Persistent differences in the immunogenicity of the two COVID-19 primary vaccines series, modulated by booster mRNA vaccination and breakthrough infection.

INTRODUCTION: The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear. METHODS: A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike1) and beta and gamma variant (Spike2) were utilized. RESULTS: A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike1 and Spike2 proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike2 response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05). CONCLUSION: Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs.

Antimicrobial Use and Carbapenem-Resistant Enterobacterales in Korea: A Nationwide Case-Control Study With Propensity Score Matching.

BACKGROUND: Nationwide research on the association between carbapenem-resistant Enterobacterales (CREs) and antibiotic use is limited. METHODS: This nested case-control study analyzed Korean National Health Insurance claims data from April 2017 to April 2019. Based on the occurrence of CRE, hospitalized patients aged ≥ 18 years were classified into CRE (cases) and control groups. Propensity scores based on age, sex, modified Charlson comorbidity score, insurance type, long-term care facility, intensive care unit stay, and acquisition of vancomycin-resistant Enterococci were used to match the case and control groups (1:3). RESULTS: After matching, the study included 6,476 participants (1,619 cases and 4,857 controls). Multivariable logistic regression analysis revealed that the utilization of broad-spectrum antibiotics, such as piperacillin/tazobactam (adjusted odds ratio [aOR], 2.178; 95% confidence interval [CI], 1.829-2.594), third/fourth generation cephalosporins (aOR, 1.764; 95% CI, 1.514-2.056), and carbapenems (aOR, 1.775; 95% CI, 1.454-2.165), as well as the presence of comorbidities (diabetes [aOR, 1.237; 95% CI, 1.061-1.443], hemiplegia or paraplegia [aOR, 1.370; 95% CI, 1.119-1.679], kidney disease [aOR, 1.312; 95% CI, 1.105-1.559], and liver disease [aOR, 1.431; 95% CI, 1.073-1.908]), were significantly associated with the development of CRE. Additionally, the CRE group had higher mortality (8.33 vs. 3.32 incidence rate per 100 person-months, P < 0.001) and a total cost of healthcare utilization per person-month (15,325,491 ± 23,587,378 vs. 5,263,373 ± 14,070,118 KRW, P < 0.001) than the control group. CONCLUSION: The utilization of broad-spectrum antibiotics and the presence of comorbidities are associated with increasing development of CRE. This study emphasizes the importance of antimicrobial stewardship in reducing broad-spectrum antibiotic use and CRE disease burden in Korea.

Prevalence and Associated Factors of Depression and Anxiety Among Healthcare Workers During the Coronavirus Disease 2019 Pandemic: A Nationwide Study in Korea.

BACKGROUND: A healthcare system's collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. METHODS: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. RESULTS: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. CONCLUSION: In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

Effect of Regdanvimab on Mortality in Patients Infected with SARS-CoV-2 Delta Variants: A Propensity Score-Matched Cohort Study.

INTRODUCTION: Regdanvimab, a monoclonal antibody pharmaceutical, is the first Korean drug approved for treating coronavirus disease 2019 (COVID-19). We analyzed the therapeutic efficacy of regdanvimab in patients with the COVID-19 delta variant infection. METHODS: We retrospectively reviewed the electronic medical records of patients hospitalized at two Korean tertiary COVID-19 hospitals with COVID-19 delta variant infection between May 26, 2021, and January 30, 2022. To analyze the therapeutic efficacy of regdanvimab, the patients were divided into regdanvimab and non-regdanvimab groups and were 1:1 propensity-score (PS)-matched on age, severity at admission, and COVID-19 vaccination history. RESULTS: Of 492 patients, 262 (53.3%) and 230 (46.7%) were in the regdanvimab and non-regdanvimab groups, respectively. After PS matching the groups on age, severity at admission, and COVID-19 vaccination history, each group comprised 189 patients. The 30-day hospital mortality rates (0.0% vs. 1.6%, p = 0.030), proportions of patients with exacerbated conditions to severe/critical/died (9.5% vs. 16.4%, p = 0.047), proportions who received oxygen therapy because of pneumonia exacerbation (7.4% vs. 16.4%, p = 0.007), and proportions with a daily National Early Warning Score ≥ 5 from hospital day 2 were significantly lower in the regdanvimab group. CONCLUSIONS: We showed that regdanvimab reduced the exacerbation rates of conditions and mortality in patients with the COVID-19 delta variant infection. Thus, it is recommended to streamline the drug approval system during epidemics of new variant viruses to improve the availability and usage of therapeutics for patients. To facilitate this, relevant institutional support is required.

Principles and practices of antimicrobial stewardship programs in Korea.

This review addresses the escalating challenge posed by antibiotic resistance, highlighting its profound impact on global public health, including increased mortality rates and healthcare expenditures. The review focuses on the need to adopt the One Health approach to effectively manage antibiotic usage across human, animal, and environmental domains. Antimicrobial stewardship programs (ASPs) are considered as comprehensive strategies that encompass both core and supplementary initiatives aimed at enhancing prudent antibiotic use. The 2021 "Guidelines on Implementing ASP in Korea" introduced such strategies, with a strong emphasis on fostering multidisciplinary and collaborative efforts. Furthermore, the "Core Elements for Implementing ASPs in Korean General Hospitals," established in 2022, provide a structured framework for ASPs, delineating leadership responsibilities, the composition of interdisciplinary ASP teams, a range of interventions, and continuous monitoring and reporting mechanisms. In addition, this review examines patient-centric campaigns such as "Speak Up, Get Smart" and emphasizes the pivotal role of a multidisciplinary approach and international cooperation in addressing the multifaceted challenges associated with antibiotic resistance.

Association between obesity and cancer risk in HIV-infected Asians.

INTRODUCTION: This study aimed to investigate the association between obesity and cancer risk as well as site-specific cancer risks in adults with HIV using a nationwide health screening database in Korea. METHODS: Of the 16,671 adults with a new diagnosis of HIV from 2004 to 2020, 456 incident cancer cases and 1,814 individually matched controls by sex, year of birth, year of HIV diagnosis, and follow-up duration (1:4 ratio) were included in this nested case-control study. The association between obesity (body mass index ≥25 kg/m 2 ) and cancer risks was estimated and presented as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the 456 cancer incident cases, there were 146 AIDS-defining cancer cases and 310 non-AIDS-defining cancer cases. Compared with non-obese adults with HIV, obese adults with HIV were at higher risk of non-AIDS-defining cancer (OR = 1.478, 95% CI = 1.118-1.955). Otherwise, the overall risk of AIDS-defining cancer (OR = 0.816, 95% CI = 0.520-1.279) and each type of AIDS-defining cancer (Kaposi sarcoma and non-Hodgkin's lymphoma) were not high in obese adults with HIV. Of the specific types of non-AIDS-defining cancers, obesity was associated with an increased risk of colorectal cancer (OR = 3.090, 95% CI = 1.110-8.604) and liver, bile duct, and pancreatic cancers (OR = 2.532, 95% CI = 1.141-5.617). CONCLUSIONS: Obesity, which is one of the important health concerns in HIV management, was associated with an increased risk of non-AIDS-defining cancer but not AIDS-defining cancer.

Characteristics of long COVID and the impact of COVID-19 vaccination on long COVID 2 years following COVID-19 infection: prospective cohort study.

This prospective cohort study aimed to identify characteristics of long COVID and any potential mitigating effects of COVID-19 vaccinations in patients 24 months following COVID-19 infection. Adult patients diagnosed with COVID-19 between February 17, 2020, and March 24, 2020, were scheduled to visit the study hospital four times (6, 12, 18, and 24 months after infection) to assess their symptoms, quality of life, and mental health. Among the 235 patients, 121 (51.5%) completed the study visits. Of these, 59.5% were female, with a median age of 52 years. Mild to moderate disease severity were identified in 101 (83.4%) patients. A total of 75 participants (62.0%) were still experiencing long COVID symptoms 24 months after acute infection. Fatigue, amnesia, difficulty concentrating, and insomnia were the most common symptoms. The frequency of neuropsychiatric symptoms did not differ based on vaccination status or the number of doses received. Quality of life improved over time for the participants, but 32.2% of respondents still reported anxiety/depression at the end of the study. Overall, our cohort demonstrates that long COVID can persist up to 24 months after COVID-19 infection, affecting mental health and quality of life.

Analysis of microbiological tests in patients withholding or withdrawing life-sustaining treatment at the end stage of life in 2 Korean hospitals.

OBJECTIVE: We evaluated the adequacy of microbiological tests in patients withholding or withdrawing life-sustaining treatment (WLST) at the end stage of life. SETTING: The study was conducted at 2 tertiary-care referral hospitals in Daegu, Republic of Korea. DESIGN: Retrospective cross-sectional study. METHODS: Demographic findings, clinical and epidemiological characteristics, statistics of microbiological tests, and microbial species isolated from patients within 2 weeks before death were collected in 2 tertiary-care referral hospitals from January to December 2018. We also reviewed the antimicrobial treatment that was given within 3 days of microbiological testing in patients on WLST. RESULTS: Of the 1,187 hospitalized patients included, 905 patients (76.2%) had WLST. The number of tests per 1,000 patient days was higher after WLST than before WLST (242.0 vs 202.4). Among the category of microbiological tests, blood cultures were performed most frequently, and their numbers per 1,000 patient days before and after WLST were 95.9 and 99.0, respectively. The positive rates of blood culture before and after WLST were 17.2% and 18.0%, respectively. Candida spp. were the most common microbiological species in sputum (17.4%) and urine (48.2%), and Acinetobacter spp. were the most common in blood culture (17.3%). After WLST determination, 70.5% of microbiological tests did not lead to a change in antibiotic use. CONCLUSIONS: Many unnecessary microbiological tests are being performed in patients with WLST within 2 weeks of death. Microbiological testing should be performed carefully and in accordance with the patient's treatment goals.

Clinical utility of quantitative immunoassays and surrogate virus neutralization tests for predicting neutralizing activity against the SARS-CoV-2 Omicron BA.1 and BA.5 variants.

Developing new antibody assays for emerging SARS-CoV-2 variants is challenging. SARS-CoV-2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT-positive sera, we noticed that log-transformed optical density (OD) ratio of wild-type (WT) sVNT exhibited better titer-correlation with plaque reduction neutralization test (PRNT) than % inhibition value. Second, we tried 798 dilutional titration tests with 103 sera, but nonlinear correlation between OD ratio and antibody concentration limited titration of sVNT. Third, the titer-correlations of two sVNT kits for BA.1 and two quantitative immunoassays for WT were evaluated with BA.1 and BA.5 PRNT. All tested kits exhibited a linear correlation with PRNT titers, but the sVNT kits exhibited high false-negative rates (cPass-BA.1 kit, 45.4% for BA.1 and 44.2% for BA.5; STANDARD F-BA.1 kit, 1.9% for BA.1 and 2.2% for BA.5), while quantitative immunoassays showed 100% sensitivity. Linear mixed-effects model suggested superior titer-correlation with PRNT for quantitative immunoassays compared to sVNT kits. Taken together, the use of quantitative immunoassays for WT, rather than rapid development of new kits, would be practical for predicting neutralizing activities against emerging new variants.

Assessment of Disease Burden and Immunization Rates for Vaccine-Preventable Diseases in People Living with HIV: The Korea HIV/AIDS Cohort Study.

BACKGROUND: Prophylactic immunization is important for human immunodeficiency virus (HIV)-infected patients; however, there are insufficient data on the burden of vaccine-preventable diseases (VPDs), vaccination rates, and factors influencing vaccination. MATERIALS AND METHODS: The incidence and prevalence of VPDs in HIV-infected patients between 2006 and 2017 were estimated using the Korean HIV/acquired immune deficiency syndrome (AIDS) cohort database. In addition, we evaluated the vaccination rates and influencing factors for vaccination in HIV-infected patients through multilevel analysis of clinico-epidemiological factors, immune status, and psychological status. A questionnaire survey was conducted among experts to determine whether they recommend vaccination for HIV-infected patients. RESULTS: The incidence rates of hepatitis B virus (HBV) infection, herpes zoster, and anogenital warts were 1.74, 7.38, and 10.85 per 1,000 person-years, respectively. The prevalence of HBV infection and anogenital warts at enrollment was 4.8% and 8.6%, respectively, which increased to 5.3% and 12.0%, respectively, by 2017. In HIV-infected patients, HBV (21.7% in 2008, 56.3% in 2013, and 75.4% in 2017) and pneumococcal vaccination rates (3.0% in 2015, 7.6% in 2016, and 9.6% in 2017) increased annually, whereas the influenza vaccination rate remained similar by season (32.7 - 35.6%). In the multilevel analysis, peak HIV viral load (≥50 copies/mL: odds ratio [OR] = 0.64, 95% confidence interval [CI]: 0.44 - 0.93; reference, <50 copies/mL) was an influencing factor for pneumococcal vaccination, while nadir CD4 T-cell counts (200 - 350 cells/mm3: OR = 0.54, 95% CI: 0.38 - 0.76; <200 cells/mm3: OR = 0.89, 95% CI: 0.62 - 1.28; reference, ≥350 cells/mm3) was an influencing factor for HBV vaccination. Influenza vaccination was associated with male sex (OR = 1.94) and the number of antiretroviral therapy (ART) regimen change (OR = 1.16), but was not significantly associated with HIV viral load or CD4 T-cell counts. Most experts responded that they administer hepatitis A virus, HBV, pneumococcal, and influenza vaccines routinely, but not human papillomavirus (12.9%) or herpes zoster vaccines (27.1%). CONCLUSION: The burden of vaccine-preventable diseases was quite high in HIV-infected patients. Nadir CD4 T-cell counts, peak HIV viral loads, and the number of ART regimen change are significant factors related to vaccination. Considering the low vaccination rates for VPDs, there was a discordance between experts' opinions and real clinical practice in the medical field.

Immunogenicity and safety of SARS-CoV-2 recombinant protein nanoparticle vaccine GBP510 adjuvanted with AS03: interim results of a randomised, active-controlled, observer-blinded, phase 3 trial.

Background: GBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) in healthy adults aged ≥18 years, up to 6 months after the second dose. Methods: This was a randomised, active-controlled, observer-blinded, parallel group, phase 3 study, conducted at 38 sites across six countries (South Korea, Philippines, Thailand, Vietnam, Ukraine and New Zealand). Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination) was randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety), while Cohort 2 (regardless of baseline serostatus) was randomised 5:1 (safety). Primary objectives were to demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 vs. ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity (long-term 6 months cut-off date: 09 August 2022). This study was registered on ClinicalTrials.gov (NCT05007951). Findings: Between 30 August 2021 and 11 January 2022, a total of 4913 participants were screened and 4036 participants (1956 in Cohort 1 and 2080 in Cohort 2) who met eligibility criteria were enrolled and randomised to receive 2 doses of GBP510/AS03 (n = 3039) or ChAdOx1-S (n = 997). Most participants were Southeast Asian (81.5%) and aged 18-64 years (94.7%). The primary objectives assessed in per-protocol set included 877 participants in GBP510/AS03 and 441 in ChAdOx1-S group: at 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03/ChAdOx1-S) in per-protocol set was 2.93 (95% CI 2.63-3.27), demonstrating superiority (95% CI lower limit >1) of GBP510/AS03; the between-group SCR difference of 10.8% (95% CI 7.68-14.32) also satisfied the non-inferiority criterion (95% CI lower limit > -5%). Neutralizing antibody titres sustained higher for the GBP510/AS03 group compared to the ChAdOx1-S group through 6 months after the second vaccination. In Safety analysis (Cohort 1 & 2), the proportion of participants with adverse events (AEs) after any vaccination was higher with GBP510/AS03 vs. ChAdOx1-S for solicited local AEs (56.7% vs. 49.2%), but was similar for solicited systemic AEs (51.2% vs. 53.5%) and unsolicited AEs (13.3% vs. 14.6%) up to 28 days after the second vaccination. No safety concerns were identified during follow-up for 6 months after the second vaccination. Interpretation: Our interim findings suggested that GBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Immune Response Kinetics Following a Third Heterologous BNT162b2 Booster Dose After Primary 2-Dose ChAdOx1 Vaccination in Relation to Omicron Breakthrough Infection: A Prospective Nationwide Cohort Study in South Korea.

Background: Immune responses to each vaccine must be investigated to establish effective vaccination strategies for the ongoing coronavirus disease (COVID-19) pandemic. We investigated the long-term kinetics of immune responses after heterologous booster vaccination in relation to Omicron breakthrough infection (BI). Methods: Our study included 373 healthcare workers who received primary ChAdOx1 vaccine doses and a third BNT162b2 vaccine dose. BIs that occurred after the third vaccine were investigated. Blood specimens were collected before and 3 months after the booster dose from participants without BI and 1, 4, and 6 months after BI from participants who experienced BI. Spike-specific binding and neutralizing antibody levels against the wild-type virus, Omicron BA.1, and Omicron BA.5, as well as cellular responses, were analyzed. Results: A total of 346 participants (82 in the no BI group; 192 in the BI group during the BA.1/BA.2 period; 72 in the BI group during the BA.5 period) were included in the analysis. Participants without BI exhibited the highest binding and neutralizing antibody concentrations and greatest cellular response 1 month after the third vaccination, which reached a nadir by the ninth month. Antibody and cellular responses in participants who experienced BI substantially increased postinfection. Neutralizing antibody titers in individuals who experienced BI during the BA.1/BA.2 period showed more robust increase against wild-type virus than against BA.1 and BA.5. Conclusions: Our findings provide evidence of antigenic imprinting in participants who received a heterologous booster vaccination, thereby serving as a foundation for further studies on the impact of BIs on immune responses.

Long COVID prevalence and impact on quality of life 2 years after acute COVID-19.

There has been an increasing interest in the long-term impact of long COVID. However, only a few studies have investigated the clinical manifestations of long COVID after 24 months of acute infection. In this study, prospective online surveys were conducted in adults previously diagnosed with coronavirus disease 2019 (COVID-19) in South Korea between February 13 and March 13, 2020, at 6, 12, and 24 months after COVID-19. We investigated self-reported symptoms and the EuroQol-5-dimension index. Among 900 individuals enrolled initially, 150 completed all 3 surveys. After excluding the cases of COVID-19 reinfection, 132 individuals were included in the final analysis. Among the 132 participants, 94 (71.2%) experienced symptoms of long COVID. The most frequently reported symptoms were fatigue (34.8%), amnesia (30.3%), concentration difficulties (24.2%), insomnia (20.5%), and depression (19.7%). Notably, no significant differences were noted in the incidence of long COVID at 24 months in terms of the number of vaccinations received. Although the neuropsychiatric quality of life improved over time, it continued to affect 32.7% of participants. Symptoms of long COVID, particularly neuropsychiatric symptoms, tend to persist over time, and COVID-19 vaccination or the number of vaccinations received may not significantly affect the incidence of long COVID.

Carbapenem Use in the Last Days of Life: A Nationwide Korean Study.

The appropriate use of carbapenem is a critical concern for patient safety and public health, and is a national priority. We investigated the nationwide status of carbapenem prescription in patients within their last 14 days of life to guide judicious-use protocols from the previous study comprised of 1350 decedents. Carbapenem use was universally controlled through computerised authorisation system at all centres during the study period. Carbapenem prescribing patterns and their optimality were evaluated. A total of 1201 patients received antimicrobial agents within the last two weeks of their lives, of whom 533 (44.4%) received at least one carbapenem. The median carbapenem treatment duration was seven days. Of the 533 patients receiving carbapenems, 510 (95.7%) patients had microbiological samples drawn and 196 (36.8%) yielded carbapenem-resistant pathogens. A total of 200 (37.5%) patients were referred to infectious disease (ID) specialists. Of the 333 patients (62.5%) who did not have ID consultations, 194 (58.2%) were assessed as "not optimal", 79 (23.7%) required escalation, 100 (30.0%) required de-escalation, and 15 (4.5%) were discontinued. Notwithstanding the existing antibiotic restriction program system, carbapenems are commonly prescribed to patients in their last days of life.

Attachment Insecurity and Stigma as Predictors of Depression and Anxiety in People Living With HIV.

OBJECTIVE: The purpose of this study was to examine whether attachment insecurity, stigma, and certain demographic and medical factors predict depression and anxiety in people living with HIV (PLWH). METHODS: Participants were 147 PLWH who visited the outpatient infection clinic in Kyungpook National University Hospital (KNUH; Daegu, South Korea) between June 2020 and January 2021. We measured HIV-related stigma, attachment anxiety and avoidance, depressive symptoms, and anxiety symptoms. RESULTS: Logistic regression analysis showed that unemployment, longer time receiving antiretroviral therapy, higher attachment avoidance, and higher attachment anxiety were significant predictors of depression. Results also showed that longer time receiving antiretroviral therapy, higher attachment anxiety, and concern with public attitudes were significant predictors of anxiety. CONCLUSION: In addition to education to reduce public stigma, interventions to reduce PLWH's self-stigma should continue. We suggest attachment-based psychotherapy as an effective intervention to improve PLWH's mental health.

Effect of characteristics on the clinical course at the initiation of treatment for human immunodeficiency virus infection using dimensionality reduction.

The beginning of human immunodeficiency virus (HIV) infection treatment depends on various factors, which are significantly correlated with the initial CD4 cell number. However, a covariate correlation between these factors may not reflect the correct outcome variable. Thus, we evaluated the effects of a combination of fixed factors (reduced dimensions), which determine when to start treatment for the first time, on short-term outcome, long-term outcome, and survival, considering correlations between factors. Multiple correspondence analysis was performed on variables obtained from 925 patients who participated in a Korean HIV/acquired immunodeficiency syndrome cohort study (2006-2017). Five reduced dimension groups were derived according to clinical data, viral load, CD4 cell count at diagnosis, initial antiretroviral therapy, and others. The dimension group with high initial viral loads (55,000 copies/mL) and low CD4 cell counts (< 200 cells/mm3) should start treatment promptly after diagnosis. Groups with high initial CD4 cell counts (> 350 cells/mm3) that did not require immediate treatment according to previous guidelines had a higher failure rate for long-term relative CD4 recovery. Our results highlight the importance of early diagnosis and treatment to positively influence long-term disease outcomes, even if the initial immune status is poor, given the patient's combination of early diagnostic symptoms.

Use of Antibiotics Within the Last 14 Days of Life in Korean Patients: A Nationwide Study.

BACKGROUND: Antimicrobial prescriptions for serious chronic or acute illness nearing its end stages raise concerns about the potential for futile use, adverse events, increased multidrug-resistant organisms, and significant patient and social cost burdens. This study investigated the nationwide situation of how antibiotics are prescribed to patients during the last 14 days of life to guide future actions. METHODS: This nationwide multicenter retrospective cohort study was conducted at 13 hospitals in South Korea from November 1 to December 31, 2018. All decedents were included in the study. Antibiotic use during the last two weeks of their lives was investigated. RESULTS: A total of 1,201 (88.9%) patients received a median of two antimicrobial agents during the last two weeks of their lives. Carbapenems were prescribed to approximately half of the patients (44.4%) in the highest amount (301.2 days of therapy per 1,000 patient-days). Among the patients receiving antimicrobial agents, 63.6% were inappropriate and only 327 patients (27.2%) were referred by infectious disease specialists. The use of carbapenem (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.13-2.03; P = 0.006), underlying cancer (OR, 1.56; 95% CI, 1.20-2.01, P = 0.047), underlying cerebrovascular disease (OR, 1.88; 95% CI, 1.23-2.89, P = 0.004), and no microbiological testing (OR, 1.79; 95% CI, 1.15-2.73; P = 0.010) were independent predictors for inappropriate antibiotic prescribing. CONCLUSION: A considerable number of antimicrobial agents are administered to patients with chronic or acute illnesses nearing their end-of-life, a high proportion of which are prescribed inappropriately. Consultation with an infectious disease specialist, in addition to an antimicrobial stewardship program, may be necessary to induce the optimal use of antibiotics.

Rate of and Risk Factors for Loss to Follow Up in HIV-Infected Patients in Korea: The Korea HIV/AIDS Cohort Study.

BACKGROUND: Owing to antiretroviral therapy (ART), acquired immune deficiency syndrome (AIDS)-related mortality has significantly decreased. Retaining in care is an essential step for human immunodeficiency virus (HIV) care cascade. This study investigated the incidence of and risk factors for loss to follow-up (LTFU) in Korean people living with HIV (PLWH). MATERIALS AND METHODS: Data from the Korea HIV/AIDS cohort study (including prospective interval cohort and retrospective clinical cohort) were analyzed. LTFU was defined as not visiting the clinic for more than 1 year. Risk factors for LTFU were identified using the Cox regression hazard model. RESULTS: The study enrolled 3,172 adult HIV patients (median age, 36 years; male 92.97%). The median CD4 T cell count at enrollment was 234 cells/mm3 (interquartile range [IQR]: 85 - 373) and the median viral load at enrollment was 56,100 copies/mL (IQR: 15,000 - 203,992). The total follow-up duration was 16,487 person-years, and the overall incidence rate of LTFU was 85/1,000 person-years. In the multivariable Cox regression model, subjects on ART were less likely to have LTFU than subjects not on ART (hazard ratio [HR] = 0.253, 95% confidence interval [CI]: 0.220 - 0.291, P <0.0001). Among PLWH on ART, female sex (HR = 0.752, 95% CI: 0.582 - 0.971, P = 0.0291) and older age (>50: HR = 0.732, 95% CI: 0.602 - 0.890; 41 - 50: HR = 0.634, 95% CI: 0.530 - 0.750; 31 - 40: HR = 0.724, 95% CI: 0.618 - 0.847; ≤30: reference, P <0.0001) were associated with high rate of retention in care. The viral load at ART initiation ≥1,000,001 (HR = 1.545, 95% CI: 1.126 - 2.121, ≤10,000: reference) was associated with a higher rate of LTFU. CONCLUSION: Young and male PLWH may have a higher rate of LTFU, and an increased rate of LTFU may induce virologic failure.

Developing Core Elements and Checklist Items for Implementing Antimicrobial Stewardship Programs in Korean General Hospitals: A Modified Delphi Survey.

BACKGROUND: Antimicrobial stewardship programs (ASPs) aim to optimize antimicrobial use by minimizing the spread of antimicrobial resistance. The core elements for implementing ASPs in healthcare facilities have been developed by the World Health Organization, international research group and government agencies of various countries. However, to date, there is no documented core elements for implementation of ASP in Korea. This survey aimed to establish a national consensus on a set of core elements and their related checklist items for the implementation of ASPs in Korean general hospitals. MATERIALS AND METHODS: The survey was conducted from July 2022 to August 2022 by the Korean Society for Antimicrobial Therapy with support from the Korea Disease Control and Prevention Agency. A literature review was conducted by searching Medline and relevant websites to retrieve a list of core elements and checklist items. These core elements and checklist items were evaluated by a multidisciplinary panel of experts using a structured modified Delphi consensus procedure, using two-step survey included online in-depth questionnaires and in-person meeting. RESULTS: The literature review identified 6 core elements (Leadership commitment, Operating system, Action, Tracking, Reporting, and Education) and 37 related checklist items. Fifteen experts participated in the consensus procedures. Ultimately, all 6 core elements were retained, and 28 checklist items were proposed, all with ≥80% agreement; in addition 9 items were merged into 2 items, 2 items were deleted, and 15 items were rephrased. CONCLUSION: This Delphi survey provides useful indicators for the implementation of ASP in Korea and suggests national policy improvement about the barriers (e.g., shortage of staffing and financial support) existing in Korea for optimal implementation of ASPs.