Cost-Effectiveness Analysis of COMT-Inhibitors as Adjuvant Treatments to Levodopa in Patients with Advanced Parkinson's Disease.

PURPOSE: We aimed to elicit scientific evidence on the cost-effectiveness of two catechol-O-methyltransferase inhibitors (COMT-i) versus no COMT-i in patients with advanced Parkinson's disease. METHODS: A mixed model of the decision tree and a Markov model with three health states by OFF-time level (<25%, ≥25%, and death) was constructed to compare opicapone (OPC), entacapone (ENT), and no COMT-i over a lifetime. A hypothetical cohort of 10,000 patients was created and simulated based on the characteristics of the BIPARK trial subjects. FINDINGS: Two COMT-i (OPC and ENT) were identified as a cost-effective option compared to no COMT-i. Probabilistic sensitivity analysis showed that over 90% of the simulations proved the robust cost-effectiveness of COMT-i. When the time horizon as the most influential factor decreases to a 5- and 10-year period, COMT-i can be a cost-saving option. Although ENT may be the preferred option over OPC economically because of its lower price, OPC can be acceptable if the drug price is reduced by 17%. IMPLICATIONS: Add-on treatment with COMT-i in patients with PD receiving levodopa/carbidopa appears to be cost-saving compared with not using COMT-i. In the future, it is necessary to evaluate the economic evaluation of COMT-i based on long-term real-world evidence.

Performance of ChatGPT on Solving Orthopedic Board-Style Questions: A Comparative Analysis of ChatGPT 3.5 and ChatGPT 4.

Background: The application of artificial intelligence and large language models in the medical field requires an evaluation of their accuracy in providing medical information. This study aimed to assess the performance of Chat Generative Pre-trained Transformer (ChatGPT) models 3.5 and 4 in solving orthopedic board-style questions. Methods: A total of 160 text-only questions from the Orthopedic Surgery Department at Seoul National University Hospital, conforming to the format of the Korean Orthopedic Association board certification examinations, were input into the ChatGPT 3.5 and ChatGPT 4 programs. The questions were divided into 11 subcategories. The accuracy rates of the initial answers provided by Chat GPT 3.5 and ChatGPT 4 were analyzed. In addition, inconsistency rates of answers were evaluated by regenerating the responses. Results: ChatGPT 3.5 answered 37.5% of the questions correctly, while ChatGPT 4 showed an accuracy rate of 60.0% (p < 0.001). ChatGPT 4 demonstrated superior performance across most subcategories, except for the tumor-related questions. The rates of inconsistency in answers were 47.5% for ChatGPT 3.5 and 9.4% for ChatGPT 4. Conclusions: ChatGPT 4 showed the ability to pass orthopedic board-style examinations, outperforming ChatGPT 3.5 in accuracy rate. However, inconsistencies in response generation and instances of incorrect answers with misleading explanations require caution when applying ChatGPT in clinical settings or for educational purposes.

Isolated Polyethylene Insert Exchange for Instability after Total Knee Arthroplasty: Comparable Survival Rates and Range of Motion and Improved Clinical Scores Regardless of Hyperextension.

Background: Isolated polyethylene insert exchange (IPIE) has not been established as a treatment option for hyperextension instability after primary total knee arthroplasty (TKA). The purpose of the study was to evaluate the survival rate and clinical outcomes of IPIE for the treatment of instability with or without hyperextension after TKA. Methods: This study retrospectively reviewed 46 patients who underwent IPIE for symptomatic prosthetic knee instability by dividing them into 2 groups based on the presence of hyperextension (without for group I and with for group IH). Patient demographics, clinical scores, radiographic data, range of motion (ROM), and surgical information were collected. Clinical failure was defined as a subsequent surgery following IPIE for any reason. The survival rate of IPIE and differences in demographics, clinical scores, and ROM were compared. Results: There were 46 patients (91% were women) with an average age of 70.1 years and a mean follow-up of 44.8 months. The average time between primary TKA and IPIE surgery was 6.5 ± 4.2 years, and during IPIE, 2 out of the 8 cruciate-retaining inserts were converted to "deep-dish" ultracongruent inserts while the insert thickness increased from 11.9 ± 1.8 mm to 17.1 ± 3.1 mm. After IPIE surgery, a significantly thicker tibial insert was used in the group with hyperextension (15.39 ± 2.4 mm for group I, 18.3 ± 2.9 mm for group IH; p < 0.001 by independent t-test), and no significant differences were observed in the ROM and clinical scores before and after IPIE between the 2 groups. The overall survival rate for IPIE was 83% at 5 years and 57% at 10 years, and there were no statistically significant differences between the groups using the Cox proportional hazards regression model. Conclusions: IPIE demonstrated an overall survival rate of 83% at 5 years with no difference in the recurrence of instability regardless of hyperextension. This study highlighted the effectiveness of using thicker inserts to resolve instability without significant differences in the ROM or clinical scores between the groups, suggesting its potential as a decision-making reference for surgeons.

In vitro antifungal and physicochemical properties of polymerized acrylic resin containing strontium-modified phosphate-based glass.

Acrylic resins are widely used as the main components in removable orthodontic appliances. However, poor oral hygiene and maintenance of orthodontic appliances provide a suitable environment for the growth of pathogenic microorganisms. In this study, strontium-modified phosphate-based glass (Sr-PBG) was added to orthodontic acrylic resin at 0% (control), 3.75%, 7.5%, and 15% by weight to evaluate the surface and physicochemical properties of the novel material and its in vitro antifungal effect against Candida albicans (C. albicans). Surface microhardness and contact angle did not vary between the control and 3.75% Sr-PBG groups (p > 0.05), and the flexural strength was lower in the experimental groups than in the control group (p < 0.05), but no difference was found with Sr-PBG content (p > 0.05). All experimental groups showed an antifungal effect at 24 and 48 h compared to that in the control group (p < 0.05). This study demonstrated that 3.75% Sr-PBG exhibits antifungal effects against C. albicans along with suitable physicochemical properties, which may help to minimize the risk of adverse effects associated with harmful microbial living on removable orthodontic appliances and promote the use of various materials.

Development and Usability of a Mobile Support Application for Sexual Violence Victims Connecting With Formal Support Organizations.

The lack of awareness and accessibility about the support organizations for preventing sexual violence and assisting victims hampers the effectiveness of the social safety net. A mobile application based on a connection to support agencies was developed and evaluated for usability. A group of 15 experts and a group of 30 users evaluated usability. The developed mobile application focused on "Emergency Report," "Support Agencies and Services," and "Counseling for Support." The strength of the application was acknowledged in providing easy-to-find, reliable, useful, and necessary information, highlighting the positive usability and applicability of the mobile support application for sexual violence victims.

Revisiting Rorschach test and Minnesota Multiphasic Personality Inventory-II patterns in Kraepelinian vs. DSM-wise Schizophrenia: How They Differ and What It Means for Diagnosis.

OBJECTIVE: This retrospective chart review study aimed to investigate the differences in the Rorschach test and Minnesota Multiphasic Personality Inventory (MMPI)-II profiles among patients with Kraepelinian schizophrenia, those with DSM-wise schizophrenia, and controls. Kraepelinian schizophrenia is characterised by a chronic, deteriorative disease course and a predominance of negative symptoms. METHODS: Patients with Kraepelinian schizophrenia were selected based on medical record reviews. We then compared their Rorschach test and MMPI-II results with those of the DSM-wise schizophrenia group and the control group. RESULTS: The Rorschach test revealed a significant increase in DV2 score and a decrease in D score in patients with Kraepelinian schizophrenia compared to those with DSM-wise schizophrenia. In the MMPI-II profiles, patients with Kraepelinian schizophrenia exhibited an elevated L relative to those with DSM-wise schizophrenia. CONCLUSION: Our results suggested the value of revisiting psychological tests in clinically delineated subgroups, such as Kraepelinian schizophrenia. Although patients fall under the same diagnostic category of schizophrenia, considering different phenotypes is important when interpreting psychological test outcomes. Additionally, our study indicated that both schizophrenia groups did not show as many abnormalities as expected compared to controls. This highlights the potential value of revisiting established profiles of certain psychological tests and calls for further research on other psychological tests.

Autophagy and lysosomal dysfunction in diabetes and its complications.

Autophagy is critical for energy homeostasis and the function of organelles such as endoplasmic reticulum (ER) and mitochondria. Dysregulated autophagy due to aging, environmental factors, or genetic predisposition can be an underlying cause of not only diabetes through ß-cell dysfunction and metabolic inflammation, but also diabetic complications such as diabetic kidney diseases (DKDs). Dysfunction of lysosomes, effector organelles of autophagic degradation, due to metabolic stress or nutrients/metabolites accumulating in metabolic diseases is also emerging as a cause or aggravating element in diabetes and its complications. Here, we discuss the etiological role of dysregulated autophagy and lysosomal dysfunction in diabetes and a potential role of autophagy or lysosomal modulation as a new avenue for treatment of diabetes and its complications.

Traditional healer support to improve HIV viral suppression in rural Uganda (Omuyambi): study protocol for a cluster randomized hybrid effectiveness-implementation trial.

BACKGROUND: Rural African people living with HIV face significant challenges in entering and remaining in HIV care. In rural Uganda, for example, there is a threefold higher prevalence of HIV compared to the national average and lower engagement throughout the HIV continuum of care. There is an urgent need for appropriate interventions to improve entry and retention in HIV care for rural Ugandans with HIV. Though many adults living with HIV in rural areas prioritize seeking care services from traditional healers over formal clinical services, healers have not been integrated into HIV care programs. The Omuyambi trial is investigating the effectiveness of psychosocial support delivered by traditional healers as an adjunct to standard HIV care versus standard clinic-based HIV care alone. Additionally, we are evaluating the implementation process and outcomes, following the Consolidated Framework for Implementation Research. METHODS: This cluster randomized hybrid type 1 effectiveness-implementation trial will be conducted among 44 traditional healers in two districts of southwestern Uganda. Healers were randomized 1:1 into study arms, where healers in the intervention arm will provide 12 months of psychosocial support to adults with unsuppressed HIV viral loads receiving care at their practices. A total of 650 adults with unsuppressed HIV viral loads will be recruited from healer clusters in the Mbarara and Rwampara districts. The primary study outcome is HIV viral load measured at 12 months after enrollment, which will be analyzed by intention-to-treat. Secondary clinical outcome measures include (re)initiation of HIV care, antiretroviral therapy adherence, and retention in care. The implementation outcomes of adoption, fidelity, appropriateness, and acceptability will be evaluated through key informant interviews and structured surveys at baseline, 3, 9, 12, and 24 months. Sustainability will be measured through HIV viral load measurements at 24 months following enrollment. DISCUSSION: The Omuyambi trial is evaluating an approach that could improve HIV outcomes by incorporating previously overlooked community lay supporters into the HIV cascade of care. These findings could provide effectiveness and implementation evidence to guide the development of policies and programs aimed at improving HIV outcomes in rural Uganda and other countries where healers play an essential role in community health. TRIAL REGISTRATION: ClinicalTrials.gov NCT05943548. Registered on July 5, 2023. The current protocol version is 4.0 (September 29, 2023).

ER-to-lysosome Ca2+ refilling followed by K+ efflux-coupled store-operated Ca2+ entry in inflammasome activation and metabolic inflammation.

We studied lysosomal Ca2+ in inflammasome. Lipopolysaccharide (LPS) + palmitic acid (PA) decreased lysosomal Ca2+ ([Ca2+]Lys) and increased [Ca2+]i through mitochondrial ROS, which was suppressed in Trpm2-KO macrophages. Inflammasome activation and metabolic inflammation in adipose tissue of high-fat diet (HFD)-fed mice were ameliorated by Trpm2 KO. ER→lysosome Ca2+ refilling occurred after lysosomal Ca2+ release whose blockade attenuated LPS + PA-induced inflammasome. Subsequently, store-operated Ca2+entry (SOCE) was activated whose inhibition suppressed inflammasome. SOCE was coupled with K+ efflux whose inhibition reduced ER Ca2+ content ([Ca2+]ER) and impaired [Ca2+]Lys recovery. LPS + PA activated KCa3.1 channel, a Ca2+-activated K+ channel. Inhibitors of KCa3.1 channel or Kcnn4 KO reduced [Ca2+]ER, attenuated increase of [Ca2+]i or inflammasome activation by LPS + PA, and ameliorated HFD-induced inflammasome or metabolic inflammation. Lysosomal Ca2+ release induced delayed JNK and ASC phosphorylation through CAMKII-ASK1. These results suggest a novel role of lysosomal Ca2+ release sustained by ER→lysosome Ca2+ refilling and K+ efflux through KCa3.1 channel in inflammasome activation and metabolic inflammation.

Dynamic Schwarz Meta-Foams: Customizable Solutions for Environmental Noise Reduction.

In an era marked by increasing environmental challenges affecting human well-being, traditional acoustic materials struggle to effectively handle the diverse and multi-frequency nature of harmful environmental noises. This has spurred a demand for innovative acoustic metamaterial solutions by utilizing sustainable design strategies. This research introduces tunable Schwarz metamaterial capable of transforming into a soft meta-foam to solve the complex problems of varying environmental noises. This study primarily focuses on adjusting single to multiple sound-blocking bandgaps mechanism using a multi-layered approach, incorporating the Schwarz P-type triply periodic minimal surface (TPMS) and its elective soft foam counterpart, known as tunable Schwarz meta-foams (TSMF-x). The tunable design parameters of the unit cell, multi-layered TPMS, and soft programmable TSMF-lichen version are comprehensively explored including a fire-safety test. The results demonstrate these enhanced flame retardant meta-foam families have the potential to be used for mid-to-high-frequency environmental noises in industrial equipment and smart homes for sustainable architecture and environmental health applications.

Difference in Baseline Antimicrobial Prescription Patterns of Hospitals According to Participation in the National Antimicrobial Monitoring and Feedback System in Korea.

This study aimed to evaluate the differences in the baseline characteristics and patterns of antibiotic usage among hospitals based on their participation in the Korea National Antimicrobial Use Analysis System (KONAS). We obtained claims data from the National Health Insurance for inpatients admitted to all secondary- and tertiary-care hospitals between January 2020 and December 2021 in Korea. 15.9% (58/395) of hospitals were KONAS participants, among which the proportion of hospitals with > 900 beds (31.0% vs. 2.6%, P < 0.001) and tertiary care (50.0% vs. 5.2%, P < 0.001) was higher than that among non-participants. The consumption of antibiotics targeting antimicrobial-resistant gram positive bacteria (33.7 vs. 27.1 days of therapy [DOT]/1,000 patient-days, P = 0.019) and antibiotics predominantly used for resistant gram-negative bacteria (4.8 vs. 3.7 DOT/1,000 patient-days, P = 0.034) was higher in KONAS-participating versus -non-participating hospitals. The current KONAS data do not fully represent all secondary- and tertiary-care hospitals in Korea; thus, the KONAS results should be interpreted with caution.

Neighborhood Social Vulnerability and Premature Cardiovascular Disease in Haiti.

Importance: Higher social vulnerability is associated with premature cardiovascular disease (CVD) and mortality but is understudied in low-income countries that have both the highest magnitude of social vulnerability and a growing CVD epidemic. Objective: To evaluate the association between social vulnerability and hypertension, CVD, and CVD subtypes in Haiti as a model for similar low-income countries. Design, Setting, and Participants: This population-based cohort study used enrollment data from adults participating in the Haiti Cardiovascular Disease Cohort Study. Recruitment occurred via multistage random sampling throughout slum and urban neighborhoods in Port-au-Prince, Haiti, from March 2019 to August 2021. Data were analyzed from May 2022 to December 2023. Exposures: A modified Haitian Social Vulnerability Index (SVI-H) was created following the US Centers for Disease Control and Prevention Social Vulnerability Index method. Twelve variables across the domains of socioeconomic status, household characteristics, and social and community context were included. The SVI-H was calculated for each study neighborhood block and then stratified into SVI-H quartiles (quartile 1 was the least vulnerable; quartile 4, the most vulnerable). Main Outcomes and Measures: Prevalent hypertension and total CVD, defined as heart failure (HF), stroke, transient ischemic attack (TIA), angina, or myocardial infarction (MI). Age-adjusted Poisson regression analysis yielded prevalence ratios (PRs) comparing the prevalence of hypertension, total CVD, and CVD subtypes across SVI-H quartiles. Results: Among 2925 adults (1704 [58.3%] female; mean [SD] age, 41.9 [15.9] years), the prevalence of hypertension was 32.8% (95% CI, 31.1%-34.5%) and the prevalence of CVD was 14.7% (95% CI, 13.5%-16.0%). Hypertension prevalence ranged from 26.2% (95% CI, 23.1%-29.3%) to 38.4% (95% CI, 34.8%-42.0%) between quartiles 1 and 4, while CVD prevalence ranged from 11.1% (95% CI, 8.8%-13.3%) to 19.7% (95% CI, 16.8%-22.6%). SVI-H quartile 4 vs 1 was associated with a greater prevalence of hypertension (PR, 1.17; 95% CI, 1.02-1.34) and CVD (PR, 1.48; 95% CI, 1.16-1.89). Among CVD subtypes, SVI-H was significantly associated with HF (PR, 1.64; 95% CI, 1.23-2.18) but not with combined stroke and TIA or combined angina and MI. Conclusions and Relevance: In urban Haiti, individuals living in neighborhoods with the highest social vulnerability had greater prevalence of hypertension and HF. Understanding CVD disparities in low-income countries is essential for targeting prevention and treatment interventions toward populations at highest risk globally.

Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Improving Function and Quality of Life in Patients with Chronic Neck Pain, Tension-Type Headache, and Forward Head Posture: The Role of Eyeball Exercise and Cervical Stabilization Programs.

BACKGROUND The purpose of this study was to investigate the effects of eyeball exercise and cervical stabilization programs to patients with chronic neck pain, tension-type headache (TTH), and forward head posture (FHP). MATERIAL AND METHODS The design of this study was a randomized controlled trial. A total of 40 participants were randomly divided into 2 groups: the experimental group (n=20) and the control group (n=20). Both groups received cervical manual therapy and biofeedback-guided stabilization exercises (30 min/session, 3 sessions/week, 6 weeks). In addition to the regular treatments, the participants in the experimental group also performed eyeball exercises for 20 minutes per session, 3 sessions per week, for a total of 6 weeks. Changes in neck pain (numeric rating scale, NRS), neck disability index (NDI), quality of life (Short Form-12 Health Survey Questionnaire, SF-12), headache impact test-6 (HIT-6), craniovertebral angle (CVA), cranial rotation angle (CRA), and muscle tone were measured. RESULTS Both groups showed significant improvements in NRS, NDI, SF-12, HIT-6 scores, CVA, CRA, and muscle tone (p<0.05). The experimental group had significant differences in NDI, SF-12, HIT-6 scores, and suboccipital muscle tone compared to the control (p<0.05). CONCLUSIONS Combining the eyeball exercise program with commonly used manual therapy and stabilization exercises for patients with chronic neck pain can help reduce nerve compression and promote muscle relaxation in the eye and neck areas. The method is thus proposed as an effective intervention to enhance function and quality of life in patients with chronic neck pain patients, TTH, and FHP.

High variance in quantification of Mycobacterium tuberculosis at low bacterial loads and with differentially detectable mycobacteria.

We examined the correlation between three different methods of Mycobacterium tuberculosis quantification: time to positivity (TTP), log10 CFU, and an assay to detect differentially detectable M. tuberculosis (DD Mtb) from three different prospective studies. Participants with DD Mtb have significantly more variation in the CFU/TTP correlation than participants with no DD Mtb (P < 0.001). This may impact the design of early bactericidal activity studies that use TTP as the primary outcome.

Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study.

BACKGROUND: In the preplanned interim analysis of the TOPAZ-1 study, durvalumab plus gemcitabine-cisplatin significantly improved overall survival versus placebo plus gemcitabine-cisplatin in participants with advanced biliary tract cancer. We aimed to report updated overall survival and safety data from TOPAZ-1 with additional follow-up and data maturity beyond the interim analysis. METHODS: TOPAZ-1 was a phase 3, randomised, double-masked, placebo-controlled, global study done at 105 sites in 17 countries. Participants aged 18 years or older with unresectable, locally advanced, or metastatic biliary tract cancer were randomly assigned (1:1) to durvalumab plus gemcitabine-cisplatin or placebo plus gemcitabine-cisplatin using a computer-generated randomisation scheme, stratified by disease status and primary tumour location. Participants received durvalumab (1500 mg) or placebo on day 1 of each cycle every 3 weeks for up to eight cycles, plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) intravenously on days 1 and 8 of each cycle every 3 weeks for up to eight cycles, followed by durvalumab (1500 mg) or placebo monotherapy every 4 weeks until disease progression or other discontinuation criteria were met. Investigators and participants were masked to study treatment. The primary endpoint was overall survival. TOPAZ-1 met its primary endpoint at the preplanned interim analysis, and the study is active but no longer recruiting participants. Updated overall survival and safety data from TOPAZ-1, with additional follow-up (data cutoff Feb 25, 2022) and data maturity beyond the interim analysis, are reported here. Efficacy was assessed in the full analysis set (all randomly assigned participants). Safety was assessed in the safety analysis set (all participants who received at least one dose of study treatment). The TOPAZ-1 study is registered with ClinicalTrials.gov, NCT03875235. FINDINGS: From April 16, 2019, to Dec 11, 2020, 914 participants were enrolled, 685 of whom were randomly assigned (341 to the durvalumab plus gemcitabine-cisplatin group and 344 to the placebo plus gemcitabine-cisplatin group). 345 (50%) participants were male and 340 (50%) were female. Median follow-up at the updated data cutoff was 23·4 months (95% CI 20·6-25·2) in the durvalumab plus gemcitabine-cisplatin group and 22·4 months (21·4-23·8) in the placebo plus gemcitabine-cisplatin group. At the updated data cutoff, 248 (73%) participants in the durvalumab plus gemcitabine-cisplatin group and 279 (81%) participants in the placebo plus gemcitabine-cisplatin group had died (median overall survival 12·9 months [95% CI 11·6-14·1] vs 11·3 months [10·1-12·5]; hazard ratio 0·76 [95% CI 0·64-0·91]). Kaplan-Meier-estimated 24-month overall survival rates were 23·6% (95% CI 18·7-28·9) in the durvalumab plus gemcitabine-cisplatin group and 11·5% (7·6-16·2) in the placebo plus gemcitabine-cisplatin group. Maximum grade 3 or 4 adverse events occurred in 250 (74%) of 338 participants in the durvalumab plus gemcitabine-cisplatin group and 257 (75%) of 342 in the placebo plus gemcitabine-cisplatin group. The most common maximum grade 3 or 4 treatment-related adverse events were decreased neutrophil count (70 [21%] vs 86 [25%]), anaemia (64 [19%] vs 64 [19%]), and neutropenia (63 [19%] vs 68 [20%]). INTERPRETATION: Durvalumab plus gemcitabine-cisplatin showed robust and sustained overall survival benefit with no new safety signals. Findings continue to support the regimen as a standard of care for people with untreated, advanced biliary tract cancer. FUNDING: AstraZeneca.

Impact of COVID-19 Infection and Its Association With Previous Vaccination in Patients With Myasthenia Gravis in Korea: A Multicenter Retrospective Study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

Spatiotemporal variations in migratory bird diversity and abundance along the coast of Gochang getbol.

Tidal flats provide critical habitat for migratory waterbird species; however, populations of migratory waterbirds have significantly declined due to tidal flat loss and degradation caused by human activities, particularly in Asia. Gochang getbol is one of tidal flats located on the southwest coast of South Korea and a center of clam production. Using bird monitoring data collected at five zones (zone1 to zone5) established across Gochang getbol and near coastal area, we examined distribution patterns of migratory bird diversity and conservation-related species along the coast of Gochang getbol. The intensity of human activity ‒ mudflat culture (mostly bivalve) and aquaculture was relatively high at zone2 and zone3, occupying > 30% of 2km circular area surrounding most sample points of these zones. Zone1 and particularly zone4 contained more natural/semi-natural habitats (less disturbed mudflats and wetlands) and zone5 had smallest mudflat than others. Shannon diversity, species richness, and abundance of migratory birds differed between zones (Anova test, P ≤ 0.02) except Shannon diversity in winter. In fall, all values were higher at zone4 than zone3 and zone5. In winter, zone1 showed greatest species richness and higher abundance than zone2, zone3, and zone5. In spring, while most differences were found between zone4 and zone5, abundance at zone4 was somewhat higher than zone2. The results from the fourth corner analysis indicated that abundance of species foraging at mudflat level was positively associated with zone1 (winter) but negatively with zone3 (fall). Sandpipers were positively associated with zone4. Abundance distribution maps of conservation-related species, created by inverse distance-weighted interpolation modeling, also showed high abundance of most conservation-related species at zone4 and 1. The findings of our study suggest the importance of natural/semi-natural habitat, and the possible link between human activity and distribution patterns of migratory birds in Gochang getbol. While we need further investigation on direct response of migratory birds to human activity, areas with low human activity with more natural/semi-natural habitat, e.g., zone4 and zone1 may be crucial for the conservation of migratory birds.

Effects of a self-managed return to work intervention for colorectal cancer survivors: A prospective randomized controlled trial.

PURPOSE: The present study aims to assess the efficacy of stage-matched, self-managed Return to Work (RTW) interventions in enhancing RTW outcomes among colorectal cancer (CRC) survivors. METHODS: This trial, conducted in South Korea, enrolled 58 unemployed survivors of colorectal cancer. Participants were randomly assigned to either an experimental or a control group. The experimental group received a self-managed return-to-work intervention based on the trans-theoretical model, while the control group received an educational booklet. Assessments were conducted at baseline and at 3, 6, and 12 months to measure changes in various factors including return-to-work status and HRQOL. RESULTS: In the experimental group, 28 participants were randomly assigned, while 30 individuals were allocated to the control group. The experimental group exhibited a higher proportion of individuals achieving RTW (64.5% vs 39.3%, p = 0.013) and demonstrated greater improvements in work ability (p = 0.001), RTW self-efficacy (p = 0.035), readiness for RTW in the prepared-for-action (p < 00.0001), uncertain maintenance (p = 0.033), and proactive maintenance (p < 00.0001) stages, quality of working life (p = 0.003), HRQOL (p < 0.05), and illness perception (p < 0.05) compared to the control group at the 12-month follow-up. CONCLUSIONS: Stage-matched self-managed RTW interventions incorporating TTM principles may effectively enhance RTW outcomes and work ability among CRC survivors.

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: In the ongoing, randomised, double-blind phase 3 TOPAZ-1 study, durvalumab, a PD-L1 inhibitor, plus gemcitabine and cisplatin was associated with significant improvements in overall survival compared with placebo, gemcitabine, and cisplatin in people with advanced biliary tract cancer at the pre-planned intermin analysis. In this paper, we present patient-reported outcomes from TOPAZ-1. METHODS: In TOPAZ-1 (NCT03875235), participants aged 18 years or older with previously untreated, unresectable, locally advanced, or metastatic biliary tract cancer with an Eastern Cooperative Oncology Group performance status of 0 or 1 and one or more measurable lesions per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) were randomly assigned (1:1) to the durvalumab group or the placebo group using a computer-generated randomisation scheme. Participants received 1500 mg durvalumab or matched placebo intravenously every 3 weeks (on day 1 of the cycle) for up to eight cycles in combination with 1000 mg/m2 gemcitabine and 25 mg/m2 cisplatin intravenously on days 1 and 8 every 3 weeks for up to eight cycles. Thereafter, participants received either durvalumab (1500 mg) or placebo monotherapy intravenously every 4 weeks until disease progression or other discontinuation criteria were met. Randomisation was stratified by disease status (initially unresectable vs recurrent) and primary tumour location (intrahepatic cholangiocarcinoma vs extrahepatic cholangiocarcinoma vs gallbladder cancer). Patient-reported outcomes were assessed as a secondary outcome in all participants who completed the European Organisation for Research and Treatment of Cancer's 30-item Quality of Life of Cancer Patients questionnaire (QLQ-C30) and the 21-item Cholangiocarcinoma and Gallbladder Cancer Quality of Life Module (QLQ-BIL21). We calculated time to deterioration-ie, time from randomisation to an absolute decrease of at least 10 points in a patient-reported outcome that was confirmed at a subsequent visit or the date of death (by any cause) in the absence of deterioration-and adjusted mean change from baseline in patient-reported outcomes. FINDINGS: Between April 16, 2019, and Dec 11, 2020, 685 participants were enrolled and randomly assigned, 341 to the durvalumab group and 344 to the placebo group. Overall, 345 (50%) of participants were male and 340 (50%) were female. Data for the QLQ-C30 were available for 318 participants in the durvalumab group and 328 in the placebo group (median follow-up 9·9 months [IQR 6·7 to 14·1]). Data for the QLQ-BIL21 were available for 305 participants in the durvalumab group and 322 in the placebo group (median follow-up 10·2 months [IQR 6·7 to 14·3]). The proportions of participants in both groups who completed questionnaires were high and baseline scores were mostly similar across treatment groups. For global health status or quality of life, functioning, and symptoms, we noted no difference in time to deterioration or adjusted mean changes from baseline were observed between groups. Median time to deterioration of global health status or quality of life was 7·4 months (95% CI 5·6 to 8·9) in the durvalumab group and 6·7 months (5·6 to 7·9) in the placebo group (hazard ratio 0·87 [95% CI 0·69 to 1·12]). The adjusted mean change from baseline was 1·23 (95% CI -0·71 to 3·16) in the durvalumab group and 0·35 (-1·63 to 2·32) in the placebo group. INTERPRETATION: The addition of durvalumab to gemcitabine and cisplatin did not have a detrimental effect on patient-reported outcomes. These results suggest that durvalumab, gemcitabine, and cisplatin is a tolerable treatment regimen in patients with advanced biliary tract cancer. FUNDING: AstraZeneca.