Increased risk of hearing loss associated with macrolide use: a systematic review and meta-analysis.

The increased risk of hearing loss with macrolides remains controversial. We aimed to systematically review and meta-analyze data on the clinical risk of hearing loss, tinnitus, and ototoxicity following macrolide use. A systematic search was conducted across PubMed, MEDLINE, Cochrane, and Embase databases from database inception to May 2023. Medical Subject Heading (MeSH) terms and text keywords were utilized, without any language restrictions. In addition to the electronic databases, two authors manually and independently searched for relevant studies in the US and European clinical trial registries and Google Scholar. Studies that involved (1) patients who had hearing loss, tinnitus, or ototoxicity after macrolide use, (2) intervention of use of macrolides such as azithromycin, clarithromycin, erythromycin, fidaxomicin, roxithromycin, spiramycin, and/or telithromycin, (3) comparisons with specified placebos or other antibiotics, (4) outcomes measured as odds ratio (OR), relative risk (RR), hazard ratio (HR), and mean difference for ototoxicity symptoms using randomized control trial (RCT)s and observational studies (case-control, cross-section, and cohort studies) were included. Data extraction was performed independently by two extractors, and a crosscheck was performed to identify any errors. ORs along with their corresponding 95% confidence intervals (CIs) were estimated using random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines for RCTs and Meta-Analysis of Observational Studies in Epidemiology guidelines for observational studies were followed. We assessed the hearing loss risk after macrolide use versus controls (placebos and other antibiotics). Based on data from 13 studies including 1,142,021 patients (n = 267,546 for macrolide and n = 875,089 for controls), the overall pooled OR was 1.25 (95% CI 1.07-1.47). In subgroup analysis by study design, the ORs were 1.37 (95% CI 1.08-1.73) for RCTs and 1.33 (95% CI 1.24-1.43) for case-control studies, indicating that RCT and case-control study designs showed a statistically significant higher risk of hearing loss. The group with underlying diseases such as multiple infectious etiologies (OR, 1.16 [95% CI 0.96-1.41]) had a statistically significant lower risk than the group without (OR, 1.53 [95% CI 1.38-1.70] P = .013). The findings from this systematic review and meta-analysis suggest that macrolide antibiotics increase the risk of hearing loss and that healthcare professionals should carefully consider this factor while prescribing macrolides.

The effect of post-stroke depression on rehabilitation outcome and the impact of caregiver type as a factor of post-stroke depression.

OBJECTIVE: To evaluate the effect of post-stroke depression (PSD) on rehabilitation outcome and to investigate the risk factors of PSD, especially, the role of caregivers type (family or professional) in subacute stroke patients. METHODS: Two hundred twenty-six stroke patients were enrolled retrospectively. All the subjects' basic characteristics, Korean version of the Beck Depression Inventory (K-BDI), Korean version of the Modified Barthel Index (K-MBI), and the modified Rankin Scale (mRS) were recorded when the patient was transferred into the Department of Rehabilitation Medicine and at the time of discharge. The results were statistically analyzed by using SPSS ver. 20.0. RESULTS: The patients' K-BDI score showed a significantly negative association with K-MBI at discharge (ß=-0.473, p<0.001) and a significantly positive association with the mRS score at discharge (ß=0.316, p<0.001). Patients with lesions on the left hemisphere (odds ratio [OR], 3.882; 95% confidence interval [CI], 1.726-8.733) and professional caregiver support (OR, 0.028; 95% CI, 0.012-0.065) had a higher rate of depression. CONCLUSION: Depression was prevalent in stroke patients, and it had a negative effect on patients' functional outcome. Patients who had a lesion on the right hemisphere had less depression. The type of caregiver was related to the incidence of subacute PSD, and family caregivers were found to lower the frequency of stroke patients' depression.

stab: an R package for drug stability data analysis.

In the pharmaceutical industry, drug stability studies are routinely performed to measure the degradation of an active pharmaceutical ingredient (API) within a drug product. The purpose of drug stability studies is to examine how the API in a drug product varies with time under influence of a variety of environmental factors. The most important study is to establish the expiration date (i.e., the shelf life) of the product. Thus, the aim of this study was to develop an R package to calculate the shelf life based on drug stability data according to the suggested algorithms by ICH Tripartite Guidelines for Q1E Evaluation.

The evaluation of free influenza vaccination in health care workers in a medical center in Taiwan.

OBJECTIVE: To evaluate the outcome of free influenza vaccination for healthcare workers in Taiwan. METHOD: A retrospective observational study was conducted in a partially vaccinated sample of healthcare workers in a medical centre in the southern part of Taiwan. A convenience sample of 500 employees received a questionnaire. MAIN OUTCOME MEASURE: Incidence of influenza like- illness (ILI), rates of absenteeism and costs savings. RESULTS: A final number of 407 returned questionnaires could be evaluated. Forty respondents were not vaccinated. The incidence of ILI was lower in the vaccinated group than the nonvaccinated group (13.6 vs. 15%). Fever was the most frequently occurring ILI. Rate of absenteeism because of ILI in the non-vaccinated employees was higher than in the group of vaccinated employees. The costs per saved lost working day was US $36. CONCLUSION: Free influenza vaccination may cause reductions in incidence, absenteeism, and costs associated with ILI in healthcare workers in Taiwan.

Analysis of pharmacokinetic parameters for assessment of dextromethorphan metabolic phenotypes.

In this study, the metabolic ratios of dextromethorphan to dextrorphan (DM/DX) in plasma were calculated at steady state after administering 2 dosage forms (Medicon) and Detusiv) of DM with different release rates. The urinary metabolic ratio for each subject was also determined based on the total drug concentration in the urine. An analysis of pharmacokinetic parameters for determining the DM metabolic phenotype was conducted. Results demonstrate that double logarithmic correlations between the metabolic ratios based on pharmacokinetic parameters of either AUC(0-tau,ss), C(max,ss), C(min,ss), or C(ave,ss) for Medicon and Detusiv and the urinary metabolic ratios were all significant. Probit plots of the metabolic ratios based on these pharmacokinetic parameters revealed 2 clusters of distribution, representing extensive and intermediate metabolizers. An antimode of 2.0 for total drug based on these pharmacokinetic parameters was determined and correspondingly referred to an antimode of 0.02 for the urinary metabolic ratio to delineate extensive and intermediate metabolizers. This model was also verified to be appropriate when using total plasma concentrations of DM and DX at any time during the period of the dosing interval at steady state to calculate the metabolic ratio for identifying extensive and intermediate metabolizers. Therefore, the metabolic ratio based on the pharmacokinetic parameters of either AUC(0-tau,ss), C(max,ss), C(min,ss), or C(ave,ss) and plasma concentrations of DM and DX in a single blood sample at steady state are proposed as an alternative way to identify phenotypes of CYP2D6.