides, head to head comparisons were limited between mirabegron and antimuscarinic agents, the prior first-line pharmacotherapy of OAB. In this regard, we performed a systematic review and meta-analysis to compare their efficacy as well as safety, especially in blood pressure changes. MATERIALS AND METHODS: Literature search was conducted in PubMed, Medline and seven randomized clinical trial (RCT) register databases of WHO, EU, USA, Taiwan, China, Japan and Cochrane. Completed RCTs for OAB with mirabegron and antimuscarinics were identified and the last comprehensive search was run in August 2017. Cochrane risk of bias tool was used to assess the potential bias, and RevMan5 software was performed for meta-analysis. RESULTS: Seven eligible RCTs (four for mirabegron vs. tolterodine and three for mirabegron vs. solifenacin) were included and demonstrated similar efficacy in micturitions, incontinence, and nocturia between mirabegron and antimuscarinics. In hypertension issue, no statistical differences were showed in risk ratio (RR) of hypertension events, change of blood pressure from baseline and change of blood pressure from placebo for all participants. On the other hand, RR of dry mouth was significantly lower in mirabegron users. CONCLUSIONS: Mirabegron was not inferior effective in improving OAB symptoms compared with antimuscarinic agents. In addition, mirabegron presented lower incidence of dry mouth and not higher risk for hypertension. Therefore, mirabegron has potential to be an alternative therapeutic option for OAB control.
