Statin Use and Liver Cancer Risk: A Meta-Epidemiological Study of Retrospective Cohort Studies by the Types of Constructed Cohort.

OBJECTIVE: Previous systematic reviews of retrospective cohorts (RSC) indicate that statin use decreases the risk of liver cancer. However, the summary effect size (sES) of the randomized controlled trials was not statistically significant. This study aimed to conduct a subgroup meta-analysis based on the types of constructed cohorts. METHODS: RSCs were selected from previous systematic reviews. Based on the characteristics of the source database (national vs. hospital) and the selection criteria of the subjects (population vs. patients), RSCs were categorized into three types of study cohorts: a national-based population cohort (NPo), national-based patient cohort (NPa), and hospital-based patient cohort (HPa). The sES and 95% confidence intervals were calculated using a random-effects model. RESULT: The 28 cohorts from 23 RSC were classified into 15 NPa, 7 NPo, and 6 HPa. The sES of 15 NPa decreased the liver cancer risk with statin intake history with statistical significance, but 7 NPo lost statistical significance. CONCLUSION: The lack of statistical significance in NPo supports the argument that the conclusions of existing systematic reviews on RSC have low validity. It is necessary to conduct a subgroup meta-analysis of the NPo, NPa, and HPa proposed in this study when conducting a systematic review of RSCs, which will evaluate various outcomes of a specific drug intake with time-varying exposure.

Trends of legionellosis reported in Jeju Province, Republic of Korea, 2015-2022.

BACKGROUND: The number of reported cases of Legionnaires' disease (LD) in the Republic of Korea surged nationally in 2016; however, in 2022, this number was higher in Jeju Province than the previous national peak. A descriptive epidemiological study was conducted to analyze trends in the incidence of reported LD cases in Jeju Island from 2015 to 2022. METHODS: The data for this study were obtained from case reports submitted to the Korea Disease Control and Prevention Agency through its Disease and Health Integrated Management System. The selection criteria were cases or suspected cases of LD reported among Jeju residents between 2015 and 2022. The 95% confidence interval of the crude incidence rate was calculated using the Poisson distribution. RESULTS: Since 2020, the incidence rate of LD in Jeju has risen sharply, showing a statistically significant difference from the national incidence rate. A particular medical institution in Jeju reported a significant number of LD cases. Screening with the urine antigen test (UAT) also increased significantly. CONCLUSION: Our findings indicate that the rapid increase in cases of LD in Jeju Province since 2020 was due to the characteristics of medical-care use among Jeju residents, which were focused on a specific medical institution. According to their clinical practice guidelines, this medical institution conducted UATs to screen patients suspected of pneumonia.

Epidemiological investigation of a food-borne outbreak in a kindergarten, Jeju Province, Korea.

OBJECTIVES: On Monday, September 6, 2021, at a kindergarten in Jeju Province, a large number of children vomited and developed food poisoning symptoms, and this necessitated an epidemiological investigation. METHODS: The team surveyed symptoms and food intake history of kindergarten children, teachers, and workers who ate lunch between September 2 (Thursday) and September 6 (Monday), excluding weekends. In addition to rectal swabs, environmental samples from preserved foods, cooking utensils, drinking water, and refrigerator handles were collected. Pulsed field gel electrophoresis (PFGE) for genetic fingerprint analysis was also performed. RESULTS: There were 19 cases among 176 subjects, which indicated an attack rate of 10.8%. The epidemic curve showed a unimodal shape, and the average incubation period was 2.6 hours. While no food was statistically significant in food intake history, the analysis of 35 rectal smear samples detected Bacillus cereus in 7 children, 4 teachers, and 1 cooking staff. Enterotoxins were also detected in 12 samples. Out of 38 environmental samples, B. cereus and enterotoxins were detected in the morning snack cereal, lunch bean sprouts, and afternoon snack steamed potatoes on Monday, September 6th. The result of the PFGE test on 10 isolates of B. cereus showed that there was no genetic homology. CONCLUSIONS: Our results indicated that this outbreak was simultaneously caused by various strains of B. cereus from the environment.

Statin Intake and Gastric Cancer Risk: An Updated Subgroup Meta-analysis Considering Immortal Time Bias.

A retrospective record-linkage study (RLS) based on medical records containing drug prescription histories involves immortal time bias (ITB). Thus, it is necessary to control for this bias in the research planning and analysis stages. Furthermore, a summary of a metaanalysis including RLSs that did not control for ITB showed that specific drugs had a preventive effect on the occurrence of the disease. Previous meta-analytic results of three systematic reviews evaluating the association between statin intake and gastric cancer risk showed that the summary hazard ratio (sHR) of the RLSs was lower than 1 and was statistically significant. We should consider the possibility of ITB in the sHR of RLSs and interpret the results carefully.

Diabetes History and Gastric Cancer Risk: Different Results by Types of Follow-Up Studies.

OBJECTIVE: The previous systematic reviews evaluating the association between diabetes history and gastric cancer risk showed inconsistent results. The aim was to check through a meta-epidemiological study that the conclusions of systematic reviews evaluating the association between diabetes history and gastric cancer risk might differ by the type of follow-up study. METHODS: The potential study subjects were follow-up studies selected from the seven systematic reviews obtained by searching PubMed using diabetes and gastric cancer keywords. The selection criterion was defined as a follow-up study for evaluating the association between the history of type 2 diabetes mellitus and the incidence of gastric cancer. And the values of RR and its 95%CI, which adjusted for the most confounders in each paper, were extracted for meta-analysis. A random-effects model meta-analysis by types of the follow-up study and sex group was performed. RESULTS: A total of 25 follow-up studies were finally selected for meta-analysis. They were classified into 16 retrospective and 9 prospective studies in types of follow-up study. The statistical significance between diabetes history and gastric cancer risk was found in retrospective studies (sRR=1.17, 95%CI: 1.02-1.34, I-squared =91.0%) but disappeared in prospective studies (sRR=1.09, 95%CI: 0.91-1.29, I-squared = 68.6%). Even in the analysis of subgroups by sex, statistical significance was not found in the prospective study, consistently. CONCLUSION: The main reason for the previous meta-analysis's diverse results for the association between diabetes history and gastric cancer risk was that the type of follow-up study was not reflected. According to the meta-analysis of prospective cohort studies, it could be concluded that there is no association between diabetes history and gastric cancer risk.

Circulating 25-hydroxyvitamin D levels and hypertension risk after adjusting for publication bias.

BACKGROUND: Previous systematic reviews reported that serum vitamin D deficiency was associated with risk of hypertension. The aim was to conduct a meta-epidemiological analysis for evaluating the potential effects of publication bias. METHODS: The selection criterion was defined as a follow-up study for evaluating the association between circulating 25-hydroxyvitam D level and hypertension risk in adults. A funnel plot and Egger's test were used to detect a publication bias. If a publication bias was identified, trim-and-fill analysis (TFA) with linear estimator was performed to estimate a summary relative risk (sRR). RESULTS: The meta-analysis of 13 cohorts resulted in the lower the vitamin D, the higher the risk of hypertension statistically significant (sRR, 1.22; 95% confidence interval [CI], 1.05 to 1.41). But The P-value of Egger's test (=0.015) and asymmetry of the funnel plot showed that there was a publication bias. TFA resulted in that statistical significance disappeared in the association between vitamin D level and hypertension risk in total cohorts (filled sRR, 1.03; 95% CI, 0.89 to 1.18) as well as men and women cohorts. CONCLUSIONS: The publication bias-adjusted results by TFA had no statistically significant association between vitamin D levels and the risk of hypertension. The significant results in previous systematic reviews might be interpreted as due to publication bias.

Human papillomavirus infection and gastric cancer risk: A meta-epidemiological review.

Gastric cancer (GC) is a multifactorial disease, and several modifiable risk factors have been reported. This review summarizes and interprets two previous quantitative systematic reviews evaluating the association between human papillomavirus (HPV) infection and GC risk. The results of two systematic reviews evaluating the same hypothesis showed a statistically significant difference in summary odds ratios and their 95% confidence intervals. Thus, it is necessary to conduct a subgroup analysis of Chinese and non-Chinese studies. Additional meta-analyses that control for heterogeneity are required. Reanalysis showed that all the Chinese studies had statistical significance, whereas the non-national studies did not. The funnel plot asymmetry and Egger's test confirmed publication bias in the Chinese studies. In addition, the proportion of HPV-positive cases in Chinese studies was 1.43 times higher than that in non-Chinese studies and 2.81 times lower in controls. Therefore, the deduced evidence is currently insufficient to conclude that HPV infection is associated with GC risk.

Sources of Infection Among Confirmed Cases of COVID-19 in Jeju Province, Korea.

OBJECTIVES: Jeju Province in Korea reported 627 coronavirus disease 2019 (COVID-19) cases between January 20, 2020, and March 31, 2021. This study analyzed the sources of infection among confirmed cases in Jeju Province, a self-governed island. METHODS: The sources of infection were broadly categorized as follows: (1) infections from overseas (confirmed patients who reported travel overseas or contact with overseas travelers); (2) infections from outside Jeju Province (confirmed patients who had visited other provinces or had contact with individuals who had traveled to other provinces in Korea); and (3) unknown sources of infection (confirmed patients who were infected following contact with an infected person whose source of infection was unknown). The chi-square test was used to analyze the differences in the distributions of related variables for each source of infection. RESULTS: Of the 627 confirmed cases, 38 (6.1%) were infections from overseas sources, 199 (31.7%) were from outside of Jeju Province, and 390 (62.2%) were from unknown sources. Jeju Province had no cases with an unknown source of infection during the first and second waves of the nationwide outbreak. CONCLUSIONS: Infections from overseas sources could be blocked from spreading to local communities in Jeju Province by conducting screening at the airport, along with the preemptive suspension of visa-free entry. In addition, considering the scale of the nationwide outbreak, measures must be established to delay outbreaks from unknown sources of infection caused by sources outside Jeju Province.

Coffee consumption and risk of type 2 diabetes mellitus in Asians: A meta-epidemiological study of population-based cohort studies.

BACKGROUND: Previous systematic reviews have consistently reported that coffee consumption has a preventive effect on the occurrence of type 2 diabetes mellitus (T2DM). However, further evaluations between coffee consumption and the risk of T2DM in Asian populations are needed. AIM: To conduct a meta-epidemiological study on systematic reviews evaluating the association between coffee consumption and the risk of T2DM in Asian people. METHODS: The selection criterion was defined as a population-based prospective cohort study evaluating the association between coffee consumption and the risk of T2DM in Asian populations, reporting the adjusted relative risk (RR) and its 95% confidence interval (CI) for potential confounders. A fixed-effect model meta-analysis was applied to calculate the summary RR and its 95%CI in less than 50% of the I 2 value indicating the level of heterogeneity. A two-stage fixed-effects dose-response meta-analysis (DRMA) was performed to calculate the risk per unit dose (a cup per day). RESULTS: A total of seven studies were selected in this meta-epidemiological study. The risk of T2DM in Asian populations was significantly reduced in the highest to the lowest dose group (summary RR = 0.73, 95%CI: 0.66-0.82; I 2 value = 0.0%). The DRMA showed that drinking one cup of coffee per day reduced the risk of T2DM in Asian populations by 8% (RR = 0.92, 95%CI: 0.90-0.95). CONCLUSION: These findings support the conclusion that coffee consumption has a protective effect on the occurrence of T2DM in Asian men and women.

Sex as an effect modifier in the association between alcohol intake and gastric cancer risk.

BACKGROUND: The results of previous meta-analyses evaluating the association between the alcohol intake and gastric cancer risk have reported that a statistical significance only for men. AIM: To investigate the different association between alcohol intake and gastric cancer risk between men and women. METHODS: The selection criteria included a prospective cohort study for evaluating alcohol intake and gastric cancer risk, with relative risks adjusted for potential confounders. Adjusted relative risk (RR) for the potential confounders and its 95% confidence interval (CI) in the highest vs lowest level were extracted from each study and a random-effects meta-analysis was conducted. Subgroup analyses by region, level of adjustment for smoking status, adjusting for body mass index, and year of publication were conducted. RESULTS: A meta-analysis of all 27 cohorts showed that alcohol intake increased the risk of gastric cancer (summary RR = 1.13, 95%CI: 1.04-1.23, I 2 = 58.2%). Further, 13 men's cohorts had higher summary RR while maintaining statistical significance, and only seven women's cohorts had no statistical significance. CONCLUSION: The present review suggests that alcohol consumption increases the risk of gastric cancer in men. These findings showed that the sex variable in the association between alcohol intake and gastric cancer risk seemed to be an effect modifier with an interaction term. It is necessary to re-estimate follow-up outcomes after stratifying for sex.

Use of oral contraceptives and risk of pancreatic cancer in women: A recalculated meta-analysis of prospective cohort studies.

In a recent systematic review and meta-analysis of observational studies, the author found potential errors in the selection and extraction processes. The recalculated summary relative risks and the results of a dose-response meta-analysis showed that oral contraceptive use may not be associated with the risk of pancreatic cancer in women.

Hormonal Replacement Therapy and Risk of Thyroid Cancer in Women: A Meta-Epidemiological Analysis of Prospective Cohort Studies.

OBJECTIVES: Many experimental studies have reported that female sex hormones involve thyroid cancer development because the incidence rate of thyroid cancer in women (TCW) is 3 times higher than in men. Three previous systematic reviews reporting no association between hormone replacement therapy (HRT) and TCW risk had the same search year of 2014. The aim was to reevaluate the association between HRT use and TCW risk using a meta-epidemiological study of prospective cohort studies. METHODS: The study preferentially used all studies selected by the existing systematic reviews and then secured an additional cohort from the list citing the studies. The selection criterion was defined as the prospective cohort study assessing the association between HRT and TCW risk by adjusted relative risk and its 95% confidence intervals (CI) from multivariate analysis. A random-effects model meta-analysis was applied to estimate summary relative risk (sRR) and its 95% CI. A publication bias was evaluated by Egger's test; moreover, the statistical significance level was set at 5%. RESULTS: Nine cohort studies were finally selected. The random-effect model was applied because of heterogeneity (I² = 64.3%). The sRR and its 95% CI from a random-effects model meta-analysis had no statistical significance in the association between HRT and TCW risk (sRR = 1.11; 95% CI, 0.98-1.26). Additionally, Egger's test revealed no statistical significance (P = 0.91). CONCLUSIONS: HRT is not associated with TCW risk based on the random-effects model meta-analysis of prospective cohort studies published until now.

History of Coffee Consumption and Risk of Alzheimer's Disease: a Meta-epidemiological Study of Population-based Cohort Studies.

BACKGROUND AND PURPOSE: Four published quantitative systematic reviews showed conflicting results involving coffee consumption and the risk of Alzheimer's disease (AD). The aim of this meta-epidemiological meta-analysis (MEMA) was to evaluate the factors underlying the conflicting results and estimate the effect size and direction of the AD risk associated with coffee consumption in population-based cohort studies. METHODS: The primary subjects of MEMA were derived from 3 cohort studies selected by the related systematic reviews. Additional studies involving the primary subjects were searched using citation discovery tools. Prospective cohort studies evaluating the association between coffee consumption and AD risk were selected. A fixed effects model was applied to estimate the summary relative risk (sRR) and its 95% confidence intervals (CIs). Subgroup analysis was conducted according to the level of coffee consumption. Egger's test was used to evaluate publication bias. RESULTS: Four cohort studies were finally selected. A total of 36,300 participants from Finland, Sweden, Germany, and the United States of America were selected. The sRR (and its 95% CI) (I-squared value) by highest-versus-lowest method was 0.98 (0.92-1.05) (0.0%). In addition, none of the results of subgroup analyses by the level of coffee consumption showed any statistical significance. CONCLUSIONS: This MEMA found that there was no association between coffee consumption and AD risk. Based on recent evidence suggesting that gene-environment interactions contribute to AD pathogenesis, it is necessary to conduct population-based cohort studies involving non-Caucasians.

Coffee Consumption and Pancreatic Cancer Risk: A Meta-Epidemiological Study of Population-based Cohort Studies.

OBJECTIVE: Previous systematic reviews evaluating the association between coffee consumption and pancreatic cancer showed inconsistent results. The aim was to conduct a meta-epidemiological study to explore further the association between coffee consumption and the incidence of pancreatic cancer. METHODS: The selection criteria were defined as a population-based prospective cohort study reporting adjusted relative risk (RR) and their 95% confidence interval (95%CI) of pancreatic cancer occurrence according to coffee consumption. Adjusted RR for the highest versus the lowest level of coffee consumption in each study was extracted. A fixed-effect model was applied to calculate a summary RR (sRR) and its 95%CI. Two-stage random-effects dose-response meta-analysis (DRMA) was performed to estimate the incidence risk per unit dose (cup per day). RESULTS: Twelve cohort studies were selected for meta-analysis. The total number of cohort participants was 3,230,053, and pancreatic cancer incidents were 10,587. The sRR of pancreatic cancer risk for the highest versus the lowest level of coffee consumption indicated no statistical significance (sRR=0.98, 95% CI: 0.88-1.10; I-squared=0.0%). Two-stage random-effect DRMA showed the non-linear relationship between the amount of coffee consumption and pancreatic cancer risk. And the RR for an increment of one cup per day of coffee consumption was 0.97 (95%CI: 0.91-1.04, P=0.42), without statistically significant. CONCLUSION: There was no association between coffee consumption habits and pancreatic cancer risk. And there was no statistical significance in the dose-response relationship between the amount of coffee consumption and pancreatic cancer risk. Finding the turning point would be important because it can be critical information for the prevention of pancreatic cancer. 
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Serum Folate Levels and Lung Cancer Risk: A Meta- Epidemiological Study of Population-based Case-Control Studies.

OBJECTIVE: While it has been claimed that lung cancer occurs due to epigenetic mechanisms, four systematic reviews were reported to investigate the association between serum folate levels and lung cancer risk. Considering some methodological problems founded in the systematic review, a meta-epidemiological study was conducted. METHODS: The selection criteria of this study were defined that a case-control study was conducted to determine the risk of lung cancer occurrence according to the concentration of serum folate and its results showed odds ratio and its 95% confidence interval. Additional paper was explored from cited lists of 4 papers selected by previous systematic reviews. Random effect model was applied if I-squared value was over 50%. RESULTS: For 5 case-control studies selected, the summary odds ratios (and their 95% confidence intervals) were 0.82 (0.74-0.90) in men, 0.70 (0.62-0.79) in former smokers, and 0.86 (0.75-1.00) in non-smokers. CONCLUSION: Higher foliate levels can decrease lung cancer risk in men and former smokers. Especially, the protective effect was highest in former smokers compared in non-smokers and current smokers. Based on these facts, folate fortification programs to reduce lung cancer risk would be focused on former smokers in men. And some epidemiological studies are needed to provide a hypothesis to explain the sex differences in the association between folate and lung cancer risk.

Coffee Consumption and Colon Cancer Risk: A Meta- Epidemiological Study of Asian Cohort Studies.

OBJECTIVE: A systematic review reported that coffee consumption would decrease risk of colon cancer in Asian women. But the systematic review arises the issue of duplication, so that a meta-epidemiological study was conducted. METHODS: The selection criteria were defined that a prospective cohort follow-up study conducted to evaluate coffee consumption and risk of colon cancer in Asian and showed adjusted relative risk and its 95% confidence interval. In order to conduct meta-analysis, the highest versus lowest method was applied to extract relative risk and its 95% confidence intervals of the highest category. Random effect model was applied if I-squared value was over 50%. RESULTS: After avoiding duplication, 9 cohort data were selected for meta-analysis. The summary relative risk (and their 95% confidence intervals) [I-square value] were 0.90 (95% CI: 0.79-1.03) [0.0%] in men, and 0.64 (95% CI: 0.36-1.15) [65.9%] in women, respectively. CONCLUSIONS: The results suggest that coffee consumption is not associated with the risk of colon cancer in Asian men and women. The findings of this study are consistent with the results of two systematic reviews conducted under the same hypothesis and selection criteria. Additional epidemiological studies are needed for the inflection of colon cancer risk as the dose of coffee increases and the difference in the protective effect by sex.

History of Diabetes Mellitus and Risk of Breast Cancer in Asian Women: A Meta-Epidemiological Analysis of Population-Based Cohort Studies.

OBJECTIVES: Previous quantitative systematic reviews conducting subgroup analyses by race have reported that the association between diabetes and breast cancer in Asian women was inconclusive. The aim of this meta-epidemiological study (MES) was to evaluate this association from additional population-based cohort studies. METHODS: The potential subjects of this MES were six Asian cohort studies selected by previous systematic reviews. Additional reports were found from the selected articles using citation discovery tools. The study with the longest follow-up period was selected among prospective studies of the same cohorts. A summary relative risk (sRR) and its 95% confidence intervals (CI) were calculated using random effect models. RESULTS: Four cohort studies on Asian women were finally selected. The participants were from the women population of Korea, Japan, China, and Taiwan and included a total of 1,448,254 women. The sRR (95% CI) (I-squared value) was 1.20 (0.98-1.46) (63.1%). CONCLUSIONS: This MES found that the history of diabetes mellitus was not associated with the risk of breast cancer in Asian women. As breast cancer in this population develops at a younger age, additional cohort studies are necessary to conduct a subgroup analysis by menopausal status at diagnosis of breast cancer in Asian women.

A Chinese Case of COVID-19 Did Not Show Infectivity During the Incubation Period: Based on an Epidemiological Survey.

Controversy remains over whether the novel coronavirus 2019 (COVID-19) virus may have infectivity during the incubation period before the onset of symptoms. The author had the opportunity to examine the infectivity of COVID-19 during the incubation period by conducting an epidemiological survey on a confirmed patient who had visited Jeju Island during the incubation period. The epidemiological findings support the claim that the COVID-19 virus does not have infectivity during the incubation period.