Comparison of active tuberculosis occurrence associated with Janus kinase inhibitors and biological DMARDs in rheumatoid arthritis.

OBJECTIVES: This study aimed to evaluate the risk of tuberculosis associated with the use of Janus kinase (JAK) inhibitors or biological disease-modifying antirheumatic drugs (bDMARDs) in patients diagnosed with rheumatoid arthritis (RA) in South Korea. METHODS: In this nationwide matched-cohort study, we retrospectively identified adult patients with new-onset RA from the National Health Insurance Service database who were prescribed bDMARDs or JAK inhibitors and recently underwent latent tuberculosis infection (LTBI) screening during 2012‒2021, and followed them up until the end of 2022 for the development of active tuberculosis. HRs were estimated using Cox proportional hazards regression in a propensity score-matched cohort. RESULTS: Among 16 760 matched patients with RA (3352 JAK inhibitor users and 13 408 bDMARD users), 18.8% received tuberculosis preventive therapy for LTBI. Overall, JAK inhibitor users had a significantly lower risk of tuberculosis than bDMARD users (HR (95% CI)=0.37 (0.22 to 0.62)). Among the patients treated for LTBI, patients with low treatment adherence had a significantly higher risk than those without LTBI (HR (95% CI)=2.78 (1.74 to 4.44)). Patients without LTBI and using JAK inhibitors had a significantly lower risk of tuberculosis across all ages and sexes compared with bDMARD users. CONCLUSION: Patients with RA using JAK inhibitors have a significantly lower risk of active tuberculosis than bDMARD users in South Korea; however, patients with RA having LTBI are equally at risk regardless of the treatment received (JAK inhibitor vs bDMARD). Therefore, vigilant tuberculosis monitoring, especially in patients with low adherence to tuberculosis preventive therapy, is essential.

A population-based cohort study of longitudinal change of high-density lipoprotein cholesterol impact on gastrointestinal cancer risk.

High-density Lipoprotein Cholesterol (HDL-C) levels have been associated with cancer. In this observational population-based cohort study using data from the Korean National Health Insurance Service system, we investigate the impact of longitudinal changes in HDL-C levels on gastrointestinal cancer risk. Individuals who underwent health examinations in 2010 and 2014 were followed-up through 2021. Among 3.131 million, 40696 gastric, 35707 colorectal, 21309 liver, 11532 pancreatic, 4225 gallbladder, and 7051 biliary cancers are newly detected. The persistent low HDL-C group increases the risk of gastric, liver, and biliary cancer comparing to persistent normal HDL-C group. HDL-C change from normal to low level increases the risk for gastric, colorectal, liver, pancreatic, gallbladder, and biliary cancers. Effects of HDL-C change on the gastrointestinal cancer risk are also modified by sex and smoking status. HDL-C changes affect the gastric and gallbladder cancer risk in age ≥60 years and the pancreatic and biliary cancer risk in age <60 years. Here, we show persistently low HDL-C and normal-to-low HDL-C change increase gastrointestinal cancer risk with discrepancies by sex, smoking status, and age.

Factor modification in the association between high-density lipoprotein cholesterol and liver cancer risk in a nationwide cohort.

BACKGROUND/AIMS: The effect modification by smoking and menopausal status in the association between high-density lipoprotein cholesterol (HDL-C) and liver cancer risk has not been reported. METHODS: This population-based cohort study included 4.486 million cancer-free individuals among those who underwent national cancer screening in 2010 and were followed up until December 2017. We conducted analyses in populations that excluded people with chronic hepatitis B, chronic hepatitis C and liver cirrhosis (Model I) and that included those diseases (Model III). HDL-C level was classified into eight groups at 10-mg/dL intervals. Liver cancer risk by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: During follow-up, 18 795 liver cancers in Model I and 20 610 liver cancers in Model III developed. In Model I, low HDL-C levels (aHR 1.83; 95% CI 1.65-2.04) and extremely high HDL-C levels (aHR 1.24; 95% CI 1.10-1.40) were associated with an increased liver cancer risk compared with a moderate HDL-C level of 50-59mg/dL. This association was similar in both men and women with larger effect size in men (aHR, 1.91; 95% CI, 1.70-2.15). The hazardous association between low HDL-C and liver cancer risk was remarkable in current smokers (aHR, 2.19; 95% CI, 1.84-2.60) and in pre-menopausal women (aHR, 2.91; 95% CI, 1.29-6.58) compared with post-menopausal women (aHR, 1.45; 95% CI, 1.10-1.93). This association was similarly observed in Model III. CONCLUSIONS: Low and extremely high HDL-C levels were associated with an increased liver cancer risk. The unfavourable association between low HDL-C and liver cancer was remarkable in smokers and pre-menopausal women.

Discrepant effect of high-density lipoprotein cholesterol on esophageal and gastric cancer risk in a nationwide cohort.

BACKGROUND: The relationship between high-density lipoprotein cholesterol (HDL-C) and gastroesophageal cancer is not constant. METHODS: In this population-based cohort study, 4.518 million cancer-free individuals among those who underwent national cancer screening in 2010 were enrolled and followed up until December 2017. HDL-C level was classified into eight groups at 10 mg/dL intervals. The risk of gastroesophageal cancers by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: During 8 years of follow-up, 38,362 gastric and 3022 esophageal cancers developed. Low HDL-C level was associated with an increased risk of gastric cancer; aHR was 1.19 (95% CI 1.09-1.30) for HDL-C < 30 mg/dL, 1.07 (95% CI 1.03-1.12) for HDL-C of 30-39 mg/dL, and 1.07 (95% CI 1.03-1.12) for HDL-C of 40-49 mg/dL comparing to HDL-C of 60-69 mg/dL. HDL-C was positively associated with esophageal cancer risk; aHR was 1.30 (1.12-1.51) for HDL-C of 70-79 mg/dL, 1.84 (1.53-2.22) for HDL-C of 80-89 mg/dL, 2.10 (1.67-2.61) for HDL-C ≥ 90 mg/dL. These site-specific effects of HDL-C were robust in sensitivity analyses. The range of HDL-C for the lowest cancer risk was different by sex and site. The hazardous effect of low HDL-C on gastric cancer was prominent in never and past smokers, and extremely high HDL-C increased gastric cancer risk (aHR 1.19; 95% CI 1.04-1.36) only in current smokers. Unfavorable effect of high HDL-C on gastroesophageal cancer risk was remarkable in smokers. CONCLUSIONS: Low HDL-C increased the risk of gastric cancer, wherein high HDL-C was associated with esophageal cancer risk with discrepancies by sex and smoking status.

Effect of chronic viral hepatitis and metabolic factors on renal cancer risk in a large cohort in Republic of Korea.

PURPOSE: We investigated the association between hepatic and metabolic factors and renal cancer risk. METHODS: This population-based cohort study included cancer-free individuals who underwent general health evaluation (January to December 2010) at the Korean National Health Insurance Service and followed-up through 2017. Hazard ratios (HR) and 95% confidence intervals (CI), determined by adjusted Cox regression analysis were used to investigate the effect of variables on renal cancer risk. RESULTS: Among 4,518,704 subjects, 6531 patients developed renal cancer. Adjusted analyses of epidemiological factors and BMI (body mass index) (Model I) showed serum high-density lipoprotein cholesterol (HDL-C) ≥60 mg/dL (adjusted HR [aHR] 0.88, 95% CI, 0.81-0.95) reduced renal cancer risk comparing to low HDL-C, whereas hepatitis B virus (HBV) antigen (aHR 1.41, 95% CI 1.19-1.68) and chronic HBV infection (aHR 1.65, 95% CI 1.26-2.17) increased its risk. Higher BMI increased renal cancer risk in dose-dependent manner (P for trend <0.001). This association persisted after adjustment for epidemiological factors and waist circumference (Model II). Sex-specific analyses showed similar effect of HBV antigen and chronic HBV infection in both sexes. Normal (50-59 mg/dL in women) or high (≥60 mg/dL in men) HDL-C reduced renal cancer risk. Alcohol consumption increased kidney cancer risk in age ≥ 60 years, but it had no association with renal cancer in age < 60 years. CONCLUSIONS: High serum HDL-C levels reduced and HBV antigen and chronic HBV infection increased renal cancer risk across different adjusted analysis models. This effect of low HDL-C and chronic HBV infection persisted in sex-based subanalysis.

Favorable Effect of High-Density Lipoprotein Cholesterol on Gastric Cancer Mortality by Sex and Treatment Modality.

Studies on the effects of high-density lipoprotein cholesterol (HDL-C) on gastric cancer mortality are few, and the results are inconsistent. In this study, we investigated the effects of HDL-C on gastric cancer mortality and conducted sub-group analysis by sex and treatment modality. Newly diagnosed patients with gastric cancer (n = 22,468) who underwent gastric cancer screening between January 2011 and December 2013 were included and followed up until 2018. A validation cohort (n = 3379) that had newly diagnosed gastric cancer from 2005 to 2013 at a university hospital, was followed up until 2017. HDL-C was inversely related with mortality; adjusted hazard ratio (aHR) 0.90 (95% confidence interval [CI], 0.83-0.98) for HDL-C of 40-49 mg/dL, 0.86 (0.79-0.93) for HDL-C of 50-59 mg/dL, 0.82 (0.74-0.90) for HDL-C of 60-69 mg/dL, and 0.78 (0.69-0.87) for HDL-C ≥ 70 mg/dL compared to HDL-C < 40 mg/dL. In the validation cohort, HDL-C was also inversely associated with mortality; aHR 0.81 (0.65-0.99) for HDL-C of 40-49 mg/dL, 0.64 (0.50-0.82) for HDL-C of 50-59 mg/dL, and 0.46 (0.34-0.62) for HDL-C ≥ 60 mg/dL compared to HDL-C < 40 mg/dL. The two cohorts demonstrated that higher HDL-C was associated with a low risk of mortality in both sexes. In validation cohort, this association was observed in both gastrectomy and endoscopic resection (p for trend < 0.001) as more remarkable in endoscopic resection group. In this study, we explored that an increased HDL-C reduced mortality in both sexes and curative resection group.

Sex-specific effects of fruit, vegetable, and red meat intake on the risk of gastric and esophageal cancer in a large cohort.

BACKGROUND: Dietary effects on gastric and esophageal cancer by sex and smoking has rarely been investigated. METHODS: Individuals who had undergone national gastric cancer screening during 2008 and had no any cancer at baseline were enrolled and followed up to 2017. The gastric and esophageal cancer risk was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: Among 3.645 million (44.1% men), 45,741 gastric cancers (67.7% men) and 3,550 esophageal cancers (89.5% men) developed during 9 years follow-up. In adjusted analysis, a frequent intake of fruit (≥ 7 servings per week) reduced the gastric cancer risk (aHR=0.91; 95% CI, 0.83-0.99) comparing to nearly no intake in women but slightly increased male gastric cancer risk (aHR=1.06; 95% CI, 1.00-1.13). A frequent intake of dietary fruit reduced the esophageal cancer risk only in men (aHR=0.75; 95% CI, 0.62-0.92). Frequent intake of red meat (3-4/week) slightly increased the gastric cancer risk only in men (aHR=1.04; 95% CI, 1.01-1.09). The favorable effect of fruit on the gastric and esophageal cancer risk was observed only in never smoker. CONCLUSIONS: The effect of fruit and red meat intake on the gastric and esophageal cancer risk differed according to sex and smoking status.

Rehabilitation Program for Improved Musculoskeletal Pain in Gastrointestinal Endoscopists: Multicenter Prospective Cohort Study.

Background/Aims: This study aimed to develop a rehabilitation program for musculoskeletal pain experienced by gastrointestinal endoscopists and to investigate its usefulness. Methods: This was a multicenter cohort study. During the first 2 weeks, a questionnaire regarding daily workload and musculoskeletal symptoms was administered. Then, a rehabilitation program including equipment/posture correction and stretching was conducted during the remaining 6 weeks. Follow-up daily workload and musculoskeletal symptom surveys were distributed during the last 2 weeks. The program satisfaction survey was performed at the 6th and 8th weeks. Results: Among 118 participants (69 men), 94% (n=111) complained of musculoskeletal pain at baseline. Various hospital activities at baseline were associated with multisite musculoskeletal pain, whereas only a few workloads were correlated with musculoskeletal pain after the rehabilitation program. Follow-up musculoskeletal pain was negatively correlated with equipment/posture program performance; arm/elbow pain was negatively correlated with elbow (R=-0.307) and wrist (R=-0.205) posture; leg/foot pain was negatively correlated with monitor position, shoulder, elbow, wrist, leg, and foot posture. Higher performance in the scope position (86.8% in the improvement vs 71.3% in the aggravation group, p=0.054) and table height (94.1% vs 79.1%, p=0.054) were associated with pain improvement. An increased number of colonoscopy procedures (6.27 in the aggravation vs 0.02 in the improvement group, p=0.017) was associated with pain aggravation. Most participants reported being average (32%) or satisfied (67%) with the program at the end of the study. Conclusions: Our rehabilitation program is easily applicable, satisfactory, and helpful for improving the musculoskeletal pain experienced by gastrointestinal endoscopists.

Risk prediction models incorporating institutional case volume for mortality after hip fracture surgery in the elderly.

INTRODUCTION: While higher institutional case volume is associated with better postoperative outcomes in various types of surgery, institutional case volume has been rarely included in risk prediction models for surgical patients. This study aimed to develop and validate the predictive models incorporating institutional case volume for predicting in-hospital mortality and 1-year mortality after hip fracture surgery in the elderly. MATERIALS AND METHODS: Data for all patients (≥ 60 years) who underwent surgery for femur neck fracture, pertrochanteric fracture, or subtrochanteric fracture between January 2008 and December 2016 were extracted from the Korean National Health Insurance Service database. Patients were randomly assigned into the derivation cohort or the validation cohort in a 1:1 ratio. Risk prediction models for in-hospital mortality and 1-year mortality were developed in the derivation cohort using the logistic regression model. Covariates included age, sex, type of fracture, type of anaesthesia, transfusion, and comorbidities such as hypertension, diabetes, coronary artery disease, chronic kidney disease, cerebrovascular disease, and dementia. Two separate models, one with and the other without institutional case volume as a covariate, were constructed, evaluated, and compared using the likelihood ratio test. Based on the models, scoring systems for predicting in-hospital mortality and 1-year mortality were developed. RESULTS: Analysis of 196,842 patients showed 3.6% in-hospital mortality (7084/196,842) and 15.42% 1-year mortality (30,345/196,842). The model for predicting in-hospital mortality incorporating the institutional case volume demonstrated better discrimination (c-statistics 0.692) compared to the model without the institutional case volume (c-statistics 0.688; likelihood ratio test p value < 0.001). The performance of the model for predicting 1-year mortality was also better when incorporating institutional case volume (c-statistics 0.675 vs. 0.674; likelihood ratio test p value < 0.001). CONCLUSIONS: The new institutional case volume incorporated scoring system may help to predict in-hospital mortality and 1-year mortality after hip fracture surgery in the elderly population.

Effect of Hospital Case-Volume on Mortality after Ovarian Cancer Surgery: A Population-Based Retrospective Cohort Study.

OBJECTIVES: The goal of ovarian cancer surgery has recently shifted from optimal cytoreduction to more complete resection. This study attempted to reassess and update the association between surgical case-volume and both in-hospital and long-term mortality after ovarian cancer surgery using recent data. DESIGN: This study is a population-based retrospective cohort study. Participants/Material: Data from all adult patients who underwent ovarian cancer surgery in Korea between 2005 and 2019 were obtained from the national database. A total of 24,620 patients underwent ovarian cancer surgery in 362 hospitals during the period. SETTING: In-hospital and 1-, 3-, 5-year mortality were set as primary and secondary outcomes. METHODS: Hospitals were categorized into high-volume (>90 cases/year), medium-volume (20-90 cases/year), and low-volume (<20 cases/year) centers considering overall distribution of case-volume. Postoperative in-hospital and long-term mortality were analyzed using logistic regression after adjusting for potential risk factors. RESULTS: Compared to high-volume centers (0.54%), in-hospital mortality was significantly higher in medium-volume (1.40%; adjusted odds ratio, 2.92; confidence interval, 1.82-3.73; p < 0.001) and low-volume (1.61%; adjusted odds ratio, 2.94; confidence interval, 2.07-4.17; p < 0.001) centers. In addition, 1-year mortality was 6.26%, 7.06%, and 7.94% for high-volume, medium-volume, and low-volume centers, respectively, and the differences among the groups were significant. However, case-volume effect was not apparent in 3- and 5-year mortality after ovarian cancer surgery. LIMITATIONS: Lacking clinical information such as staging or histologic diagnosis due to the nature of the administrative data should be considered in interpreting the data. CONCLUSIONS: Case-volume effect was observed for in-hospital and 1-year mortality after ovarian cancer surgery, while it was not clearly found in 3- or 5-year mortality. Dilution of the case-volume effect might be attributed to the high accessibility to care.

Hospital case-volume and mortality after lung cancer surgery: A population-based retrospective cohort study.

OBJECTIVES: Recent advances in lung cancer treatment warrants reassessment of the volume-outcome association in lung cancer surgery. This study reassessed the relationship between surgical case-volume and both in-hospital and long-term mortality after lung cancer surgery using a current database to reflect recent advances. MATERIALS AND METHODS: Using the database of the National Health Insurance Service in Korea, data of all adult patients who underwent lung cancer surgery in Korea between 2005 and 2019 were obtained. Hospitals were categorized by the annual number of lung cancer surgeries. Risk-adjusted in-hospital and 1, 3, 5-year mortality after surgery were assessed. RESULTS: A total of 84,194 lung cancer surgeries were performed in 163 centers during the study period. High-volume centers were defined as > 200 cases/year, medium-volume centers as 60-200 cases/year, and low-volume centers as < 60 cases/year. After adjustment, in-hospital mortality was significantly lower in high-volume centers (1.03%) compared to medium-volume centers (2.06%, adjusted odds ratio [OR], 1.43; 95% confidence interval [CI], 1.23-1.65; P < 0.001), and low-volume centers (3.08%, OR, 1.32; 95% CI, 1.16-1.51; P < 0.001). Long-term mortality was also significantly lower in high-volume centers compared to the other groups. CONCLUSION: High-volume centers showed lower in-hospital and long-term mortality compared to centers with less case-volume.

Healthcare Resource Utilization After Living Liver Donation: A Retrospective Case-Control Study.

BACKGROUND: Living liver donation is generally considered safe, but donors may experience short- or long-term complications. The purpose of this study was to assess healthcare resource utilization after liver donation in living liver donors in comparison with the general population. METHODS: Outpatient or emergency department visits and hospital admissions were compared between living liver donors who underwent hepatic resection for living liver donation between 2004 and 2018 and the matched general population. Healthcare resource utilization data for 5 y after liver donation were collected from the National Health Insurance Service database. For every living liver donor, 4 individually matched nondonors were selected from the National Health Insurance Service database using age, sex, preexisting comorbidities, and previous healthcare utilization history. RESULTS: A total of 1886 living liver donors and 7309 nondonors were included. In the first year after donation, living liver donors required more outpatient department visits (7 [4-13] versus 3 [1-7], P < 0.001) and more emergency department visits (13.33% versus 0.15%, P < 0.001) compared with matched nondonors. A similar trend persisted for 5 y after donation. The number of hospital admissions of living liver donors was higher for up to 2 y after donation with longer hospital length of stay (13.0 [10.5-16.0] d versus 5.0 [3.0-9.0] d, P < 0.0001). CONCLUSIONS: Healthcare resource utilization in living liver donors for 5 y after donation was higher compared with matched nondonors. The higher healthcare resource demand may be related to postoperative complications or lowered threshold for healthcare resource utilization after donation.

The sex discrepancy effects of fruit and vegetable intake on pancreatic cancer risk; a large Korean cancer screening cohort study.

BACKGROUND: Although several risk factors have been identified for the development of pancreatic cancer, the effects of fruit and vegetables on the disease remains controversial. METHODS: Individuals without cancer at baseline, who underwent national health examinations during 2008, were enrolled and followed-up to 2017. Vegetable intake was measured by assessing the intake of daily vegetables (types). Fruit intake was also assessed on a weekly basis. We evaluated the risk of pancreatic cancer using adjusted hazard ratio (aHR) and 95% confidence interval (95% CI). RESULTS: Of 3,605,959 individuals (44% men), pancreatic cancer occurred in 10,469 subjects (5,384 men) during the 9 year follow-up. In adjusted analyses, the daily intake of more than five vegetable types reduced pancreatic cancer compared to no vegetable intake (aHR = 0.82; 95% CI, 0.71-0.94). Using sex-specific analyses, vegetable intake markedly reduced pancreatic cancer in women (aHR = 0.84 for 1-2 vegetable types, 0.84 for 3-4 and 0.69 for ≥ 5), but no effects were observed in men. Sex-specific analyses revealed that fruit intake reduced pancreatic cancer in men (aHR = 0.87 for 3-4 servings/week, and 0.84 for ≥ 7), but no effects were observed in women. CONCLUSIONS: High intakes of dietary vegetables and fruit reduce pancreatic cancer development in women and men, respectively.

Institutional case volume-incorporated mortality risk prediction model for cardiac surgery.

BACKGROUND: Most risk prediction models predicting short-term mortality after cardiac surgery incorporate patient characteristics, laboratory data, and type of surgery, but do not account for surgical experience. Considering the impact of case volume on patient outcome after high-risk procedures, we attempted to develop a risk prediction model for mortality after cardiac surgery that incorporates institutional case volume. METHODS: Adult patients who underwent cardiac surgery from 2009 to 2016 were identified. Patients who underwent cardiac surgery (n = 57,804) were randomly divided into the derivation cohort (n = 28,902) or the validation cohorts (n = 28,902). A risk prediction model for in-hospital mortality and 1-year mortality was developed from the derivation cohort and the performance of the model was evaluated in the validation cohort. RESULTS: The model demonstrated fair discrimination (c-statistics, 0.76 for in-hospital mortality in both cohorts; 0.74 for 1-year mortality in both cohorts) and acceptable calibration. Hospitals were classified based on case volume into 50 or less, 50-100, 100-200, or more than 200 average cardiac surgery cases per year and case volume was a significant variable in the prediction model. CONCLUSIONS: A new risk prediction model that incorporates institutional case volume and accurately predicts in-hospital and 1-year mortality after cardiac surgery was developed and validated.

The association between hospital case-volume and postoperative outcomes after esophageal cancer surgery: A population-based retrospective cohort study.

BACKGROUND: Recent advances in esophageal cancer treatment require a reevaluation of the relationship between institutional case-volume and patient outcome. The aim of this study was to analyze and update the association between surgical case-volume and both in-hospital and long-term mortality after esophagectomy for esophageal cancer. METHODS: Data of all adult patients who received esophageal cancer surgery in Korea between 2004 and 2017 were extracted from the database of the National Health Insurance Service. Hospitals were categorized into three groups according to the average annual number of esophageal cancer surgery: low-volume (<12 cases/year), medium-volume (12-48 cases/year), and high-volume centers (>48 cases/year). Postoperative in-hospital and 1-, 3-, and 5-year mortality were analyzed according to the categorized groups using logistic regression. RESULTS: In total, 11, 346 esophageal cancer surgeries in 122 hospitals were analyzed. In-hospital mortality in the high-, medium-, and low-volume centers were 3.4%, 6.4%, and 11.1%, respectively. In-hospital mortality was significantly higher in low- volume (adjusted odds ratio, 3.91; confidence interval, 3.18-4.80; p < 0.001) and medium volume (adjusted odds ratio, 2.21; confidence interval, 1.80-2.74, p < 0.001) centers compared to high-volume centers. Patients who received esophageal cancer surgery in a low-or medium-volume center also had higher 1-, 3-, and 5-year mortality compared to patients who received the surgery in a high-volume center. Conclusions Centers with lower case-volume showed higher in-hospital mortality and long-term mortality after esophageal cancer surgery.

Long-term impacts of appendectomy associated with increased incidence of inflammatory bowel disease, infection, and colorectal cancer.

PURPOSE: Although the appendix has been suggested to play a role in maintaining the gut microbiome and immune system, the ramifications of appendectomy on the development inflammatory bowel disease, sepsis, and colorectal cancer are yet to be determined. The purpose of this study was to evaluate the potential long-term impacts of appendectomy, with a focus on inflammatory bowel disease, infection, and colorectal cancer, using the National Healthcare Insurance Service (NHIS) database of Korea. METHODS: The National Healthcare Insurance Service database in Korea was used for analysis. Adult patients who received appendectomy between 2005 and 2013 were identified. The control group consisted of patients who did not receive appendectomy were matched by baseline characteristics including comorbidities and frequency of healthcare resource utilization. The primary outcome was the incidence-rate ratio (IRR) of Crohn's disease, ulcerative colitis, Clostridium difficile infection, sepsis, and colorectal cancer after appendectomy or the index date. RESULTS: We identified 914,208 patients who underwent appendectomy, and after matching with control patients, a total of 486,844 patients were included for analysis. Patients who underwent appendectomy showed a significantly higher incidence of Crohn's disease (IRR 4.40, 95% confidence interval (CI) 3.78-5.13) and ulcerative colitis (IRR 1.78, 95% CI 1.63-1.93) compared to the control group during the 5-year follow-up period. The associations between appendectomy and Clostridium difficile infection, sepsis, and colorectal cancer were all found to be significant. CONCLUSION: Patients who underwent appendectomy may be at increased risk for developing Crohn's disease, ulcerative colitis, Clostridium difficile infection, sepsis, and colorectal cancer.

Effect of institutional case volume on mid-term mortality after coronary artery bypass grafting surgery.

OBJECTIVE: The impact of center case volume on mid-term postoperative outcome after coronary artery bypass grafting surgery (CABG) is still controversial and requires investigation. The aim of this study was to compare mid-term survival after CABG according to the institutional annual CABG case volume. METHODS: Adult patients (≥ 18 years) who underwent CABG from 2009 to 2016 were identified by searching National Health Insurance database of Korea for CABG procedure codes. Hospitals were classified into three groups based on annual case volume; low-volume centers (< 20 cases/year), medium-volume centers (20-50 cases/year), and high-volume centers (> 50 cases/year). RESULTS: A total of 22,575 CABG were performed in 95 centers during the study period, and 14,697 (65.1%) cases performed at 15 high-volume centers, 5,262 (23.3%) cases at 26 medium-volume centers, and 2,616 (11.6%) cases at 54 low-volume centers. The overall 1-year mortality rate was the lowest in high-volume centers (6.5%), followed by medium-volume centers (10.6%) and low-volume centers (15.2%). Logistic regression identified medium-volume centers (adjusted OR 1.30 [95% CI 1.15-1.49], P < 0.01) and low-volume centers (adjusted OR 1.75 [95% CI 1.51-2.03], P < 0.01) as risk factors for 1-year mortality after CABG compared to high-volume centers. In the Cox proportional hazard model, low- and medium-volume centers were significantly risk factors for poor survival (adjusted HR 1.41 [95% CI 1.31-1.54], P < 0.01 and HR 1.26 [95% CI 1.17-1.35], P < 0.01 for low- and medium-volume centers, respectively). CONCLUSIONS: Higher institutional case volume of CABG was associated with lower mid-term mortality.

The association between hospital case volume and in-hospital and one-year mortality after hip fracture surgery.

AIMS: Hospital case volume is shown to be associated with postoperative outcomes in various types of surgery. However, conflicting results of volume-outcome relationship have been reported in hip fracture surgery. This retrospective cohort study aimed to evaluate the association between hospital case volume and postoperative outcomes in patients who had hip fracture surgery. We hypothesized that higher case volume would be associated with lower risk of in-hospital and one-year mortality after hip fracture surgery. METHODS: Data for all patients who underwent surgery for hip fracture from January 2008 to December 2016 were extracted from the Korean National Healthcare Insurance Service database. According to mean annual case volume of surgery for hip fracture, hospitals were classified into very low (< 30 cases/year), low (30 to 50 cases/year), intermediate (50 to 100 cases/year), high (100 to 150 cases/year), or very high (> 150 cases/year) groups. The association between hospital case volume and in-hospital mortality or one-year mortality was assessed using the logistic regression model to adjust for age, sex, type of fracture, type of anaesthesia, transfusion, comorbidities, and year of surgery. RESULTS: Between January 2008 and December 2016, 269,535 patients underwent hip fracture surgery in 1,567 hospitals in Korea. Compared to hospitals with very high volume, in-hospital mortality rates were significantly higher in those with high volume (odds ratio (OR) 1.10, 95% confidence interval ((CI) 1.02 to 1.17, p = 0.011), low volume (OR 1.22, 95% CI 1.14 to 1.32, p < 0.001), and very low volume (OR 1.25, 95% CI 1.16 to 1.34, p < 0.001). Similarly, hospitals with lower case volume showed higher one-year mortality rates compared to hospitals with very high case volume (low volume group, OR 1.15, 95% CI 1.11 to 1.19, p < 0.001; very low volume group, OR 1.10, 95% CI 1.07 to 1.14, p < 0.001). CONCLUSION: Higher hospital case volume of hip fracture surgery was associated with lower in-hospital mortality and one-year mortality in a dose-response fashion. Cite this article: Bone Joint J 2020;102-B(10):1384-1391.

Comparisons of exacerbations and mortality among regular inhaled therapies for patients with stable chronic obstructive pulmonary disease: Systematic review and Bayesian network meta-analysis.

BACKGROUND: Although exacerbation and mortality are the most important clinical outcomes of stable chronic obstructive pulmonary disease (COPD), the drug classes that are the most efficacious in reducing exacerbation and mortality among all possible inhaled drugs have not been determined. METHODS AND FINDINGS: We performed a systematic review (SR) and Bayesian network meta-analysis (NMA). We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the European Union Clinical Trials Register, and the official websites of pharmaceutical companies (from inception to July 9, 2019). The eligibility criteria were as follows: (1) parallel-design randomized controlled trials (RCTs); (2) adults with stable COPD; (3) comparisons among long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled corticosteroids (ICSs), combined treatment (ICS/LAMA/LABA, LAMA/LABA, or ICS/LABA), or a placebo; and (4) study duration ≥ 12 weeks. This study was prospectively registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42017069087). In total, 219 trials involving 228,710 patients were included. Compared with placebo, all drug classes significantly reduced the total exacerbations and moderate to severe exacerbations. ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk (odds ratio [OR] = 0.57; 95% credible interval [CrI] 0.50-0.64; posterior probability of OR > 1 [P(OR > 1)] < 0.001). In addition, in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reducing mortality than placebo (OR = 0.74, 95% CrI 0.59-0.93, P[OR > 1] = 0.004; and OR = 0.86, 95% CrI 0.76-0.98, P[OR > 1] = 0.015, respectively). The results minimally changed, even in various sensitivity and covariate-adjusted meta-regression analyses. ICS/LAMA/LABA tended to lower the risk of cardiovascular mortality but did not show significant results. ICS/LAMA/LABA increased the probability of pneumonia (OR for triple therapy = 1.56; 95% CrI 1.19-2.03; P[OR > 1] = 1.000). The main limitation is that there were few RCTs including only less symptomatic patients or patients at a low risk. CONCLUSIONS: These findings suggest that triple therapy can potentially be the best option for stable COPD patients in terms of reducing exacerbation and all-cause mortality.

Effects of maternal influenza vaccination on adverse birth outcomes: A systematic review and Bayesian meta-analysis.

BACKGROUND: Although pregnant women are a priority group for influenza vaccination, its effect on birth outcomes has long been debated. Numerous observational studies and a few randomized controlled studies have been conducted, with inconsistent results. OBJECTIVES: To evaluate the association of influenza vaccination in pregnancy with adverse birth outcomes. DATA SOURCE: The Cochrane Library, PubMed, EMBASE, Web of Science, and Scopus were searched. STUDY ELIGIBILITY CRITERIA: This analysis included randomized placebo-controlled studies, cohort studies, and case-control studies, in which inactivated influenza vaccination was given during pregnancy and fetal adverse birth outcomes were assessed. PARTICIPANTS & INTERVENTION: Women who received inactivated influenza vaccine during pregnancy and their offspring. STUDY APPRAISAL AND SYNTHESIS: Two independent reviewers and a third reviewer collaborated in study selection and data extraction. A Bayesian 3-level random-effects model was utilized to assess the impact of maternal influenza vaccination on birth outcomes, which were presented as odds ratios (ORs) with 95% credible interval (CrIs). Bayesian outcome probabilities (P) of an OR<1 were calculated, and values of at least 90% (0.9) were deemed to indicate a significant result. RESULTS: Among the 6,249 identified publications, 48 studies were eligible for the meta-analysis, including 2 randomized controlled trials, 41 cohort studies, and 5 case-control studies. The risk of none of the following adverse birth outcomes decreased significantly: preterm birth (OR = 0.945, 95% CrI: 0.736-1.345, P = 73.3%), low birth weight (OR = 0.928, 95% CrI: 0.432-2.112, P = 76.7%), small for gestational age (OR = 0.971, 95% CrI: 0.249-4.217,P = 63.3%), congenital malformation (OR = 1.026, 95% CrI: 0.687-1.600, P = 38.0%), and fetal death (OR = 0.942, 95% CrI: 0.560-1.954, P = 61.6%). Summary estimates including only cohort studies showed significantly decreased risks for preterm birth, small for gestational age and fetal death. However, after adjusting for season at the time of vaccination and countries' income level, only fetal death remained significant. CONCLUSION: This Bayesian meta-analysis did not find a protective effect of maternal influenza vaccination against adverse birth outcomes, as reported in previous studies. In fact, our results showed evidence of null associations between maternal influenza vaccination and adverse birth outcomes.