Risk factors for delirium among patients with advanced cancer in palliative care: a multicenter, patient-based registry cohort in South Korea

OBJECTIVE: Previous studies have comprehensively investigated the preva-lence and various potential risk factors for de-lirium among patients with advanced cancer ad-mitted to the acute palliative care unit (APCU). Our objective was to evaluate the comprehen-sive association between delirium and various risk factors among patients with advanced can-cer in an acute palliative care setting using a pa-tient-based multicenter registry cohort.PATIENTS AND METHODS: We performed a multicenter, patient-based registry cohort study collected in South Korea between January 1, 2019, and December 31, 2020. Delirium was identified using a medical record review based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.RESULTS: In total, 2,124 eligible patients with advanced cancer in the APCU met the inclu-sion criteria. There were 127 out of 2,124 pa-tients (prevalence, 6.0%;95% CI, 5.0 to 7.1) with delirium during admission. Delirium in patients with advanced cancer was associated with age >70 years (OR, 1.793;95% CI, 1.246 to 2.581), male sex (OR, 1.675;95% CI, 1.131 to 2.479), no chemotherapy during hospitalization (OR, 2.019;95% CI, 1.236 to 3.298), hearing impairment (OR, 3.566;95% CI, 1.176 to 10.810), underweight (OR, 1.826;95% CI, 1.067 to 3.124), current use of opioid medication (OR, 1.942;95% CI, 1.264 to 2.982), previous history of delirium (OR, 12.497;95% CI, 6.920 to 22.568), and mental illness (OR, 2.333;95% CI, 1.251 to 4.352).CONCLUSIONS: In a large-scale multicenter patient-based registry cohort, delirium was asso-ciated with old age, male sex, no chemotherapy during hospitalization, hearing impairment, un-derweight, current use of opioid medication, and a history of delirium and mental illness. Our find-ings suggest physicians should pay attention to delirium in patients with advanced cancer admit-ted to the APCU with the above risk factors.

National trends in suicide-related behaviors among youths between 2005-2020, including COVID-19: a Korean representative survey of one million adolescents.

OBJECTIVE: It is difficult to conclude that COVID-19 is associated with a decrease in the suicide attempts rate by comparing only a short-term period. Therefore, it is necessary to examine attempted suicide rates through a trend analysis over a longer period. This study aimed to investigate an estimated long-term trend regarding the prevalence of suicide-related behaviors among adolescents in South Korea from 2005 to 2020, including COVID-19. SUBJECTS AND METHODS: We sourced data from a national representative survey (Korea Youth Risk Behavior Survey) and analyzed one million Korean adolescents aged 13 to 18 years (n=1,057,885) from 2005 to 2020. The 16-year trends regarding the prevalence of sadness or despair and suicidal ideation and attempt and the trend changes before and during COVID-19. RESULTS: Data of 1,057,885 Korean adolescents was analyzed (weighted mean age, 15.03 years; males, 52.5%; females, 47.5%). Although the 16-year trend in the prevalence of sadness or despair and suicide ideation and attempt consistently decreased (prevalence of sadness or despair between 2005-2008, 38.0% with 95% confidence interval [CI], 37.7 to 38.4 vs. prevalence in 2020, 25.0% [24.5 to 25.6]; suicide ideation between 2005-2008, 21.9% [21.6 to 22.1] vs. prevalence in 2020, 10.7% [10.3 to 11.1]; and suicide attempt between 2005-2008, 5.0% [4.9 to 5.2] vs. prevalence in 2020, 1.9% [1.8 to 2.0]), the downward slope decreased during COVID-19 (ßdiff in sadness, 0.215 with 95% CI 0.206 to 0.224; ßdiff in suicidal ideation, 0.245 [0.234 to 0.256]; and ßdiff in suicide attempt, 0.219 [0.201 to 0.237]) compared with pre-pandemic period. CONCLUSIONS: This study found that the observed risk of suicide-related behaviors during the pandemic was higher than expected through long-term trend analysis of the prevalence of sadness/despair and suicidal ideation and attempts among South Korean adolescents. We need a profound epidemiologic study of the change in mental health due to the pandemic's impact and the establishment of prevention strategies for suicide ideation and attempt.

17-year trends of body mass index, overweight, and obesity among adolescents from 2005 to 2021, including the COVID-19 pandemic: a Korean national representative study.

OBJECTIVE: There is a lack of pediatric studies that have analyzed trends in mean body mass index (BMI) and the prevalence of obesity and overweight over a period that includes the mid-stage of the COVID-19 pandemic. Thus, we aimed to investigate trends in BMI, overweight, and obesity among Korean adolescents from 2005 to 2021, including the COVID-19 pandemic. SUBJECTS AND METHODS: We used data from the Korea Youth Risk Behavior Web-based Survey (KYRBS), which is nationally representative of South Korea. The study included middle- and high-school students between the ages of 12 and 18. We examined trends in mean BMI and prevalence of obesity and/or overweight during the COVID-19 pandemic and compared these to those of pre-pandemic trends in each subgroup by gender, grade, and residential region. RESULTS: Data from 1,111,300 adolescents (mean age: 15.04 years) were analyzed. The estimated weighted mean BMI was 20.48 kg/m2 (95% CI, 20.46-20.51) between 2005 and 2007, and this was 21.61 kg/m2 (95% CI, 21.54-21.68) in 2021. The prevalence of overweight and obesity was 13.1% (95% CI, 12.9-13.3%) between 2005 and 2007 and 23.4% (95% CI, 22.8-24.0%) in 2021. The mean BMI and prevalence of obesity and overweight have gradually increased over the past 17 years; however, the extent of change in mean BMI and in the prevalence of obesity and overweight during the pandemic was distinctly less than before. The 17-year trends in the mean BMI, obesity, and overweight exhibited a considerable rise from 2005 to 2021; however, the slope during the COVID-19 pandemic (2020-2021) was significantly less prominent than in the pre-pandemic (2005-2019). CONCLUSIONS: These findings enable us to comprehend long-term trends in the mean BMI of Korean adolescents and further emphasize the need for practical prevention measures against youth obesity and overweight.

Cerebral venous thrombosis after ChAdOx1 nCoV-19 vaccination: a systematic review

OBJECTIVE: To perform a systematic review of case reports or case series regarding thrombosis with thrombocytopenia syndrome (TTS) and cerebral venous thrombosis (CVT) related to ChAdOx1 nCoV-19 vaccination to address the clinical features, laboratory findings, treatment modalities, and prognosis related with CVT. SUBJECTS AND METHODS: We included 64 TTS patients from 19 articles, 6 case series and 13 case reports, in which thrombosis occurred after the first dose of ChAdOx1 nCoV-19 vaccination published up to 30 June 2021 in Embase, ePubs, Medline/PubMed, Scopus, and Web of Science databases. RESULTS: Of the 64 TTS patients, 38 (59.3%) had CVT. Patients with CVT were younger (median 36.5 vs. 52.5 years, p<0.001), had lower fibrinogen levels (130 vs. 245 mg/dL, p=0.008), had more frequent history of intracerebral hemorrhage (ICH), and had higher mortality rate (48.6% vs. 19.2%, p=0.020) than that of patients without CVT. In multivariable analysis, the possibility of presence of CVT was higher in younger age groups [odd ratio (OR): 0.91, 95% confidence interval (CI): (0.86-0.97, p<0.001)] and those with accompanying intracerebral hemorrhage (ICH) (OR: 13.60, 95% CI (1.28-144.12, p=0.045). CONCLUSIONS: Our study demonstrated that CVT related to ChAdOx1 nCoV-19 vaccination was associated with younger age, low levels of fibrinogen, presence of ICH and more frequent mortality compared to those of non-CVT. If TTS occurs after ChAdOx1 nCoV-19 vaccination, the presence of CVT in patients with young age or ICH should be considered.

Cerebral venous thrombosis after ChAdOx1 nCoV-19 vaccination: a systematic review.

OBJECTIVE: To perform a systematic review of case reports or case series regarding thrombosis with thrombocytopenia syndrome (TTS) and cerebral venous thrombosis (CVT) related to ChAdOx1 nCoV-19 vaccination to address the clinical features, laboratory findings, treatment modalities, and prognosis related with CVT. SUBJECTS AND METHODS: We included 64 TTS patients from 19 articles, 6 case series and 13 case reports, in which thrombosis occurred after the first dose of ChAdOx1 nCoV-19 vaccination published up to 30 June 2021 in Embase, ePubs, Medline/PubMed, Scopus, and Web of Science databases. RESULTS: Of the 64 TTS patients, 38 (59.3%) had CVT. Patients with CVT were younger (median 36.5 vs. 52.5 years, p<0.001), had lower fibrinogen levels (130 vs. 245 mg/dL, p=0.008), had more frequent history of intracerebral hemorrhage (ICH), and had higher mortality rate (48.6% vs. 19.2%, p=0.020) than that of patients without CVT. In multivariable analysis, the possibility of presence of CVT was higher in younger age groups [odd ratio (OR): 0.91, 95% confidence interval (CI): (0.86-0.97, p<0.001)] and those with accompanying intracerebral hemorrhage (ICH) (OR: 13.60, 95% CI (1.28-144.12, p=0.045). CONCLUSIONS: Our study demonstrated that CVT related to ChAdOx1 nCoV-19 vaccination was associated with younger age, low levels of fibrinogen, presence of ICH and more frequent mortality compared to those of non-CVT. If TTS occurs after ChAdOx1 nCoV-19 vaccination, the presence of CVT in patients with young age or ICH should be considered.

Apparently healthy adults with high serum gamma-glutamyl transferase levels are at increased risk of asthma development in the near future: a Korean nationwide cohort study

OBJECTIVE: Serum gamma-glutamyl transferase (GGT). an indicator of oxidative stress and/or a chronic inflammatory process, is associated with the levels of leukotrienes and other inflammatory mediators that play a critical role in the pathogenesis of asthma. This study aimed at investigating whether apparently healthy subjects with higher serum GGT levels at a national health check-up are at an increased risk of developing asthma in the near future. PATIENTS AND METHODS: We analyzed 564.213 Korean adults, aged 20-80 years who underwent a national general health examination, including measurement of baseline serum GGT between 2003 and 2015. using data from a largescale representative cohort of the Korean population. Data were analyzed using a Cox proportional hazards regression analysis. RESULTS: In total, 516,956 participants were included in the final analysis. During the mean follow-up period of 8 years (standard deviation, 4.0), 7,439 incident asthma events occurred. We then classified the male and female participants according to quartiles of blood GGT levels (males: <= 20, 21-30, 31-51, and >= 52 IU/L: females: <= 12. 13-16, 17-22, and >= 23 IU/L. respectively). The adjusted hazard ratio (aHR) for incident asthma was significantly greater for subjects in the highest GGT quartile than for those in the lowest GGT quartile (aHR, 1.47: 95% confidence intervals, 1.36-1.59). Further, there was a significant linear trend across quartiles with regard to asthma (p(trend)<0 .001). We estimated the optimal cut-off values (using the minimum p-value approach) as 35IU/L for the total population. 35 IU/L for males, and 36 IU/L for females, respectively. CONCLUSIONS: Clinicians should be aware of the risk of incident asthma in healthy subjects with elevated GGT levels. Our findings advance our understanding of asthma pathogenesis.

Trends in body mass index changes among Korean adolescents between 2005-2020, including the COVID-19 pandemic period: a national representative survey of one million adolescents.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on weight gain in children and adolescents remains unknown. We aimed to identify an estimated 15-year trend in mean body mass index (BMI) changes and prevalence of obesity and overweight among Korean adolescents from 2005 to 2020, including the period of the COVID-19 pandemic. PATIENTS AND METHODS: We analyzed data taken from a nationwide survey (Korea Youth Risk Behavior Survey), between 2005 and 2020. Representative samples of one million Korean adolescents aged 13-18 years (n=1,057,885) were examined. The 15-year trends in mean BMI and proportion of obesity or overweight, and the changes due to the COVID-19 pandemic were analyzed. RESULTS: The data of 1,057,885 Korean adolescents were analyzed (mean age: 14.98 years; females, 48.4%). The estimated weighted mean BMI was 20.5 kg/m2 [95% confidence interval (CI), 20.4-20.5] from 2005 to 2008 and 21.5 kg/m2 (95% CI, 21.4-21.6) in 2020 (during the COVID-19 pandemic). Although the 15-year trend of mean BMI gradually increased, the change in mean BMI before and during the pandemic significantly lessened (ßdiff, -0.027; 95% CI, -0.028 to -0.026). The 15-year (2005-2020) trend changes in the prevalence of obesity and overweight were similar (obesity prevalence from 2005-2008, 3.2%; 95% CI, 3.1-3.3 vs. obesity prevalence in 2020, 8.6%; 95% CI, 8.2-9.0; ßdiff, -0.309; 95% CI, -0.330 to -0.288). CONCLUSIONS: The 15-year trend of overall mean BMI and obesity and overweight prevalence demonstrated a significant increase; however, its slope decreased during the pandemic. These landmark results suggest the need for the development of precise strategies to prevent pediatric obesity and overweight during the COVID-19 pandemic.

COVID-19 susceptibility and clinical outcomes in autoimmune inflammatory rheumatic diseases (AIRDs): a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to assess the susceptibility to and clinical outcomes of COVID-19 in autoimmune inflammatory rheumatic disease (AIRD) and following AIRD drug use. MATERIALS AND METHODS: We included observational and case-controlled studies assessing susceptibility and clinical outcomes of COVID-19 in patients with AIRD as well as the clinical outcomes of COVID-19 with or without use of steroids and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). RESULTS: Meta-analysis including three studies showed that patients with AIRD are not more susceptible to COVID-19 compared to patients without AIRD or the general population (OR: 1.11, 95% CI: 0.58 to 2.14). Incidence of severe outcomes of COVID-19 (OR: 1.34, 95% CI: 0.76 to 2.35) and COVID-19 related death (OR: 1.21, 95% CI: 0.68 to 2.16) also did not show significant difference. The clinical outcomes of COVID-19 among AIRD patients with and without csDMARD or steroid showed that both use of steroid (OR: 1.69, 95% CI: 0.96 to 2.98) or csDMARD (OR: 1.35, 95% CI: 0.63 to 3.08) had no effect on clinical outcomes of COVID-19. CONCLUSIONS: AIRD does not increase susceptibility to COVID-19, not affecting the clinical outcome of COVID-19. Similarly, the use of steroids or csDMARDs for AIRD does not worsen the clinical outcome.

Prevalence of allergic diseases among Korean adolescents during the COVID-19 pandemic: comparison with pre-COVID-19 11-year trends.

OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, emergency department utilization and hospitalization rates for allergic diseases declined and the severity of allergies among admitted patients was low. This study aimed to determine the prevalence of allergic diseases among adolescents and the changes in trend during the COVID-19 pandemic compared with those during the preceding 11 years. SUBJECTS AND METHODS: We analyzed data from the nationwide web-based self-report Korea Youth Risk Behavior Survey. From 2009 to 2020, adolescents aged 13-18 years participated in the survey. The survey period was divided into pre-pandemic Periods I (2009-2011), II (2012-2014), III (2015-2017), and IV (2018-2019) and the pandemic period (Period V, 2020). The current prevalence of asthma, allergic rhinitis, atopic dermatitis, allergic morbidity (having at least one of the three conditions) and changes in the prevalence before and during the COVID-19 pandemic were analyzed. RESULTS: Data of 787,043 participants were analyzed after weighting the study population (mean age, 15.1 years; males, 52.3%). The prevalence of asthma, allergic rhinitis, atopic dermatitis, and allergic morbidity was 2.1%, 18.4%, 6.8%, and 23.6%, respectively. The prevalence of allergic morbidity increased between Periods I and IV but declined significantly from Periods IV to V. From Periods I to IV, the prevalence of asthma decreased, the prevalence of allergic rhinitis increased, and the prevalence of atopic dermatitis remained unchanged. During Period V, the prevalence of all three conditions decreased. CONCLUSIONS: It is necessary to update management measures and develop relevant policies in response to the altered prevalence of allergic diseases since the outbreak of COVID-19.

Neuropsychological adverse drug reactions of Remdesivir: analysis using VigiBase, the WHO global database of individual case safety reports

OBJECTIVE: Although remdesivir (GS-5734) has recently demonstrated clinical benefits against the pandemic outbreak of coronavirus disease 2019 (COVID-19), neuropsychological adverse reactions (ADRs) remain to be examined in real-world settings. Therefore, we aimed to identify and characterize the neuropsychological ADRs associated with remdesivir use. MATERIALS AND METHODS: We obtained data for this international pharmacovigilance cohort study from individual case safety reports (ICSRs) in a World Health Organization database (VigiBase) from the first report on remdesivir on February 17, 2020, until August 30, 2020 (n=1,403,532). ADRs reported to be relevant to remdesivir were compared with the full database by using a Bayesian neural network method to calculate the information component (IC). RESULTS: A total of 2,107 reported cases of neuropsychological ADRs suspected to be associated with remdesivir were identified from among all ICSRs in the database during the observation period. Although 108 neuropsychological ADRs (64 neurologic events and 44 psychologic events) were reported in association with the medication, no statistically significant pharmacovigilance signal could be detected;the ICO25 value was negative for all of the neuropsychological dysfunctions (anxiety [n=13, 0.62%], seizures [n=12, 0.57%], lethargy [n=6, 0.28%], agitation [n=5, 0.25%], cerebral infarction [n=3, 0.14%]. ischemic stroke [n=3, 0.14%], and hemiparesis [n=3, 0.14%]). CONCLUSIONS: Our study demonstrates that remdesivir, a novel drug applied to the treatment of COVID-19, does not have a significant association with adverse neurologic or psychiatric reactions in the real-world setting.

ASSOCIATION BETWEEN EPIRETINAL MEMBRANE, EPIRETINAL PROLIFERATION, AND PROGNOSIS OF FULL-THICKNESS MACULAR HOLE CLOSURE

Purpose: To demonstrate the effects of epiretinal membrane (ERM) and epiretinal proliferation on surgical outcomes for full-thickness macular hole. Methods: Nested case-control study with propensity score matching. Patients operated on for full-thickness macular hole between January 2011 and March 2020 were enrolled. The primary outcome was failure of the macular hole closure, and the secondary outcome was unfavorable hole closure (V or l type closure) at 6 months after the surgery. Results: Five hundred and thirty-four eyes of 534 patients met the inclusion criteria. After 1:1 propensity score matching (127 pairs), patients demonstrating ERM were more likely to have a failure of hole closure (adjusted odds ratio, 2.71;95% confidence interval, 1.19-6.14) and unfavorable hole closure (adjusted odds ratio, 2.07;95% confidence interval, 1.16-3.71). Epiretinal membrane spanning the hole margin (hole marginal ERM) greatly increased the likelihood of unfavorable hole closure (adjusted odds ratio, 2.13;95% confidence interval, 1.12-4.07). Patients with hole marginal-ERM + epiretinal proliferation were more likely to have a failure of hole closure (38.4%) compared with those with no ERM (11.8%). Conclusion: Patients with ERM had a higher risk for adverse surgical outcomes for full-thickness macular hole closure. The location of the ERM relative to the macular hole and the presence of epiretinal proliferation might affect the surgical outcomes for full-thickness macular hole closure.

Suicide associated with COVID-19 infection: an immunological point of view.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a pandemic and leading cause of death. Beyond the deaths directly caused by the virus and the suicides related to the psychological response to the dramatic changes as socioeconomic related to the pandemic, there might also be suicides related to the inflammatory responses of the infection. Infection induces inflammation as a cytokine storm, and there is an increasing number of studies that report a relationship between infection and suicide. MATERIALS AND METHODS: We searched the World Health Organization status report and the PubMed database for keywords (COVID-19, suicide, infection, inflammation, cytokines), and reviewed five cytokine pathways between suicide and inflammation using two meta-analyses and two observational studies starting from November 31, 2020, focusing on the relationship between suicide and inflammation by infection. First, we discussed existing evidence explaining the relationship between suicidal behaviors and inflammation. Second, we summarized the inflammatory features found in COVID-19 patients. Finally, we highlight the potential for these factors to affect the risk of suicide in COVID-19 patients. RESULTS: Patients infected with COVID-19 have high amounts of IL-1ß, IFN-γ, IP10, and MCP1, which may lead to Th1 cell response activation. Also, Th2 cytokines (e.g., IL-4 and IL-10) were increased in COVID-19 infection. In COVID-19 patients, neurological conditions, like headache, dizziness, ataxia, seizures, and others have been observed. CONCLUSIONS: COVID-19 pandemic can serve as a significant environmental factor contributing directly to increased suicide risk; the role of inflammation by an infection should not be overlooked.

Epidemiological and clinical characteristics of 5,628 patients with coronavirus disease 2019 in South Korea: A nationwide multicenter study

Purpose: There are limited data on the epidemiological and clinical characteristics and outcomes in Korean patients with laboratory-confirmed coronavirus disease 2019 (COVID-19). We aimed to describe the epidemiological and clinical characteristics and outcomes of patients with COVID-19 using the Korean nationwide multicenter database. Methods: In this nationwide multicenter study, we included all confirmed patients of COVID-19 in South Korea from February 1 to April 30, 2020. Subjects were classified into 3 age groups: those at younger than 10 years (children), 10 to 20 years (adolescents), and 20 years or more (adults). Cases were confirmed by laboratory testing using real-time reverse transcriptase-polymerase chain reaction assay and analyzed for epidemiological and clinical features and outcomes. Patents were followed up until April 30, 2020. Results: Of 5,628 patients with COVID-19 (2,320 males [41.2%] and 3,308 females [58.8%]), there were 66 children (1.2%), 206 adolescents (3.7%), and 5,356 adults (95.2%). The common comorbidities were hypertension (1,201, 21.3%), diabetes (691, 12.3%), dementia (224, 4.0%), chronic heart disease (179, 3.2%), cancer (145, 2.6%), and asthma (128, 2.3%). The common presenting symptoms were cough (2,341, 41.6%), sputum (1,619, 28.8%), fever (1,305, 23.2%), headache (967, 17.2%), myalgia (926, 16.5%), and pharyngodynia (881, 15.7%). One hundred sixty-five patients (2.1%) were confirmed as having moderate or severe COVID-19 and 118 (2.1%) as having severe COVID-19. Conclusion: Our descriptive study provides the epidemiological and clinical characteristics and outcomes of patients with laboratory-confirmed COVID-19 in South Korea.

Risk factors of COVID-19 mortality: a systematic review of current literature and lessons from recent retracted articles.

OBJECTIVE: Recently, two influential articles that reported the association of (hydroxy)chloroquine or angiotensin converting enzyme (ACE) inhibitors and coronavirus disease 2019 (COVID-19) mortality were retracted due to significant methodological issues. Therefore, we aimed to analyze the same clinical issues through an improved research method and to find out the differences from the retracted papers. We systematically reviewed pre-existing literature, and compared the results with those of the retracted papers to gain a novel insight. MATERIALS AND METHODS: We extracted common risk factors identified in two retracted papers, and conducted relevant publication search until June 26, 2020 in PubMed. Then, we analyzed the risk factors for COVID-19 mortality and compared them to those of the retracted papers. RESULTS: Our systematic review demonstrated that most demographic and clinical risk factors for COVID-19 mortality were similar to those of the retracted papers. However, while the retracted paper indicated that both (hydroxy)chloroquine monotherapy and combination therapy with macrolide were associated with higher risk of mortality, our study showed that only combination therapy of hydroxychloroquine and macrolide was associated with higher risk of mortality (odds ratio 2.33; 95% confidence interval 1.63-3.34). In addition, our study demonstrated that use of ACE inhibitors or angiotensin receptor blockers (ARBs) was associated with reduced risk of mortality (0.77; 0.65-0.91). CONCLUSIONS: When analyzing the same clinical issues with the two retracted papers through a systematic review of randomized controlled trials and relevant cohort studies, we found out that (hydroxy)chloroquine monotherapy was not associated with higher risk of mortality, and that the use of ACE inhibitors or ARBs was associated with reduced risk of mortality in COVID-19 patients.