Incidence and risk of pancreatic cancer in patients with acute or chronic pancreatitis: a population-based cohort study.

We aimed to evaluate the incidence and risk of pancreatic cancer (PC) in pancreatitis. We identified patients with acute pancreatitis (AP) (n = 225,811, 50.0%) and chronic pancreatitis (CP) (n = 225,685, 50.0%) from Korean population-based data and matched them with age- and sex-matched controls (n = 4,514,960). We analyzed the incidence and adjusted hazard ratios (aHRs) of PC among patients followed for more than 2 years or 5 years, and assessed risk changes over time in single episode of AP (SAP), recurrent AP (RAP), CP with AP, and CP without AP groups. We also performed subgroup analysis for both sexes. The incidences (per 104 person-years) and risks (aHR) of PC were higher in the RAP (12.69, 5.00) or CP with AP (12.12, 5.74) groups compared to the SAP (2.31, 1.32) or CP without AP (2.28, 1.57) groups. The risks of PC decreased over time, however, the risk of PC remained elevated in the RAP and CP with AP groups for more than 8 years. Females with RAP, SAP, and CP with AP had higher risks of PC than males. The risk of PC is higher and persists for longer duration in patients with RAP and CP with AP compared to those with SAP or CP without AP.

Familial Risk and Interaction With Smoking and Alcohol Consumption in Bladder Cancer: A Population-Based Cohort Study.

Background: Although genetic factors are known to play a role in the pathogenesis of bladder cancer, population-level familial risk estimates are scarce. We aimed to quantify the familial risk of bladder cancer and analyze interactions between family history and smoking or alcohol consumption. Methods: Using the National Health Insurance database, we constructed a cohort of 5,524,403 study subjects with first-degree relatives (FDRs) and their lifestyle risk factors from 2002 to 2019. Familial risk was calculated using hazard ratios (HRs) with 95% confidence intervals (CIs) that compare the risk of individuals with and without affected FDRs. Interactions between family history and smoking or alcohol intake were assessed on an additive scale using the relative excess risk due to interaction (RERI). Results: Offspring with an affected parent had a 2.09-fold (95% CI: 1.41 - 3.08) increased risk of disease compared to those with unaffected parents. Familial risks of those with affected father and mother were 2.26 (95% CI: 1.51 - 3.39) and 1.10 (95% CI: 0.27 - 4.41), respectively. When adjusted for lifestyle factors, HR reduced slightly to 2.04 (95% CI: 1.38 - 3.01), suggesting that a genetic predisposition is the main driver in the familial aggregation. Smokers with a positive family history had a markedly increased risk of disease (HR: 3.60, 95% CI: 2.27 - 5.71), which exceeded the sum of their individual risks, with statistically significant interaction (RERI: 0.72, 95% CI: 0.31 - 1.13). For alcohol consumption, drinkers with a positive family history also had an increased risk of disease, although the interaction was not statistically significant (RERI: 0.05, 95% CI: -3.39 - 3.48). Conclusion: Smokers and alcohol consumers with a positive family history of bladder cancer should be considered a high-risk group and be advised to undergo genetic counseling.

Incidence and Mortality of Vertebral Compression Fracture Among All Age Groups: A Nationwide, Population-based Study in the Republic of Korea.

BACKGROUND: Although several studies have examined the epidemiological features of vertebral compression fractures (VCF) among elderly patients, few studies have reported the epidemiology of VCF among younger individuals. OBJECTIVE: To examine trends in the incidence and mortality of VCF in both the old (>= 65 years) and young (< 65 years) age groups. This study aimed to investigate the incidence and mortality of VCF among all age groups in Korea. STUDY DESIGN: Population-based cohort study. SETTING: A nationwide, population-based setting. METHODS: Using the Korean National Health Insurance database, which has complete population coverage, we identified patients diagnosed with VCF between 2005 to 2018. Differences in incidence, survival and mortality were compared across groups using Kaplan-Meier analysis and Cox regression for all age groups and both genders. RESULTS: We identified a total of 742,993 VCF patients and the annual incidence was 140.09/100,000 individuals. Although the incidence of VCF was significantly higher in the older age compared to younger age group (556.38/100,000 vs. 44.09/100,000 individuals), the mortality rate ratio for VCF patients was higher among younger compared to older individuals (old: 1.59 vs. young: 2.87). In our multivariable-adjusted analysis, the hazard ratio for multiple fractures, traumatic injury and osteoporosis were higher in patients aged < 65 years compared to patients aged >= 65 years, suggesting that the impact of these clinical variables on mortality is more significant in the younger age group. LIMITATION: A limitation of this study was its lack of information on clinical features, such as disease severity and laboratory data. The precise cause of death of VCF patients could not be confirmed from the study database. CONCLUSIONS: The mortality rate ratio and hazard ratio were significantly higher among younger patients with VCF, indicating the need for further research on VCF in younger age groups.

Familial Risk of Graves Disease Among First-Degree Relatives and Interaction With Smoking: A Population-Based Study.

CONTEXT: Population-based studies on the familial aggregation of Graves disease (GD) are scarce and gene-environment interactions are not well-studied. OBJECTIVE: We evaluated the familial aggregation of GD and assessed interactions between family history and smoking. METHODS: Using the National Health Insurance database, which includes information on familial relationships and lifestyle risk factors, we identified 5 524 403 individuals with first-degree relatives (FDRs). Familial risk was calculated using hazard ratios (HRs), comparing the risk of individuals with and without affected FDRs. Interactions between smoking and family history were assessed on an additive scale using relative excess risk due to interaction (RERI). RESULTS: The HR among individuals with affected FDRs was 3.39 (95% CI, 3.30-3.48) compared with those without affected FDR, and among individuals with affected twin, brother, sister, father, and mother, the HRs were 36.53 (23.85-53.54), 5.26 (4.89-5.66), 4.12 (3.88-4.38), 3.34 (3.16-3.54), and 2.63 (2.53-2.74), respectively. Individuals with both a positive family history and smoking had an increased risk of disease (HR 4.68) with statistically significant interaction (RERI 0.94; 95% CI, 0.74-1.19). Heavy smokers with a positive family history showed a nearly 6-fold increased risk, which was higher than moderate smoking, suggesting a dose-response interaction pattern. Current smoking also showed a statistically significant interaction with family history (RERI 0.52; 95% CI, 0.22-0.82), while this was not observed for former smoking. CONCLUSION: A gene-environment interaction can be suggested between smoking and GD-associated genetic factors, which diminishes after smoking cessation. Smokers with a positive family history should be considered a high-risk group and smoking cessation should be advised.

Familial Risk of Gout and Interaction With Obesity and Alcohol Consumption: A Population-Based Cohort Study in Korea.

OBJECTIVE: Population-based studies of the familial aggregation of gout are scarce, and gene/environment interactions are not well studied. This study was undertaken to evaluate the familial aggregation of gout as well as assess interactions between family history and obesity or alcohol consumption on the development of gout. METHODS: Using the Korean National Health Insurance database, which includes information regarding familial relationships and risk factor data, we identified 5,524,403 individuals from 2002 to 2018. Familial risk was calculated using hazard ratios (HRs) with 95% confidence intervals (95% CIs) to compare the risk in individuals with and those without affected first-degree relatives. Interactions between family history and obesity/alcohol consumption were assessed on an additive scale using the relative excess risk due to interaction (RERI). RESULTS: Individuals with a gout-affected first-degree relative had a 2.42-fold (95% CI 2.39, 2.46) increased risk of disease compared to those with unaffected first-degree relatives. Having both a family history of gout and being either overweight or having moderate alcohol consumption was associated with a markedly increased risk of disease, with HRs of 4.39 (95% CI 4.29, 4.49) and 2.28 (95% CI 2.22, 2.35), respectively, which exceeded the sum of their individual risks but was only statistically significant in overweight individuals (RERI 0.96 [95% CI 0.85, 1.06]). Obese individuals (RERI 1.88 [95% CI 1.61, 2.16]) and heavy drinkers (RERI 0.36 [95% CI 0.20, 0.52]) had a more prominent interaction compared to overweight individuals and moderate drinkers, suggesting a dose-response interaction pattern. CONCLUSION: Our findings indicate the possibility of an interaction between gout-associated genetic factors and obesity/alcohol consumption.

Familial risk of seropositive rheumatoid arthritis and interaction with smoking: a population-based cohort study.

OBJECTIVES: We evaluated the familial risk of seropositive rheumatoid arthritis (RA) and examined interactions between family history and smoking. METHODS: Using the National Health Insurance and Health Screening Program databases, which include information on familial relationships and lifestyle factors, we identified 5 524 403 individuals with first-degree relatives (FDRs) from 2002-2018. We calculated familial risk using hazard ratios (HRs) with 95% CIs which compare the risk of individuals with and without affected FDRs. Interactions between smoking and family history were assessed on an additive scale using the relative excess risk due to interaction (RERI). RESULTS: Individuals with affected FDR had 4.52-fold (95% CI 3.98, 5.12) increased risk of disease compared with those with unaffected FDR. Familial risk adjusted for lifestyle factors decreased slightly (HR 4.49), suggesting that a genetic contribution is the predominant driver in the familial aggregation of RA. Smoking was associated with an increased risk of disease that was more pronounced among heavy (HR 1.92 95% CI 1.70, 2.18) compared with moderate (HR 1.15 95% CI 1.04, 1.28) smoking. In the interaction analysis, the risk associated with the combined effect of smoking and family history was higher than the sum of their individual effects, though statistically non-significant (RERI 1.30 95% CI ‒0.92, 3.51). Heavy smokers with a positive family history showed a prominent interaction (RERI 4.13 95% CI ‒0.88, 9.13) which exceeded moderate smokers (RERI 0.61 95% CI ‒1.90, 3.13), suggesting a dose-response interaction pattern. CONCLUSION: Our findings indicate the possibility of an interaction between RA-associated genes and smoking.

Cholecystectomy reduces the risk of myocardial and cerebral infarction in patients with gallstone-related infection.

We compared the risk of myocardial infarction (MI) or cerebral infarction (CI) in patients with or without-gallstone-related infection (GSI) and change in the risk following cholecystectomy. GSI (n = 84,467) and non-GSI (n = 406,800) patients with age- and sex-matched controls (n = 4,912,670) were identified from Korean population based data. The adjusted hazard ratios (aHRs) of MI or CI were analyzed in both groups treated with or without cholecystectomy. Subgroup analysis was performed for both sexes and different ages. The risk of MI or CI was higher in the GSI group than in the non-GSI group (aHR for MI; 1.32 vs. 1.07, aHR for CI; 1.24 vs. 1.06, respectively). The risk reduction rate of MI following cholecystectomy was 11.4% in the GSI group, whereas it was 0% in the non-GSI group. The risk of CI after cholecystectomy was more reduced in the GSI group than in the non-GSI group (16.1% and 4.7%, respectively). The original risk of MI or CI in patients with gallstones and risk reduction rates following cholecystectomy were higher in females and younger patients than in males and older patients. Increased risk of MI or CI and greater risk reduction following cholecystectomy were seen in patients with GSI.

Familial Risk of Renal Cell Cancer and Interaction with Obesity and Hyperglycemia: A Population-Based Study.

PURPOSE: We quantified the familial risk of renal cell cancer (RCC) among first-degree relatives (FDRs) on a population level, and examined interactions between family history and body mass index or blood glucose. MATERIALS AND METHODS: Using the National Health Insurance database, which covers the entire Korean population, and the National Health Screening Program, we constructed a cohort of 5,524,403 individuals with blood-related FDRs and their lifestyle factors from 2002 to 2018. We calculated familial risk using incidence risk ratios (IRRs) with 95% confidence intervals, which compares the risk of individuals with and without FDR. The combined effect and interaction of a given risk factor and family history of RCC were measured by the relative excess risk due to interaction. RESULTS: Individuals with affected FDRs showed a 2.29-fold (95% CI 1.68-3.13) increased risk of disease. Familial risk adjusted for lifestyle factors showed minimal attenuation (IRR 2.25; 95% CI: 1.65-3.08), suggesting that genetic predisposition is the main contributor in the familial aggregation of RCC. Individuals with both a positive family history and overweight/obesity (IRR 3.71, 95% CI 2.50-4.92) or hyperglycemia (IRR 4.52, 95% CI 2.59-6.45) had a significantly higher risk that exceeded the sum of their individual risks, suggesting an interaction that was statistically significant (relative excess risk due to interaction 95% CI: 0.91, -0.21-2.12; 2.21, 0.28-4.14). CONCLUSIONS: Our findings suggest an interaction between genetic and environmental factors, namely obesity and hyperglycemia. Individuals with both factors should be considered a high-risk group and advised to undergo genetic counseling.

The incidence, comorbidity and mortality of sarcoidosis in Korea, 2008-2015: a nationwide population-based study.

BACKGROUND: Few national level, population-based studies are present on the epidemiology of sarcoidosis and it is unclear whether these patients have higher mortality than the general population. The objective of this study was to investigate the nationwide epidemiology, comorbidity and mortality in sarcoidosis in Korea. MATERIAL AND METHODS: For the period between 2008 to 2015, we used the national population-based database operated by Rare Intractable Disease registration program in which patients' diagnosis are based on uniform criteria. All sarcoidosis patients were identified and followed-up using the National Health Insurance database to determine their incidence, comorbidity, mortality, causes of death and standardised mortality ratio (SMR). RESULTS: During the study period, we identified 3,259 new sarcoidosis patients. The average annual incidence was 0.81 per 100,000. The annual mortality rate was 9.26 per 1,000 person-years. The mortality rate were significantly higher than those of the general population (SMR 1.91, 95% confidence interval 1.62-2.25). The major comorbidities of sarcoidosis patients were the diseases of the respiratory system (17.64%), heart (5.43%), eyes (4.27%) and cancer (2.3%). Mortality was higher in patients with lung involvement. Of the 84 deaths identified in this study from 2008-2013, the most common cause of death was cancer (41.7%), followed by respiratory disease (13.1%), sarcoidosis (13.1%) and heart disease (8.3%). CONCLUSIONS: We reported a nationwide incidence of sarcoidosis as 0.81 per 100,000 in Korea. The mortality of sarcoidosis patients was higher compared to the general population and the major causes of death were cancer, respiratory disease and sarcoidosis. Sarcoidosis patients with comorbid diseases showed increased mortality. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 24-36).

Nationwide population-based study showed that the rotavirus vaccination had no impact on the incidence of biliary atresia in Korea.

AIM: Rotaviruses have been associated with biliary atresia. This study investigated whether the rotavirus vaccine, which was introduced to Korea in 2008, had an impact on the incidence of biliary atresia. METHODS: We identified all rotavirus infections (n = 436 826) and biliary atresia cases (n = 528) diagnosed from 2006 to 2015 from insurance and health databases. The annual and seasonal incidence of biliary atresia and rotavirus infection rates in neonates and children were calculated. The difference in the risk of biliary atresia between rotavirus-infected and non-infected neonates was analysed. RESULTS: The incidence of rotavirus infections was 20.6 versus 13.4 per 1000 cases before (2006-2008) and after (2009-2015) vaccine implementation. However, neonatal rotavirus infection rates did not decrease, with an incidence of 14.5 versus 14.8 per 1000 cases before and after vaccination. The biliary atresia incidence remained constant at 12.0 per 100 000 cases. Rotavirus infections in neonates were a risk factor for biliary atresia (odds ratio 3.14, 95% confidence interval 1.87-5.26). CONCLUSION: Rotavirus vaccination had no impact on the incidence of biliary atresia, possibly because the vaccination did not change the neonatal rotavirus infection rate through herd immunity. However, rotavirus infections in neonates were significantly associated with biliary atresia.

Incidence and Mortality Rates of Second Pancreatic Cancer Among Survivors of Digestive Cancers: A Nationwide Population-Based Study.

OBJECTIVES: We analyzed the incidence and mortality rates of second pancreatic ductal adenocarcinoma (PDAC) among survivors of digestive cancers in South Korea. METHODS: We evaluated data from the Korea National Health Insurance to identify individuals with digestive cancers in 2005 to 2015. The standardized incidence ratios (SIRs) of second PDACs and survival rates were evaluated. RESULTS: Among 772,534 patients with first digestive cancers, 1696 (0.22%) developed second PDACs. The incidence of second PDACs increased until 10 years since the first cancer diagnosis. Patients with biliary tract cancers (BTCs) showed a higher incidence of second PDACs than did those with gastrointestinal cancers or hepatocellular carcinoma. In ages 20 to 49 years, SIRs (95% confidence interval) were higher in survivors of hepatocellular carcinoma (3.08; 1.04-3.08), gastric cancer (3.40; 1.90-3.40), colorectal cancer (5.00; 2.75-5.00), gallbladder cancer (58.52; 11.81-58.52), intrahepatic cholangiocarcinoma (86.99; 1.73-86.99), extrahepatic cholangiocarcinoma (89.41; 27.42-89.41), and ampulla of Vater cancer (156.78; 48.08-156.78). In ages 50 to 64 years, colorectal cancer (1.42; 1.04-1.42), gastric cancer (1.66; 1.29-1.66), and BTCs revealed higher SIRs. In ages more than 65 years, SIR was increased only in BTCs. Second PDACs revealed a more favorable prognosis than first PDACs. CONCLUSIONS: Careful surveillance for second PDACs after curative treatment of BTCs and colorectal cancers should be considered.

Collaboration Matters: Honey Bee Health as a Transdisciplinary Model for Understanding Real-World Complexity.

We develop a transdisciplinary deliberative model that moves beyond traditional scientific collaborations to include nonscientists in designing complexity-oriented research. We use the case of declining honey bee health as an exemplar of complex real-world problems requiring cross-disciplinary intervention. Honey bees are important pollinators of the fruits and vegetables we eat. In recent years, these insects have been dying at alarming rates. To prompt the reorientation of research toward the complex reality in which bees face multiple challenges, we came together as a group, including beekeepers, farmers, and scientists. Over a 2-year period, we deliberated about how to study the problem of honey bee deaths and conducted field experiments with bee colonies. We show trust and authority to be crucial factors shaping such collaborative research, and we offer a model for structuring collaboration that brings scientists and nonscientists together with the key objects and places of their shared concerns across time.

Incidence and Prognosis of Subsequent Cholangiocarcinoma in Patients with Hepatic Resection for Bile Duct Stones.

BACKGROUND AND AIM: Cholangiocarcinoma (CCA) often develops after the hepatic resection for hepatolithiasis as well as indwelling it. We studied the incidence and prognosis of subsequent CCA in patients with hepatolithiasis in South Korea. METHODS: We identified individuals with diagnosed CCA at the time of or after surgery, during 2002-2016, from the Korean National Health Insurance. The incidences and survival rates of subsequent CCA were analyzed and compared with concomitant CCA. The standardized incidence ratios (SIRs) of CCA in this cohort were evaluated in the standard Korean population. All data were stratified by the presence of intrahepatic or extrahepatic CCA, age and sex. RESULTS: Of the 7852 patients with hepatectomy for BDS, 433 (5.84%) had concomitant CCA. Over the 12-year follow-up, 107 of 7419 (1.98%) patients were diagnosed with subsequent CCA. Patients with hepatic resection for BDS revealed higher SIRs for subsequent CCA (12.89, 95% CI 10.96-15.15) in cases of both intrahepatic CCA (13.40, 10.55-17.02) and extrahepatic CCA (12.42, 9.98-15.46). The median survival time for subsequent CCA was 0.87 years, while that for concomitant CCA was 2.79 years. Having subsequent CCA (HR 2.71, 95% CI 2.17-3.40) and being male (HR 1.28, 1.05-1.57) were related to a shorter survival time. The CCA site and age at CCA diagnosis were not related to prognoses. CONCLUSIONS: Subsequent CCA developed in 2% of the patients with hepatic resection for benign BDS until 10 years and was associated with poorer prognoses than concomitant CCA. Future studies focused on the long-term surveillance for CCA in such patients are needed.

Evaluation of a real-time polymerase chain reaction assay for the diagnosis of malaria in patients from Thailand.

We compared the diagnosis of malaria in 297 patients from Thailand by a real-time polymerase chain reaction (PCR) assay using the LightCycler with conventional microscopy using Giemsa-stained thick and thin blood films. The PCR assay can be completed in one hour and has the potential to detect and identify four species of Plasmodium in a single reaction by use of melting temperature curve analysis (however, we did not detect Plasmodium ovale in this study). Blood was collected, stored, and transported on IsoCode STIX, which provide a stable matrix for the archiving and rapid simple extraction of DNA. A genus-specific primer set corresponding to the 18S ribosomal RNA was used to amplify the target sequence. Fluorescence resonance energy technology hybridization probes were designed for P. falciparum over a region containing basepair mismatches, which allowed differentiation of the other Plasmodium species. The PCR results correlated with the microscopic results in 282 (95%) of 297 patient specimens. Most of these were single-species infections caused by P. vivax (150) and P. falciparum (120), along with 5 P. malariae, 2 mixed infections (P. falciparum and P. vivax), and 5 negative specimens. No negative microscopy specimens were positive by PCR (100% specificity for detection of any Plasmodium). The 15 discrepant results could not be resolved, but given the subjective nature of microscopy and the analytical objectivity of the PCR, the PCR results may be correct. The ability of the PCR method to detect mixed infections or to detect P. ovale could not be determined in this study. Within the limitations of initial equipment costs, this real-time PCR assay is a rapid, accurate, and efficient method for the specific diagnosis of malaria. It may have application in clinical laboratories, as well as in epidemiologic studies and antimalarial efficacy trials.