Post-Marketing Safety Surveillance of Quadrivalent Influenza Vaccine (VaxigripTetra) in Children Aged 6 to 35 Months in South Korea.

INTRODUCTION: The quadrivalent inactivated split-virion influenza vaccine (QIV; VaxigripTetra®) was initially licensed in South Korea in 2017 for immunization against seasonal influenza in those aged ≥ 3 years, with the indicated age subsequently lowered to include those aged ≥ 6 months in 2018. Here, to comply with South Korean licensure requirements, we undertook a post-marketing surveillance study to assess the safety of QIV in children aged 6-35 months (i.e., extension of the previous age indication to include these young children) in routine clinical practice. METHODS: A multicenter, observational, active safety surveillance of children aged 6-35 months who received a single dose of QIV during a routine healthcare visit was undertaken in South Korea from 15 June 2018 to 14 June 2022. Solicited adverse events (AEs) and unsolicited non-serious AEs were recorded in diary cards, with serious adverse events (SAEs) notified to study investigators. RESULTS: This safety analysis included 676 participants. No AEs led to study termination, and no SAEs were reported. The most frequent solicited injection site reaction was pain in both the ≤ 23-month (12.2% [55/450]) and ≥ 24-month (15.5% [35/226]) age groups. The most frequent solicited systemic reactions were pyrexia and somnolence in the ≤ 23-month age group (6.0% [27/450] each), and malaise (10.6% [24/226]) in the ≥ 24-month age group. Overall, 208 (30.8%) participants experienced 339 unsolicited non-serious AEs, with nasopharyngitis the most common (14.1% [95/676]), and nearly all events (98.8% [335/339]) were considered unrelated to QIV. Grade 3 solicited reactions and unsolicited non-serious AEs were reported in five (0.7%) and three (0.4%) participants, respectively, all of whom recovered by day 7 after vaccination. CONCLUSION: This active safety surveillance study confirms that QIV is well tolerated in children aged 6-35 months in routine clinical practice in South Korea. There were no safety concerns observed in these young children.

Intentions to undergo primary screening with colonoscopy under the National Cancer Screening Program in Korea.

BACKGROUND: We sought to investigate intentions to undergo primary screening with colonoscopy in an attempt to predict future colorectal cancer screening behaviors and the feasibility of implementing colonoscopy as the primary screening modality for colorectal cancer in the National Cancer Screening Program (NCSP) of Korea. METHODS: Data were obtained from a nationwide online survey conducted in 2018. The survey included a total of 800 eligible adults aged over 45 years. Study measures included the history of screening colonoscopy within the past 10 years and intentions to undergo primary screening with colonoscopy under the NCSP based on the five constructs of the Health Belief Model. Logistic regression analysis was conducted to examine factors associated with intentions to undergo primary screening with colonoscopy. RESULTS: Approximately 77% of the participants expressed strong willingness to undergo primary screening with colonoscopy under the NCSP. Higher perceived severity and perceived benefits were significantly associated with stronger intentions to undergo screening with colonoscopy (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.10-2.14 and aOR, 2.74; 95% CI, 1.76-4.28, respectively). Greater perceived barriers (aOR, 0.65; 95% CI, 0.45-0.93) were significantly associated with weaker intentions. Cues to action elicited the strongest screening intentions (aOR, 8.28; 95% CI, 5.23-13.12). CONCLUSION: The current study findings highlight the need for increasing awareness of the severity of CRC and the benefits of colonoscopy screening. Family-orientated recommendation strategies and reducing complications may boost an individual's intentions to undergo colonoscopy.

Long-term Survival of 10,116 Korean Live Liver Donors.

OBJECTIVE: To evaluate the long-term mortality of Korean live liver donors using data from a national donor registry by comparing it with the mortality of the general population. SUMMARY OF BACKGROUND DATA: Although live liver donors generally have a healthy status, their long-term mortality has not been properly addressed in a large donor registry. METHODS: Data of 10,116 live liver donors were drawn from a mandated national registry of Korean live liver donors between 2000 and 2015. Matched controls were selected from the Korean National Health Insurance System-National Sample Cohort (NHIS-NSC). Median (range) follow-up of liver donors was 5.7 (0-15.9) years. Donors were 1:3 individually matched to controls by sex and 5-year age group; potential controls were from the whole NHIS-NSC (Control 1) or from NHIS-NSC after excluding people with contraindications to be organ donors (Control 2) (donor, n = 7538; Control 1, n = 28,248; Control 2, n = 28,248). RESULTS: Fifty-three deaths occurred after donation. Ten-year cumulative mortality of live liver donors was 0.9%. The most common cause of death was suicide (n = 19) followed by cancer (n = 9) and traffic accident (n = 7). In the matched control analysis, overall risk of death was significantly lower in donors than in Control 1 (P < 0.001), but higher than in Control 2 (P < 0.001). CONCLUSIONS: Liver donors have increased long-term mortality risk compared to similar healthy controls without contraindications to be organ donors. Therefore, long-term follow-up, including psychosocial support, is needed for live liver donors.

Smoking status before and after colorectal cancer diagnosis and mortality in Korean men: A population-based cohort study.

BACKGROUND: Smoking is a well-known risk factor for colorectal cancer incidence; however, the effect of smoking before and after cancer diagnosis on mortality has not been addressed well. Thus, we aimed to evaluate the association of prediagnosis and postdiagnosis smoking status and mortality among colorectal cancer patients. METHODS: A retrospective cohort consisted of 37,079 male colorectal cancer patients. Smoking status was defined from information within 2 years of colorectal cancer diagnosis for prediagnosis and at least 1 year later for postdiagnosis. The prediagnostic and postdiagnostic smoking status were categorized into four groups (nonsmoker/nonsmoker, nonsmoker/smoker, smoker/nonsmoker, and smoker/smoker). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazard model. RESULTS: During a median of 6.3 years of follow-up, a total of 3980 deaths and 2137 deaths from colorectal cancer occurred. The number of prediagnosis smokers were 11,100 and 62.4% of them quitted smoking after the diagnosis. Significantly elevated mortality rate in prediagnosis smokers was observed regardless of postdiagnosis smoking status (smoker/nonsmoker [HR, 1.30; 95% CI, 1.20-1.41] and smoker/smoker [HR, 1.21; 95% CI, 1.09-1.34]). Among patients treated with surgical operation only, those who quit smoking after diagnosis showed lower mortality rates compared to continual smokers (HR, 0.80; 95% CI, 0.67-0.96). CONCLUSIONS: Smoking before cancer diagnosis rather than postdiagnosis has stronger impact on prognosis colorectal cancer patients, and quitting smoking may improve survival, especially among early stage colorectal cancer patients.

Gallstones, Cholecystectomy and the Risk of Hepatobiliary and Pancreatic Cancer: A Nationwide Population-based Cohort Study in Korea.

Several epidemiological studies suggest a potential association between gallstones or cholecystectomy and hepatobiliary and pancreatic cancers (HBPCs). The aim of this study was to evaluate the risk of HBPCs in patients with gallstones or patients who underwent cholecystectomy in the Korean population. A retrospective cohort was constructed using the National Health Insurance Service-National Sample Cohort (NHIS-NSC). Gallstones and cholecystectomy were defined by diagnosis and procedure codes and treated as time-varying covariates. Hazard ratios (HRs) in relation to the risk of HBPCs were estimated by Cox proportional hazard models. Among the 704,437 individuals who were included in the final analysis, the gallstone prevalence was 2.4%, and 1.4% of individuals underwent cholecystectomy. Between 2002 and 2015, 487 and 189 individuals developed HBPCs in the gallstone and cholecystectomy groups, respectively. A significant association was observed between gallstones and all HBPCs (HR 2.16; 95% CI 1.92-2.42) and cholecystectomy and all HBPCs (HR 2.03; 95% CI 1.72-2.39). However, when 1-, 3-, and 5-year lag periods were applied, the HBPC and subsites risk approached zero. A significant association was observed between cholecystectomy and intrahepatic bile duct cancer (IBDC) (HR 2.68; 95% CI 1.63-4.40). When 1-, 3- and 5-year lag periods were applied, the IBDC risk after cholecystectomy was 2.86-fold (95% CI 1.68-4.85), 2.92-fold (95% CI 1.51-5.64), and 4.08-fold (95% CI 1.94-8.61) higher, respectively, than that in the comparison group. In conclusion, gallstone diagnosis and cholecystectomy seem to correlate with HBPCs, especially cholecystectomy and IBDC.

Wireless Ultrasound Surgical System with Enhanced Power and Amplitude Performances.

A wireless ultrasound surgical system (WUSS) with battery modules requires efficient power consumption with appropriate cutting effects during surgical operations. Effective cutting performances of the ultrasound transducer (UT) should be produced for ultrasound surgical knives for effective hemostasis performance and efficient dissection time. Therefore, we implemented a custom-made UT with piezoelectric material and re-poling process, which is applied to enhance the battery power consumption and output amplitude performances of the WUSS. After the re-poling process of the UT, the quality factor increased from 1231.1 to 2418 to minimize the unwanted heat generation. To support this UT, we also developed a custom-made generator with a transformer and developed 2nd harmonic termination circuit, control microcontroller with an advanced reduced instruction set computer machine (ARM) controller, and battery management system modules to produce effective WUSS performances. The generator with a matching circuit in the WUSS showed a peak-to-peak output voltage and current amplitude of 166 V and 1.12 A, respectively, at the resonant frequency. The performance with non-contact optical vibrators was also measured. In the experimental data, the developed WUSS reduced power consumption by 3.6% and increased the amplitude by 20% compared to those of the commercial WUSS. Therefore, the improved WUSS performances could be beneficial for hemostatic performance and dissection time during surgical operation because of the developed UT with a piezoelectric material and re-poling process.

Development of an Accurate Resonant Frequency Controlled Wire Ultrasound Surgical Instrument.

Our developed wire ultrasound surgical instrument comprises a bolt-clamped Langevin ultrasonic transducer (BLUT) fabricated by PMN-PZT single crystal material due to high mechanical quality factor and electromechanical coupling coefficient, a waveguide in the handheld instrument, and a generator instrument. To ensure high performance of wire ultrasound surgical instruments, the BLUT should vibrate at an accurate frequency because the BLUT's frequency influences hemostasis and the effects of incisions on blood vessels and tissues. Therefore, we implemented a BLUT with a waveguide in the handheld instrument using a developed assembly jig process with impedance and network analyzers that can accurately control the compression force using a digital torque wrench. A generator instrument having a main control circuit with a low error rate, that is, an output frequency error rate within ±0.5% and an output voltage error rate within ±1.6%, was developed to generate the accurate frequency of the BLUT in the handheld instrument. In addition, a matching circuit between the BLUT and generator instrument with a network analyzer was developed to transfer displacement vibration efficiently from the handheld instrument to the end of the waveguide. Using the matching circuit, the measured S-parameter value of the generator instrument using a network analyzer was -24.3 dB at the resonant frequency. Thus, our proposed scheme can improve the vibration amplitude and accuracy of frequency control of the wire ultrasound surgical instrument due to developed PMN-PZT material and assembly jig process.

Prognosis of Patients with Colorectal Cancer with Diabetes According to Medication Adherence: A Population-Based Cohort Study.

BACKGROUND: Diabetes mellitus is known to have a negative effect on colorectal cancer survival due to hyperinsulinemia or hyperglycemia, and medications such as metformin, which targets insulin resistance and hyperinsulinemia, have a preventive effect on the risk of death. The aim of this study was to compare the risk of death among patients with colorectal cancer with diabetes with different levels of adherence to oral antidiabetics. METHODS: National Health Information Database was used, which has all claims data for those who are registered for national health insurance in Korea, from 2002 to 2016, for conducting a retrospective cohort study. Newly diagnosed patients with colorectal cancer among diabetics were followed up from the date of diagnosis until death or December 31, 2016. The medication adherence was calculated as the proportion of days covered (PDC). The HR and 95% confidence interval (CI) for death were estimated using the low-adherence patients as a reference. RESULTS: A total of 33,841 diabetic patients with newly diagnosed colorectal cancer were followed for an average of 4.7 years. Patients with colorectal cancer with good adherence (PDC ≥ 80%) showed a reduced risk of death [HR (95% CI), 0.82 (0.78-0.86)] compared with those with poor adherence (PDC < 80%). A reduced risk of death was observed for all cancer subsites. CONCLUSIONS: The maintenance of good medication adherence for diabetes mellitus was related to a favorable prognosis of colorectal cancer. IMPACT: This study provides evidence that patients with colorectal cancer who are adherent to their diabetes medication will have better survival than patients who are not adherent.

Validity of Self-reported Stroke and Myocardial Infarction in Korea: The Health Examinees (HEXA) Study.

OBJECTIVES: Self-reported disease history is often used in epidemiological studies. In this study, we acquired the hospital records of subjects who self-reported stroke or myocardial infarction (MI) and evaluated the validity of the participants' self-reported disease history. We also determined the level of agreement between specialists and non-specialists. METHODS: Among the participants in the Health Examinees study, 1488 subjects self-reported stroke or MI during 2012-2017, and medical records were acquired for the 429 subjects (28.8%) who agreed to share their medical information. Each record was independently assigned to 2 medical doctors for review. The records were classified as 'definite,' 'possible,' or 'not' stroke or MI. If the doctors did not agree, a third doctor made the final decision. The positive predictive value (PPV) of self-reporting was calculated with the doctors' review as the gold standard. Kappa statistics were used to compare the results between general doctors and neurologists or cardiologists. RESULTS: Medical records from 208 patients with self-reported stroke and 221 patients with self-reported MI were reviewed. The PPV of self-reported disease history was 51.4% for stroke and 32.6% for MI. If cases classified as 'possible' were counted as positive diagnoses, the PPV was 59.1% for stroke and 33.5% for MI. Kappa statistics showed moderate levels of agreement between specialists and non-specialists for both stroke and MI. CONCLUSIONS: The validity of self-reported disease was lower than expected, especially in those who reported having been diagnosed with MI. Proper consideration is needed when using these self-reported data in further studies.

The Risk of Colorectal Cancer After Cholecystectomy or Appendectomy: A Population-based Cohort Study in Korea.

OBJECTIVES: We investigated the association between cholecystectomy or appendectomy and the subsequent risk of colorectal cancer (CRC) in the Korean population. METHODS: A retrospective cohort study was conducted with the National Health Insurance Service-National Sample Cohort of Korea; this sample was followed up from January 1, 2002, until the date of CRC incidence, loss to follow-up, or December 31, 2015. The exposure status of cholecystectomy and appendectomy was treated as a time-varying covariate. The calculated risk of CRC was stratified by follow-up period, and the association between these surgical procedures and CRC was investigated by a Cox regression model applying appropriate lag periods. RESULTS: A total of 707 663 individuals were identified for analysis. The study population was followed up for an average of 13.66 years, and 4324 CRC cases were identified. The hazard ratio (HR) of CRC was elevated in the first year after cholecystectomy (HR, 1.71; 95% confidence interval [CI], 1.01 to 2.89) and in the first year and 2-3 years after appendectomy (HR, 4.22; 95% CI, 2.87 to 6.20; HR, 2.34; 95% CI, 1.36 to 4.03, respectively). The HRs of CRC after applying 1 year of lag after cholecystectomy and 3 years of lag after appendectomy were 0.80 (95% CI, 0.57 to 1.13) and 0.77 (95% CI, 0.51 to 1.16), respectively. CONCLUSIONS: The risk of CRC increased in the first year after cholecystectomy and appendectomy, implying the possibility of bias. When appropriate lag periods after surgery were applied, no association was found between cholecystectomy or appendectomy and CRC.

Radiographic and histologic observations of sequential healing processes following ridge augmentation after tooth extraction in buccal-bone-deficient extraction sockets in beagle dogs.

OBJECTIVES: To evaluate dimensional ridge alterations and sequential healing processes following ridge augmentation after tooth extraction in damaged extraction sockets with buccal-bone-deficiency. MATERIAL AND METHODS: Bilateral dental roots of three mandibular premolars were extracted with entire removal of the buccal-bone plate in eight beagle dogs. Unilateral sites were grafted with biomaterials (test group) and contralateral sites were healed without grafting (control group). Observations were made after 1, 2, 4, and 8 weeks, and all sites were distributed evenly (n = 6 for each group and period). Radiographic/histomorphometric analyses were performed. RESULTS: In spontaneous healing of damaged extraction sockets, the dimension of regenerated alveolar ridge gradually increased until 4 weeks and then remained stable, but radiographic/histomorphometric analyses revealed evident dimensional shrinkage compared to the pristine tissue at 8 weeks in the coronal and middle areas. Bone grafting retained the pristine dimension of alveolar ridge, and newly formed bone area within the augmented space continuously expanded during the observational period to the outermost border of the space. CONCLUSIONS: Spontaneous healing of damaged extraction sockets caused substantial dimensional shrinkage. However, ridge augmentation can provide space into which new bone may grow continuously, resulting in the final dimensions comparable to those of the pristine alveolar ridge.

Trends in incidence and survival of esophageal cancer in Korea: Analysis of the Korea Central Cancer Registry Database.

BACKGROUND AND AIM: The diagnostic and therapeutic modalities of esophageal cancer have recently improved in Asia, and its prognosis is expected to change. This study provides a population-based report on the epidemiology of esophageal cancer in Korea. METHODS: Cancer incidence data from 1999 to 2013 were obtained from the Korea Central Cancer Registry, covering the entire population. Age-standardized incidence rates and annual percent changes were calculated according to subsites and histological types. Five-year relative survival rates were estimated for cases diagnosed between 1993 and 2013. Relative excess rates were compared between patients diagnosed from 2009 to 2013 and 2006 to 2008. RESULTS: The age-standardized incidence rates decreased from 8.8 per 100 000 populations in 1999 to 5.9 in 2013 with an annual percent change of -2.6% in men and -2.2% in women. The most common histological type was squamous cell carcinoma, accounting for 90.2% of all esophageal cancers in 2013, followed by adenocarcinomas (3.1%), and their incidences decreased. The proportion of localized and regional cancer tended to increase compared with that of distant cancer. Five-year relative survival of squamous cell carcinoma improved from 12.1% (1993-1995) to 34.6% (2009-2013). Relative excess rate was 0.72 (95% confidence interval 0.65-0.80) in localized stage and 0.88 (95% confidence interval, 0.82-0.95) in regional stage comparing patients diagnosed from 2009 to 2013 and 2006 to 2008. CONCLUSIONS: The incidence of esophageal cancer has decreased in Korea for the past 15 years, and 5-year survival rates have improved significantly. These increases may be attributable to more effective detection of early-stage disease.