Trends of anti-seizure medication prescribing pattern in traumatic brain injury patients for the prevention of posttraumatic seizure in Taiwan.

Traumatic brain injury (TBI) patients are recommended to receive anti-seizure medication (ASM) as posttraumatic seizure (PTS) prophylaxis. However, the utilization of ASM, including the prescription patterns and associated clinical characteristics, is limited in Taiwan. Thus, this study aimed to investigate the ASM trends and clinical characteristics. This retrospective cohort study enrolled TBI patients who received levetiracetam, phenytoin, and valproic acid during hospitalization using the National Health Insurance Research Database between 2012 and 2019. The primary outcome was the trend of the ASMs based on the index year. The duration of levetiracetam prescription was categorized as short-term (seven days or less) or long-term (more than seven days). Logistic regression identified the factors associated with long-term usage. A total of 64,461 TBI patients were included. Levetiracetam usage increased yearly, while phenytoin declined. Among the levetiracetam users, 5681 (30.38%) were short-term users, and 13,016 (69.62%) were long-term users. Diagnoses of contusions, intracranial hemorrhage, other intracranial injuries, receiving operations, and a history of cerebrovascular disease were significantly associated with longer duration. Conclusions This study revealed the rising trend of levetiracetam usage, indicating its potential as an alternative to phenytoin. TBI patients with more severe conditions were more likely to receive longer prescriptions.

Using PIM-Taiwan, PRISCUS, and Beers criteria to assess potentially inappropriate medication use among older adults with 90-day rehospitalization: a population-based study in Taiwan.

Background: Multimorbidity and polypharmacy increase the risk of hospitalization in older adults receiving potentially inappropriate medication (PIM). The current study compared the ability of PIM-Taiwan, PRISCUS, and Beers criteria to predict 90-day rehospitalization in older patients with and without PIM. Methods: The retrospective cohort study used Taiwan's Longitudinal Health Insurance Database to retrieve quarterly information about prescribed medication for adults aged ≥65 years hospitalized between 2001 and 2018. We analyzed the association of PIM with 90-day rehospitalization using logistic regression. Results: The study cohort included 206,058 older adults (mean age: 72.5 years). In the analysis, 133,201 (64.6%), 97,790 (47.5%), and 147,450 (71.6%), were identified as having PIM exposure in PIM-Taiwan, PRICUS, and Beers criteria, respectively. PIM-Taiwan criteria found exposure to PIM affecting the cardiovascular (adjusted OR [aOR] 1.37, 95% confidence interval [CI] = 1.32-1.41), gastrointestinal (aOR 1.26, 95% CI = 1.23-1.30), central nervous (aOR 1.11, 95% CI = 1.08-1.14), and respiratory (aOR 1.16, 95% CI = 1.12-1.20) systems significantly increased the risk of 90-day rehospitalization, after adjustment for covariates. In PRISCUS criteria, exposure to PIM affecting the respiratory (aOR 1.48, 95% CI = 1.41-1.56), central nervous (aOR 1.12, 95% CI = 1.09-1.15), and cardiovascular (aOR 1.20, 95% CI = 1.16-1.24) systems significantly increased the risk. In Beers criteria, exposure to PIM affecting the cardiovascular (aOR 1.37, 95% CI = 1.32-1.41), gastrointestinal (aOR 1.38, 95% CI = 1.35-1.42), central nervous (aOR 1.18, 95% CI = 1.15-1.21), endocrine (aOR 1.10, 95% CI = 1.06-1.15), and respiratory (aOR 1.09, 95% CI = 1.04-1.13) systems significantly increased the risk. Patients with 90-day rehospitalization had higher rates of the potentially harmful drug-drug interaction (DDI) pairs of serotonin syndrome (n = 19; 48.8%), QT prolongation (n = 4; 30.8%), extrapyramidal symptoms (EPS) (n = 102; 24.5%), and hypokalemia (n = 275; 20.1%). Conclusion: Beers criteria was more efficient in predicting 90-day rehospitalization among older adults experiencing PIM in Taiwan than either PIM-Taiwan or PRISCUS. The risk of 90-day rehospitalization was associated with the potentially harmful DDI classes of serotonin syndrome, QT prolongation, EPS, and hypokalemia.

Proton pump inhibitors reduce the survival of advanced lung cancer patients with therapy of gefitinib or erlotinib.

Gefitinib and erlotinib are the first-line tyrosine kinase inhibitors (TKI) for advanced non-small-cell lung cancer. However, co-administration of either drug with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) may reduce TKI's bioavailability. Therefore, we aimed to investigate the effects of these drug-drug interactions. We surveyed nationwide population-based databases between Jan 1, 2010, and Dec 30, 2018. Newly diagnosed patients with advanced lung adenocarcinoma who received first-line gefitinib or erlotinib were identified. Effects on overall survival (OS) and time to next treatment (TTNT) association between PPIs or H2RAs and co-administrated gefitinib or erlotinib were evaluated. PPIs or H2RAs users were defined if the period overlapped with TKIs by ≥ 20%. A total of 4340 gefitinib and 1635 erlotinib users were included. PPI group had the shortest median OS and TTNT compared to the H2RA and non-user groups (in gefitinib cohort: OS: 14.35 vs. 17.67 vs. 21.87 months; P < 0.0001, TTNT: 8.47 vs. 10.78 vs. 10.33 months; P < 0.0001); (in erlotinib cohort: OS: 16.97 vs. 20.07 vs. 23.92 months; P < 0.0001, TTNT: 9.06 vs. 11.85 vs. 10.90 months; P = 0.0808). Compared with the non-user group, the adjusted hazard ratio (aHR) of the PPI group in the gefitinib was 1.58 on OS (95% CI 1.42-1.76), 1.37 on TTNT (95% CI 1.24-1.52); in the erlotinib was 1.54 on OS (95% CI 1.30-1.82) and 1.19 on TTNT (95% CI 1.01-1.39). Concurrent use of PPIs with first-line gefitinib or erlotinib therapy was associated with a worse OS and TTNT in patients with lung adenocarcinoma harboring EGFR mutations.

Prognostic impact of angiotensin-converting enzyme inhibitors and angiotensin receptors blockers in esophageal or gastric cancer patients with hypertension - a real-world study.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are used in treating cardiovascular diseases. Previous studies indicated that ACEIs/ARBs may benefit cancer patients by inhibiting tumor angiogenesis and proliferation. The effect of ACEIs/ARBs on cancer survival in esophageal and gastric cancer is still unclear. This study is to investigate the association between ACEIs/ARBs usage and esophageal and gastric cancer prognosis. METHODS: This retrospective cohort study identified esophageal and gastric cancer patients during 2008-2016 from the Taiwan Cancer Registry, and obtained medication usage and follow-up information from the National Health Insurance Research Database and Death Registry. Analysis groups were defined as ACEIs/ARBs user or non-user based on the usage of ACEIs/ARBs within the 6 months after cancer diagnosis. The stabilized inverse probability of treatment weighting using propensity scores was applied to balance covariates between study groups. We also used Kaplan-Meier estimates and Cox regression to compare survival outcome and estimate hazard ratios (HRs). RESULTS: We identified 14,463 and 21,483 newly-diagnosed esophageal and gastric cancer patients during 2008-2016. ACEIs/ARBs users were associated with lower risk of cancer-specific mortality, although only significantly in gastric cancer (gastric: adjusted HR = 0.87, 95% CI = 0.78-0.97; esophageal: adjusted HR =0.88, 95% CI = 0.76-1.02). A better survival outcome was observed among patients who received higher cumulative defined daily dose of ACEIs/ARBs. CONCLUSIONS: We found that using ACEIs/ARBs after cancer diagnosis were associated with lower risk of mortality. Our results add to the knowledge of the benefit of ACEIs/ARBs against mortality in individuals with esophageal/gastric cancer patients with hypertension.

Investigating the effectiveness of adjuvant therapy for patients with hormone receptor-positive ductal carcinoma in situ.

BACKGROUND: This study compared the recurrence risk of single versus dual adjuvant radiotherapy (RT) and hormonal therapy (HT) following breast-conserving surgery (BCS) in patients with hormone receptor-positive ductal carcinoma in situ (DCIS). METHODS: This retrospective cohort study used the Taiwan Cancer Registry database linking to the Taiwan National Health Insurance data from 2011 to 2016. We compared the recurrence risk between BCS-based regimens in Cox regressions and presented as adjusted hazard ratio (HR) and 95% confidence interval (95%CI). RESULTS: The 1,836 study cohort with a low-to-intermediate risk of recurrence was grouped into BCS alone (6.1%), BCS+RT (6.2%), BCS+HT (23.4%) and BCS+HT+RT (64.3%) according to the initial treatments. During the follow-up (median: 3.3 years), the highest 5-year recurrence-free survival rate was in BCS+RT (94.1%) group and followed by BCS+HT+RT (92.8%), BCS+HT (87.4%) and BCS alone (84.9%). Of the single adjuvant therapies, RT was more effective than HT. Both BCS+HT (HR: 1.52, 95%CI: 0.99-2.35) and BCS+RT (HR: 1.10, 95%CI: 0.50-2.41) did not significantly increase recurrence risk comparing against the BCS+HT+RT group. CONCLUSION: Single adjuvant demonstrated a similar subsequent recurrence risk with dual adjuvant. This study supports the proposition to de-escalate adjuvant treatments in patients with low-to-intermediate risk of DCIS recurrence.

Comparing survival and subsequent treatment of first-line tyrosine kinase inhibitors in patients of advanced lung adenocarcinoma with epidermal growth factor receptor mutation.

BACKGROUND/PURPOSE: Three first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely available to treat advanced lung adenocarcinoma harboring EGFR mutation. However, studies comparing efficacy or effectiveness of these EGFR TKIs came out with inconclusive results. METHODS: In this real-world data analysis with a nationwide retrospective cohort design, adult patients with newly diagnosed advanced lung adenocarcinoma with EGFR mutation between 2011 and 2016, who received a first-line EGFR TKI, were included. Overall survival (OS) and time to next treatment (TTNT) were compared between patients receiving different EGFR TKIs after overlap weighting. RESULTS: We enrolled 10,431 patients, including 6,230, 2,359, and 1842 in gefitinib, erlotinib, and afatinib groups, respectively. The median (95% confidence interval [CI]) OS were 24.2 (22.9-26.2), 25.7 (24.0-27.9), and 29.1 (25.8-32.1) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p = 0.001). The hazard ratios (95% CI) for the afatinib group were 0.85 (0.74-0.98) and 0.91 (0.79-1.05) comparing with the gefitinib and erlotinib groups, respectively. The median (95% CI) TTNT were 10.9 (10.4-11.2), 11.7 (11.3-12.1), 13.4 (12.5-14.3) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p < 0.001). The hazard ratios (95% CI) for the afatinib group were 0.79 (0.70-0.88) and 0.89 (0.79-1.00) comparing with the gefitinib and erlotinib groups, respectively. There were 6111 (59%) patients receiving subsequent therapies, and the majority of them received a second-line chemotherapy, particularly platinum-based chemotherapy. CONCLUSION: Afatinib, compared with gefitinib, might provide better effectiveness as the first-line targeted therapy for patients of advanced lung adenocarcinoma with EGFR mutation.

Comparison of effectiveness and safety between ticagrelor and clopidogrel in patients with acute coronary syndrome and on dialysis in Taiwan.

AIMS: This study aimed to evaluate and compare the effectiveness and safety between clopidogrel and ticagrelor in acute coronary syndrome (ACS) with renal dysfunction. METHODS: We conducted a retrospective cohort study on patients on chronic dialysis and whose admission diagnosis between 1 July 2013 and 31 December 2016 included ACS. The primary effectiveness endpoint was a major adverse cardiovascular event (MACE), and the primary safety endpoint was a major bleeding event. The application of propensity scores through the inverse probability of treatment weighting (IPTW) was applied to the study groups. Cox regression was used to estimate hazard ratios (aHRs) of study endpoints. In addition, the competing risk was adjusted using the Fine and Gray competing risk model. RESULTS: There were 1915 patients in the clopidogrel group and 270 patients in the ticagrelor group. At 12 months, the ticagrelor group had higher risks for MACE (aHR with IPTW: 1.29; 95% CI 1.16-1.44); death (aHR with IPTW: 1.65; 95% CI 1.47-1.86) and cardiac death (subdistribution HR [SHR] with IPTW: 1.64; 95% CI 1.41-1.91), compared with those in the clopidogrel group. For major bleeding event, the risk was significantly higher with ticagrelor than with clopidogrel (SHR with IPTW: 1.49; 95% CI 1.34-1.65). In terms of the risk for any bleeding event, there was no significant difference between the two groups (SHR with IPTW: 1.05; 95% CI 0.95-1.17). CONCLUSIONS: Compared with clopidogrel, ticagrelor was associated with higher MACE, death, cardiac death and major bleeding risk within 12 months in patients with ACS and on dialysis.

Cardiovascular events in patients with chronic myeloid leukaemia treated with tyrosine kinase inhibitors in Taiwan: a nationwide population-based study.

AIMS: New-generation breakpoint cluster region-Abelson tyrosine kinase inhibitors (TKIs) have a higher incidence of cardiovascular events than imatinib in patients with chronic myeloid leukaemia (CML). However, this knowledge is insufficiently proven. Hence, this study aimed to explore the association between cardiovascular events and TKIs in patients with CML. METHODS AND RESULTS: This retrospective population-based cohort study enrolled first-time users of imatinib, dasatinib, and nilotinib between 1 January 2007 and 31 December 2016. Arterial thromboembolic events (ATEs) were the primary outcome, while other cardiovascular-related events were the secondary outcomes. The event rates were estimated using Kaplan-Meier estimates, and the hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. Additionally, the competing risk was adjusted using the Fine and Gray competing risk model. We included 1207 patients. Nilotinib had a significantly higher ATE risk (subdistribution HR = 4.92, 95% CI = 1.68-14.36) than imatinib. Conversely, no difference was found for other cardiovascular-related events. Risks of ATE and other cardiovascular-related events were similar between dasatinib and imatinib and between nilotinib and dasatinib. The risk of ATE hospitalization consistently increased throughout the main analyses and sensitivity analyses. CONCLUSION: Nilotinib-treated patients had a significantly higher risk of developing ATE than imatinib-treated patients. However, the risks of ATE and other cardiovascular-related events were not significantly different between dasatinib and imatinib.

Importance of medication adherence in treatment needed diabetic retinopathy.

We aim to investigate the role of medication adherence history in treatment needed diabetic retinopathy (TNDR). We conducted a retrospective nested case-control study using 3 population-based databases in Taiwan. The major one was the 2-million-sample longitudinal health and welfare population-based database from 1997 to 2017, a nationally representative random sample of National Health Insurance Administration enrolled beneficiaries in 2010 (LHID2010). The national death registry and national cancer registry were also checked to verify the information. The outcome was defined as the TNDR. The Medication possession ratio (MPR) was defined as the ratio of total days of diabetes mellitus (DM) medication supply divided by total observation days. MPR ≥ 80% was proposed as good medication adherence. The association of MPR and the TNDR was analyzed. Other potential confounders and MPR ratio were also evaluated. A total of (n = 44,628) patients were enrolled. Younger aged, male sex and patients with less chronic illness complexity or less diabetes complication severity tend to have poorer medication adherence. Those with severe comorbidity or participating pay-for-performance program (P4P) revealed better adherence. No matter what the characteristics are, patients with good MPR showed a significantly lower likelihood of leading to TNDR after adjustment with other factors. The protection effect was consistent for up to 5 years. Good medication adherence significantly prevents treatment needed diabetic retinopathy. Hence, it is important to promote DM medication adherence to prevent risks of diabetic retinopathy progression, especially those who opt to have low medication adherence.

Is colistin-associated acute kidney injury clinically important in adults? A systematic review and meta-analysis.

Colistin is the last-resort antimicrobial agent against infections caused by multidrug-resistance Gram-negative bacteria (MDR-GNB). However, a differing risk of colistin-associated acute kidney injury (CA-AKI) has been demonstrated without affecting mortality, thus the association and its importance needs to be questioned. To assess the impact of this adverse effect, a meta-analysis comparing colistin with other antibiotics in treating MDR-GNB infections was conducted. The PubMed, Embase and Cochrane Library electronic databases were searched up to 31 December 2018 for cohort studies and randomised controlled trials with at least two arms with one arm containing colistin-based treatment. The primary endpoint was the incidence of AKI. The secondary endpoint was 30-day all-cause mortality. A total of 34 studies, including 26 regarding colistin-based therapy versus other antibiotics and 9 regarding colistin monotherapy versus combination therapy, were included. The incidence of CA-AKI was 32.3%. Colistin was associated with an 82% higher incidence of AKI than other antibiotics [odd ratio (OR) = 1.82, 95% confidence interval (CI) 1.13-2.92; P = 0.01]. Most CA-AKI events were mild and reversible without a higher rate of mortality or the requirement for renal replacement therapy (RRT). Only 1.0% of patients required RRT for > 4 weeks. Compared with colistin monotherapy, combination therapy was associated with a significantly lower incidence of AKI (OR = 1.46, 95% CI 1.10-1.94; P = 0.009), particularly in combination with a carbapenem (OR = 1.97, 95% CI 1.30-2.99; P = 0.001). In conclusion, CA-AKI might not be an important limitation of colistin in MDR-GNB therapy.

Role of cyclooxygenase-2 inhibitors in the survival outcome of colorectal cancer patients: A population-based cohort study.

The aim of this study is to investigate whether use of cyclooxygenase-2 (COX-2) inhibitors as auxiliary drug in colorectal cancer (CRC) patients will lead to better survival outcome. This population-based retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. The cohort consisted of newly diagnosed CRC adult patients during 2003-2010 with at least one prescription of nonsteroidal anti-inflammation drugs. Analysis groups were defined as users or nonusers of COX-2 inhibitors based on their usage prior to or 1 year after diagnosis of CRC. The outcome measurement was overall survival. The application of propensity scores through the inverse probability of treatment weighting (IPTW) was applied to the study groups. Subgroup analyses included stratification of different cancer site, treatment modalities, and first chemotherapy regimens. Kaplan-Meier estimates and Cox regressions were used to compare survival outcome. We identified 14,688 patients with newly diagnosed CRC. The adjusted hazard ratio (HR) with IPTW was 0.91 [95% confidence interval (CI), 0.86-0.96] in patients using COX-2 inhibitors in before and after diagnosis groups, and statistical significance was not reached for usages at only prior to or only after diagnosis. In subgroup analyses, patients with rectal cancer (adjusted HR with IPTW=0.86; 95% CI, 0.79-0.94) who received surgery followed by chemoradiation (adjusted HR with IPTW=0.57; 95% CI, 0.47-0.77) and with adjuvant chemotherapy of FOLFOX regimen (adjusted HR with IPTW=0.81; 95% CI, 0.67-0.99) had survival benefits in using COX-2 inhibitors both prior to and after diagnosis. Use of COX-2 inhibitors was found to be associated with reduction in mortality for CRC patients when taken both prior to and after cancer diagnosis.

Determination of deferasirox in human plasma by short-end injection and sweeping with a field-amplified sample stacking and micellar electrokinetic chromatography.

A field-amplified sample stacking-sweeping micellar electrokinetic chromatography with short-end injection was established for determination of deferasirox (DFX) in plasma. DFX was extracted from plasma and reconstituted with deionized water (lower conductivity solution). Capillary (effective length, 10cm) was filled with background electrolyte (40mM phosphate buffer, pH 4.5, containing 20% methanol). After sample loading from outlet end at 5psi for 15s, separation was carried out by applying high voltage at 15kV for 10min. Sodium dodecyl sulfate (SDS) was used to sweep DFX for enhancing sensitivity. The optimal CE separation conditions were 40mM phosphate buffer at pH 4.5 containing 100mM SDS and 20% methanol. The analysis time was about 3.5min for DFX. The calibration curve of DFX was ranged from 1 to 20µg/ml. The linearity (r) was more than 0.998. RSD and RE in intra- and inter-day assays were all below 12.14%. The limit of detection (LOD, S/N=3) for DFX was 0.3µg/ml. The sensitivity enhancement factor between sweeping-FASS MEKC and capillary zone electrophoresis is 3.3. Finally, the method was applied for determination of DFX in ß-thalassemia patients.

Antipsychotic medications and dental caries in newly diagnosed schizophrenia: A nationwide cohort study.

We investigated the association between antipsychotic medications and the risk of dental caries in patients with schizophrenia. We enroled a nationwide cohort of patients with newly diagnosed schizophrenia within 1 year of dental caries development. Exposure to antipsychotics and other medications was categorised according to their type and duration, and the association between exposure and dental caries was assessed through logistic regressions. Of the 3610 patients with newly diagnosed schizophrenia, 2149 (59.5%) exhibited an incidence of treated dental caries. Logistic regression analysis identified a younger age, female sex, high income, a 2-year history of dental caries, and exposure to first-generation antipsychotics, and antihypertensives as independent risk factors for treated dental caries in patients with schizophrenia. Hyposalivation, the adverse effect of first-generation antipsychotics and antihypertensives, was associated with an increased risk of treated dental caries. However, hypersalivation from first-generation antipsychotics for dental caries was associated with a protective factor. These findings suggest that clinicians should pay attention to the aforementioned risk factors for dental caries in patients with schizophrenia, particularly while prescribing first-generation antipsychotics and antihypertensives to such patients.

Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study.

BACKGROUND: Lithium inhibits glycogen synthase kinase-3, which is an enzyme involved in the pathogenesis of cancer. AIMS: To investigate the association between lithium and cancer risk in patients with bipolar disorder. METHOD: A retrospective cohort study was designed using the National Health Insurance Research Database (NHIRD) in Taiwan. Patients using lithium comprised the index drug group and patients using anticonvulsants only comprised the control group. Time-dependent Cox regression was used to evaluate the hazard ratios (HRs) for risk of cancer. RESULTS: Compared with anticonvulsant-only exposure, lithium exposure was associated with significantly lower cancer risk (HR = 0.735, 95% CI 0.554-0.974). The hazard ratios for the first, second and third tertiles of the cumulative defined daily dose were 0.762 (95% CI 0.516-1.125), 0.919 (95% CI 0.640-1.318) and 0.552 (95% CI 0.367-0.831), respectively. CONCLUSIONS: Lithium is associated with reduced overall cancer risk in patients with bipolar disorder. A dose-response relationship for cancer risk reduction was observed.

Risk factors for pneumonia among patients with Parkinson's disease: a Taiwan nationwide population-based study.

OBJECTIVE: Pneumonia is the leading cause of death in patients with Parkinson's disease (PD). However, few studies have been performed to explore the risk factors for pneumonia development in patients with PD. METHODS: We conducted a nationwide population-based cohort study of patients with PD to identify the risk factors for these patients developing pneumonia. Participants with newly diagnosed PD between 2000 and 2009 were enrolled from the 2000-2010 National Health Insurance Research Database in Taiwan. We compared patients with PD with an incidence of hospitalization with pneumonia vs those without, and Cox proportional hazard models were used to estimate the risk of pneumonia. RESULTS: Of the 2,001 enrolled patients (mean follow-up duration 5.8 years, range: 2.7-14.7 years), 381 (19.0%) had an incidence of hospitalization with pneumonia during the study period. Multivariate Cox proportional hazards analysis identified older age group (≥80 years of age, hazard ratio [HR] =3.15 [95% confidence interval 2.32-4.28]), male sex (HR =1.59 [1.29-1.96]), certain geographic regions (northern, HR =1.36 [1.04-1.78], southern and eastern, HR =1.40 [1.05-1.88]), rural areas (HR =1.34 [1.05-1.72]), chronic heart failure (HR =1.53 [1.02-2.29]), and chronic kidney disease (HR =1.39 [1.03-1.90]) as risk factors for hospitalization with pneumonia in patients with PD. However, treatment for dental caries was a protective factor (HR =0.80 [0.64-0.99]). CONCLUSION: The results of this study highlight risk factors that are associated with hospitalization with pneumonia, and, for the first time, suggest a link between treated dental caries and a diminished risk of hospitalization with pneumonia in patients with PD.

Topical simvastatin promotes healing of Staphylococcus aureus-contaminated cutaneous wounds.

Cutaneous wounds are prompt to be contaminated by bacteria, but the clinical benefits of applying antibiotics and antiseptics in wound management have not been proven. Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors commonly used to lower cholesterol levels. Studies indicated that statins, especially simvastatin, promote wound healing in experimental models. As Staphylococcus aureus is one of the most important microorganism responsible for wound infections, the aims of this study were to characterise the anti-staphylococcal activity of simvastatin and to evaluate the application of simvastatin as a topical therapy for S. aureus-contaminated wounds. In the present study, simvastatin was bacteriostatic against S. aureus at sub-inhibitory concentrations up to 8 hours after exposure. Further increased concentrations of simvastatin above the minimal inhibitory concentration (MIC) did not enhance the growth inhibitory effect. By contrast, the ability of simvastatin to inhibit S. aureus biofilm formation was concentration dependent. Topical application of simvastatin at its MIC against S. aureus accelerated the healing and bacterial clearance of S. aureus-contaminated wounds in an excisional mice wound model. This effective concentration is well below the safe concentration for topical use. Collectively, topical application of simvastatin has the potential as a novel modality for managing wound infections and promoting wound healing.

Rivaroxaban in preventing venous thromboembolism after arthroplastic surgery in Taiwan.

Venous thromboembolism (VTE) is one of the severe complications of total hip arthroplasty (THA) and total knee arthroplasty (TKA). The incidence of VTE could be reduced if preventive antithrombotic medicines are used; however, the incidence of bleeding may increase. Rivaroxaban is a factor Xa inhibitor that prevents VTE after THA or TKA. This study is designed to confirm the efficacy and safety of rivaroxaban in Taiwan. This is a retrospective database study based on the data of 6996 patients provided by the Taiwan National Health Insurance Research Database from 2008 to 2012. The data included the number of prescription, the cost of prescription, and case number for patients treated with antithrombotic agents for the prevention or treatment of joint arthroplasty complications (including THA, TKA, partial hip arthroplasty, revision THA and TKA), and the incidence of thrombosis and hemorrhage from year 2008 to 2012. The overall postoperative VTE rate was 0.49%. Compared with other antithrombotic drugs, rivaroxaban and heparin analogs can reduce the percentage of thrombosis. We also found that the expenditure and hospitalization was less in the rivaroxaban group than in the heparin analogs group. Because some benefits of rivaroxaban were found in our study, further cost-effective and drug safety studies are warranted. It is important to consider the cost-effective principle for the use of antithrombotic drugs in preventing thromboembolic complications after total joint arthroplasty.

Hepatitis C Virus Infection Is Associated With an Increased Risk of Active Tuberculosis Disease: A Nationwide Population-Based Study.

Tuberculosis (TB) and hepatitis C virus (HCV) infection contribute to major disease mortality and morbidity worldwide. However, the causal link between HCV infection and TB risk remains unclear. We conducted a population-based cohort study to elucidate the association between HCV infection and TB disease by analyzing Taiwan National Health Insurance Database. We enrolled 5454 persons with HCV infection and 54,274 age- and sex-matched non-HCV-infected persons between January 1998 and December 2007. Time-dependent Cox proportional hazards regression analysis was used to measure the association between HCV infection and active TB disease. Incidence rate of active TB disease was higher among HCV infection than in control (134.1 vs 89.1 per 100,000 person-years; incidence rate ratio 1.51; P = 0.014). HCV infection was significantly associated with active TB disease in multivariate Cox regression (adjusted hazard ratio [HR] 3.20; 95% confidence interval [CI], 1.85-5.53; P < 0.001) and competing death risk event analysis (adjusted HR 2.11; 95% CI, 1.39-3.20; P < 0.001). Multivariate stratified analysis further revealed that HCV infection was a risk of active TB disease in most strata. This nationwide cohort study suggests that HCV infection is associated with a higher risk of developing active TB disease.

Risks of nonadherence to hormone therapy in Asian women with breast cancer.

The aim of this study was to quantify the hormone therapy (HT) nonadherence patterns and to assess the associated risk factors in Asian women with breast cancer. This retrospective cohort study used the Taiwan Health Insurance Research Database from 2003 to 2011. Data from women with newly diagnosed primary breast cancer were identified, and persistence (without HT prescribing gap ≥ 180 days) to HT was defined through records of dispensing prescriptions. Study cohorts were further classified as adjuvant and primary HT groups. Each individual's HT utilization patterns and the medication possession ratio at overall HT course were measured. The odds ratios (ORs) of nonadherence (medication possession ratio, <80%) in adjuvant and primary HT patients were estimated using logistic regressions with adjustment of potential confounding variables. These patients had 15.6% and 23.4% nonadherence rates to HT in adjuvant and primary HT groups, respectively. In the adjuvant HT group, older age groups (≥50 years) and taking aromatase inhibitors were less likely to show nonadherence (p < 0.05). In the primary HT group, women older than 70 years were significantly less likely to exhibit nonadherence (OR = 0.53; 95% confidence interval, 0.28-0.99); however, women with presence of HT-related adverse events had significantly increased risk (OR = 1.44; 95% confidence interval, 1.02-2.03). Young age and experience of musculoskeletal and joint symptoms were identified as risk factors for nonadherence.

A competing risk analysis of hormone therapy interruption in Asian women with breast cancer.

PURPOSE: This study aimed to use a competing risk approach to evaluate the probability of the occurrence of hormone therapy (HT) interruption and to assess its associated predictors in Asian women with breast cancer. METHODS: This retrospective cohort study used the Taiwan Health Insurance Research Database from 2003 to 2011. Reimbursement data for women with newly diagnosed primary breast cancer were extracted. Interruption (gap ≥ 180 days) and time to first interruption of HT were identified. The probability of interruption was analysed by Kaplan-Meier (KM) method and cumulative incidence competing risk (CICR) method. Competing risk regressions were used to assess the predictors of interruption. RESULTS: The 5-year cumulative incidence of first HT interruption was 14% versus 13% estimated by the KM and the CICR methods, respectively. The estimated incidences from CICR method tended to be around 11% lower than KM method in various HT utilization patterns. Younger (≤50 years) age at diagnosis, switching HT and the presence of HT-related adverse events were identified as predictors of interruption in competing risk regressions. CONCLUSIONS: The competing risk approach provided lower probabilities and estimates when investigating the incidence of first interruption than the standard survival analysis. The competing risk method, which takes into account the competing risks from cancer recurrence and death, should be considered in future analysis. In terms of improving persistence of HT, it is important to focus on patients of younger age at diagnosis, HT switching and experiencing adverse events.