Therapeutic effects of methimazole on 3,4-methylenedioxymethamphetamine-induced hyperthermia and serotonergic neurotoxicity.

3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug, however over 200 studies demonstrate that acute (e.g. hyperthermia, rhabdomyolysis) and chronic (e.g. neurotoxicity) toxicity effects of MDMA were observed in different animals. Methimazole (MMI), an inhibitor of thyroid hormone synthesis, was found to significantly reduce the HSP72 expression of heat stress induced in fibroblasts. Hence, we attempted to understand the effects of MMI on MDMA induced changes in vivo. Male SD rats were randomly divided into four groups as follows:(a) water-saline (b) water-MDMA (c) MMI-saline and (d) MMI-MDMA group. In the temperature analysis test, MMI was found to alleviate MDMA-induced hyperthermia and increase the heat loss index (HLI), revealing its peripheral vasodilation effect. PET experiment suggested that MDMA induced elevated glucose uptake by skeletal muscles, which was resolved by MMI pretreatment. IHC staining (serotonin transporter, SERT) showed the evidence of neurotoxicity caused by MDMA (serotonin fiber loss), which was alleviated by MMI. Furthermore, the animal behaviour test (forced swimming test, FST) showed higher swimming time but lower immobility time in MMI-MDMA and MMI-saline groups. Taken together, treatment of MMI shows benefits such as lowered body temperature, alleviation of neurotoxicity and excited behaviour. However, further investigations should be conducted in the future to provide in-depth evidence for its clinical use.

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.

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.

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.

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.

Association of Benzodiazepine Receptor Agonist Use With Changes in Psoriasis Severity in Adult Population: A Population-Based Study.

To date, it remains uncertain whether benzodiazepine receptor agonists (BZRAs) are aggravating factors even though these drugs can elevate the levels of biomarkers associated with the development of psoriasis. Therefore, this study aimed to investigate the association of BZRA use with changes in psoriasis severity. All data were sourced from the National Health Insurance system in Taiwan. We conducted a population-based retrospective cross-sectional study of 15,727 psoriasis patients who received BZRAs (BZRA users), and 18,856 psoriasis patients who did not receive BZRAs (nonusers). At least a 1-year washout period without any BZRA prescriptions was required. The main outcome was the change in psoriasis severity between before and after BZRA exposure. This study detected the exacerbation of psoriasis severity in mild psoriasis population by using a logistic model. Then, this study carried another logistic model among those patients who had severe psoriasis to calculate the odds ratios (ORs) for the improvement of the psoriasis severity. Among patients with mild psoriasis, BZRA users had a significantly higher probability of psoriasis severity exacerbation (IPTW-adjusted OR = 1.46). Mild psoriasis patients who received high and low doses of BZRAs had 1.70- and 1.39-fold higher probabilities of psoriasis severity exacerbation, respectively, than the non-users. Furthermore, in the severe psoriasis population, more low-dose BZRA users improved psoriasis severity than non-users. In conclusion, this study provided clinical evidence of the effects of BZRA use on patients with psoriasis severity. Among patients with mild psoriasis, high-dose BZRA users may be associated with the changes in psoriasis severity. However, low-dose BZRA exposure only slightly exacerbated disease severity among patients with mild psoriasis. Accordingly, clinicians should evaluate the risks and benefits of the BZRA usage.

Antidepressants and risk of sudden sensorineural hearing loss: a population-based cohort study.

BACKGROUND: Increasing numbers of animal studies have found that sudden sensorineural hearing loss (SSNHL) is related to the mechanism of serotonergic modulation. However, the relationship between antidepressants and SSNHL is unclear in humans. Therefore, this study aimed to evaluate the association between antidepressant use and risk of SSNHL. METHODS: Data from 218 466 antidepressant users and 1 116 518 nonusers were obtained from the Taiwan Longitudinal Health Insurance Database. We used propensity-score matching (PSM) and inverse-probability treatment weighting (IPTW) to eliminate any bias. Each patient was tracked for 5 years to ascertain whether or not they were diagnosed with SSNHL. Cox proportional-hazard regression analyses were performed to calculate the SSNHL risk. RESULTS: The adjusted hazard ratio (aHR) of SSNHL for antidepressant users was 1.36 compared with nonusers in the full cohort study. The aHR for antidepressant users was 1.44 and 1.49 compared with the nonusers in the IPTW and PSM cohorts, respectively. All classes of antidepressants consistently increased the SSNHL risk. Additionally, patients receiving four classes of antidepressants were associated with a much higher SSNHL risk (aHR, 2.05) and those receiving one or two classes of antidepressants had a relatively lower SSNHL risk. CONCLUSION: Antidepressants increased SSNHL risk, regardless of their class. Furthermore, patients who took a higher number of antidepressant classes showed an increased risk of developing SSNHL than those who took a lower number of antidepressant classes. Therefore, physicians should estimate the risks and benefits of antidepressant use and avoid prescribing antidepressants concurrently.

Major depressive disorder increased risk of psoriasis: A propensity score matched cohort study.

BACKGROUND: Reports showed that elevated proinflammatory cytokines, as detected in patients with psoriasis, was noted in individuals with major depressive disorder (MDD). Therefore, this study aimed to clarify the association of MDD and prospective incidence of psoriasis in human using a nationwide study. METHOD: This population-based cohort study used the data from the Taiwan National Health Insurance system. 64,486 patients were defined as MDD cohort and 64,486 propensity score matched subjects without MDD were identified as comparison cohort. Each patient was independently tracked for a 5-year study period to assure them for a psoriasis diagnosis after the index date. Stratified Cox proportional hazard models were used to calculate the hazard ratio (HRs) for 5-year psoriasis risk. RESULTS: After adjustments, the HR of psoriasis for MDD patients was 1.32 compared with subjects without MDD. The stratified analyses present that MDD patients had approximately 1.30-fold significantly higher risk of psoriasis than comparison subjects in most subgroups. Furthermore, compared with the matched subjects without MDD, the adjusted HRs of psoriasis in the 2-, 3-, 4- and 5-year study periods were 1.33, 1.32, 1.33 and 1.32, respectively. LIMITATIONS: Several patients with MDD or psoriasis might not include in this study, because of using a medical claims database. CONCLUSIONS: This study provides population-based evidence that MDD is an independent risk factor of developing psoriasis, with an increased risk in the male sex. Additional investigations verifying our findings and exploring possible pathological mechanisms would be of great interest and value to the psychiatric field.

Protective Effects of Anti-depressants against the Subsequent Development of Psoriasis in Patients with Major Depressive Disorder: a Cohort Study.

BACKGROUND: Inflammation may mediate the relationship between major depressive disorder (MDD) and psoriasis. However, it is unclear whether anti-depressants can decrease the subsequent risk of psoriasis among MDD patients. This study investigated the effects of anti-depressants on the subsequent risk of psoriasis in MDD patients. METHODS: This was a population-based cohort study in Taiwan. 58,454 MDD patients who had received anti-depressants and 6,034 MDD patients who did not receive anti-depressants were included. Each patient was tracked for 5 years to confirm a diagnosis of psoriasis following the index date. Cox proportional hazards models were performed to estimate the hazard ratio (HR) for psoriasis. RESULTS: In this study, after using time-dependent Cox regression with both inverse probability of treatment weighting (IPTW) and adjustment for confounders, anti-depressant users had a significantly lower risk of psoriasis than the nonusers (IPTW-adjusted HR [aHR] = 0.69). Additionally, most types and dosages of anti-depressants tended to protect against psoriasis. Selective serotonin reuptake inhibitor use (IPTW-aHR = 0.67) and low-dose anti-depressant use (IPTW-aHR = 0.66) had significant protective effects even after IPTW and adjustment for confounders. LIMITATIONS: This study had no information about over-the-counter medications. CONCLUSIONS: This study revealed the protective effects of anti-depressants on psoriasis risk in patients with MDD. Antidepressant users had significantly lower risk of psoriasis than the nonusers. Further analyses indicated that the usage of SSRIs and low antidepressant dosage could statistically decrease risk of psoriasis.

Hp-s1 Ganglioside Suppresses Proinflammatory Responses by Inhibiting MyD88-Dependent NF-κB and JNK/p38 MAPK Pathways in Lipopolysaccharide-Stimulated Microglial Cells.

Hp-s1 ganglioside is isolated from the sperm of sea urchin (Hemicentrotus pulcherrimus). In addition to neuritogenic activity, the biological function of Hp-s1 in neuroinflammation is unknown. In this study, we investigated the anti-neuroinflammatory effect of Hp-s1 on lipopolysaccharide (LPS)-stimulated microglial cells. MG6 microglial cells were stimulated with LPS in the presence or absence of different Hp-s1 concentrations. The anti-inflammatory effect and underlying mechanism of Hp-s1 in LPS-activated microglia cells were assessed through a Cell Counting kit-8 assay, Western blot analysis, and immunofluorescence. We found that Hp-s1 suppressed not only the expression of inducible nitric oxide synthase and cyclooxygenase-2 but also the expression of proinflammatory cytokines, such as TNF-α, IL-1ß, and IL-6. Hp-s1 inhibited the LPS-induced NF-κB signaling pathway by attenuating the phosphorylation and translocation of NF-κB p65 and by disrupting the degradation and phosphorylation of inhibitor κB-α (IκBα). Moreover, Hp-s1 inhibited the LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Hp-s1 also reduced the expression of myeloid differentiation factor 88 (MyD88) and TNF receptor-associated factors 6 (TRAF6), which are prerequisites for NF-κB and MAPKs activation. These findings indicated that Hp-s1 alleviated LPS-induced proinflammatory responses in microglial cells by downregulating MyD88-mediated NF-κB and JNK/p38 MAPK signaling pathways, suggesting further evaluation as a new anti-neuroinflammatory drug.

The Association Between Parkinson's Disease and Attention-Deficit Hyperactivity Disorder.

While Parkinson's disease (PD) and attention-deficit hyperactivity disorder (ADHD) are two distinct conditions, it has been hypothesized that they share several overlapping anatomical and neurochemical changes. In order to investigate that hypothesis, this study used claims data from Taiwan's Longitudinal Health Insurance Database 2000 to provide the significant nationwide population-based evidence of an increased risk of PD among ADHD patients, and the connection between the two conditions was not the result of other comorbidities. Moreover, this study showed that the patients with PD were 2.8 times more likely to have a prior ADHD diagnosis compared with those without a prior history of ADHD. Furthermore, an animal model of ADHD was generated by neonatally injecting rats with 6-hydroxydopamine (6-OHDA). These rats were subjected to behavior tests and the 99mTc-TRODAT-1 brain imaging at the juvenile stage. Compared to control group rats, the 6-OHDA rats showed a significantly reduced specific uptake ratio in the striatum, indicating an underlying PD-linked pathology in the brains of these ADHD phenotype-expressing rats. Overall, these results support that ADHD shares a number of anatomical and neurochemical changes with PD. As such, improved knowledge of the neurochemical mechanisms underlying ADHD could result in improved treatments for various debilitating neurological disorders, including PD.

Dextromethorphan Attenuates Sensorineural Hearing Loss in an Animal Model and Population-Based Cohort Study.

The effect of dextromethorphan (DXM) use in sensorineural hearing loss (SNHL) has not been fully examined. We conducted an animal model and nationwide retrospective matched-cohort study to explore the association between DXM use and SNHL. Eight-week-old CBA/CaJ hearing loss was induced by a white noise 118 dB sound pressure level for 3 h. DXM (30 mg/kg) was administered intraperitoneally for 5 days and boost once round window DXM socking. In population-based study, we examined the medical records over 40 years old in Taiwan's National Health Insurance Research Database between 2000 and 2015 to establish retrospective matched-cohort to explore the correlation between DXM use and SNHL. Using click auditory brainstem response (ABR), hearing threshold was measured as 48.6 ± 2.9 dB in control mice compared with 42.6 ± 7.0 dB in DXM mice, which differed significantly (p = 0.002) on day 60 after noise exposure with a larger ABR wave I amplitude in DXM mice. In human study, we used a Cox regression hazard model to indicate that a significantly lower percentage individuals developed SNHL compared with and without DXM use (0.44%, 175/39,895 vs. 1.05%, 1675/159,580, p < 0.001). After adjustment for age and other variables [adjusted hazard ratio: 0.725 (95% confidence interval: 0.624-0.803, p < 0.001)], this study also demonstrated that DXM use appeared to reduce the risk of developing SNHL. This animal study demonstrated that DXM significantly attenuated noise-induced hearing loss. In human study, DXM use may have a protective effect against SNHL.

Association between Anemia and Auditory Threshold Shifts in the US Population: National Health and Nutrition Examination Survey.

Existing evidence indicates that both iron deficiency anemia and sickle cell anemia have been previously associated with hearing loss. However, human data investigating the association between anemia and auditory threshold shifts at different frequencies in the adolescent, adult and elderly population are extremely limited to date. Therefore, this cross-sectional study used the dataset from the US National Health and Nutrition Examination Survey from 2005 to 2012 to explore differences in low- or high-frequency hearing thresholds and hearing loss prevalence between participants with and without anemia. A total of 918 patients with anemia and 8213 without anemia were included. Results indicated that low- and high-frequency pure tone average were significantly higher in patients with anemia than that in those without anemia in the elderly, but not in adult or adolescent population. In addition, the prevalence of low-frequency hearing loss but not high-frequency hearing loss was also higher in patients with anemia than in those without anemia in the elderly population. After adjusting various confounders, multiple regression models still indicated that patients with anemia tended to have larger threshold shift. In conclusion, anemia was associated with auditory threshold shifts in the elderly population, especially those vulnerable to low-frequency hearing loss.

Lysosomal Dysfunction and Autophagy Blockade Contribute to MDMA-Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells.

Methylenedioxymethamphetamine (MDMA) is a psychostimulant with high abuse potential and severe neurotoxicity. According to our previous study, MDMA promotes autophagosome accumulation and contributes to cell death in cultured cortical and serotonergic neurons. However, the detailed mechanism underlying autophagy dysfunction remains unclear. Lysosomes play an important role in autophagic degradation. The present study aimed to examine the role of lysosomal function in autophagic flux in neuronal cultures exposed to MDMA. We showed that MDMA induced enlarged vesicles that accumulate in SH-SY5Y neuroblastoma cells. In addition, we demonstrated that MDMA stimulated dynamin-dependent but clathrin-independent endocytosis, which might contribute to vacuole expansion. Morphological and Western blot analyses revealed that MDMA induced lysosomal swelling, whereas the activity of the lysosomal hydrolytic enzymes cathepsin B and cathepsin D was decreased in SH-SY5Y and cultured cortical neurons, which might lead to autophagosome accumulation and autophagic degradation blockage. Intriguingly, inactivation of cathepsins B and D led to cell death and autophagy-lysosomal dysregulation, which mimicked MDMA-induced neurotoxicity. Consequently, impairment of lysosomal proteolysis and blockage of autophagy degradation contributed to MDMA-induced neurotoxicity in neuronal cultures.

Digoxin use and following risk of psoriasis: A population-based cohort study in Taiwan.

This study examined the association between digoxin use and subsequent psoriasis risk using a population-based database in Taiwan. This cohort study enrolled 15 545 digoxin users and 15 545 propensity score-matched non-users from the Taiwan National Health Insurance Research Database. Each patient was independently followed up for 5 years to confirm whether they had been diagnosed with psoriasis. Cox proportional hazard regression was used to estimate psoriasis risk among digoxin users. Subgroup and sensitivity analyses were also performed. The psoriasis incidence rates were 3.02 and 2.27 per 1000 person-years among digoxin users and non-users, respectively. After adjustment for confounders, psoriasis risk was significantly higher among digoxin users than among non-users. Notably, in most subgroup analyses, digoxin use tended to increase psoriasis risk, particularly among patients with heart failure, diabetes, hypertension and hyperlipidaemia. Moreover, significantly increased psoriasis risk was noted over 2, 3, 4 and 5 years of digoxin use. In conclusion, our findings confirm that digoxin use increases subsequent psoriasis risk. Thus, physicians should be aware of this association and accordingly estimate the risks and benefits of digoxin use. Nevertheless, some patient variables, such as body mass index and obesity, were unavailable in this study. The findings in this study should be elucidated carefully because the potential effects of these factors could not be considered.

Androgen deprivation therapy and the risk of iron-deficiency anaemia among patients with prostate cancer: a population-based cohort study.

OBJECTIVES: The administration of androgen deprivation therapy (ADT) to patients with metastatic prostate cancer might be associated with some adverse effects such as anaemia; however, few studies have been performed in East Asian populations. This study aimed to investigate the association between ADT and iron-deficiency anaemia (IDA) among patients with prostate cancer in a population-based nationwide cohort. DESIGN: Cohort study. SETTING: Taiwan. PARTICIPANTS: Data for the cohort study were retrieved from the Taiwan National Health Insurance Research Database. Propensity score matching was used to select 7262 patients with prostate cancer who received ADT as the study group and 3631 patients who did not receive ADT as the control group. PRIMARY AND SECONDARY OUTCOME MEASURES: This study individually tracked patients over a 3-year study period and identified those who were subsequently diagnosed with IDA following the index date. RESULTS: The incidence rates of IDA in the study and control groups were 1.66 (95% CI CI 1.45 to 1.86) and 1.01 per 100 person-years (95% CI 0.78 to 1.25), respectively. Furthermore, proportional Cox regression revealed an HR of 1.62 (95% CI 1.24 to 2.12) for IDA in the study group after adjusting for patients' age, monthly income, geographic location, residential urbanisation level and incidence of hyperlipidaemia, diabetes, hypertension, coronary heart disease, inflammatory bowel disease, other cancers and gastrointestinal bleeding. CONCLUSION: Compared with its non-use among patients with prostate cancer, ADT use was associated with a higher risk of IDA.

Protective Association Between Calcium Channel Blocker Use and Breast Cancer Recurrence in Postsurgical Women: A Population-Based Case-Control Study in Taiwan.

Neoadjuvant chemotherapy induces metastasis of residual breast cancers through activation of tumor-associated macrophages. Previous studies have indicated that calcium channel blockers (CCBs) exert anti-inflammatory and antimigratory effects on macrophages via attenuating Ca2+ entry into macrophages. However, no existing empirical research has addressed the relationship between previous CCB use and breast cancer recurrence. In this study, 4840 Taiwanese women aged ≥20 years with breast cancer who underwent breast surgery from January 1, 2007, to December 31, 2015, were enrolled. The date of cancer recurrence was defined as the index date. Logistic regression was performed to evaluate the relationship between previous CCB exposure and cancer recurrence among female patients who underwent surgery for breast cancer. After adjusting for demographic characteristics, comorbidities, and tumor-node-metastasis stage, the adjusted odds ratio (OR) for CCB exposure within 5 years before the index date in women with recurrence compared with nonrecurrent controls was 0.73 (95% confidence interval [CI], 0.53-0.97). Further analysis revealed that the adjusted OR for CCB exposure between the surgery and index dates in women with recurrence relative to nonrecurrent controls was 0.72 (95%CI, 0.66-0.95). In particular, prior CCB use was significantly associated with a lower risk (34%) of breast cancer recurrence among women 20 to 54 years old (OR, 0.66; 95%CI, 0.47-0.83). This study uncovered a protective association between previous CCB use and breast cancer recurrence.

Association between major depressive disorder and subsequent tinnitus: A population-based study.

BACKGROUND: Previous studies have presented an unclear association between major depressive disorder (MDD) and tinnitus. Therefore, in this study, we aimed to demonstrate the actual association between MDD and new-onset tinnitus using a large, population-based dataset in Taiwan. METHOD: This case-control study used the data from the National Health Insurance Database. In total, 18,365 patients with tinnitus were recruited as cases, and 18,365 propensity score-matched patients without tinnitus were identified as controls. Logistic regression models were constructed to calculate the odds ratios (ORs) and to estimate the association between prior MDD and tinnitus. RESULTS: MDD was found in 396 (2.16%) patients with tinnitus and 228 (1.24%) controls without tinnitus. The logistic regression model indicated that prior MDD was associated with tinnitus (adjusted OR, 1.74; 95% CI, 1.47-2.05). Moreover, MDD was positively associated with tinnitus among most subgroups. Notably, a significant association between MDD and tinnitus was observed among patients with diabetes (adjusted OR, 2.05) and hyperlipidemia (adjusted OR, 1.94). Furthermore, sensitivity analyses consistently found a relationship between prior MDD and tinnitus. LIMITATIONS: The database used in this study does not provide information regarding the lifestyle and gene factors. CONCLUSIONS: Our results showed a positive association between prior MDD and tinnitus. In addition, MDD may be one of the risk factors for tinnitus onset. Therefore, we recommended that the clinicians should be alert about the tinnitus condition among patients with MDD and provide appropriate interventions for them.

Transplant Recipients Using Tacrolimus Had Higher Utilization of Healthcare Services Than Those Receiving Cyclosporine in Taiwan.

To date, population-based studies on the healthcare service utilization among stable heart, kidney, and liver transplant recipients with different calcineurin inhibitors are still scarce. Therefore, we used the Taiwan National Health Insurance Research Database to conduct a nationwide cross-sectional study to estimate the healthcare utilization of stable transplant recipients with tacrolimus or cyclosporine (n = 3,482). The sampled patients in this study comprised 377 heart, 1,693 kidney, and 1,412 liver transplant recipients between 1 January 2011 and 31 December 2011. Each subject was followed for a 1-year period to evaluate his/her healthcare service utilization. Outcome variables of the healthcare service utilization were stated as below: numbers of outpatient visits, outpatient costs, numbers of inpatient days, inpatients costs, and total costs of all healthcare services. As for all healthcare service utilization, stable transplant recipients on tacrolimus had significantly more outpatient visits (40.7 vs. 38.6), outpatient costs (US$10,383 vs. US$8,155), and total costs (US$12,516 vs. US$10,372) of all healthcare services than those on cyclosporine during the 1-year follow-up period. Additionally, further analysis showed that heart transplant recipients receiving tacrolimus incurred 1.7-fold higher inpatient costs compared to patients receiving cyclosporine. We concluded that transplant recipients using tacrolimus had significantly higher utilization of all healthcare services than those receiving cyclosporine as immunosuppressive therapy.