Background: Human papillomavirus (HPV) infection is a major global disease burden and the main cause of cervical cancer. Certain HPV genotypes, with are the most common etiologic pathogens and cause a significant disease burden, are being targeted for vaccine development. However, few studies have focused on the comparative effectiveness of the bivalent HPV (2v-HPV), quadrivalent HPV (4v-HPV), and nonavalent HPV (9v-HPV) vaccines against HPV strain-specific infection. This study investigated the comparative effects of these vaccines against genotype-specific infection. Materials and Methods: We conducted a pairwise and network meta-analysis of published randomized clinical trials of HPV vaccines according to sex and HPV infection status for nine HPV genotypes (HPV 6/11/16/18/31/33/45/52/58). Results: Overall, 10 randomized controlled trials (12 articles) were included in this study. In the network metaanalysis, no statistically significant differences were observed in the prevention of carcinogenic HPV strains (16/18/31/33/45/52/58) between the 2v-HPV and 4v-HPV vaccines in female HPV infection–naïve populations. However, the 9v-HPV vaccine showed a significantly superior effect compared with 2v-HPV and 4v-HPV vaccines in preventing HPV 31/33/45/52/58 infections. Although 2v-HPV and 4v-HPV vaccines provided some cross-protection against HPV 31/33/45/52/58 infections, the effect was significant only on HPV 31 infection. For HPV 16 and 18, neither statistically significant nor small differences were found in the prevention of HPV infection among the 2v-HPV, 4v-HPV, and 9v-HPV vaccines. Conclusion Our study complements previous understanding of how the effect of HPV vaccines differs according to the HPV genotype. This is important because HPV genotype prevalence varies among countries. We advocate for continued efforts in vaccinating against HPV, while public health agencies should consider the difference in the vaccine effect and HPV genotype prevalence when implementing HPV vaccination in public vaccination programs.

Background: External ventricular drain (EVD)-related infection (ERI) is a serious complication in neurosurgical patients. The estimated ERI rates range from 5 to 20 cases per 1,000 EVD catheter days. The pathophysiology of ERI is similar to central line-associated bloodstream infections (CLABSIs) stemming from skin-derived bacterial colonization. The use of bundle management can reduce CLABSI rates. Due to the pathogenic similarities between infections related to the two devices, we developed and evaluated the effectiveness of an ERI-bundle protocol based on CLABSI bundles. Methods: From November 2016 to November 2021, we conducted a study to evaluate the effectiveness of an ERI-bundle protocol. This study adopted a before-and-after trial, comparing the ERI rates for the 2 years before and 3 years after the introduction of the newly developed ERI-bundle protocol. We also analyzed the contributing factors to ERI using logistic regression analysis. Results: A total of 183 patients with 2,381 days of catheter use were analyzed. The ERI rate decreased significantly after the ERI-bundle protocol from 16.7% (14 of 84; 14.35 per 1,000 catheter days) to 4.0% (4 of 99; 3.21 per 1,000 catheter days) (P = 0.004). Conclusion Introduction of the ERI-bundle protocol was very effective in reducing ERI.

Background: Despite the advances in neonatology, the incidence of bronchopulmonary dysplasia (BPD) is increasing. It is important to prevent the development of BPD in the first place. The online BPD outcome estimator from National Institute of Children Health and Human Development and Neonatal Research Network is available. However, it is not applicable for Asians. Moreover, limits are set for birth weight and gestational weeks excluding those who may still have BPD. The aim of this study was to develop a prediction model for BPD using first hour perinatal and neonatal factors in Korean very low birth weight infants (VLBWIs). Methods: Data were collected for 8,022 VLBWIs with gestational age (GA) ≥ 22 weeks who were born between January 1, 2013 and December 31, 2016, and admitted to the neonatal intensive care units of the KNN. Multiple logistic regression models reanalyzed by stepwise selection with significant clinical indicators for BPD. PROC package was used to calculate the area under curve (AUC) and corresponding 95% confidence intervals. Moreover, it was used to search the best cut-off value. External validation was performed with the 2017 Korean neonatal network (KNN) data. Results: After all missing data were excluded, 4,600 VLBWIs were included in the training dataset of the prediction model. Predictability of presence of BPD was 90.8% and prediction P value cut off was 0.550. Five-minute Apgar score, birth weight, GA, sex, surfactant use were significant indicators. Predictability of severe BPD was 81.5% and prediction P value cut off was 0.160. Five-minute Apgar score, birth weight, maternal PIH, chronic maternal hypertension, GA, sex, respiratory distress syndrome, need of resuscitation at birth were significant indicators. After external validation, sensitivity and specificity did not change significantly. Conclusion From this study, high predictability was obtained using clinical parameters obtained within one hour of life. P value for prediction of each grade of BPD and equation for calculation was presented. It can be helpful for the early prediction of BPD in Korean VLBWI. This study will contribute to the prediction of BPD in Asians especially Korean VLBWIs, not currently included in the NICHD BPD online BPD predictor. In addition, the predictive power may be continuously increased with the cumulative data of KNN.

Background: Preterm infants are prone to sepsis owing to their immature innate immunity and prolonged hospitalization. We aimed to evaluate the association between late-onset sepsis (LOS) during hospitalization and neurodevelopmental delay at 18–24 months of corrected age in very low birth weight infants (VLBWIs), and to ascertain this association when adjusted for perinatal risk factors. Methods: This is a population-based study of VLBWIs born at 23–32 weeks of gestation between January 2014 and December 2017 who were enrolled in the Korean Neonatal Network. Bayley scales of infant development were evaluated at 18–24 months of corrected age in 2,098 infants. To test for LOS as a risk factor for neurodevelopmental delay, multiple logistic regression was used and adjusted for parental education status and clinical variables. Results: Blood culture positive LOS was identified in 419 (20.0%) infants. Cognitive and motor delays were found in 392 (18.7%) and 347 (16.5%) infants, respectively. When multivariate analysis was performed, LOS had a significant association with cognitive delay (odds ratio, 1.48; 95% confidence interval, 1.02–2.16), but no association with motor delay in VLBWIs. Both delays were significantly more frequent in cases of intraventricular hemorrhage (IVH) ≥ grade 3, periventricular leukomalacia (PVL), and intrauterine growth restriction (IUGR) and duration of mechanical ventilation. Male sex and necrotizing enterocolitis ≥ grade 2 had an effect on motor delay, whereas paternal college graduation affected cognitive delay. Conclusion In VLBWIs with LOS, there is a heightened risk of cognitive delays at 18–24 months of corrected age. Brain injury, such as severe IVH and PVL, duration of mechanical ventilation, and IUGR, were also associated with cognitive and motor delays.

Background: Despite the advances in neonatology, the incidence of bronchopulmonary dysplasia (BPD) is increasing. It is important to prevent the development of BPD in the first place. The online BPD outcome estimator from National Institute of Children Health and Human Development and Neonatal Research Network is available. However, it is not applicable for Asians. Moreover, limits are set for birth weight and gestational weeks excluding those who may still have BPD. The aim of this study was to develop a prediction model for BPD using first hour perinatal and neonatal factors in Korean very low birth weight infants (VLBWIs). Methods: Data were collected for 8,022 VLBWIs with gestational age (GA) ≥ 22 weeks who were born between January 1, 2013 and December 31, 2016, and admitted to the neonatal intensive care units of the KNN. Multiple logistic regression models reanalyzed by stepwise selection with significant clinical indicators for BPD. PROC package was used to calculate the area under curve (AUC) and corresponding 95% confidence intervals. Moreover, it was used to search the best cut-off value. External validation was performed with the 2017 Korean neonatal network (KNN) data. Results: After all missing data were excluded, 4,600 VLBWIs were included in the training dataset of the prediction model. Predictability of presence of BPD was 90.8% and prediction P value cut off was 0.550. Five-minute Apgar score, birth weight, GA, sex, surfactant use were significant indicators. Predictability of severe BPD was 81.5% and prediction P value cut off was 0.160. Five-minute Apgar score, birth weight, maternal PIH, chronic maternal hypertension, GA, sex, respiratory distress syndrome, need of resuscitation at birth were significant indicators. After external validation, sensitivity and specificity did not change significantly. Conclusion From this study, high predictability was obtained using clinical parameters obtained within one hour of life. P value for prediction of each grade of BPD and equation for calculation was presented. It can be helpful for the early prediction of BPD in Korean VLBWI. This study will contribute to the prediction of BPD in Asians especially Korean VLBWIs, not currently included in the NICHD BPD online BPD predictor. In addition, the predictive power may be continuously increased with the cumulative data of KNN.

Background: Preterm infants are prone to sepsis owing to their immature innate immunity and prolonged hospitalization. We aimed to evaluate the association between late-onset sepsis (LOS) during hospitalization and neurodevelopmental delay at 18–24 months of corrected age in very low birth weight infants (VLBWIs), and to ascertain this association when adjusted for perinatal risk factors. Methods: This is a population-based study of VLBWIs born at 23–32 weeks of gestation between January 2014 and December 2017 who were enrolled in the Korean Neonatal Network. Bayley scales of infant development were evaluated at 18–24 months of corrected age in 2,098 infants. To test for LOS as a risk factor for neurodevelopmental delay, multiple logistic regression was used and adjusted for parental education status and clinical variables. Results: Blood culture positive LOS was identified in 419 (20.0%) infants. Cognitive and motor delays were found in 392 (18.7%) and 347 (16.5%) infants, respectively. When multivariate analysis was performed, LOS had a significant association with cognitive delay (odds ratio, 1.48; 95% confidence interval, 1.02–2.16), but no association with motor delay in VLBWIs. Both delays were significantly more frequent in cases of intraventricular hemorrhage (IVH) ≥ grade 3, periventricular leukomalacia (PVL), and intrauterine growth restriction (IUGR) and duration of mechanical ventilation. Male sex and necrotizing enterocolitis ≥ grade 2 had an effect on motor delay, whereas paternal college graduation affected cognitive delay. Conclusion In VLBWIs with LOS, there is a heightened risk of cognitive delays at 18–24 months of corrected age. Brain injury, such as severe IVH and PVL, duration of mechanical ventilation, and IUGR, were also associated with cognitive and motor delays.

Purpose: The aim of this study was to evaluate the physiological and behavioral effects of auditory stimulation with their own parent’s voice on heart rate and sleep states of very-low-birth-weight infants (VLBWIs) in neonatal intensive care unit. Methods: The data of 28 VLBWIs at the Ewha Womans University Mokdong Hospital between October 2016 and May 2017 was analyzed. They were exposed to sounds similar to those of mothers’ heartbeat they had heard in the uterus and their own parent’s voice. Heart rate was assessed as the physiological responses and sleep state of infants as behavioral response. The sleep states were categorized into six states. The music intervention program was provided twice a week. Results: Twenty-eight babies with an average gestational age of 28 weeks (average birth weight of 1.09 kg) had undergone the sessions (average of 16 times) average of 16 times. During the initial period, there were no meaningful differences of the heart rates measured by the physiological functions before and after the sessions. However, as we move to the adaptive phase, the average heart rate was 156.96±12.22, and the pre-discharge was 149.11±12.01, which indicates meaningful differences (P<0.05). Infants’ behavioral function was statistically insignificant. Conclusion The music intervention techniques in the neonatal intensive care unit environment in Korea have provided positive influence to VLBWIs' physiological reactions. We were not able to come up with the relevant indicators during this phase of the study but we do plan to announce the future study results after indexing the observation results.

Purpose: The aim of this study was to evaluate the physiological and behavioral effects of auditory stimulation with their own parent’s voice on heart rate and sleep states of very-low-birth-weight infants (VLBWIs) in neonatal intensive care unit. Methods: The data of 28 VLBWIs at the Ewha Womans University Mokdong Hospital between October 2016 and May 2017 was analyzed. They were exposed to sounds similar to those of mothers’ heartbeat they had heard in the uterus and their own parent’s voice. Heart rate was assessed as the physiological responses and sleep state of infants as behavioral response. The sleep states were categorized into six states. The music intervention program was provided twice a week. Results: Twenty-eight babies with an average gestational age of 28 weeks (average birth weight of 1.09 kg) had undergone the sessions (average of 16 times) average of 16 times. During the initial period, there were no meaningful differences of the heart rates measured by the physiological functions before and after the sessions. However, as we move to the adaptive phase, the average heart rate was 156.96±12.22, and the pre-discharge was 149.11±12.01, which indicates meaningful differences (P<0.05). Infants’ behavioral function was statistically insignificant. Conclusion The music intervention techniques in the neonatal intensive care unit environment in Korea have provided positive influence to VLBWIs' physiological reactions. We were not able to come up with the relevant indicators during this phase of the study but we do plan to announce the future study results after indexing the observation results.

OBJECTIVE: To evaluate the effectiveness and safety of the combination of pegylated liposomal doxorubicin with carboplatin (CD) compared with those of carboplatin and paclitaxel (CP) for platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer in a real-world setting in Korea.METHODS: We enrolled relevant patients from 9 institutions. All patients received CD or CP as the second- or third-line chemotherapy in routine clinical practice during 2013–2018. The primary endpoints were progression-free survival (PFS) and toxicity. The secondary endpoint included the objective response rate (ORR).RESULTS: Overall, 432 patients (224 and 208 in the CD and CP groups, respectively) were included. With a median follow-up of 18.9 months, the median PFS was not different between the groups (12.7 vs. 13.6 months; hazard ratio, 1.161; 95% confidence interval, 0.923–1.460; p=0.202). The ORR was 74.6% and 80.1% in the CD and CP group, respectively (p=0.556). Age and surgery at relapse were independent prognostic factors. More patients in the CD group significantly experienced a grade 3 to 4 hematologic toxicity and hand-foot syndrome (13.8% vs. 6.3%), whereas grade 2 or more alopecia (6.2% vs. 36.1%), peripheral neuropathy (4.4% vs. 11.4%), and allergic/hypersensitivity reaction (0.4% vs. 8.5%) developed more often in the CP group.CONCLUSIONS: The safety and effectiveness of chemotherapy with CD in a real-world setting were consistent with the results from a randomized controlled study. The different toxicity profiles between the 2 chemotherapy (CD and CP) regimens should be considered in the clinical practice.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03562533
Alopecia ; Carboplatin ; Cohort Studies ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Follow-Up Studies ; Hand-Foot Syndrome ; Humans ; Korea ; Ovarian Neoplasms ; Paclitaxel ; Peripheral Nervous System Diseases ; Platinum ; Prognosis ; Recurrence ; Retrospective Studies

Background: and Purpose: The myelin oligodendrocyte glycoprotein (MOG) antibody is detected at a high rate in childhood acquired demyelinating syndrome (ADS). This study aimed to determine the diagnostic value of the MOG antibody in ADS and the spectrum of MOGantibody-positive demyelinating diseases in children. Methods: This study included 128 patients diagnosed with ADS (n=94) or unexplained encephalitis (n=34). The MOG antibody in serum was tested using an in-house live-cell-based immunofluorescence assay. Results: The MOG antibody was detected in 48 patients (46 ADS patients and 2 encephalitis patients, comprising 23 males and 25 females). Acute disseminated encephalomyelitis (ADEM) (35.4%) was the most-common diagnosis, followed by the unclassified form (17.4%), isolated optic neuritis (ON) (15.2%), neuromyelitis optica spectrum disorder (13.0%), multiple sclerosis (MS) (10.8%), other clinically isolated syndromes [monophasic event except ADEM, isolated ON, or transverse myelitis (TM)] (8.7%), and unexplained encephalitis (4.3%). At the initial presentation, 35 out of the 46 patients with ADS had brain lesions detected in magnetic resonance imaging, and 54% of these 35 patients had encephalopathy. Nine of the 11 patients without brain lesions exhibited only ON. Thirty-nine percent of the patients experienced a multiphasic event during the mean follow-up period of 34.9 months (range 1.4–169.0 months). Encephalopathy at the initial presentation was frequently confirmed in the monophasic group (p= 0.011). Conclusions MOG antibodies were identified in all pediatric ADS phenotypes except for monophasic TM. Therefore, the MOG antibody test is recommended for all pediatric patients with ADS, especially before a diagnosis of MS and for patients without a clear diagnosis.