Yaa-Hui Dong

Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials

Background The active-treatment comparative safety information for all inhaled medications in patients with chronic obstructive pulmonary disease (COPD) is limited. We aimed to compare the risk of overall and cardiovascular death for inhaled medications in patients with COPD. Methods Through systematic database searching, we identified randomised controlled trials of tiotropium Soft Mist Inhaler, tiotropium HandiHaler, long-acting β2 agonists (LABAs), inhaled corticosteroids (ICS), and LABA-ICS combination with at least a 6-month treatment duration. Direct comparison and mixed treatment comparison (MTC) meta-analyses were conducted to estimate the pooled ORs of death for each comparison. Results 42 trials with 52 516 subjects were included. The MTC meta-analysis with the fixed effect model indicated tiotropium Soft Mist Inhaler was associated with an universally increased risk of overall death compared with placebo (OR 1.51; 95% CI 1.06 to 2.19), tiotropium HandiHaler (OR 1.65; 95% CI 1.13 to 2.43), LABA (OR 1.63; 95% CI 1.10 to 2.44) and LABA-ICS (OR 1.90; 95% CI 1.28 to 2.86). The risk was more evident for cardiovascular death, in patients with severe COPD, and at a higher daily dose. LABA-ICS was associated with the lowest risk of death among all treatments. No excess risk was noted for tiotropium HandiHaler or LABA. The results were similar for MTC and direct comparison meta-analyses, with less precision in the random effects model. Conclusion Our study provided a comparative safety spectrum for each category of inhaled medications. Tiotropium Soft Mist Inhaler had a higher risk of mortality and should be used with caution.

Anaemia and related nutrient deficiencies after Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis

Objective To obtain a pooled risk estimate on the long-term impact of anaemia and related nutritional deficiencies in patients receiving Roux-en-Y gastric bypass (RYGB) surgery. Design Systematic review and meta-analysis. Data sources MEDLINE, EMBASE and Cochrane databases were searched to identify English reports published before 16 May 2014. Eligibility criteria Articles with case numbers >100, follow-up period >12 months, and complete data from both before and after surgery were selected. Outcomes of interest were changes in baseline measurements of proportion of patients with anaemia, by haemoglobin, haematocrit, ferritin, iron, vitamin B12 and folate levels. Data collection and analysis Two reviewers independently reviewed data and selected six prospective and nine retrospective studies with a total of 5909 patients. A random effect model with inverse variance weighting was used to calculate summary estimates of outcomes at 6, 12, 24 and 36 months postoperatively. Results Proportion of patients with anaemia was 12.2% at baseline, which, respectively, increased to 20.9% and 25.9% at 12 and 24 months follow-up, consistent with decreases in haemoglobin and haematocrit levels. Although the serum iron level did not change substantially after surgery, the frequency of patients with ferritin deficiency increased from 7.9% at baseline to 13.4% and 23.0% at 12 and 24 months, respectively, postoperation. Vitamin B12 deficiency increased from 2.3% at baseline to 6.5% at 12 months after surgery in those subjects receiving RYGB. There was no obvious increase in folate deficiency. Conclusions RYGB surgery is associated with an increased risk of anaemia and deficiencies of iron and vitamin B12, but not folate. Ferritin is more sensitive when serum iron level is within normal range.

Predicting healthcare utilization using a pharmacy-based metric with the WHO's Anatomic Therapeutic Chemical algorithm.

Background:Automated pharmacy claim data have been used for risk adjustment on health care utilization. However, most published pharmacy-based morbidity measures incorporate a coding algorithm that requires the medication data to be coded using the US National Drug Codes or the American Hospital Formulary Service drug codes, making studies conducted outside the US operationally cumbersome. Objective:This study aimed to verify that the pharmacy-based metric with the World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) algorithm can be used to explain the variations in health care utilization. Research Design:The Longitudinal Health Insurance Database of Taiwan’s National Health Insurance enrollees was used in this study. We chose 2006 as the baseline year to predict the total cost, medication cost, and the number of outpatient visits in 2007. The pharmacy-based metric with 32 classes of chronic conditions was modified from a revised version of the Chronic Disease Score. Results:The ordinary least squares (OLS) model and log-transformed OLS model adjusted for the pharmacy-based metric had a better R2 in concurrently predicting total cost compared with the model adjusted for Deyo’s Charlson Comorbidity Index and Elixhauser’s Index. The pharmacy-based metric models also provided a superior performance in predicting medication cost and number of outpatient visits. For prospectively predicting health care utilization, the pharmacy-based metric models also performed better than the models adjusted by the diagnosis-based indices. Conclusions:The pharmacy-based metric with the WHO ATC algorithm and the matching ATC codes were tested and found to be valid for explaining the variation in health care utilization.

Use of Inhaled Corticosteroids in Patients With COPD and the Risk of TB and Influenza: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: The use of inhaled corticosteroids (ICSs) is associated with an increased risk of pneumonia in patients with COPD. However, the risks of other respiratory infections, such as TB and influenza, remain unclear.Methods: Through a comprehensive literature search of MEDLINE, EMBASE, CINAHL, Cochrane Library, and ClinicalTrials.gov from inception to July 2013, we identified randomized controlled trials of ICS therapy lasting at least 6 months. We conducted meta-analyses by the Peto, Mantel-Haenszel, and Bayesian approaches to generate summary estimates comparing ICS with non-ICS treatment on the risk of TB and influenza.Results: Twenty-fi ve trials (22,898 subjects) for TB and 26 trials (23,616 subjects) for influenza were included. Compared with non-ICS treatment, ICS treatment was associated with a significantly higher risk of TB (Peto OR, 2.29; 95% CI, 1.04-5.03) but not influenza (Peto OR, 1.24;95% CI, 0.94-1.63). Results were similar with each meta-analytic approach. Furthermore, the number needed to harm to cause one additional TB event was lower for patients with COPD treated with ICSs in endemic areas than for those in nonendemic areas (909 vs 1,667, respectively).Conclusions: This study raises safety concerns about the risk of TB and influenza associated with ICS use in patients with COPD, which deserve further investigation.

Risk of mortality with concomitant use of tamoxifen and selective serotonin reuptake inhibitors: multi-database cohort study

Objective To compare differences in mortality between women concomitantly treated with tamoxifen and selective serotonin reuptake inhibitors (SSRIs) that are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) versus tamoxifen and other SSRIs. Design Population based cohort study. Setting Five US databases covering individuals enrolled in private and public health insurance programs from 1995 to 2013. Participants Two cohorts of women who started taking tamoxifen. In cohort 1, women started taking an SSRI during tamoxifen treatment. In cohort 2, women were already taking an SSRI when they started taking tamoxifen. Main outcome measures All cause mortality in each cohort in women taking SSRIs that are potent inhibitors of CYP2D6 (paroxetine, fluoxetine) versus other SSRIs. Propensity scores were used to match exposure groups in a variable ratio fashion. Results were measured separately for each cohort and combined hazard ratios calculated from Cox regression models across the two cohorts with random effects meta-analysis. Results There were 6067 and 8465 new users of tamoxifen in cohorts 1 and 2, respectively. Mean age was 55. A total of 991 and 1014 deaths occurred in cohorts 1 and 2 during a median follow-up of 2.2 (interquartile range 0.9-4.5) and 2.0 (0.8-3.9) years, respectively. The pooled hazard ratio for death for potent inhibitors (rate 58.6/1000 person years) compared with other SSRIs (rate 57.9/1000 person years) across cohorts 1 and 2 was 0.96 (95% confidence interval 0.88 to 1.06). Results were consistent across sensitivity analyses. Conclusion Concomitant use of tamoxifen and potent CYP2D6 inhibiting SSRIs versus other SSRIs was not associated with an increased risk of death.

Development and Validation of a Pharmacy-Based Comorbidity Measure in a Population-Based Automated Health Care Database

To develop the Pharmacy‐Based Disease Indicator (PBDI), and to evaluate its performance versus the diagnosis‐based Deyo version of the Charlson Index in predicting subsequent‐year hospitalization in adults.

Statins and the risk of liver injury: a population-based case-control study.

This case‐control study investigated the association between statin use and liver injury using Taiwans National Health Insurance Research Database.

Risk factors of ifosfamide-related encephalopathy in adult patients with cancer: A retrospective analysis.

BACKGROUND/PURPOSE Ifosfamide, a widely used chemotherapeutic agent, has been frequently associated with encephalopathy. A larger-scale study was conducted to identify risk factors of ifosfamide-related encephalopathy, including hepatic function. METHODS Adult patients who had completed at least one cycle of ifosfamide between January 2008 and December 2010 were included. Those with renal failure or liver failure were excluded. Data were collected through chart review. Patients with encephalopathy and patients without encephalopathy were compared on age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), baseline serum creatinine (SCr) level, albumin level, white blood cell count, liver function, brain metastasis, and dosage of ifosfamide. Chi-square test or Fishers exact test, Student t test, and univariate and multivariate logistic regressions were used for analysis. RESULTS This study enrolled 337 patients. Thirty-eight patients (11%) had ifosfamide-related encephalopathy. They had poorer ECOG PS; higher SCr level, white blood cell count, and aspartate aminotransferase level; and lower serum albumin level compared with patients without encephalopathy. Ifosfamide dosage, brain metastasis, and age were not significant risk factors. Multivariate analysis indicated that only ECOG PS, SCr level, and albumin level contributed significantly to the risk. CONCLUSION To date, this is the largest-scale study to have analyzed the risk factors of ifosfamide-related encephalopathy. This study confirms that an ECOG PS of 2-4 and increased SCr level are significant risk factors of ifosfamide-related encephalopathy, whereas increased albumin level decreases the risk, consistent with previous reports. Higher aspartate aminotransferase levels have no significant impact. In contrast to previous studies, ifosfamide dosage and brain metastasis are not significant contributing factors.

Comparative Cardiovascular and Cerebrovascular Safety of Inhaled Long-Acting Bronchodilators in Patients with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study.

Inhaled long‐acting bronchodilators are commonly used as maintenance therapy in chronic obstructive pulmonary disease (COPD). We compared the risk of cardiovascular and cerebrovascular events among patients with COPD treated with inhaled long‐acting bronchodilator monotherapy and combination therapy.

Comparing the risks of hospitalized heart failure associated with glinide, sulfonylurea, and acarbose use in type 2 diabetes: A nationwide study

BACKGROUND Increasing evidence suggests that certain newer anti-diabetic drugs are associated with an increased risk of hospitalized heart failure (HHF). However, the potential risks associated with the use of sulfonylurea and glinide have not been carefully evaluated. METHODS A retrospective cohort study using the Taiwan National Health Insurance claims database was conducted to examine the risks of HHF among newly diagnosed type 2 diabetic patients who initiated glinide, sulfonylurea, or acarbose therapy during 2006-2012. The outcome of interest was hospitalization due to heart failure after treatment initiation, defined by ICD-9-CM code. A Cox proportional hazard regression model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) using acarbose as the reference group. RESULTS A total of 25,638 glinide, 272,140 sulfonylurea, and 29,376 acarbose initiators were included in the analysis. Patients who initiated glinide had the highest crude HHF incidence. In the analysis adjusted for baseline differences, a significantly higher risk of HHF was found for glinide (adjusted HR, 1.53; 95% CI, 1.24-1.88), but not for sulfonylurea (adjusted HR, 0.94; 95% CI, 0.80-1.11), as compared with acarbose. The elevated risk remained consistent across different subgroups of patients as well as several sensitivity analyses including exploring the impact of potential unmeasured confounding. CONCLUSIONS These findings indicated that, as compared with acarbose, glinide may be associated with a higher risk of HHF for type 2 diabetic patients. Further researchis needed to fully evaluate the risks and benefits of glinide therapy relative to other oral anti-diabetic agents.