Shih-Hao Lee

Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone

IMPORTANCE Fluoroquinolones have been associated with collagen degradation, raising safety concerns related to more serious collagen disorders with use of these antibiotics, including aortic aneurysm and dissection. OBJECTIVE To examine the relationship between fluoroquinolone therapy and the risk of developing aortic aneurysm and dissection. DESIGN, SETTING, AND PARTICIPANTS We conducted a nested case-control analysis of 1477 case patients and 147 700 matched control cases from Taiwans National Health Insurance Research Database (NHIRD) from among 1 million individuals longitudinally observed from January 2000 through December 2011. Cases patients were defined as those hospitalized for aortic aneurysm or dissection. One hundred control patients were matched for each case based on age and sex. EXPOSURES Current, past, or any prior-year use of fluoroquinolone. Current use was defined as a filled fluoroquinolone prescription within 60 days of the aortic aneurysm or dissection; past use refers to a filled fluoroquinolone prescription between 61 and 365 days prior to the aortic aneurysm; and any prior-year use refers to having a fluoroquinolone prescription filled for 3 or more days any time during the 1-year period before the aortic aneurysm or dissection. MAIN OUTCOMES AND MEASURES Risk of developing aortic aneurysm or dissection. RESULTS A total of 1477 individuals who experienced aortic aneurysm or dissection were matched to 147 700 controls. After propensity score adjustment, current use of fluoroquinolones was found to be associated with increased risk for aortic aneurysm or dissection (rate ratio [RR], 2.43; 95% CI, 1.83-3.22), as was past use, although this risk was attenuated (RR, 1.48; 95% CI, 1.18-1.86). Sensitivity analysis focusing on aortic aneurysm and dissection requiring surgery also demonstrated an increased risk associated with current fluoroquinolone use, but the increase was not statistically significant (propensity score-adjusted RR, 2.15; 95% CI, 0.97-4.60). CONCLUSIONS AND RELEVANCE Use of fluoroquinolones was associated with an increased risk of aortic aneurysm and dissection. While these were rare events, physicians should be aware of this possible drug safety risk associated with fluoroquinolone therapy.

Statin treatment is associated with a decreased risk of active tuberculosis: an analysis of a nationally representative cohort

Background Epidemiological data suggest that statins improve the clinical outcome of respiratory infections. We sought to examine whether statin therapy decreases the risk of active TB. Methods We conducted a nested case-control study on data obtained from a national health insurance claims database between 1999 and 2011. The use of statins was classified as current, recent, past or chronic use. Three conditional logistic regression models were used to estimate the incidence rate ratios (RRs). The first assessed the effect of statin use without further adjustment; the second adjusted (individually) for 75 potential confounders; and the third adjusted for the Disease Risk Score (DRS). Results A total of 8098 new TB cases and 809 800 control patients were examined. All four types of statin users showed a decreased risk of active TB. Chronic use (>90 days in a calendar year) of statins was associated with the lowest unadjusted risk of TB (RR 0.74; 95% CI 0.63 to 0.87). The protective effect of active TB remained after adjusting for individual confounders (RR 0.66; 95% CI 0.56 to 0.78) and after DRS adjustment (RR 0.62; 95% CI 0.53 to 0.72). The effect estimates obtained for chronic and current use of statins were very similar. We also found that the active TB protection increased with increasing length of statin prescription. Conclusions We found that statin therapy was associated with a decreased risk of active TB, and the length of statin therapy affected the TB protection. Given the observational nature of this study, the protective effect against active TB must be confirmed in future randomised trials.

A comparison of vasopressin, terlipressin, and lactated ringers for resuscitation of uncontrolled hemorrhagic shock in an animal model.

Aim The aim of this study is to compare the effect of lactated ringer (LR), vasopressin (Vaso) or terlipressin (Terli) on uncontrolled hemorrhagic shock (UHS) in rats. Methods 48 rats were divided into four treatment groups for UHS study. Vaso group was given bolus vasopressin (0.8 U/kg); the Terli group was given bolus terlipressin (15 mcg/kg); LR group was given LR and the sham group was not given anything. Mean arterial pressure (MAP), serum lactate level, plasma cytokine levels, lung injury and mortality are investigated for these different treatment groups. Results Compared with LR group, vasopressin and terlipressin-treated groups were associated with higher MAP, lowered mortality rates, less lung injury, lowered serum lactate level, less proinflammatory and more anti-inflammatory cytokine production at certain time points. Comparing between vasopressin and terlipressin treated groups, there is no statistical difference in mortality rates, lung injury, serum lactate level and cytokine level. However, there is a difference in the length of time in maintaining a restored level of MAP (80 to 110 mmHg). The terlipressin treated rats can maintain this restored level of MAP for 45 minutes, but the vasopressin treated rats can only maintain this restored level of MAP for 5 minutes before decreasing gradually to the MAP observed in LR group (40 mmHg). Conclusion Early optimization of hemodynamics with terlipressin or vasopressin in an animal model of UHS was associated with improved hemodynamics and inflammatory cytokine profile than the LR control. Compared with vasopressin, terlipressin has the advantage of ease of use and sustained effects.

Trends and Outcomes of Surgical Treatment for Colorectal Cancer between 2004 and 2012- an Analysis using National Inpatient Database

Limited data are available for the epidemiology and outcome of colorectal cancer in relation to the three main surgical treatment modalities (open, laparoscopic and robotic). Using the US National Inpatient Sample database from 2004 to 2012, we identified 1,265,684 hospitalized colorectal cancer patients. Over the 9 year period, there was a 13.5% decrease in the number of hospital admissions and a 43.5% decrease in in-hospital mortality. Comparing the trend of surgical modalities, there was a 35.4% decrease in open surgeries, a 3.5 fold increase in laparoscopic surgeries, and a 41.3 fold increase in robotic surgeries. Nonetheless, in 2012, open surgery still remained the preferred surgical treatment modality (65.4%), followed by laparoscopic (31.2%) and robotic surgeries (3.4%). Laparoscopic and robotic surgeries were associated with lower in-hospital mortality, fewer complications, and shorter length of stays, which might be explained by the elective nature of surgery and earlier tumor grades. After excluding patients with advanced tumor grades, laparoscopic surgery was still associated with better outcomes and lower costs than open surgery. On the contrary, robotic surgery was associated with the highest costs, without substantial outcome benefits over laparoscopic surgery. More studies are required to clarify the cost-effectiveness of robotic surgery.

Risk of skin ulcerations associated with oral nicorandil therapy: a population-based study

Although healthcare products regulatory agencies have issued warnings on risk of ulceration associated with the use of nicorandil, a population‐based study has not been carried out.

Comparative effectiveness of different oral antibiotics regimens for treatment of urinary tract infection in outpatients: an analysis of national representative claims database.

AbstractThere are very limited data on the postmarketing outcome comparison of different guideline antibiotic regimens for patients with urinary tract infections (UTIs).We carried out a population-based comparative effectiveness study from year 2000 through 2009, using the administrative data of 2 million patients from the National Health Informatics Project of Taiwan. Treatment failure was defined as either hospitalization or emergency department visits for UTI. Odd ratios were computed using conditional logistic regression models matched on propensity score.We identified 73,675 individuals with UTI, of whom 54,796 (74.4%) received trimethoprim–sulfamethoxazole (TMP-SMX), 4184 (5.7%) received ciprofloxacin, 3142 (4.3%) received levofloxacin, 5984 (8.1%) received ofloxacin, and 5569 (7.6%) received norfloxacin. Compared with TMP-SMX, the composite treatment failure was significantly lowered for norfloxacin in propensity score (PS) matching analyses (OR, 0.73; 95% CI, 0.54–0.99). Both norfloxacin (PS-matched OR, 0.68; 95% CI, 0.47–0.98) and ofloxacin (PS-matched OR, 0.70; 95% CI, 0.49–0.99) had significantly lowered composite treatment failure rate when compared with ciprofloxacin. Subgroup analysis suggested that both norfloxacin and ofloxacin were more effective in female patients without complications (W/O indwelling catheters, W/O bedridden status and W/O spinal cord injury), when compared with either TMP-SMX or ciprofloxacin.Among outpatients receiving oral fluoroquinolone therapy for UTIs, there was evidence of superiority of norfloxacin or ofloxacin over ciprofloxacin or TMP-SMX in terms of treatment failure. Given the observational nature of this study and regional difference in antibiotic resistance patterns, more studies are required to validate our results.

Risk of incident active tuberculosis and use of corticosteroids.

OBJECTIVE To examine the association between corticosteroid use and risk of active tuberculosis (TB) disease. METHODS We conducted a population-based nested case-control study based on Taiwans National Health Insurance Research Database between January 1999 and December 2011. Each case of incident active TB was matched to 100 controls using a risk-set sampling scheme. RESULTS From a participant cohort of 1 million, 6229 cases of new active TB and 622,900 controls were identified. Current, recent, past, ever and chronic use of corticosteroids were associated with an increased risk of developing incident active TB, with adjusted rate ratios of respectively 2.76 (95%CI 2.44-3.11), 1.99 (95%CI 1.73-2.31), 1.17 (95%CI 1.06-1.29), 1.60 (95%CI 1.49-1.72), and 1.58 (95%CI 1.43-1.75). For subgroup analysis, the increased risk of TB in chronic corticosteroids users was substantially higher in subjects aged ≤70 years and female subjects. CONCLUSION In this relatively high TB prevalence setting, we found that use of corticosteroids was associated with an increased risk of TB. Current use of corticosteroids was associated with the highest risk of TB.

Use of nicorandil is Associated with Increased Risk for Gastrointestinal Ulceration and Perforation- A Nationally Representative Population-based study

Nicorandil is a vasodilatory drug used to relieve angina symptoms. Several healthcare products regulatory agencies have issued a warning associating the use of nicorandil and gastrointestinal (GI) ulceration. We aimed to evaluate the association between use of nicorandil and GI ulceration/perforation. A population-based cohort study involving 1 million randomly sampled participants in Taiwan’s National Health Insurance Research Database was carried out. We estimated the association between use of nicorandil and GI ulceration/perforation by a Cox proportional hazards regression model. A nicorandil-specific propensity score (PS) was also created for adjustment of 75 covariates and matching. 25.8% (183/710) of nicorandil-treated patients developed new GI ulcer events and 1.6% (20/1254) developed new GI perforation events in the three-year follow-up period, as compared to 9.3% (61,281/659,081) and 0.3% (2,488/770,537) in the general population comparator cohort. Patients treated with nicorandil were at significantly increased risk of GI ulcer (PS adjusted hazard ratio 1.43, 95% CI, 1.23 to 1.65, 6848 excess cases per 100,000 person years) or GI perforation (aHR 1.60, 95% CI 1.02–2.51, 315 excess cases per 100,000 person years) compared with the nicorandil unexposed population. Our finding may warn the clinicians to weigh the overall risk-benefit balance of nicorandil treatment in patients.

Comparative Treatment Failure Rates of Respiratory Fluoroquinolones or β-Lactam + Macrolide Versus β-Lactam Alone in the Treatment for Community-Acquired Pneumonia in Adult Outpatients: An Analysis of a Nationally Representative Claims Database

AbstractNo comparative effectiveness study has been conducted for the following 3 antibiotics: respiratory fluoroquinolone, &bgr;-lactam, and &bgr;-lactam + advanced macrolide. To gain insights into the real-world clinical effectiveness of these antibiotics for community-acquired pneumonia in adult outpatients, our study investigated the treatment failure rates in 2 million representative participants from the National Health Informatics Project (NHIP) of Taiwan.A new-user cohort design was used to follow NHIP participants from January 2000 until December 2009. Treatment failure was defined by either one of the following events: a second antibiotic prescription, hospitalization due to CAP, an emergency department visit with a diagnosis of CAP, or 30-day nonaccident-related mortality.From 2006 to 2009, we identified 9256 newly diagnosed CAP outpatients, 1602 of whom were prescribed levofloxacin, 2100 were prescribed moxifloxacin, 5049 were prescribed &bgr;-lactam alone, and 505 were prescribed advanced macrolide + &bgr;-lactam. Compared with the &bgr;-lactam-based regimen, the propensity score-matched odds ratio for composite treatment failure was 0.81 (95% CI, 0.67–0.97) for moxifloxacin, 1.10 (95% CI, 0.90–1.35) for levofloxacin, and 0.95 (95% CI, 0.67–1.35) for macrolide +&bgr;-lactam.Moxifloxacin was associated with lower treatment failure rates compared with &bgr;-lactam alone, or levofloxacin in Taiwanese CAP outpatients. However, due to inherent limitations in our claims database, more randomized controlled trials are required before coming to a conclusion on which antibiotic is more effective for Taiwanese CAP outpatients. More population-based comparative effectiveness studies are also encouraged and should be considered as an integral piece of evidence in local CAP treatment guidelines.

Angiotensin-Converting Enzyme Inhibitors and Active Tuberculosis: A Population-Based Study

AbstractNumerous epidemiological data suggest that the use of angiotensin-converting enzyme inhibitors (ACEis) can improve the clinical outcomes of pneumonia. Tuberculosis (TB) is an airborne bacteria like pneumonia, and we aimed to find out whether the use of ACEis can decrease the risk of active TB.We conducted a nested case–control analysis by using a 1 million longitudinally followed cohort, from Taiwan national health insurance research database. The rate ratios (RRs) for TB were estimated by conditional logistic regression, and adjusted using a TB-specific disease risk score (DRS) with 71 TB-related covariates.From January, 1997 to December, 2011, a total of 75,536 users of ACEis, and 7720 cases of new active TB were identified. Current use (DRS adjusted RR, 0.87 [95% CI, 0.78–0.97]), but not recent and past use of ACEis, was associated with a decrease in risk of active TB. Interestingly, it was found that chronic use (>90 days) of ACEis was associated with a further decrease in the risk of TB (aRR, 0.74, [95% CI, 0.66–0.83]). There was also a duration response effect, correlating decrease in TB risk with longer duration of ACEis use. The decrease in TB risk was also consistent across all patient subgroups (age, sex, heart failure, cerebrovascular diseases, myocardial infraction, renal diseases, and diabetes) and patients receiving other cardiovascular medicine.In this large population-based study, we found that subjects with recent and chronic use of ACEis were associated with decrease in TB risk.