Effect of smoking cessation on psoriasis vulgaris, palmoplantar pustulosis and generalized pustular psoriasis.

BACKGROUND: Smoking is a known risk factor for psoriasis; however, the impact of smoking cessation on psoriasis has seldom been evaluated. OBJECTIVES: We aimed to examine the effects of smoking cessation on the development of psoriasis vulgaris (PsV), palmoplantar pustulosis (PPP) and generalized pustular psoriasis (GPP). METHODS: Using the Korean National Health Insurance Service database, we retrospectively compiled a cohort of 5 784 973 participants without psoriasis, analysed their changes in smoking status from 2004 to 2007 and followed up new cases of psoriasis until 2021. The psoriasis risks were compared with those of sustained smokers, smoking quitters, sustained ex-smokers and never smokers using multivariate Cox proportional hazard models. RESULTS: The mean age of the participants was 47.1 years (SD 13.5) and 3 092 426 (53.5%) were male. During 77 990 688 person-years, 67 364 psoriasis cases were identified. Compared with sustained smokers, smoking quitters showed a reduced risk of developing psoriasis [adjusted hazard ratio (aHR) 0.91; 95% confidence interval (CI) 0.87-0.95], specifically PsV (aHR 0.92; 95% CI 0.88-0.97) and PPP (aHR 0.71; 95% CI 0.63-0.79). The reduction in risk due to smoking cessation was more prominent in sustained ex-smokers (psoriasis: aHR 0.77, 95% CI 0.74-0.79; PsV: aHR 0.76, 95% CI 0.73-0.79; PPP: aHR 0.56, 95% CI 0.51-0.61; GPP: aHR 0.64; 95% CI 0.52-0.78). When conducting sensitivity analyses to address the potential for changes in smoking habits after 2007, the results and trends were consistent with the main findings, and a more pronounced significance was observed. CONCLUSIONS: Compared with continuous smoking, smoking cessation was associated with a decreased risk of developing psoriasis. The risk-reducing effect of smoking cessation was more pronounced in those maintaining a smoke-free status. Smoking cessation and the maintenance of a smoke-free status should be encouraged to prevent the development of psoriasis and all other smoking-related diseases.

Psoriasis vulgaris (PsV) is a chronic inflammatory skin condition that causes scaly plaques on the body. Pustular psoriasis [including palmoplantar pustulosis (PPP) and generalized pustular psoriasis (GPP)] is a variant characterized by sterile pustules. Limited evidence exists on how quitting smoking affects psoriasis and its subtypes. In this study conducted in South Korea, we aimed to investigate how changes in smoking habits, especially quitting smoking, could impact the development of psoriasis. We used medical claims records from the Korean National Health Insurance Service database, which included data from over 5.7 million people participating in health checkups between 2004 and 2007. We divided people into four groups based on their smoking habits: sustained smokers, smoking quitters, sustained ex-smokers and never smokers. We found that smoking quitters had a lower risk of developing psoriasis, especially PsV and PPP. Even people who had quit smoking and remained smoke-free for an extended period (sustained ex-smokers) showed a more pronounced reduction in the risk of psoriasis, including PsV, PPP and GPP. Our findings remained consistent across various groups of people, considering factors such as age, sex, weight and overall health. The results suggest that encouraging people to quit smoking and maintain a smoke-free lifestyle may help to prevent the onset of psoriasis. In conclusion, this large-scale study from South Korea provides real-world evidence to suggest that quitting smoking could reduce the risk of developing psoriasis. These findings are valuable for public health initiatives, emphasizing the benefits of quitting smoking for skin health.

Effectiveness of mixed reality-based rehabilitation on hands and fingers by individual finger-movement tracking in patients with stroke.

BACKGROUND: Mixed reality (MR) is helpful in hand training for patients with stroke, allowing them to fully submerge in a virtual space while interacting with real objects. The recognition of individual finger movements is required for MR rehabilitation. This study aimed to assess the effectiveness of updated MR-board 2, adding finger training for patients with stroke. METHODS: Twenty-one participants with hemiplegic stroke (10 with left hemiplegia and 11 with right hemiplegia; nine female patients; 56.7 ± 14.2 years of age; and onset of stroke 32.7 ± 34.8 months) participated in this study. MR-board 2 comprised a board plate, a depth camera, plastic-shaped objects, a monitor, a palm-worn camera, and seven gamified training programs. All participants performed 20 self-training sessions involving 30-min training using MR-board 2. The outcome measurements for upper extremity function were the Fugl-Meyer assessment (FMA) upper extremity score, repeated number of finger flexion and extension (Repeat-FE), the thumb opposition test (TOT), Box and Block Test score (BBT), Wolf Motor Function Test score (WMFT), and Stroke Impact Scale (SIS). One-way repeated measures analysis of variance and the post hoc test were applied for the measurements. MR-board 2 recorded the fingers' active range of motion (AROM) and Dunnett's test was used for pairwise comparisons. RESULTS: Except for the FMA-proximal score (p = 0.617) and TOT (p = 0.005), other FMA scores, BBT score, Repeat-FE, WMFT score, and SIS stroke recovery improved significantly (p < 0.001) during MR-board 2 training and were maintained until follow-up. All AROM values of the finger joints changed significantly during training (p < 0.001). CONCLUSIONS: MR-board 2 self-training, which includes natural interactions between humans and computers using a tangible user interface and real-time tracking of the fingers, improved upper limb function across impairment, activity, and participation. MR-board 2 could be used as a self-training tool for patients with stroke, improving their quality of life. TRIAL REGISTRATION NUMBER: This study was registered with the Clinical Research Information Service (CRIS: KCT0004167).

Intraparenchymal metastases as a cause for local recurrence of pancreatic cancer.

Using CODA, a technique for three-dimensional reconstruction of large tissues, Kiemen et al. report observation of a microscopic focus of pancreatic cancer found in the vasculature of grossly normal human pancreas tissue resected adjacent to a large tumour. They use TP53 and SMAD4 staining to relate the small focus to the primary tumour. This report describes a represents a probable case of intraparenchymal metastasis of pancreatic cancer, revealing a probable cause of local recurrence.

A Comprehensive Landscape of De Novo Malignancy After Double Lung Transplantation.

Although the association between post-transplant malignancy (PTM) and immunosuppressive therapy after organ transplantation has been studied, an integrated review of PTM after lung transplantation is lacking. We investigated the incidence and types of de novo PTM and its impact on survival following double lung transplantation (DLT). The incidence and type of PTM as well as the annual and cumulative risks of each malignancy after DLT were analyzed. The overall survival (OS) of recipients with or without PTM was compared by the Kaplan-Meier survival method and landmark analysis. There were 5,629 cases (23.52%) with 27 types of PTMs and incidences and OS varied according to the types of PTMs. The recipients with PTM showed a significantly longer OS than those without PTM (p < 0.001). However, while the recipients with PTM showed significantly better OS at 3, and 5 years (p < 0.001, p = 0.007), it was worse at the 10-year landmark time (p = 0.013). And the single PTM group showed a worse OS rate than the multiple PTM group (p < 0.001). This comprehensive report on PTM following DLT can help understand the risks and timing of PTM to improve the implementation of screening and treatment.

Simultaneous spatial smoothing and outlier detection using penalized regression, with application to childhood obesity surveillance from electronic health records.

Electronic health records (EHRs) have become a platform for data-driven granular-level surveillance in recent years. In this paper, we make use of EHRs for early prevention of childhood obesity. The proposed method simultaneously provides smooth disease mapping and outlier information for obesity prevalence that are useful for raising public awareness and facilitating targeted intervention. More precisely, we consider a penalized multilevel generalized linear model. We decompose regional contribution into smooth and sparse signals, which are automatically identified by a combination of fusion and sparse penalties imposed on the likelihood function. In addition, we weigh the proposed likelihood to account for the missingness and potential nonrepresentativeness arising from the EHR data. We develop a novel alternating minimization algorithm, which is computationally efficient, easy to implement, and guarantees convergence. Simulation studies demonstrate superior performance of the proposed method. Finally, we apply our method to the University of Wisconsin Population Health Information Exchange database.

Measurement of Nasalance Scores Without Touching the Philtrum for Better Comfort During Speech Assessment and Therapy: A Preliminary Study.

OBJECTIVE: The Kay Pentax nasometer uses a separator plate that touches the philtrum of a patient to separate the nasal and oral sound energies for nasalance measurement. However, the separator plate can restrict the natural movement of the patient's upper lip and generate unpleasant pressure on the patient's philtrum. The present study was intended to measure nasalance scores without touching the philtrum for better comfort during speech assessment and therapy. METHODS: Nasalance scores of 10 males and 10 females having no speech disorders were measured under 4 levels (0, 5, 10, and 15 mm) of the gap between the plate and the philtrum (denoted as plate-to-philtrum gap) using Nasometer II 6450 for nasal (Nasal Sentences) and oral (Zoo Passage) stimuli. Regression formulas were established to examine the relationships between nasalance score and plate-to-philtrum gap for the stimuli. To provide nasalance scores equivalent to those measured for the contact condition, compensation factors for the 5 mm plate-to-philtrum gap measurement condition were identified for the stimuli. RESULTS: The nasalance scores were significantly different between the 4 different plate-to-philtrum gaps for the stimuli. Compensation factors for the Nasal Sentences and the Zoo Passage were identified as 1.17 and 0.71, respectively. CONCLUSIONS: The 5 mm plate-to-philtrum gap condition after multiplying the compensation factors can provide equivalent nasalance scores to the conventional contact measurement condition which may provide better comfort in speech assessment and therapy.

Development of an Ultrasonic Doppler Sensor-Based Swallowing Monitoring and Assessment System.

Existing swallowing evaluation methods using X-ray or endoscopy are qualitative. The present study develops a swallowing monitoring and assessment system (SMAS) that is nonintrusive and quantitative. The SMAS comprises an ultrasonic Doppler sensor array, a microphone, and an inertial measurement unit to measure ultrasound signals originating only from swallowing activities. Ultrasound measurements were collected for combinations of two viscosity conditions (water and yogurt) and two volume conditions (3 mL and 9 mL) from 24 healthy participants (14 males and 10 females; age = 30.5 ± 7.6 years) with no history of swallowing disorders and were quantified for 1st peak amplitude, 2nd peak amplitude, peak-to-peak (PP) time interval, duration, energy, and proportion of two or more peaks. The peak amplitudes and energy significantly decreased by viscosity and the PP time interval and duration increased by volume. The correlation between the time measures were higher (r = 0.78) than that of the amplitude measures (r = 0.30), and the energy highly correlated with the 1st peak amplitude (r = 0.86). The proportion of two or more peaks varied from 76.8% to 87.9% by viscosity and volume. Further research is needed to examine the concurrent validity and generalizability of the ultrasonic Doppler sensor-based SMAS.

Effect of smartphone application-supported self-rehabilitation for frozen shoulder: a prospective randomized control study.

OBJECTIVES:: To evaluate the clinical efficacy of smartphone-assisted self-rehabilitation in patients with frozen shoulder. DESIGN:: A single-center, randomized controlled trial. SETTING:: Orthopedic department of a university hospital. SUBJECTS:: A total of 84 patients with frozen shoulder were recruited. INTERVENTION:: Patients were randomly divided into two groups: a smartphone-assisted exercise group ( n = 42) and a conventional self-exercise group ( n = 42). The study was performed over three months, during which each group performed home-based rehabilitation. MAIN MEASURES:: Visual analogue scale for pain and passive shoulder range of motion were assessed at baseline and after 4, 8, and 12 weeks of treatment. Technology Acceptance Model-2 and Usefulness, Satisfaction, and Ease of Use scores were evaluated in the smartphone group. RESULTS:: Initial visual analogue scale for pain of the smartphone group was 6.0 ± 2.2 and ended up with 1.8 ± 2.5 after 12 weeks, whereas the self-exercise group showed 5.8 ± 2.3 for the baseline visual analogue scale for pain and 2.2 ± 1.7 at the end. Significant time-dependent improvements in all measured values were observed in both groups (all Ps < 0.001), but no significant intergroup difference was observed after 4, 8, or 12 weeks of treatment. In the smartphone group, Technology Acceptance Model-2 and Usefulness, Satisfaction, and Ease of Use scores showed high patient satisfaction with smartphone-assisted exercise. CONCLUSION:: There was no difference between home-based exercise using a smartphone application and a conventional self-exercise program for the treatment of frozen shoulder in terms of visual analogue scale for pain and range of motions.

Effects of virtual reality-based planar motion exercises on upper extremity function, range of motion, and health-related quality of life: a multicenter, single-blinded, randomized, controlled pilot study.

BACKGROUND: Virtual reality (VR)-based rehabilitation is considered a beneficial therapeutic option for stroke rehabilitation. This pilot study assessed the clinical feasibility of a newly developed VR-based planar motion exercise apparatus (Rapael Smart Board™ [SB]; Neofect Inc., Yong-in, Korea) for the upper extremities as an intervention and assessment tool. METHODS: This single-blinded, randomized, controlled trial included 26 stroke survivors. Patients were randomized to the intervention group (SB group) or control (CON) group. During one session, patients in the SB group completed 30 min of intervention using the SB and an additional 30 min of standard occupational therapy; however, those in the CON group completed the same amount of conventional occupational therapy. The primary outcome was the change in the Fugl-Meyer assessment (FMA) score, and the secondary outcomes were changes in the Wolf motor function test (WMFT) score, active range of motion (AROM) of the proximal upper extremities, modified Barthel index (MBI), and Stroke Impact Scale (SIS) score. A within-group analysis was performed using the Wilcoxon signed-rank test, and a between-group analysis was performed using a repeated measures analysis of covariance. Additionally, correlations between SB assessment data and clinical scale scores were analyzed by repeated measures correlation. Assessments were performed three times (baseline, immediately after intervention, and 1 month after intervention). RESULTS: All functional outcome measures (FMA, WMFT, and MBI) showed significant improvements (p < 0.05) in the SB and CON groups. AROM showed greater improvements in the SB group, especially regarding shoulder abduction and internal rotation. There was a significant effect of time × group interactions for the SIS overall score (p = 0.038). Some parameters of the SB assessment, such as the explored area ratio, mean reaching distance, and smoothness, were significantly associated with clinical upper limb functional measurements with moderate correlation coefficients. CONCLUSIONS: The SB was available for improving upper limb function and health-related quality of life and useful for assessing upper limb ability in stroke survivors. TRIAL REGISTRATION: The study was registered with the clinical research information service (CRIS) ( KCT0003783 , registered 15 April 2019; retrospectively registered).

Effects of virtual reality-based rehabilitation on distal upper extremity function and health-related quality of life: a single-blinded, randomized controlled trial.

BACKGROUND: Virtual reality (VR)-based rehabilitation has been reported to have beneficial effects on upper extremity function in stroke survivors; however, there is limited information about its effects on distal upper extremity function and health-related quality of life (HRQoL). The purpose of the present study was to examine the effects of VR-based rehabilitation combined with standard occupational therapy on distal upper extremity function and HRQoL, and compare the findings to those of amount-matched conventional rehabilitation in stroke survivors. METHODS: The present study was a single-blinded, randomized controlled trial. The study included 46 stroke survivors who were randomized to a Smart Glove (SG) group or a conventional intervention (CON) group. In both groups, the interventions were targeted to the distal upper extremity and standard occupational therapy was administered. The primary outcome was the change in the Fugl-Meyer assessment (FM) scores, and the secondary outcomes were the changes in the Jebsen-Taylor hand function test (JTT), Purdue pegboard test, and Stroke Impact Scale (SIS) version 3.0 scores. The outcomes were assessed before the intervention, in the middle of the intervention, immediately after the intervention, and 1 month after the intervention. RESULTS: The improvements in the FM (FM-total, FM-prox, and FM-dist), JTT (JTT-total and JTT-gross), and SIS (composite and overall SIS, SIS-social participation, and SIS-mobility) scores were significantly greater in the SG group than in the CON group. CONCLUSIONS: VR-based rehabilitation combined with standard occupational therapy might be more effective than amount-matched conventional rehabilitation for improving distal upper extremity function and HRQoL. TRIAL REGISTRATION: This study is registered under the title "Effects of Novel Game Rehabilitation System on Upper Extremity Function of Patients With Stroke" and can be located in https://clinicaltrials.gov with the study identifier NCT02029651 .

Smoking Cessation and Risk of Hidradenitis Suppurativa Development.

Importance: Although tobacco smoking is established as a risk factor for hidradenitis suppurativa (HS), studies on the effects of smoking cessation on HS are limited, and evidence is lacking. Objective: To examine the association between changes in smoking status and the development of HS. Design, Setting, and Participants: This population-based cohort study enrolled participants from the Korean National Health Insurance Service database who had undergone 2 consecutive biennial health examinations (2004-2005 and 2006-2007) as the primary cohort. Within the primary cohort, the secondary cohort comprised individuals who underwent all biennial health examinations throughout the follow-up period and maintained the same smoking status from 2006 to 2007 to the end of the follow-up period. Data were analyzed from July to December 2023. Exposures: Changes in smoking habit status. Main Outcomes and Measures: Risk of HS development. The HS risk according to change in smoking status between the 2 consecutive health examinations was estimated using a Cox proportional hazards model. Results: Of the 6 230 189 participants enrolled, the mean (SD) age was 47.2 (13.5) years, and 55.6% were male. During 84 457 025 person-years of follow-up, 3761 HS events occurred. In the primary cohort, compared to those who consistently reported active smoking at both checkups (ie, sustained smokers), lower HS risk was seen among those who were confirmed to smoke initially but quit by the second checkup (ie, smoking quitters) (adjusted hazard ratio [AHR], 0.68; 95% CI, 0.56-0.83), those who maintained cessation status throughout (AHR, 0.67; 95% CI, 0.57-0.77), and those who reported never smoking at either checkup (ie, never smokers) (AHR, 0.57; 95% CI, 0.52-0.63). Those who initially quit smoking but resumed by the second checkup and those who had no previous smoking history but started at the second checkup (ie, new smokers) exhibited similar HS risk as sustained smokers. The secondary cohort results aligned with those of the primary cohort, showing a more pronounced risk reduction with smoking cessation (AHR, 0.57; 95% CI, 0.39-0.83). Considering time-smoking interaction, the cumulative incidence and the risk of HS in smoking quitters were similar to those in sustained smokers in the early stages of observation. However, 3 to 4 years after smoking cessation, the rate decelerated, resembling that of never smokers, and there was a statistically significant decrease in the risk that persisted (between 3 and 6 years from the index date: AHR, 0.58; 95% CI, 0.36-0.92; and ≥12 years from the index date: AHR, 0.70; 95% CI, 0.50-0.97). New smokers initially paralleled never smokers but accelerated after 2 to 3 years, reaching sustained smokers' levels. Conclusions and Relevance: In this cohort study, quitting smoking and sustaining a smoke-free status were associated with a reduced risk of HS development compared to continuous smoking. In contrast, resuming or initiating smoking may have as detrimental an effect on HS development as continual smoking.

Discrimination between genetically identical peony roots from different regions of origin based on 1H-nuclear magnetic resonance spectroscopy-based metabolomics: determination of the geographical origins and estimation of the mixing proportions of blended samples.

Sixty peony root training samples of the same age were collected from various regions in Korea and China, and their genetic diversity was investigated for 23 chloroplast intergenic space regions. All samples were genetically indistinguishable, indicating that the DNA-based techniques employed were not appropriate for determining the samples' regions of origin. In contrast, (1)H-nuclear magnetic resonance ((1)H-NMR) spectroscopy-based metabolomics coupled with multivariate statistical analysis revealed a clear difference between the metabolic profiles of the Korean and Chinese samples. Orthogonal projections on the latent structure-discrimination analysis allowed the identification of potential metabolite markers, including γ-aminobutyric acid, arginine, alanine, paeoniflorin, and albiflorin, that could be useful for classifying the samples' regions of origin. The validity of the discrimination model was tested using the response permutation test and blind prediction test for internal and external validations, respectively. Metabolomic data of 21 blended samples consisting of Korean and Chinese samples mixed at various proportions were also acquired by (1)H-NMR analysis. After data preprocessing which was designed to eliminate uncontrolled deviations in the spectral data between the testing and training sets, a new statistical procedure for estimating the mixing proportions of blended samples was established using the constrained least squares method for the first time. The predictive procedure exhibited relatively good predictability (adjusted R (2) = 0.7669), and thus has the potential to be used in the quality control of peony root by providing correct indications for a sample's geographical origins.

The association between the risk perceptions of COVID-19, trust in the government, political ideologies, and socio-demographic factors: A year-long cross-sectional study in South Korea.

Risk perception research, targeting the general public, necessitates the study of the multi-faceted aspects of perceived risk through a holistic approach. This study aimed to investigate the association between the two dimensions of risk perception of COVID-19, i.e., risk as a feeling and analysis, trust in the current government, political ideologies, and socio-demographic factors in South Korea. This study used a year-long repeated cross-sectional design, in which a national sample (n = 23,018) participated in 23 consecutive telephone surveys from February 2020 to February 2021. Most factors differed in the magnitude and direction of their relationships with the two dimensions of risk perception. However, trust in the current government, alone, delineated an association in the same direction for both dimensions, i.e., those with a lower level of trust exhibited higher levels of cognitive and affective risk perception. Although these results did not change significantly during the one-year observation period, they are related to the political interpretation of risk. This study revealed that affective and cognitive risk perceptions addressed different dimensions of risk perception. These findings could help governments and health authorities better understand the nature and mechanisms of public risk perception when implementing countermeasures and policies in response to the COVID-19 pandemic and other public health emergencies.

Identifying patients with deteriorating generalized pustular psoriasis: Development of a prediction model.

Generalized pustular psoriasis (GPP) is a life-threatening condition; however, little is known about the factors that can predict GPP patients manifesting a deteriorating course. To investigate the demographics and clinical features of adult inpatient GPP and propose a prediction model for detecting fatal GPP (fGPP) and GPP requiring intensive care unit admission (iGPP) patients, a nationwide population-based retrospective cohort study was conducted. The adult inpatients with GPP from January 2007 to December 2020 were assessed. The 800 cases were aged 51.0 years (median [interquartile range, 37.0-64.0]). Overall, 21 iGPP (64.0 years [54.0-77.0]) and 17 fGPP (75.0 years [68.0-77.0]) cases were identified as deteriorating GPP. Renal disease (odds ratio [OR], 7.31), myocardial infarction history (OR, 4.29), liver disease (OR, 2.82), and diabetes mellitus (OR, 2.34) were identified as predictors for iGPP. For fGPP, myocardial infarction history (OR, 5.10) and psoriasis history (OR, 3.13) were established as predictors. A prediction model with scores ranging 0-11 points showed a reliable diagnostic value in detecting deteriorating GPP (area under the curve = 0.75 for iGPP and 0.83 for fGPP). In conclusion, this study provides the clinical features of deteriorating GPP. A prediction model may help physicians to identify patients with deteriorating GPP.

The feasibility of mixed reality-based upper extremity self-training for patients with stroke-A pilot study.

Mixed reality (MR), which combines virtual reality and tangible objects, can be used for repetitive training by patients with stroke, allowing them to be immersed in a virtual environment while maintaining their perception of the real world. We developed an MR-based rehabilitation board (MR-board) for the upper limb, particularly for hand rehabilitation, and aimed to demonstrate the feasibility of the MR-board as a self-training rehabilitation tool for the upper extremity in stroke patients. The MR-board contains five gamified programs that train upper-extremity movements by using the affected hand and six differently shaped objects. We conducted five 30-min training sessions in stroke patients using the MR-board. The sensor measured hand movement and reflected the objects to the monitor so that the patients could check the process and results during the intervention. The primary outcomes were changes in the Box and Block Test (BBT) score, and the secondary outcomes were changes in the Fugl-Meyer assessment and Wolf Motor Function Test (WMFT) scores. Evaluations were conducted before and after the intervention. In addition, a usability test was performed to assess the patient satisfaction with the device. Ten patients with hemiplegic stroke were included in the analysis. The BBT scores and shoulder strength in the WMFT were significantly improved (p < 0.05), and other outcomes were also improved after the intervention. In addition, the usability test showed high satisfaction (4.58 out of 5 points), and patients were willing to undergo further treatment sessions. No safety issues were observed. The MR-board is a feasible intervention device for improving upper limb function. Moreover, this instrument could be an effective self-training tool that provides training routines for stroke patients without the assistance of a healthcare practitioner. Trial registration: This study was registered with the Clinical Research Information Service (CRIS: KCT0004167).

Estimation and inference on high-dimensional individualized treatment rule in observational data using split-and-pooled de-correlated score.

With the increasing adoption of electronic health records, there is an increasing interest in developing individualized treatment rules, which recommend treatments according to patients' characteristics, from large observational data. However, there is a lack of valid inference procedures for such rules developed from this type of data in the presence of high-dimensional covariates. In this work, we develop a penalized doubly robust method to estimate the optimal individualized treatment rule from high-dimensional data. We propose a split-and-pooled de-correlated score to construct hypothesis tests and confidence intervals. Our proposal adopts the data splitting to conquer the slow convergence rate of nuisance parameter estimations, such as non-parametric methods for outcome regression or propensity models. We establish the limiting distributions of the split-and-pooled de-correlated score test and the corresponding one-step estimator in high-dimensional setting. Simulation and real data analysis are conducted to demonstrate the superiority of the proposed method.

The association between immunosuppressants use and COVID-19 adverse outcomes: national COVID-19 cohort in South Korea.

BACKGROUND: There is uncertainty of the effect of immunosuppression, including corticosteroids, before COVID-19 infection on COVID-19 outcomes. The aim of this study was to investigate the relationship between prehospitalization immunosuppressants use (exposure) and COVID-19 patient outcomes. METHODS: We conducted a population-based retrospective cohort study using a nationwide healthcare claims database of South Korea as of May 15, 2020. Confirmed COVID-19 infection in hospitalized individuals aged 40 years or older were included for analysis. We defined exposure variable by using inpatient and outpatient prescription records of immunosuppressants from the database. Our primary endpoint was a composite endpoint of all-cause death, intensive care unit (ICU) admission, and mechanical ventilation use. Inverse probability of treatment weighting (IPTW)-adjusted logistic regression analyses were used, to estimate odds ratio (OR) and 95% confidence intervals (CI), comparing immunosuppressants users and non-users. RESULTS: We identified 4,349 patients, for which 1,356 were immunosuppressants users and 2,993 were non-users. Patients who used immunosuppressants were at increased odds of the primary endpoint of all-cause death, ICU admission and mechanical ventilation use (IPTW OR =1.32; 95% CI: 1.06-1.63), driven by higher odds of all-cause mortality (IPTW OR =1.63; 95% CI: 1.21-2.26). Patients who used corticosteroids (n=1,340) were at increased odds of the primary endpoint (IPTW OR =1.33; 95% CI: 1.07-1.64). CONCLUSIONS: Immunosuppressant use was associated with worse outcomes among COVID-19 patients. These findings support the latest guidelines from the CDC that people on immunosuppressants are at high risk of severe COVID-19 and that immunocompromised people may benefit from booster COVID-19 vaccinations.

The prognostic role of anticoagulants in COVID-19 patients: national COVID-19 cohort in South Korea.

BACKGROUND: There currently exists a paucity of data on whether pre-admission anticoagulants use may have benefits among COVID-19 patients by preventing COVID-19 associated thromboembolism. The aim of this study was to assess the association between pre-admission anticoagulants use and COVID-19 adverse outcomes. METHODS: We conducted a population-based cohort studying using the Health Insurance Review and Assessment Service (HIRA) claims data released by the South Korean government. Our study population consisted of South Koreans who were aged 40 years or older and hospitalized with COVID-19 between 1 January 2020 through 15 May 2020. We defined anticoagulants users as individuals with inpatient and outpatient prescription records in 120 days before cohort entry. Our primary endpoint was a composite of all-cause death, intensive care unit (ICU) admission, and mechanical ventilation use. Individual components of the primary endpoint were secondary endpoints. We compared the risk of endpoints between the anticoagulants users and non-users by logistic regression models, with the standardized mortality ratio weighting (SMRW) adjustment. RESULTS: In our cohort of 4,349 patients, for the primary endpoint of mortality, mechanical ventilation and ICU admission, no difference was noted between anticoagulants users and non-users (SMRW OR 1.11, 95% CI: 0.60-2.05). No differences were noted, among individual components. No effect modification was observed by age, sex, history of atrial fibrillation and thromboembolism, and history of cardiovascular disease. When applying the inverse probability of treatment weighting (IPTW) and SMRW with doubly robust methods in sensitivity analysis, anticoagulants use was associated with increased odds of the primary endpoint. CONCLUSIONS: Pre-admission anticoagulants were not determined to have a protective role against severe COVID-19 outcomes.

The association between statin and COVID-19 adverse outcomes: national COVID-19 cohort in South Korea.

BACKGROUND: There currently exist limited and conflicting clinical data on the use of statins in coronavirus disease 2019 (COVID-19) patients. The aim of this paper was to compare hospitalized patients with COVID-19 who did and did not receive statins. METHODS: We performed a population-based retrospective cohort study using South Korea's nationwide healthcare claim database. We identified consecutive patients hospitalized with COVID-19 and aged 40 years or older. Statin users were individuals with inpatient and outpatient prescription records of statins in the 240 days before cohort entry to capture patients who are chronic statin users and, therefore, receive statin prescriptions as infrequently as every 8 months. Our primary endpoint was a composite of all-cause death, intensive care unit (ICU) admission, mechanical ventilation use and cardiovascular outcomes [myocardial infarction (MI), transient cerebral ischemic attacks (TIA) or stroke]. We compared the risk of outcomes between statin users and non-users using logistic regression models after inverse probability of treatment weighting (IPTW) adjustment. RESULTS: Of 234,427 subjects in the database, 4,349 patients were hospitalized with COVID-19 and aged 40+ years. In total, 1,115 patients were statin users (mean age =65.9 years; 60% female), and 3,234 were non-users (mean age =58.3 years; 64% female). Pre-hospitalization statin use was not significantly associated with increased risk of the primary endpoint [IPTW odds ratio (OR) 0.82; 95% confidence interval (CI): 0.60-1.11]. Subgroup analysis showed a protective role of antecedent statin use for individuals with hypertension (IPTW OR 0.40; 95% CI: 0.23-0.69, P for interaction: 0.0087). CONCLUSIONS: Pre-hospitalization statin use is not detrimental and may be beneficial amongst hypertensive COVID-19 patients. Further investigation into statin is needed for more conclusive effects of statins for treatment of COVID-19.