Treatment outcomes for multidrug-resistant tuberculosis in Eastern Taiwan.

OBJECTIVES: The objective of this study is to evaluate the treatment outcomes of patients with multidrug-resistant tuberculosis (MDR-TB) under special programmatic management in Eastern Taiwan over the past 10 years. MATERIALS AND METHODS: All newly diagnosed MDR-TB patients and MDR-TB patients enrolled previously with persistent positive cultures were included in this study, from May 2007 to April 2017, in Eastern Taiwan. A panel of pulmonologists designed the initial MDR-TB regimens. Subsequently, regimens were adjusted according to drug susceptibility test results for second-line drugs. Mobile teams were organized for treatment support, and several measures were adapted to safeguard effective treatment support. RESULTS: A total of 178 patients with bacteriological confirmed pulmonary MDR-TB were identified, of whom 167 had treatment outcomes when the study was conducted. Of these 167 patients, 120 (71.9%) were cured, 11 (6.5%) completed therapy (78.4% had successful treatment), 25 (15.0%) died, 9 (5.4%) had treatment failure, none were transferred out, and 2 (1.2%) were lost to follow-up. Surgery was performed on 8 (4.8%). CONCLUSIONS: This is an analysis of the treatment outcomes after adopting the Directly Observed Treatment, Short-course Plus program to treat MDR-TB patients in Eastern Taiwan. We had a low proportion of loss-to-follow-up, resulting in a high treatment success rate. This program serves as an effective model in providing quality care to patients with MDR-TB.

Comparative effectiveness of allopurinol, febuxostat and benzbromarone on renal function in chronic kidney disease patients with hyperuricemia: a 13-year inception cohort study.

Background: Direct comparisons of the effectiveness of allopurinol with that of other urate-lowering agents in chronic kidney disease (CKD) populations, as well as guideline recommendations for clinical practice, are lacking. Methods: We constructed a pharmacoepidemiology cohort study by including patients from Taiwan's long-term integrated CKD care program to compare the effectiveness among allopurinol, febuxostat and benzbromarone in reducing the risk of progression to dialysis. A total of 874 patients with hyperuricemia who were newly treated with allopurinol, febuxostat or benzbromarone were included. The primary and secondary outcomes were incident end-stage renal disease (ESRD) and the serum uric acid (SUA) changes from baseline, respectively. The results were analyzed using multiple Cox proportional models adjusted for multinomial propensity scores. For subgroup analyses, we further stratified patients according to whether their latest SUA level reached the therapeutic target. Results: Compared with allopurinol, benzbromarone therapy was associated with a reduced risk of progression to dialysis, the adjusted hazard ratio was 0.50 (95% confidence interval, 0.25-0.99). Patients who received allopurinol or febuxostat exhibited a comparable risk of ESRD [adjusted hazard ratio, 0.99 (0.40-2.44)]. Febuxostat was significantly more potent than allopurinol or benzbromarone in lowering SUA levels in the fully adjusted model. Among patients who reached the therapeutic target, those with febuxostat and benzbromarone initiation had a significantly lower risk of ESRD. Conclusions: In conclusion, compared with conventional allopurinol, febuxostat and benzbromarone may be more effective in reducing the risk of progression to dialysis and in lowering SUA levels in CKD populations.

Effects of atorvastatin and rosuvastatin on renal function in patients with type 2 diabetes mellitus.

We performed this population-based study to investigate the effects of atorvastatin and rosuvastatin on renal function in patients with type 2 diabetes. From the Taiwan National Health Insurance Pay-for-Performance program for diabetes mellitus database, 2006 to 2009, type 2 diabetic patients aged 40 to 100 years with the first prescription of atorvastatin or rosuvastatin were identified. All the data were linked to the National Health Insurance claims database, 2000 to 2010, to construct longitudinal health care data. The Modification of Diet in Renal Disease equation was used to calculate the estimated glomerular filtration rate (eGFR), and the eGFRs between baseline and the end of follow-up (maximum 2 years) were compared. Totally, 3,601 new users of atorvastatin and 1,968 new users of rosuvastatin were included. The median follow-up was 238 days in atorvastatin users and 210 days in rosuvastatin users. The eGFR at baseline was 72.3 ± 25.9 ml/min/1.73 m(2) in atorvastatin users and 73.7 ± 27.3 ml/min/1.73 m(2) in rosuvastatin users. In both statin groups, we found no significant change in eGFR (+0.1 ml/min/1.73 m(2), 95% confidence interval -0.4 to 0.7, p = 0.62 in atorvastatin users; -0.1 ml/min/1.73 m(2), 95% confidence interval -0.8 to 0.6, p = 0.77 in rosuvastatin users). In conclusion, neither treatment with atorvastatin nor rosuvastatin was associated with a significant change of renal function in type 2 diabetic patients.

Initial outcomes of an integrated outpatient-based screening program for oral cancers.

OBJECTIVE: To evaluate the feasibility of an integrated outpatient-based screening program for oral cancer. STUDY DESIGN: An automated system was used to refer high-risk patients presenting to the outpatient clinic for oral cavity examination. The outcomes between the screened and concurrently symptomatic cohorts were compared to assess the program's effectiveness at identifying oral cancers. RESULTS: Among the 38,693 candidates flagged as high-risk patients by our automated referral system, a total of 8037 participants were recruited to our screened cohort; 1664 patients were identified with positive lesions, and 302 patients underwent a biopsy. Five patients were diagnosed with oral cancer and 121 with dysplastic precancers. The symptomatic cohort comprised 157 patients with oral cancers and 61 with precancers. The screening program identified earlier stages of oral cancers than in the symptomatic cohort. CONCLUSION: Automated outpatient-based oral cancer screening programs may be a practicable strategy to identify precancerous lesions or early-stage cancers in high-risk adults.

Risks of cardiac arrhythmia and mortality among patients using new-generation macrolides, fluoroquinolones, and ß-lactam/ß-lactamase inhibitors: a Taiwanese nationwide study.

BACKGROUND: Previous studies have demonstrated increased cardiovascular mortality related to azithromycin and levofloxacin. Risks associated with alternative drugs in the same class, including clarithromycin and moxifloxacin, were unknown. We used the Taiwan National Health Insurance Database to perform a nationwide, population-based study comparing the risks of ventricular arrhythmia and cardiovascular death among patients using these antibiotics. METHODS: Between January 2001 and November 2011, a total of 10 684 100 patients were prescribed oral azithromycin, clarithromycin, moxifloxacin, levofloxacin, ciprofloxacin, or amoxicillin-clavulanate at outpatient visits. A logistic regression model adjusted for propensity score was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for adverse cardiac outcomes occurring within 7 days after the initiation of antibiotic treatment. RESULTS: Compared with amoxicillin-clavulanate treatment, the use of azithromycin and moxifloxacin was associated with significant increases in the risks of ventricular arrhythmia and cardiovascular death. The adjusted ORs for ventricular arrhythmia were 4.32 (95% CI, 2.95-6.33) for azithromycin, 3.30 (95% CI, 2.07-5.25) for moxifloxacin, and 1.41 (95% CI, .91-2.18) for levofloxacin. For cardiovascular death, the adjusted ORs for azithromycin, moxifloxacin, and levofloxacin were 2.62 (95% CI, 1.69-4.06), 2.31 (95% CI, 1.39-3.84), and 1.77 (95% CI, 1.22-2.59), respectively. No association was noted between clarithromycin or ciprofloxacin and adverse cardiac outcomes. CONCLUSIONS: Healthcare professionals should consider the small but significant increased risk of ventricular arrhythmia and cardiovascular death when prescribing azithromycin and moxifloxacin. Additional research is needed to determine whether the increased risk of mortality is caused by the drugs or related to the severity of infection or the pathogens themselves.

Evaluation and development of a real-time predictive model for ultrasound investigation of malignant thyroid nodules.

Ultrasound investigations and correct identification of malignant thyroid nodules depend on the experience and qualifications of the investigators; thus, a model that provides better evaluation before needle aspiration is desired. Data from 687 patients with 726 thyroid nodules comprising 65 malignant nodules (61 papillary and 4 follicular carcinoma) and 661 benign nodules were used to construct a predictive model. Presence of micro-calcification, taller-than-wide shape, predominant solid echostructure, and irregular margins were shown to be good independent predictive parameters. A thyroid nodule was predicted as malignant with a score ≥3.3. Internal validation of this predictive tool by the bootstrapping method showed excellent overall model performance.

Treatment outcomes of injection laryngoplasty using cross-linked porcine collagen and hyaluronic acid.

OBJECTIVE: To investigate the treatment outcomes and prognostic factors of injection laryngoplasty (IL) using cross-linked porcine collagen (PC) and hyaluronic acid (HA) in unilateral vocal fold paralysis (UVFP). STUDY DESIGN: Case series with chart review. SETTING: A tertiary teaching hospital. SUBJECTS AND METHODS: This study reviewed 60 consecutive patients with UVFP who underwent IL with PC (n = 33) or HA (n = 27). Objective evaluations included maximal phonation time (MPT) and 10-item voice handicap index (VHI-10). Kaplan-Meier method was applied to evaluate the subjective treatment outcomes according to the patients' self-assessment of symptom recurrence via chart review for the follow-up period of 15 months. Log-rank tests were applied to evaluate the association between clinical factors and subjective treatment outcomes. RESULTS: Objective outcome measurements revealed significantly improved MPT and VHI-10 at 1, 3, and 6 months posttreatment, with nonsignificant differences between the PC and HA groups. Subjective treatment outcomes also revealed a nonsignificant difference between the 2 groups. The median symptom-free durations were 10.9 and 14.4 months for the PC and HA groups, respectively. Subsequent analyses failed to identify prognostic significance of sex, time to treatment, etiology, side, injection approaches, and the presence of aspiration. No significant adverse effects occurred during the follow-up period. CONCLUSION: This study demonstrated comparable subjective and objective improvements following IL using PC or HA in patients with UVFP. No significant prognostic factor of IL was discovered in the present research. Porcine collagen and HA as medium duration materials might play a role in the future of IL.

Risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in Taiwan.

BACKGROUND: Observational studies and fatal case reports raise concern about the safety of severe dysglycemia associated with fluoroquinolone use. The objective of this study was to assess the risk of severe dysglycemia among diabetic patients who received different fluoroquinolones. METHODS: In a population-based inception cohort study of diabetic patients covering the period from January 2006 to November 2007, outpatient new users of levofloxacin, ciprofloxacin, moxifloxacin, cephalosporins, and macrolides orally were identified. Study events were defined as emergency department visits or hospitalization for dysglycemia within 30 days following the initiation of antibiotic therapy. Results were analyzed with adjusted multinomial propensity score. RESULTS: A total of 78 433 diabetic patients receiving the antibiotics of interest were included in the study. The absolute risk of hyperglycemia per 1000 persons was 6.9 for moxifloxacin and 1.6 for macrolides. In contrast, the risk of hypoglycemia was 10.0 for moxifloxacin and 3.7 for macrolides. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) of levofloxacin, ciprofloxacin, and moxifloxacin compared with macrolides were 1.75 (1.12-2.73), 1.87 (1.20-2.93), and 2.48 (1.50-4.12), respectively, for hyperglycemia and 1.79 (1.33-2.42), 1.46 (1.07-2.00), and 2.13 (1.44-3.14), respectively, for hypoglycemia. Patients taking moxifloxacin faced a significantly higher risk of hypoglycemia than those receiving ciprofloxacin. A significant increase in the risk of hypoglycemia was also observed among patients receiving moxifloxacin concomitantly with insulin (AOR, 2.28; 95% CI, 1.22-4.24). CONCLUSIONS: Diabetics using oral fluoroquinolones faced greater risk of severe dysglycemia. The risk of hypoglycemia varied according to the type of fluoroquinolone administered, and was most commonly associated with moxifloxacin.

The impact of second primary malignancies on head and neck cancer survivors: a nationwide cohort study.

BACKGROUND: Head and neck cancer (HNC) is associated with a high rate of developing second primary malignancies(SPMs). But the impact on survival remains poorly understood before. Therefore, we want to estimate the impact of SPMs on HNC survivors. METHODS AND FINDINGS: Between 1986 and 2008, a total of 9,996 SPMs were recorded for 93,891 patients with an initial diagnosis of HNC by the Taiwan Cancer Registry. Patients were followed with national death registry database to 2011.Using the Kaplan-Meier method, a time-dependent covariate was employed to compare the survival rates between patients with and without SPMs. A Cox proportional hazards model that treated age and sex as confounders was used to examine the hazard ratios of SPMs. The relative survival rates were calculated using age- and sex-specific life tables for the population. Parametric mixture cure fraction models were then employed to estimate the percentage of cancer survivors who would be cured. Use of the Kaplan-Meier method showed that the crude survival rates differed significantly for patients with and patients without SPMs (log-rank test <0.01). For the results of Cox proportional hazards regression analysis, SPMs had a significant influence on survival rates with univariate (HR 2.59,95% CI 2.53 to 2.65) and multivariate analysis (HR 2.34, 2.28 to 2.40). Patients with SPMs of nasopharyngeal carcinoma (NPC) had the highest cure rate at 39%, where as esophageal and lung cancer had the worst prognosis, with a cure rate of 11%. CONCLUSIONS: A worse prognosis was found for second primary cancer such as esophageal or lung cancer. Patients and healthcare providers must strongly consider and have a high clinical suspicion of these SPMs.

Treatment outcome of additional dextran to corticosteroid therapy on sudden deafness: propensity score-matched cohort analysis.

OBJECTIVE: This study aimed to investigate whether adding low-molecular-weight dextran to oral steroids in patients with idiopathic sudden sensorineural hearing loss resulted in better hearing outcomes than those in patients receiving oral corticosteroids alone. STUDY DESIGN: Historical cohort study. SETTING: Tertiary teaching hospital. SUBJECTS AND METHODS: The authors reviewed the clinical records of 166 patients with idiopathic sudden sensorineural hearing loss. Therapeutic effectiveness was measured by the gain of pure-tone averages and 4 categories of hearing outcome (complete recovery, marked recovery, mild improvement, or no improvement). To manage potential confounding factors associated with treatment allocation, the authors matched the subjects from each group according to the propensity score (ie, the predicted probability that they would receive a specific treatment). RESULTS: The authors identified 50 pairs of propensity score-matched subjects (n = 100) without significant difference of all clinical factors (P > .05). Subsequent analyses demonstrated that the average hearing gain in subjects receiving additional dextran to oral steroid was 31.7 ± 21.5 dB, which did not differ from 33.0 ± 21.8 dB in subjects receiving steroids alone (P = .76). Difference of hearing outcomes between the 2 groups was also nonsignificant (P = .92). CONCLUSION: Matching propensity scores successfully balanced the heterogeneity between the dextran and steroid groups. Analytical results demonstrated that adding low-molecular-weight dextran to oral corticosteroids was not associated with greater hearing gain or better hearing outcome in idiopathic sudden sensorineural hearing loss.

Risk of new acute myocardial infarction hospitalization associated with use of oral and parenteral non-steroidal anti-inflammation drugs (NSAIDs): a case-crossover study of Taiwan's National Health Insurance claims database and review of current evidence.

BACKGROUND: Previous studies have documented the increased cardiovascular risk associated with the use of some nonsteroidal anti-inflammatory drugs (NSAIDs). Despite this, many old NSAIDs are still prescribed worldwide. Most of the studies to date have been focused on specific oral drugs or limited by the number of cases examined. We studied the risk of new acute myocardial infarction (AMI) hospitalization with current use of a variety of oral and parenteral NSAIDs in a nationwide population, and compared our results with existing evidence. METHODS: We conducted a case-crossover study using the Taiwan's National Health Insurance claim database, identifying patients with new AMI hospitalized in 2006. The 1-30 days and 91-120 days prior to the admission were defined as case and matched control period for each patient, respectively. Uses of NSAIDs during the respective periods were compared using conditional logistic regression and adjusted for use of co-medications. RESULTS: 8354 new AMI hospitalization patients fulfilled the study criteria. 14 oral and 3 parenteral NSAIDs were selected based on drug utilization profile among 13.7 million NSAID users. The adjusted odds ratio, aOR (95% confidence interval), for risk of AMI and use of oral and parenteral non-selective NSAIDs were 1.42 (1.29, 1.56) and 3.35 (2.50, 4.47), respectively, and significantly greater for parenteral than oral drugs (p for interaction<0.01). Ketorolac was associated with the highest AMI risk among both of oral and parenteral NSAIDs studied, the aORs were 2.02 (1.00, 4.09) and 4.27 (2.90, 6.29) respectively. Use of oral flurbiprofen, ibuprofen, sulindac, diclofenac, and parenteral ketoprofen were also significantly associated with increased AMI risk. The results of the present study were consistent with the majority of evidence from previous studies. CONCLUSIONS: The collective evidence revealed the tendency of increased AMI risk with current use of some NSAIDs. A higher AMI risk associated with use of parenteral NSAIDs was observed in the present study. Ketorolac had the highest associated risk in both oral and parenteral NSAIDs studied. Though further investigation to confirm the association is warranted, prescribing physicians and the general public should be cautious about the potential risk of AMI when using NSAIDs.

Is it appropriate to routinely use a nucleic acid amplification test for the diagnosis of tuberculosis?

The purpose of this study was to compare the usefulness of the nucleic acid amplification (NAA) test against conventional tests under normal laboratory operational conditions. The NAA test was performed on the first sputum specimen of all patients. Liquid media culture, solid media culture, and Ziehl-Neelsen stain for an acid-fast bacilli (AFB) smear were performed on three sputum specimens. The results were calculated using the gold standard of either the culture results or the clinical diagnosis. Of the 593 patients tested, 151 (25.5%) were diagnosed with pulmonary tuberculosis. The sensitivity of the first specimen only was 64% for the NAA test, 54% for the AFB smear, 77% for BACTEC MGIT 960 culture, 40% for Lowestain-Jensen (LJ) culture, and 25% for 7H11 culture. The sensitivity when using all three specimens increased to 63% for AFB smear, 87% for BACTEC MGIT 960 culture, 51% for LJ culture, and 40% for 7H11 culture. The specificity was 100% for all culture tests, 99% for the AFB smear, and 99.5% for NAA test. The mean turnaround time was 1.34 days for NAA, 0.59 days for AFB smear, 11 days for BACTEC MGIT 960 culture, 23 days for LJ culture, and 20 days for 7H11 culture. We conclude that the sensitivity of NAA is still far from ideal, and the test is not cost effective. Thus, the COBAS AMPLICOR PCR system is not suitable for routine use in microbiology laboratories.