Propensity Score-matched Control Research Articles

Health Behaviors among Stroke Survivors in the United States: A Propensity Score-Matched Study

The American Heart Association/American Stroke Association has specific recommendations for secondary stroke prevention. The aim of this study was to compare health behaviors engagement between stroke survivors and propensity score-matched controls. We conducted a retrospective, cross-sectional, matched case-control study using data from the 2015 Behavioral Risk Factor Surveillance System (BRFSS) survey. We included older adults aged 50 or older who participated in the 2015 BRFSS survey and completed the interview. Each case was matched to 3 controls (1:3) based on propensity scores to increase the power of the analyses. Stroke survivors were compared with controls on their physical activity, smoking, alcohol use, body mass index (BMI), last flu immunization, last physical checkup, last blood cholesterol check, heavy drinking, and vegetable and fruit consumption. We used binomial logistic regression to assess health behaviors among stroke survivors compared with controls. The final study sample consisted of 13,249 stroke survivors and 39,747 controls without stroke after propensity score matching. Multivariable analyses revealed that there were significant differences between stroke survivors and matched controls in terms of BMI, physical activity, smoking status, alcohol consumption, and vegetable and fruit consumption. For example, stroke survivors were 51% more likely to be smokers (adjusted odds ratio [AOR] 1.51, 95% confidence interval [CI], 1.32-1.73) and 14% less likely to consume alcohol (AOR .86, 95% CI .78-.95). Findings from our study indicate that compared with propensity score-matched controls, stroke survivors engage in poorer health behaviors with the exception of alcohol consumption.

Metformin-associated Chemopreventive Effects on Recurrence After Hepatic Resection of Hepatocellular Carcinoma: From In Vitro to a Clinical Study

We investigated metformin-induced cytotoxic effects in vitro and assessed the chemopreventive effects of metformin in patients undergoing hepatic resection (HR) for hepatocellular carcinoma (HCC). This study consisted of laboratory and clinical studies. In vitro study using HCC cell lines revealed noticeable cytotoxic effects of metformin, that were largely weaker than those of sorafenib. In the clinical study, no statistical differences were found in tumor recurrence or overall survival between metformin and control groups. In contrast, there was a non-significant difference in tumor recurrence between metformin and propensity score-matched control groups, but there was a significant difference in overall patient survival. Metformin administration was an independent risk factor for patient survival. In conclusion, our in vitro laboratory study demonstrated the presence of cytotoxic effects of metformin. Metformin administration was associated with reduced tumor recurrence and helped induce significant improvements in overall patient survival in patients who underwent HR for HCC.

Efficacy and safety of endoscopic submucosal dissection for gastric neoplasms in patients with compensated liver cirrhosis: a propensity score–matched case-control study

The clinical outcomes of endoscopic submucosal dissection (ESD) for gastric neoplasms in liver cirrhosis patients have not been adequately reported, leading to clinician concerns about adverse events, including bleeding and the deterioration of liver function. We compared the efficacy and safety of ESD between cirrhosis and noncirrhosis patients. Between January 2005 and December 2014, 158 cirrhosis patients underwent ESD for gastric neoplasms at a tertiary medical institution. Their clinical outcomes were compared with those of a propensity score-matched control group (158 patients) selected from noncirrhosis patients, using age, sex, histology, tumor location, and lesion size as variables. En bloc resection (96.8%), curative resection (89.9%), and adverse event (bleeding [10.1%] and perforation [1.9%]) rates in the cirrhosis group did not differ significantly from those in the noncirrhosis group. The median procedure time (25.0 vs 23.0 minutes) was also comparable between the groups. In a survival analysis cirrhosis patients exhibited a significantly higher mortality risk than noncirrhosis patients (hazard ratio [HR], 3.52; 95% confidence interval [CI], 1.35-9.23; P= .01). Cirrhosis patients without hepatocellular carcinoma (HCC) showed no statistically significant difference in mortality compared with the noncirrhosis group (HR, 2.14; 95% CI, .72-6.39; P= .171). Three of 153 patients (2%) exhibited a deterioration of prognosis from Child-Pugh class A to B. In compensated cirrhosis patients, especially those without HCC, ESD for gastric epithelial neoplasms can be performed with safety and efficacy comparable with that in noncirrhosis patients, without deterioration in liver function.

A Comparison of Bleeding Complications in Patients Undergoing Percutaneous Renal Cryoablation Using Cryoprobes with and without Heat-Based Track Ablation

PurposeTo determine if the use of heat-based track ablation with new-generation cryoprobes is associated with decreased renal cryoablation bleeding complications. Materials and MethodsEighty-nine patients who underwent percutaneous cryoablation for treatment of a solitary renal mass with the use of cryoprobes with track ablation (CwTA) from October 29, 2015, to May 18, 2017, were compared with a propensity score–matched control group of 178 patients who underwent treatment with the use of cryoprobes without track ablation (Cw/oTA) from January 5, 2012, to October 28, 2015. Bleeding complications were assessed with the use of the Clavien-Dindo classification system and compared between the matched patient groups by means of conditional logistic regression, both univariately and in a multivariate model to adjust for imbalanced covariates. Change in patient hemoglobin was evaluated as a secondary measure of periprocedural bleeding. ResultsSeven of the 89 patients (7.9%) who underwent percutaneous renal cryoablation with the use of CwTA developed major (grade ≥3) bleeding complications, versus 13 of the 178 patients (7.3%) treated with the use of Cw/oTA. Conditional logistic regression analysis adjusted for potential confounders showed that major, minor, and overall bleeding complications were not associated with the type of cryoprobes used for treatment (P values .727, .370, and .733, respectively). There was also no significant difference in postprocedural change in hemoglobin for patients treated with the use of CwTA compared with Cw/oTA (P = .909). Furthermore, total duration of track ablation in patients with bleeding complications (mean 169 seconds, SD 68, range 60–240) was not significantly different than in patients without bleeding complications (mean 171 seconds, SD 86, range 30–360; P = .940). ConclusionsThe use of cryoprobes with heat-based track ablation did not decrease the incidence of bleeding complications after renal cryoablation compared with procedures performed without track ablation.

Digoxin and Mortality in Patients WithAtrial Fibrillation.

Digoxin is widely used in patients with atrial fibrillation (AF). The goal of this paper was to explore whether digoxin use was independently associated with increased mortality in patients with AF and if the association was modified by heart failure and/or serum digoxin concentration. The association between digoxin use and mortality was assessed in 17,897 patients by using a propensity score-adjusted analysis and in new digoxin users during the trial versus propensity score-matched control participants. Theauthors investigated the independent association between serum digoxin concentration and mortality after multivariable adjustment. At baseline, 5,824 (32.5%) patients were receiving digoxin. Baseline digoxin use was not associated with an increased risk of death (adjusted hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 0.96 to 1.23; p=0.19). However, patients with a serum digoxin concentration≥1.2ng/ml had a 56% increased hazard of mortality (adjusted HR: 1.56; 95%CI: 1.20to 2.04) compared with those not on digoxin. When analyzed as a continuous variable, serum digoxin concentration was associated with a 19% higher adjusted hazard of death for each 0.5-ng/ml increase (p=0.0010); these results were similar for patients with and without heart failure. Compared with propensity score-matched control participants, the risk of death (adjusted HR: 1.78; 95% CI: 1.37 to 2.31) and sudden death (adjusted HR: 2.14; 95% CI: 1.11 to 4.12) was significantly higher in new digoxinusers. In patients with AF taking digoxin, the risk of death was independently related to serum digoxin concentration and was highest in patients with concentrations≥1.2ng/ml. Initiating digoxin was independently associated with higher mortality in patients with AF, regardless of heart failure.

Bladder pain syndrome/interstitial cystitis is associated with asthma: A case-control study.

Although asthma and bladder pain syndrome/interstitial cystitis (BPS/IC) are considered to share similar pathophysiological pathways, the relationship between asthma and BPS/IC is uncertain. This case-control study aimed to investigate the relationship between prior asthma and BPS/IC using a large database in Taiwan. This study used data from the Taiwan Longitudinal Health Insurance Database 2005. We identified 500 female patients with BPS/IC as cases and 500 propensity score-matched females without BPS/IC as controls. We conducted logistic regressions to estimate the odds ratio (OR) and 95% confidence interval (CI) for prior asthma between cases and controls. Results indicated that 143 (14.30%) of the total sampled patients had received a prior diagnosis of asthma. Moreover, prior asthma was found in 86 (17.20%) cases and 57 (11.40%) controls. The OR of prior asthma for cases was 1.61 (95%CI: 1.13-2.32) compared to propensity score-matched controls. Additionally, the ORs of prior asthma for females with BPS/IC aged 18-59 and ≥60 years were 1.72 (95%CI: 1.11-2.69) and 1.40 (95%CI: 0.74-2.62), respectively, compared to controls. We concluded that prior asthma was significantly associated with BPS/IC in a female Taiwanese population.

Lung transplantation after allogeneic stem cell transplantation: a pan-European experience.

Late-onset noninfectious pulmonary complications (LONIPCs) affect 6% of allogeneic stem cell transplantation (SCT) recipients within 5 years, conferring subsequent 5-year survival of 50%. Lung transplantation is rarely performed in this setting due to concomitant extrapulmonary morbidity, excessive immunosuppression and concerns about recurring malignancy being considered contraindications. This study assesses survival in highly selected patients undergoing lung transplantation for LONIPCs after SCT.SCT patients undergoing lung transplantation at 20 European centres between 1996 and 2014 were included. Clinical data pre- and post-lung transplantation were reviewed. Propensity score-matched controls were generated from the Eurotransplant and Scandiatransplant registries. Kaplan-Meier survival analysis and Cox proportional hazard regression models evaluating predictors of graft loss were performed.Graft survival at 1, 3 and 5 years of 84%, 72% and 67%, respectively, among the 105 SCT patients proved comparable to controls (p=0.75). Sepsis accounted for 15 out of 37 deaths (41%), with prior mechanical ventilation (HR 6.9, 95% CI 1.0-46.7; p<0.001) the leading risk factor. No SCT-specific risk factors were identified. Recurring malignancy occurred in four patients (4%). Lung transplantation <2 years post-SCT increased all-cause 1-year mortality (HR 7.5, 95% CI 2.3-23.8; p=0.001).Lung transplantation outcomes following SCT were comparable to other end-stage diseases. Lung transplantation should be considered feasible in selected candidates. No SCT-specific factors influencing outcome were identified within this carefully selected patient cohort.

Absence of antitumor effects of metformin in sorafenib-treated patients with hepatocellular carcinoma recurrence after hepatic resection and liver transplantation.

Backgrounds/AimsHepatocellular carcinoma (HCC) recurrence following hepatic resection (HR) and liver transplantation (LT) remains a great concern. We assessed the antitumor effects of metformin in patients treated with sorafenib for HCC recurrence after HR or LT.MethodsThe two clinical retrospective studies involved metformin therapy of 304 HR patients and 74 LT recipients who were treated with sorafenib.ResultsIn the study involving patients who had undergone HR, death occurred in 245 of the 304 patients (80.6%) during a median follow-up of 10.2 months after sorafenib administration. The metformin HR group (group 1; n=40) showed no prognostic difference in progression-free and overall survival rates compared with the all-HR control group (group 3; n=241) and propensity score-matched HR control group (group 4; n=80). In the clinical study of recipients exposed to LT, death occurred in 62 of the 74 patients (83.8%) during a median follow-up of 13.6 months (range: 3–76 months) after sorafenib administration. The metformin LT group (group 5; n=14) showed no prognostic difference in progression-free and overall survival rates compared with the all-LT control group (group 7; n=43) and propensity score-matched LT control group (group 8; n=28).ConclusionsOur clinical studies demonstrated absence of synergistic antitumor effects of metformin. Further high-volume studies are necessary to assess the role of metformin in patients treated with sorafenib for advanced HCC.

Generation of student interest in an inquiry-based mobile learning environment

A declining trend in adolescents’ interest in science learning and attitudes towards science-related careers has been reported during recent years. There has been a call for more motivating learning environments that inspire students to develop interest towards science. This study examines students’ interest development in STEM subjects in an ecologically valid setting during one school year and how features of the learning environment affect students’ generation of interest. In a quasi-experimental study design, one class of 7th grade (aged 12 to 13 years) students (N = 18) studied in an inquiry-based mobile learning environment that had a special emphasis on integrated curriculum. Interest variables were measured three times and focus group interviews were held twice during the school year. From a group of 113 students studying in an ordinary learning setting, a propensity score-matched control group of 18 students was selected based on general self-efficacy, intrinsic goal orientation, interest in technology, and web-user self-efficacy. Results from the quantitative analyses revealed only minor differences between the two groups. Results from the qualitative analyses indicate that students found the new environment to be interest generating, thus ascribing to the general idea and aim of the new environment, but also that the implementation was in many cases far from ideal, indicating that much of its potential was unrealized.

Migraine and risk of narcolepsy in children: A nationwide longitudinal study.

BackgroundThe association between migraine and narcolepsy remains controversial. We aim to investigate whether migraine is associated with an increased risk of developing narcolepsy in children.MethodsIn this longitudinal study, nationwide medical-claims data of pediatric patients (0-17y) with migraine are identified using the National Health Insurance Research Database (NHIRD) between 1997 and 2010 in Taiwan. Two cohorts are selected: migraine cases (n = 8,923) and propensity score-matched non-migraine controls (n = 35,692). Children with previous history of narcolepsy or headache before the index date are excluded. Cohorts are followed until the end of 2012, their withdrawal from the NHI program, or incidence of narcolepsy (ICD-9-CM: 347). Cox proportional hazards regression models are used to estimate hazard ratios (HRs) and 95% confidence intervals of developing narcolepsy in children with migraine compared to their non-migraine controls.ResultsA total of 13 incident cases with narcolepsy are observed during follow-up, with incidence rates of 0.1915 and 0.0278 per 1,000 person-years in migraine and non-migraine children, respectively. After a mean follow-up period of 4.68 and 5.04 years in the case and control cohort, respectively, the former exhibited a greater risk of developing narcolepsy compared to the latter (adjusted hazard ratio (aHR) = 5.30, 95% confidence interval (CI): 1.61, 17.4; p = 0.006). This finding persisted after controlling for potential confounders like baseline comorbidities and concurrent medication uptake, and in our analyses with migraine subtypes.ConclusionsMigraine is an independent risk factor for narcolepsy development in children. Further studies are needed to validate our findings and to explore the exact pathophysiological mechanisms linking migraine and narcolepsy.

Healthcare utilization and costs among patients with herpes zoster and solid tumor malignancy on chemotherapy: A retrospective cohort study.

Immunosuppressed patients with solid tumor malignancies (STMs) are particularly vulnerable to herpes zoster (HZ). This study estimated the incidence of HZ and evaluated healthcare resource utilization and costs for persons with STM receiving chemotherapy with and without incident HZ.We conducted a retrospective claims study of adults with STM receiving chemotherapy between January 1, 2010 and June 30, 2014. Patients were followed from their first chemotherapy date through development of HZ, health plan disenrollment, the study end date, or 24 months. HZ incidence was calculated and stratified by patient characteristics. Adjusted HZ incidence was estimated using Poisson regression. Healthcare resource utilization and costs were compared between patients with HZ (cases) and propensity score-matched controls without HZ during a variable follow-up period. Adjusted healthcare costs were estimated using Lin regression to control for informative censoring.Of 155,480 patients with STM receiving chemotherapy, 3100 (2.0%) developed HZ, yielding an adjusted HZ incidence rate of 13.8/1000 person-years (PY). HZ cases (n = 3004) had significantly higher healthcare resource utilization than matched controls (n = 15,020). Adjusted annual costs were $48,077 for cases vs $41,645 for matched controls, corresponding to a differential cost of $6432 annually.After adjustment for potential confounders, patients with STM receiving chemotherapy had an HZ incidence of 13.8/1000 PY; those who developed HZ used more healthcare resources and incurred higher costs than those who did not. These findings suggest that HZ prevention by vaccination could improve outcomes and reduce costs in this population.

Attributable Cost of Clostridium difficile Infection in Pediatric Patients.

OBJECTIVES The attributable cost of Clostridium difficile infection (CDI) in children is unknown. We sought to determine a national estimate of attributable cost and length of stay (LOS) of CDI occurring during hospitalization in children. DESIGN AND METHODS We analyzed discharge records of patients between 2 and 18 years of age from the Agency for Healthcare Research and Quality (AHRQ) Kids' Inpatient Database. We created a logistic regression model to predict CDI during hospitalization based on demographic and clinical characteristics. Predicted probabilities from the logistic regression model were then used as propensity scores to match 1:2 CDI to non-CDI cases. Charges were converted to costs and compared between patients with CDI and propensity-score-matched controls. In a sensitivity analysis, we adjusted for LOS as a confounder by including it in both the propensity score and a generalized linear model predicting cost. RESULTS We identified 8,527 pediatric hospitalizations (0.53%) with a diagnosis of CDI and 1,597,513 discharges without CDI. In our matched cohorts, the attributable cost of CDI occurring during a hospitalization ranged from $1,917 to $8,317, depending on whether model was adjusted for LOS. When not adjusting for LOS, CDI-associated hospitalizations cost 1.6 times more than non-CDI associated hospitalizations. Attributable LOS of CDI was approximately 4 days. CONCLUSIONS Clostridium difficile infection in hospitalized children is associated with an economic burden similar to adult estimates. This finding supports a continued focus on preventing CDI in children as a priority. Pediatric CDI cost analyses should account for LOS as an important confounder of cost. Infect Control Hosp Epidemiol 2017;38:1472-1477.

Antidepressant Exposure During Pregnancy and Risk of Autism in the Offspring, 2: Do the New Studies Add Anything New?

During the past year, at least 5 new studies, all observational in design, examined the risk of autism spectrum disorder (ASD) in children exposed to antidepressant medication in utero. These studies had not found inclusion in the many systematic reviews and meta-analyses that had also been published in the past year. Noteworthy methods and findings of the new studies are summarized. One of these studies is examined in detail to help the reader understand methodological and conceptual issues that are critical in the field. Some general caveats in the interpretation of the literature are also discussed. In order to reduce the limitations associated with their observational design, the new studies used many innovations, including maternal controls with mental illness, propensity score-matched controls, preconception antidepressant exposure controls, sibling controls, paternal antidepressant user controls, and modeling for the presence of an unknown confound. Two studies found an association between maternal antidepressant use during pregnancy and the risk of ASD in the offspring; these associations remained statistically significant even after covariate adjustments. The other 3 studies found that the significant association between antidepressant exposure and ASD risk was lost after statistical adjustment; that preconception antidepressant exposure was also associated with increased risk of ASD; that siblings discordant for antidepressant exposure had similar ASD risk; and that paternal antidepressant use was also associated with increased risk. The new studies do not change the conclusions of the available meta-analyses. In fact, at least some of the new data strengthen the conclusion that antidepressant use during pregnancy is likely to be a marker of more severe illness and that inadequately measured, unmeasured, or unknown genetic, behavioral, and environmental confounds associated with more severe illness (rather than the antidepressant exposure by itself) may be responsible for the increased risk of ASD.

Association between malignancies and Marfan syndrome: a population-based, nested case–control study in Taiwan

ObjectiveMarfan syndrome (MFS) involves a deficiency of the structural extracellular matrix component fibrillin-1 and overactivation of the transforming growth factor-β (TGF-β) signalling pathway. The TGF-β signalling pathway also actively participates...

Cholera Vaccine Use Is Associated With a Reduced Risk of Death in Patients With Colorectal Cancer: A Population-Based Study

Cholera toxin can act as a modulator of the immune response with anti-inflammatory effects; it reduces development of colon polyps in mouse models of colorectal cancer (CRC). We performed a population-based study to determine whether, in patients with a diagnosis of CRC, subsequent administration of the cholera vaccine (killed Vibrio cholerae O1 whole cells and recombinant cholera toxin B subunit) affects mortality. We identified patients from the Swedish Cancer Register who were diagnosed with CRC from July 2005 through December 2012. These patients were linked to the Swedish Prescribed Drug Register toretrieve cholera vaccine use. We used Cox regression analysis to calculate the hazard ratio (HR) of death from CRC and overall mortality in patients with post-diagnostic use of cholera vaccine compared with matched controls. A total of 175 patients were diagnosed with CRC and given a prescription for the cholera vaccine after their cancer diagnosis. Compared with propensity score-matched controls and adjusted for confounding factors, patients with CRC whoreceived the cholera vaccine had a decreased risk of death from CRC (HR, 0.53; 95% CI, 0.29-0.99) and a decreased risk of death overall (HR, 0.59; 95% CI, 0.37-0.94). The decrease in mortality with cholera vaccination was largely observed, irrespective of patient age or tumor stage at diagnosis or sex. In a population-based study, we associated administration of the cholera vaccine after CRC diagnosis withdecreased risk of death from CRC and overall mortality.

Effect of Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir and Ledipasvir/Sofosbuvir Regimens on Survival Compared With Untreated Hepatitis C Virus-Infected Persons: Results From ERCHIVES.

Interferon-based regimens are associated with a substantial survival benefit for persons infected with hepatitis C virus (HCV). Survival data with direct-acting antiviral agents are not available. We conducted this study to quantify the effect of paritaprevir/ritonavir, ombitasvir, dasabuvir (PrOD) and ledipasvir/sofosbuvir (LDV/SOF) regimens upon mortality. In the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well-established national cohort of HCV-infected Veterans, we identified HCV-infected persons initiated on PrOD or LDV/SOF, excluding those with human immunodeficiency virus, hepatitis B surface antigen positivity, hepatocellular carcinoma, or missing HCV RNA or FIB-4 scores. For each case, we identified a propensity score-matched control never initiated on treatment. Primary outcome was survival. Outcomes were assessed using frequency of events, Kaplan-Meier curves, and Cox proportional hazards regression analyses. We identified 1473 persons on PrOD, 5497 on LDV/SOF, and 6970 propensity score-matched untreated persons. Treated persons were more likely to be obese and have cirrhosis, but less likely to have stage 3-5 chronic kidney disease (CKD), alcohol or drug abuse or dependence diagnosis, and anemia. The proportion of persons who died was higher in the untreated group compared with either treatment group (PrOD, 0.3%; LDV/SOF, 1.4%; untreated controls, 2.5%; P < .001). A significantly larger percentage of treated patients survived to 18 months of follow-up, compared with untreated controls (P < .001). In multivariable Cox regression analysis, treatment with either regimen (hazard ratio [HR], 0.43; 95% confidence interval [CI], .33-.57) and attainment of sustained virologic response (SVR) were associated with significantly lower mortality (HR, 0.57; 95% CI, .33-.99). Treatment with PrOD or LDV/SOF and SVR are associated with a significant mortality benefit, apparent within the first 18 months of treatment.

Insurance Transitions and Changes in Physician and Emergency Department Utilization: An Observational Study.

Shopping for health insurance is encouraged as a way to find the most affordable coverage that best meets an enrollee's needs. However, the extent to which individuals switch insurance and subsequent changes in health care utilization that might arise, particularly new physician visits, are not well understood. To examine the relationship between insurance switching and new physician and emergency department visits around the time of a switch. Observational study using a difference-in-differences design to compare those switching insurance carriers with propensity score-matched controls who did not switch, stratified based on whether individuals initially had private or Medicaid insurance coverage. All analyses adjusted for individual and insurance characteristics. Continuously insured, non-elderly individuals with private or Medicaid insurance coverage in Massachusetts from 2010 to 2013. Rates of new primary care and specialist physician visits, as well as rates of emergency department visits. Before matching, among 1,628,057 continuously insured individuals, 418,231 (26%) switched insurance carriers during a 2-year period. Characteristics of switchers and non-switchers were similar after matching (n=316,343 in each group). After matching, switching plans was associated with a 203% and 47.5% increase in the rate of new primary care physician visits following switching for those initially with Medicaid or private coverage, respectively (both p<0.001), with a large short-term increase, diminishing over time. Among those with Medicaid coverage, switching was associated with a 14.9% higher rate of ED visits during the month of switching (p<0.001), but otherwise decreased modestly after switching. Insurance switching is common, and is associated with increased new physician visits and temporarily increased ED use among the publicly insured. As insurance markets become more volatile in the current policy environment, understanding changes in utilization after insurance switching may become increasingly important.

Proton-Pump Inhibitor Use and the Risk of First-Time Ischemic Stroke in the General Population: A Nationwide Population-Based Study.

An increased risk of adverse cardiovascular events was reported for concomitant use of proton-pump inhibitors (PPIs) in patients taking antiplatelet agents. The present study aimed at determining whether PPI use alone could be associated with first-time ischemic stroke. This was a retrospective nationwide study using database from Taiwan National Health Insurance and involved subjects aged ≥20 years. In propensity score-matched analysis, patients with current PPI use were compared with propensity score-matched PPI non-use controls at a 1:1 ratio. Patients with prior stroke or hospitalization before the index date were excluded. The primary outcome measure was hospitalization with a primary diagnosis of ischemic stroke during 120-day follow-up. A parallel analysis adopting a nested case-control design was carried out. Patients hospitalized for a first-time ischemic stroke were identified and were compared with matched controls using conditional logistic regression analyses focusing on PPI use before the index date. The propensity score-matched analysis included 198,148 PPI treatment courses and control periods without PPI use. PPI use was associated with a higher risk of hospitalization due to ischemic stroke with a hazard ratio of 1.36 (95% confidence interval (CI) 1.14-1.620, P=0.001). Based on subgroup analysis, patients aged <60 years were more susceptible (P=0.043 for interaction), whereas gender, history myocardial infarction, diabetes mellitus, hypertension, use of antiplatelet agents of non-steroidal anti-inflammatory drugs, or type of PPIs had no effect on the risk. In the nested case-control analysis, 15,378 patients hospitalized owing to ischemic stroke were identified and were compared with 15,378 matched controls. An association between PPI use and increased cerebrovascular risks was identified, and the adjusted odds ratios for PPI use were 1.77 (95% CI 1.45-2.18, P<0.001) within 30 days, 1.65 (95% CI 1.31-2.08, P<0.001) between 31 and 90 days, and 1.28 (95% CI 1.03-1.59, P=0.025) between 91 and 180 days before the onset of first-time ischemic stroke. PPI use is associated with an increased risk of first-time ischemic stroke in the general population, and the risk is independent of antiplatelet agents. However, caution should be exercised when considering its clinical relevance as the magnitude of association was modest and a cause-and-effect relationship remained to be established.

Correction: Adverse Outcomes after Non-Chest Surgeries in Patients with Pulmonary Tuberculosis: A Nationwide Study.

[This corrects the article DOI: 10.1371/journal.pone.0133064.].

Predictors and prognostic significance of atrial fibrillation developed during dobutamine stress echocardiography: Apropensity score-matched comparison.

Atrial fibrillation (AF) uncommonly occurs during dobutamine stress echocardiography (DSE). We aimed to characterize the predictors and long-term prognostic significance of AF during DSE. The clinical, echocardiographic, and outcome data of patients in sinus rhythm who developed AF during DSE were reviewed and compared to a propensity score-matched group of controls. Atrial fibrillation developed in 73 (1% of 7026) patients (age 70±10years, 58% men). Compared to 144 propensity score-matched controls without AF during DSE, those with AF were more likely to have had history of prior AF (23% vs 8%, P=.002), known coronary artery disease (CAD; 22% vs 10%, P=.037), enlarged left ventricle (LV; 27% vs 9%, P=.002), LV wall-motion abnormality (33% vs 12%, P<.0001), enlarged aortic root (22% vs 8%, P=.009), or dilated left atrium (52% vs 30%, P=.002). Multivariate logistic regression analysis identified prior history of AF (OR=3.7, 95% CI 1.5-9.0, P=.005), larger LV size (OR=3.1, 95% CI 1.3-7.3, P=.009), and lower LV ejection fraction (OR=-0.95, 95% CI -0.92 to -0.99, P=.02) as independent predictors of AF during DSE. At a mean follow-up period of 3.4 (0.5-7.3)years, those with AF during DSE were more likely to develop new coronary events (22% vs 10%, P=.0372), new-onset heart failure (19% vs 4%, P=.0003), or die from any cause (27% vs 6%, P<.0001). Kaplan-Meier curves demonstrated significantly lower event-free survival in patients compared to controls (P by log-rank test=.001) over the follow-up period. Dobutamine-induced AF occurs more commonly in those with prior history of AF and remodeled LV and is associated with unfavorable outcomes.