Xin-yi-san contains potent human CYP1A2 inhibitors and its combined use with theophylline in treatment increases adverse risks in patients.

BACKGROUND: The Xin-yi-san herbal decoction (XYS) is commonly used to treat patients with allergic rhinitis in Taiwan. Theophylline is primarily oxidized with high affinity by human cytochrome P450 (CYP)1A2, and has a narrow therapeutic index. PURPOSE: This study aimed to investigate the inhibition of human CYP1A2-catalyzed theophylline oxidation (THO) by XYS and its adverse effects in patients. METHODS: Human CYPs were studied in recombinant enzyme systems. The influence of concurrent XYS usage in theophylline-treated patients was retrospectively analyzed. RESULTS: Among the major human hepatic and respiratory CYPs, XYS inhibitors preferentially inhibited CYP1A2 activity, which determined the elimination and side effects of theophylline. Among the herbal components of XYS decoction, Angelicae Dahuricae Radix contained potent THO inhibitors. Furanocoumarin imperatorin was abundant in XYS and Angelicae Dahuricae Radix decoctions, and non-competitively inhibited THO activity with Ki values of 77‒84 nM, higher than those (20‒52 nM) of fluvoxamine, which clinically interacted with theophylline. Compared with imperatorin, the intestinal bacterial metabolite xanthotoxol caused weaker THO inhibition. Consistent with the potency of the inhibitory effects, the docking analysis generated Gold fitness values in the order-fluvoxamine > imperatorin > xanthotoxol. During 2017‒2018, 2.6 % of 201,093 theophylline users consumed XYS. After inverse probability weighting, XYS users had a higher occurrence of undesired effects than non-XYS users; in particular, there was an approximately two-fold higher occurrence of headaches (odds ratio (OR), 2.14; 95 % confidence interval (CI), 1.99‒2.30; p < 0.001) and tachycardia (OR, 1.83; 95 % CI, 1.21‒2.77; p < 0.05). The incidence of irregular heartbeats increased (OR, 1.36; 95 % CI, 1.07‒1.72; p < 0.05) only in the theophylline users who took a high cumulative dose (≥ 24 g) of XYS. However, the mortality in theophylline users concurrently taking XYS was lower than that in non-XYS users (OR, 0.24; 95 % CI, 0.14‒0.40; p < 0.001). CONCLUSION: XYS contains human CYP1A2 inhibitors, and undesirable effects were observed in patients receiving both theophylline and XYS. Further human studies are essential to reduce mortality and to adjust the dosage of theophylline in XYS users.

Depressive disorder and elevated risk of bell's palsy: a nationwide propensity score-weighting study.

BACKGROUND: Prior studies have reported a potential relationship between depressive disorder (DD), immune function, and inflammatory response. Some studies have also confirmed the correlation between immune and inflammatory responses and Bell's palsy. Considering that the pathophysiology of these two diseases has several similarities, this study investigates if DD raises the risk of developing Bell's palsy. METHODS: This nationwide propensity score-weighting cohort study utilized Taiwan National Health Insurance data. 44,198 patients with DD were identified as the DD cohort and 1,433,650 adult subjects without DD were identified as the comparison cohort. The inverse probability of treatment weighting (IPTW) strategy was used to balance the differences of covariates between two groups. The 5-year incidence of Bell's palsy was evaluated using the Cox proportional-hazard model, presenting results in terms of hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The average age of DD patients was 48.3 ± 17.3 years, and 61.86% were female. After propensity score-weighting strategy, no significant demographic differences emerged between the DD and comparison cohort. The Cox proportional hazards model revealed a statistically significant adjusted IPTW-HR of 1.315 (95% CI: 1.168-1.481) for Bell's palsy in DD patients compared to comparison subjects. Further independent factors for Bell's palsy in this model were age (IPTW-HR: 1.012, 95% CI: 1.010-1.013, p < 0.0001), sex (IPTW-HR: 0.909, 95% CI: 0.869-0.952, p < 0.0001), hypertension (IPTW-HR: 1.268, 95% CI: 1.186-1.355, p < 0.0001), hyperlipidemia (IPTW-HR: 1.084, 95% CI: 1.001-1.173, p = 0.047), and diabetes (IPTW-HR: 1.513, 95% CI: 1.398-1.637, p < 0.0001) CONCLUSION: This Study confirmed that individuals with DD face an elevated risk of developing Bell's palsy. These findings hold significant implications for both clinicians and researchers, shedding light on the potential interplay between mental health and the risk of certain physical health outcomes.

Association between amiodarone use and risk of cataract: a population-based active-comparator study.

BACKGROUND: Despite previous concerns about ocular side effects related to amiodarone, the relationship between amiodarone and cataract remains uncertain. Therefore, this study aimed to assess the potential association between amiodarone use and the subsequent risk of cataract, taking into account potential confounders. METHODS: This population-based, active comparator-controlled cohort study utilized the data from the Taiwan National Health Insurance program and involved adults over 40 years old between 2001 and 2013. We analyzed 12 055 new amiodarone users and contrasted them with a propafenone user cohort. The primary outcome was the incidence of cataract. Inverse-probability treatment-weighting (IPTW) was further used to eliminate the potential confounding effects, and Cox proportional-hazard regression analyses were performed to calculate the risk of cataract. Serial subgroup analyses were also performed. RESULTS: In the main analysis, amiodarone users did not exhibit a significant causal relationship in both full cohort [adjusted hazard ratio (aHR): 0.994, 95% confidence interval (CI): 0.913-1.082] and IPTW cohort (IPTW-aHR 0.977, 95% CI: 0.900-1.060). Furthermore, it is important to highlight a significantly reduced risk of cataract among patients with heart failure (IPTW-aHR 0.708, 95% CI: 0.554-0.905) and during the 2-year follow-up period (IPTW-aHR 0.889, 95% CI: 0.794-0.996), implying potential advantages linked to the use of amiodarone. CONCLUSIONS: The study found no increased risk of cataract with amiodarone, one of the most frequently used antiarrhythmic medications, compared to the use of propafenone. Future research is recommended to explore potential mechanisms and their implications for clinical practice.

Sleep Duration and Kidney Function - Does Weekend Sleep Matter?

Objective: Weekend sleep duration is linked to health issues, including mortality. However, how weekend sleep duration can impact chronic kidney disease (CKD) still needs to be understood. Therefore, we aimed to analyze how weekend sleep duration is associated with kidney function. Methods: This is a cross-sectional study. Data were obtained from the 2017-2018 National Health and Nutrition Examination Survey. We included 5362 study participants and categorized them into nine subgroups by sleep duration (short: ≤6 hours, normal: 6-9 hours, and long: ≥9 hours) on weekdays and weekends and analyzed for the respective association with renal function using stratified multivariable linear regression. Results: Weekend sleep duration for 9 hours or more was associated with decreasing estimated glomerular filtration rate (eGFR) levels by 2.8 to 6.4 mL/min/1.73 m2 among people with long to short weekday sleep duration compared with short weekday and weekend sleep durations (control group) after adjusting for demographic characteristics, body measurement, sleep quality, smoking, and comorbidities. The study population with short weekday sleep duration (sWK) and long weekend sleep duration (lWD) had the most significant decline in eGFR. For the study population with sWK, eGFR level significantly decreased by 1.1 mL/min/1.73 m2 as sleep duration on weekends increased by one hour. Conclusion: The underlying mediators of lWD and CKD could be the dysregulation of human behaviors, metabolism, or biological functions. Longer weekend sleep duration was linked to a decrease in eGFR levels. It warrants further study to clarify the mediators.

Trend Analysis of Palliative Care Utilization in Patients with Chronic Obstructive Pulmonary Disease During Hospitalization from 2007 to 2018 in Taiwan.

Purpose: Palliative care utilization among hospitalized patients with advanced chronic obstructive pulmonary disease (COPD) in Taiwan remains low despite its costs making it eligible for reimbursement since 2009. Few studies have examined the trends of palliative care utilization. We analyzed the annual rate, associated factors, and timing of the inpatient palliative care utilization by hospitalized patients with COPD. Patients and Methods: We conducted a cross-sectional observational study between 1 January 2007 and 31 December 2018. Population-based claims data were extracted from Taiwan's National Health Insurance Research Database to identify patients aged ≧40 years with COPD five years before the first instance of inpatient palliative care utilization. Results: There were 24,502 patients with COPD receiving inpatient palliative care. Our results indicated that older age, concomitant chronic conditions-especially cancer-and severity of comorbidities were associated with a higher rate of palliative care utilization by hospitalized patients with chronic obstructive pulmonary disease. In our study, the proportion of hospitalized patients with COPD receiving inpatient palliative care and having a Charlson comorbidity index score of 1-2 was lower than that of patients with cancer and a Charlson comorbidity index score ≧3 during the 12-year study-observation period. In addition, approximately 50% of hospitalized patients with COPD received palliative care within 18 months after their initial admission for COPD during the study period. However, individuals with a CCI score of 1-2 exhibited a slower entry into palliative care, with nearly 50% initiating it within the first two years. Conclusion: Inpatient palliative care utilization by hospitalized patients with advanced COPD remains low due to various causes. Our findings highlight that palliative care may be considered by professional care providers as routine care and as a way to manage problematic symptoms during hospitalization.

Identification of the perpetrator imperatorin in Xin-yi-san-theophylline interaction: observed and predicted herb-drug interaction in rats.

OBJECTIVES: Theophylline is a bronchodilator with a narrow therapeutic index and primarily metabolised by cytochrome P450 (CYP) 1A2. Xin-yi-san (XYS) is a herbal formula frequently used to ameliorate nasal inflammation. This study aimed to investigate the effects of XYS and its ingredient, imperatorin, on theophylline pharmacokinetics in rats. METHODS: The kinetics of XYS- and imperatorin-mediated inhibition of theophylline oxidation were determined. Pharmacokinetics of theophylline were analysed. Comparisons were made with the CYP1A2 inhibitor, fluvoxamine. KEY FINDINGS: XYS extract and its ingredient, imperatorin, non-competitively inhibited theophylline oxidation. Fluvoxamine (50 and 100 mg/kg) and XYS (0.5 and 0.9 g/kg) significantly prolonged the time to reach the maximum plasma concentration (tmax) of theophylline by 3-10 fold. In a dose-dependent manner, XYS and imperatorin (0.1-10 mg/kg) treatments significantly decreased theophylline clearance by 27-33% and 19-56%, respectively. XYS (0.9 g/kg) and imperatorin (10 mg/kg) significantly prolonged theophylline elimination half-life by 29% and 142%, respectively. Compared with the increase (51-112%) in the area under curve (AUC) of theophylline by fluvoxamine, the increase (27-57%) by XYS was moderate. CONCLUSIONS: XYS decreased theophylline clearance primarily through imperatorin-suppressed theophylline oxidation. Further human studies are essential for the dose adjustment in the co-medication regimen.

Increased risk of olfactory and taste dysfunction in the United States psoriasis population.

BACKGROUND: It is plausible that immunopathological processes associated with psoriasis might contribute to the occurrence of olfactory or taste dysfunction. However, the actual association was still unknown. PURPOSE: To determine the relationship between olfactory or taste dysfunction and psoriasis. METHODS: Two cross-sectional studies were performed by using National Health and Nutrition Examination Survey (NHANES) data. Participants with psoriasis were defined as cases and those without psoriasis were identified as controls. Taste and smell self-reported questionnaires were used to define smell/taste alterations and identification tests were used to assure the smell/taste dysfunctions. Logistic regression models with inverse probability treatment weighting (IPTW) strategies were conducted to investigated the relationship between psoriasis and olfactory or taste dysfunction. RESULTS: Self-reported questionnaires indicated that psoriasis patients were more likely to have perceived taste alteration (IPTW-aOR = 1.43) and smell alteration (IPTW-aOR = 1.22). Identification tests revealed that psoriasis was associated with taste dysfunction (IPTW-aOR = 1.28) and olfactory dysfunction (IPTW-aOR = 1.22). Relevant findings showed that psoriasis may be significantly associated with taste or olfactory dysfunction regardless of the questionnaire data or identification examination data used. CONCLUSION: Olfactory and taste dysfunction could be considered comorbidities in patients with psoriasis based on our observational study. Therefore, physicians should be cautious of olfaction and taste alterations among patients with psoriasis.

Knowledge and practices related to antibiotic use among women in Malang, Indonesia.

Background: Antimicrobial resistance is a public health problem that threatens the efficacy of antibiotics. Incorrect knowledge of antibiotics may lead to their inappropriate use, hinder their effectiveness, and cause antibiotic resistance. Population-based educational campaigns have been found to have either mixed or no effect on improving knowledge and appropriate antibiotic practices, suggesting the need for more targeted approaches in tailoring education for specific subpopulations. Women are the primary caregivers of their families and are more willing to contact healthcare providers. They had greater knowledge of antibiotics and better adherence to the completion of the antibiotic regimen. Therefore, they are suitable for prioritization in a campaign program. Objective: This study examined the knowledge and practices of female visitors to health centers in Malang, Indonesia with respect to antibiotic use. Methods: This cross-sectional study was conducted in Malang, Indonesia, in July and August 2018. Data were collected from 677 women. Multivariate logistic regression was performed to identify the potential factors associated with antibiotic knowledge, self-medication, and completion of antibiotic regimens. Results: Overall, 82.7% of respondents were aware that antibiotics are used against bacteria, while 38.4% reported self-medication with antibiotics and 51.7% reported completing antibiotic regimens. Women with higher education, previous antibiotic use experience, and very easy accessibility to primary doctors were more likely to have high antibiotic knowledge than those with primary education, no antibiotic use in the previous year, and easy/other level of accessibility to primary doctors. Subjects residing in urban areas and with less accessibility to primary doctors were more likely to self-medicate with antibiotics. Additionally, the completion of antibiotic regimens was positively associated with access to a primary care doctor and high antibiotic knowledge. Conclusion: IF Policymakers tend to reduce inappropriate antibiotic use among women. Priority advocates are recommended for urban residents who have experiences of antibiotic use in the previous year. It is therefore important to increase their awareness, particularly regarding diseases against which antibiotics are effective, and activities such as unnecessary use of antibiotics in healthy animals, which may affect their overall effectiveness among humans. More communication channels should be included in the overall scheme to improve the public awareness and accessibility of health professionals.

Anabolic Effects of a Novel Simvastatin Derivative on Treating Rat Bone Defects.

Large bone defects may develop fracture nonunion, leading to disability and psychosocial burdens. Bone grafting with anabolic agents is a good autografting alternative. Simvastatin, as a cholesterol-lowering agent worldwide, is proven to enhance osteogenesis. Considering its dose-dependent adverse effects, we developed a simvastatin derivative, named KMUHC-01, which has bone anabolic capacity and lower cytotoxicity than simvastatin. We hypothesize that KMUHC-01 could help bone formation in bone-defect animal models. We used rat models of critical calvarial and long-bone defects to evaluate the effects of KMUHC-01 and simvastatin on biological changes at the bone defect through histology, immunohistology, and mechanical testing using three-point bending and evaluated the new bone formation microstructure through microcomputed tomography analysis. The newly formed bone microstructure at the calvarial defect site showed a significantly improved trabecular bone volume in the KMUHC-01 1-µM group compared with that in the control and simvastatin groups. The biomechanical study revealed a significantly increased maximal strength in the KMUHC-01 1-µM group compared with that in the control group. KUMHC-01, as a simvastatin derivative, showed a great anabolic effect in promoting bone defect healing. However, further studies will be conducted to prove the bioavailability and bone-forming efficacy of KMUHC-01 via systemic administration.

Evidence of the need for modified well-stirred model in vitro to in vivo extrapolation.

In vitro to in vivo extrapolation (IVIVE), an approach for hepatic clearance (CLH) prediction used worldwide, remains controversial due to systematic underprediction. Among the various probable factors, the original assumption of the hepatic mathematical model (i.e., the well-stirred model, WSM) may become problematic, leading to the underestimation of drug CLH. Having a similar prerequisite that the well-stirred conditions are homogenous with perfectly mixed reactants, but using a different driving concentration, the modified well-stirred model (MWSM) stands apart from the WSM. However, we believe that both models should coexist so that the entire well-stirred scenario can be completely illustrated. Consequently, we collected published data from the literature and employed a logistic regression method to differentiate the optimal timing of use between WSM and MWSM in drug CLH prediction. Generally, variances adopted in the regression, including partition coefficient (logP), fraction unbound (fu), volumes of distribution at steady-state (Vss), and mean residence time (MRT), corresponded to our assumption when protein-facilitated uptake was considered. Furthermore, a new empirical approach was introduced to allow practical use of the MWSM. The results showed that this model could provide a more precise prediction compared to previous empirical approaches. Therefore, these preliminary results not only delineated a more detailed structure and mechanism of MWSM but also highlighted its necessity and potential.

Emergency SARS-CoV-2 variants of concern: rapidly direct RT-qPCR detection without RNA extraction, clinical comparison, cost-effective, and high-throughput.

Since the late 2020, the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern has been characterized by the emergence of spike protein mutations, and these variants have become dominant worldwide. The gold standard SARS-CoV-2 diagnosis protocol requires two complex processes, namely, RNA extraction and real-time reverse transcriptase polymerase chain reaction (RT-PCR). There is a need for a faster, simpler, and more cost-effective detection strategy that can be utilized worldwide, especially in developing countries. We propose the novel use of direct RT-qPCR, which does not require RNA extraction or a preheating step. For the detection, retrospectively, we used 770 clinical nasopharyngeal swabs, including positive and negative samples. The samples were subjected to RT-qPCR in the N1 and E genes using two different thermocyclers. The limit of detection was 30 copies/reaction for N1 and 60 copies/reaction for E. Analytical sensitivity was assessed for the developed direct RT-qPCR; the sensitivity was 95.69%, negative predictive value was 99.9%, accuracy of 99.35%, and area under the curve was 0.978. This novel direct RT-qPCR diagnosis method without RNA extraction is a reliable and high-throughput alternative method that can significantly save cost, labor, and time during the coronavirus disease 2019 pandemic.

Modified-Dose Pembrolizumab and Prognostic Outcomes among Non-Small Cell Lung Cancer Patients: A Chart Review Study.

The modified dose (MD) regimen of pembrolizumab (2 mg/kg or 100 mg every 3 weeks) is an alternative option to reduce the financial burden resulting from the extremely high cost of the standard dose (SD) regimen (200 mg every 3 weeks). However, the clinical effectiveness and prognostic outcomes have not been fully elucidated in real-word clinical practice. Sixty-four consecutive patients in Taiwan receiving pembrolizumab for advanced NSCLC between 2018 and 2020 were recruited in this study. Comparisons of overall survival (OS) and progression-free survival (PFS) were performed using Kaplan−Meier survival curves. Additionally, 12 predictors, including pembrolizumab regimen, dose, neutrophil-to-lymphocyte ratio (NLR), age, sex, histopathology, smoking history, ECOG PS, EGFR mutation, PD-L1 expression, distant metastases and treatment line, were analyzed in multivariable Cox models for predicting OS and PFS. The results showed that the MD group and the SD group had similar OS and PFS, especially in patients beyond first-line treatment or with a pretreatment NLR < 5. The NLR was the only independent factor associated with both OS (adjusted HR = 0.052; p = 0.010) and PFS (adjusted HR = 0.259; p = 0.021). The results of this study assure the clinical effectiveness of MD pembrolizumab and suggest that the pretreatment NLR could highlight patients who may benefit from MD pembrolizumab.

Illicit Drug Use and Smell and Taste Dysfunction: A National Health and Nutrition Examination Survey 2013-2014.

Taste and smell dysfunction are suspected to be associated with substance use. However, representative epidemiological studies remain insufficient. This cross-sectional study explored the relationship between drug use (including cannabis or hashish, cocaine, heroin, and methamphetamine) and olfactory/gustatory dysfunction using data from the 2013-2014 National Health and Nutrition Examination Survey. In this study, participants who completed the smell examination with mean age of 59 were classified into four groups: cannabis users (n = 845), participants without cannabis use (n = 794), illicit drug users (n = 450), and participants without illicit drug use (n = 2000). Participants who completed the taste examination with mean age of 58 were also categorised into four groups: cannabis users (n = 810), participants without cannabis use (n = 714), illicit drug users (n = 428), and participants without illicit drug use (n = 1815). Logistic regression models investigated the association between cannabis or illicit drug use and smell or taste dysfunctions among study participants. Odds ratios and 95% confidence intervals were calculated. Finally, we did not find correlations between illicit drug use and dysfunction of taste or smell senses; our findings were consistent in many subgroup analyses. We recommend that further studies explore the mechanism and dose of illicit drug use that could have chemosensory impacts.

Simple and Efficient Pressure Ulcer Reconstruction via Primary Closure Combined with Closed-Incision Negative Pressure Wound Therapy (CiNPWT)-Experience of a Single Surgeon.

BACKGROUND: In this study, we aimed to analyze the clinical efficacy of closed-incision negative pressure wound therapy (CiNPWT) when combined with primary closure (PC) in a patient with pressure ulcers, based on one single surgeon's experience at our medical center. METHODS: We retrospectively reviewed the data of patients with stage III or IV pressure ulcers who underwent reconstruction surgery. Patient characteristics, including age, sex, cause and location of defect, comorbidities, lesion size, wound reconstruction methods, operation time, debridement times, application of CiNPWT to reconstructed wounds, duration of hospital stay, and wound complications were analyzed. RESULTS: Operation time (38.16 ± 14.02 vs. 84.73 ± 48.55 min) and duration of hospitalization (36.78 ± 26.92 vs. 56.70 ± 58.43 days) were shorter in the PC + CiNPWT group than in the traditional group. The frequency of debridement (2.13 ± 0.98 vs. 2.76 ± 2.20 times) was also lower in the PC + CiNPWT group than in the traditional group. The average reconstructed wound size did not significantly differ between the groups (63.47 ± 42.70 vs. 62.85 ± 49.94 cm2), and there were no significant differences in wound healing (81.25% vs. 75.38%), minor complications (18.75% vs. 21.54%), major complications (0% vs. 3.85%), or mortality (6.25% vs. 10.00%) between the groups. CONCLUSIONS: Our findings indicate that PC combined with CiNPWT represents an alternative reconstruction option for patients with pressure ulcers, especially in those for whom prolonged anesthesia is unsuitable.

Activities of imipenem-relebactam combination against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan.

BACKGROUND: Imipenem-relebactam is a new ß-lactam and ß-lactamase inhibitor combination to treat carbapenem-resistant gram-negative bacteria infections. However, difference in carbapenem resistant mechanisms existed with geographic variations. OBJECTIVE: To evaluate the susceptibility of imipenem-relebactam to 660 carbapenem-nonsusceptible Enterobacteriaceae isolates in Taiwan and to identify the in vivo efficacy with a Caenorhabditis elegans model. METHODS: 188 carbapenem-nonsusceptible Escherichia coli isolates and 472 carbapenem-nonsusceptible Klebsiella pneumoniae isolates were collected from a national surveillance study in Taiwan. The antimicrobial susceptibility profiles and carbapenemase distributions were determined. An agar dilution method was performed to evaluate the in vitro activities of imipenem monotherapy and imipenem-relebactam combination. Contributions of metallo-carbapenemase to imipenem-relebactam susceptibility was investigated via EDTA treatment. A C. elegans model was used to evaluate the in vivo efficacy of imipenem-relebactam combination. RESULTS: 87.8% and 82.2% susceptibility to imipenem-relebactam was observed for 188 carbapenem-nonsusceptible E. coli and 472 carbapenem-nonsusceptible K. pneumoniae, respectively. However, poor activities of imipenem-relebactam was observed against 23 metallo-carbapenemase producers tested in this study. In the in vivo C. elegans model, imipenem-relebactam significantly rescued nematodes from the infection of a blaKPC-producing K. pneumoniae isolate. CONCLUSION: Our study supports that imipenem-relebactam is a potential therapy against carbapenem-nonsusceptible Enterobacteriaceae, and to our knowledge, this is the first report of evaluation for imipenem-relebactam efficacy against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan.

Long-Term Use of Statins Lowering the Risk of Rehospitalization Caused by Ischemic Stroke Among Middle-Aged Hyperlipidemic Patients: A Population-Based Study.

Background: The long-term effects of statin use on rehospitalization due to ischemic stroke (reHospIS) in hyperlipidemic patients are still unknown. Therefore, we aimed to assess the long-term risks of reHospIS for hyperlipidemic patients who were taking statins and nonstatin lipid-lowering medicines on a regular basis. Methods and Materials: The National Health Insurance Research Database in Taiwan was used to conduct a 6-year cohort study of patients >45 years old (n = 9,098) who were newly diagnosed with hyperlipidemia and hospitalized for the first or second time due to ischemic stroke (IS). The risk of reHospIS was assessed using Cox proportional hazards regression model. Results: Nonstatin lipid-lowering medicines regular users were associated with a higher risk of reHospIS compared to stains users (hazard ratio, HR = 1.29-1.39, p < 0.05). Rosuvastatin was the most preferred lipid-lowering medicine with lower HRs of reHospIS in hyperlipidemic patients whether they developed diabetes or not. Bezafibrate regular users of hyperlipidemic patients developing diabetes (HR = 2.15, p < 0.01) had nearly 50% lower reHospIS risks than those without diabetes (HR = 4.27, p < 0.05). Age, gender, drug dosage, comorbidities of diabetes and heart failure (HF), and characteristics of the first hospitalization due to IS were all adjusted in models. Moreover, increasing trends of HRs of reHospIS were observed from Rosuvastatin, nonstatin lipid-lowering medicines, Lovastatin, and Gemfibrozil to Bezafibrate users. Conclusion: Statins were associated with long-term secondary prevention of reHospIS for hyperlipidemic patients. Rosuvastatin seemed to have the best protective effects. On the other hand, Bezafibrate appears to be beneficial for hyperlipidemic patients developing diabetes. Further research into the combination treatment of statin and nonstatin lipid-lowering medicines in hyperlipidemic patients developing diabetes is warranted.

Illegal Drug Use and Risk of Hearing Loss in the United States: A National Health and Nutrition Examination Survey.

The use of illegal drugs may be a risk factor of hearing loss. However, very few studies with large sample size have investigated the relationship between illegal drug use and hearing loss. Therefore, to evaluate the association between illegal drug use and hearing loss, this cross-sectional population-based study collected data from the US National Health and Nutrition Examination Survey 2011. The study included 1772 participants aged 20 to 59 years who underwent the Drug Use Questionnaire and Audiometry Examination. Of the 1772 participants in this study, 865 were men (48.8%) and 497 were illegal drug users. The mean (SD) age of the patients was 40.0 (11.4) years. After considering age, sex, and comorbidities, the participants who used illegal drugs were found to have higher risks of high-frequency hearing loss (adjusted odds ratio (OR), 1.69; 95% confidence interval (CI), 1.35-2.10) and overall hearing loss (adjusted OR, 1.69; 95% CI, 1.36-2.12) as compared with the nonusers. In the second analysis, the participants who used ≥ 2 types of illegal drugs were associated with higher risks of high-frequency hearing loss (adjusted OR, 1.57; 95% CI, 1.06-2.32) and overall hearing loss (adjusted OR, 1.60; 95% CI, 1.08-2.37). In the third analysis, cocaine use was associated with increased risks of high-frequency hearing loss (adjusted OR, 1.34; 95% CI, 1.01-1.77) and overall hearing loss (adjusted OR, 1.38; 95% CI, 1.04-1.82). The adjusted OR for overall hearing loss in the methamphetamine users was 1.54 (95% CI, 1.05-2.27) as compared with that in the nonusers. This study shows that illegal drug users might have a higher risk of overall hearing loss than nonusers. In addition, the analysis results demonstrated that the more kinds of illegal drugs used, the higher the risk of hearing loss. Further experimental and longitudinal research studies are required to confirm the causal relationship between illegal drug use and hearing loss.

Patients with alcohol use disorder increase pain and analgesics use: A nationwide population-based cohort study.

BACKGROUND: Alcohol has dual effects on many systems, including the pain system. We will test whether and how chronic alcohol consumption enhances pain sensation to develop pain disorder. METHODS: We conducted a retrospective matched cohort study using data from the National Health Insurance Research Database (NHIRD) in Taiwan, in patients with and without alcohol use disorder (AUD). This study enrolled 19,174 individuals with AUD as study cohort and 19,174 propensity score-matched individuals without AUD as comparison cohort. The outcome was the incidence of pain disorders and the need for analgesics. The hazard ratios of pain disorders and the need for analgesics were evaluated using Cox proportional hazard regression analysis after adjusting for age, sex, index year, comorbidities, urbanization, areas of residence, and insurance premium. RESULTS: The 14 years of follow-up showed that AUD patients had a higher adjusted hazard ratio (aHR) for developing pain disorders than in non-AUD controls [aHR= 1.290, 95% confidence interval (CI): 1.045-1.591]. Besides, AUD patients had a higher risk of analgesic use (aHR = 1.081, 95% CI: 1.064-1.312), including opioids and non-opioid analgesics. Most importantly, AUD patients required more days of analgesic use, increased dose of analgesics, and higher costs of analgesics. Moreover, AUD patients had more anemia (aHR=2.772, 95% CI: 2.581-2.872), which could be a mediating factor. CONCLUSIONS: AUD patients had higher risks of developing pain disorders and subsequently increased analgesic demand. These results suggest that AUD worsened pain, and pain syndrome is correlated with the duration of chronic alcohol exposure.

Pulsed Radiofrequency Upregulates Serotonin Transporters and Alleviates Neuropathic Pain-Induced Depression in a Spared Nerve Injury Rat Model.

Neuropathic pain (NP) is difficult to treat due to complex pathophysiological mechanisms. Pulsed radiofrequency (RRF) has been used widely with neuromodulation effect in refractory chronic pain treatment. A recent study found that PRF treatment may decrease chronic pain-related anxiety-depressant symptoms in patients, even though the mechanisms are unclear. Additionally, accumulated evidence has shown serotonin uptake is correlated with various neuropsychiatric diseases. Therefore, we investigated the effects and underlying mechanisms of PRF on depression-like behaviors, resulting from spared nerve injury (SNI)-induced NP. We examined the indexes of mechanical allodynia, cold allodynia, depression-like behavior, and blood cytokines by dynamic plantar aesthesiometry, acetone spray test, forced swimming test, and ProcartaPlex multiplex immunoassays in male Wistar rats, respectively. Serotonin transporters (SERTs) in rat brains were examined by using 4-[18F]-ADAM/PET imaging. We found that specific uptake ratios (SURs) of SERTs were significantly decreased in the brain regions of the thalamus and striatum in rats with SNI-induced NP and depression-like behaviors. Additionally, the decrease in SERT density was correlated with the development of a depression-like behavior indicated by the forced swimming test results and pronounced IL-6 cytokines. Moreover, we demonstrated that PRF application could modulate the descending serotoninergic pathway to relieve pain and depression behaviors.