Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics.

BACKGROUND: To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). METHODS: This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. RESULTS: Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. CONCLUSIONS: Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.

EVATOM: an optical, label-free, machine learning assisted embryo health assessment tool.

The combination of a good quality embryo and proper maternal health factors promise higher chances of a successful in vitro fertilization (IVF) procedure leading to clinical pregnancy and live birth. Of these two factors, selection of a good embryo is a controllable aspect. The current gold standard in clinical practice is visual assessment of an embryo based on its morphological appearance by trained embryologists. More recently, machine learning has been incorporated into embryo selection "packages". Here, we report EVATOM: a machine-learning assisted embryo health assessment tool utilizing an optical quantitative phase imaging technique called artificial confocal microscopy (ACM). We present a label-free nucleus detection method with, to the best of our knowledge, novel quantitative embryo health biomarkers. Two viability assessment models are presented for grading embryos into two classes: healthy/intermediate (H/I) or sick (S) class. The models achieve a weighted F1 score of 1.0 and 0.99 respectively on the in-distribution test set of 72 fixed embryos and a weighted F1 score of 0.9 and 0.95 respectively on the out-of-distribution test dataset of 19 time-instances from 8 live embryos.

Vertically Stackable Ovonic Threshold Switch Oscillator Using Atomic Layer Deposited Ge0.6Se0.4 Film for High-Density Artificial Neural Networks.

Nanodevice oscillators (nano-oscillators) have received considerable attention to implement in neuromorphic computing as hardware because they can significantly improve the device integration density and energy efficiency compared to complementary metal oxide semiconductor circuit-based oscillators. This work demonstrates vertically stackable nano-oscillators using an ovonic threshold switch (OTS) for high-density neuromorphic hardware. A vertically stackable Ge0.6Se0.4 OTS-oscillator (VOTS-OSC) is fabricated with a vertical crossbar array structure by growing Ge0.6Se0.4 film conformally on a contact hole structure using atomic layer deposition. The VOTS-OSC can be vertically integrated onto peripheral circuits without causing thermal damage because the fabrication temperature is <400 °C. The fabricated device exhibits oscillation characteristics, which can serve as leaky integrate-and-fire neurons in spiking neural networks (SNNs) and coupled oscillators in oscillatory neural networks (ONNs). For practical applications, pattern recognition and vertex coloring are demonstrated with SNNs and ONNs, respectively, using semiempirical simulations. This structure increases the oscillator integration density significantly, enabling complex tasks with a large number of oscillators. Moreover, it can enhance the computational speed of neural networks due to its rapid switching speed.

Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics

Abstract Background To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). Methods This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. Results Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. Conclusions Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.

Potentials of ionic liquids to overcome physical and biological barriers.

Over the last decades, ionic liquids (IL) have shown great potential in non-invasive delivery starting from synthetic small molecules to biological large molecules. ILs are emerging as a particular class of drug delivery systems due to their unique physiochemical properties, simple surface modification, and functionalization. These features of IL help achieve specific design principles that are essential for a non-invasive drug delivery system. In this review, we have discussed IL and their applications in non-invasive drug delivery systems. We evaluated state-of-the-art development and advances of IL aiming to mitigate the biological and physical barriers to improve transdermal and oral delivery, summarized in this review. We also provided an overview of the various factors determining the systemic transportation of IL-based formulation. Additionally, we have emphasized how the ILs facilitate the transportation of therapeutic molecules by overcoming biological barriers.

Catalytic hydrolysis of agar using magnetic nanoparticles: optimization and characterization.

BACKGROUND: Agar is used as a gelling agent that possesses a variety of biological properties; it consists of the polysaccharides agarose and porphyrin. In addition, the monomeric sugars generated after agar hydrolysis can be functionalized for use in biorefineries and biofuel production. The main objective of this study was to develop a sustainable agar hydrolysis process for bioethanol production using nanotechnology. Peroxidase-mimicking Fe3O4-MNPs were applied for agar degradation to generate agar hydrolysate-soluble fractions amenable to Saccharomyces cerevisiae and Escherichia coli during fermentation. RESULTS: Fe3O4-MNP-treated (Fe3O4-MNPs, 1 g/L) agar exhibited 0.903 g/L of reducing sugar, which was 21-fold higher than that of the control (without Fe3O4-MNP-treated). Approximately 0.0181% and 0.0042% of ethanol from 1% of agar was achieved using Saccharomyces cerevisiae and Escherichia coli, respectively, after process optimization. Furthermore, different analytical techniques (FTIR, SEM, TEM, EDS, XRD, and TGA) were applied to validate the efficiency of Fe3O4-MNPs in agar degradation. CONCLUSIONS: To the best of our knowledge, Fe3O4-MNP-treated agar degradation for bioethanol production through process optimization is a simpler, easier, and novel method for commercialization.

Machine learning assisted health viability assay for mouse embryos with artificial confocal microscopy (ACM).

The combination of a good quality embryo and proper maternal health factors promise higher chances of a successful in vitro fertilization (IVF) procedure leading to clinical pregnancy and live birth. Of these two factors, selection of a good embryo is a controllable aspect. The current gold standard in clinical practice is visual assessment of an embryo based on its morphological appearance by trained embryologists. More recently, machine learning has been incorporated into embryo selection "packages". Here, we report a machine-learning assisted embryo health assessment tool utilizing a quantitative phase imaging technique called artificial confocal microscopy (ACM). We present a label-free nucleus detection method with novel quantitative embryo health biomarkers. Two viability assessment models are presented for grading embryos into two classes: healthy/intermediate (H/I) or sick (S) class. The models achieve a weighted F1 score of 1.0 and 0.99 respectively on the in-distribution test set of 72 fixed embryos and a weighted F1 score of 0.9 and 0.95 respectively on the out-of-distribution test dataset of 19 time-instances from 8 live embryos.

Preferred versus Actual Place of Care and Factors Associated with Home Discharge among Korean Patients with Advanced Cancer: A Retrospective Cohort Study.

Respecting the preference for a place of care is essential for advance care planning in patients with advanced cancer. This retrospective study included adult patients with cancer referred to an inpatient palliative care consultation team at a tertiary acute care hospital in South Korea between April 2019 and December 2020. Patients' preference for place of care and demographic and clinical factors were recorded, and the actual discharge locations were categorized as home or non-home. Patients discharged home but with unintended hospital visits within 2 months were also investigated. Of the 891 patients referred to the palliative care consultation team, 210 (23.6%) preferred to be discharged home. Among them, 113 (53.8%) were discharged home. No significant differences were found between patients who preferred home discharge and those who did not. Home discharge was higher among female patients (p = 0.04) and lower in those with poor oral intake (p < 0.001) or dyspnea (p = 0.02). Of the 113 patients discharged home, 37 (32.8%) had unintended hospital visits within 2 months. Approximately one-quarter of hospitalized patients with advanced cancer preferred to be discharged home, but only half of them received the home discharge. To meet patients' preferences for end-of-life care, individual care planning considering relevant factors is necessary.

Ethical Issues Referred to Clinical Ethics Support at a University Hospital in Korea: Three-Year Experience After Enforcement of Life-Sustaining Treatment Decisions Act.

BACKGROUND: Clinical ethics support is a form of preventive ethics aimed at mediating ethics-related conflicts and managing ethical issues arising in the healthcare setting. However, limited evidence exists regarding the specific ethical issues in clinical practice. This study aimed to explore the diverse ethical issues of cases referred to clinical ethics support after the new legislation on hospice palliative care and end-of-life decision-making was implemented in Korea in 2018. METHODS: A retrospective study of cases referred to clinical ethics support at a university hospital in Korea from February 2018 to February 2021 was conducted. The ethical issues at the time of referral were analyzed via qualitative content analysis of the ethics consultation-related documents. RESULTS: A total of 60 cases of 57 patients were included in the study, of whom 52.6% were men and 56.1% were older than 60 years of age. The majority of cases (80%) comprised patients from the intensive care unit. One-third of the patients were judged as being at the end-of-life stage. The most frequent ethical categories were identified as goals of care/treatment (78.3%), decision-making (75%), relationship (41.7%), and end-of-life issues (31.7%). More specifically, best interests (71.7%), benefits and burdens/harms (61.7%), refusal (53.3%), and surrogate decision-making (33.3%), followed by withholding or withdrawal (28.3%) were the most frequent ethical issues reported, which became diversified by year. In addition, the ethical issues appeared to differ by age group and judgment of the end-of-life stage. CONCLUSION: The findings of this study expand the current understanding of the diverse ethical issues including decision-making and goals of care/treatment that have been referred to clinical ethics support since the enforcement of the new legislation in Korea. This study suggests a need for further research on the longitudinal exploration of ethical issues and implementation of clinical ethics support in multiple healthcare centers.

Inoculation of ACC deaminase-producing endophytic bacteria down-regulates ethylene-induced pathogenesis-related signaling in red pepper (Capsicum annuum L.) under salt stress.

Pathogenesis-related (PR) signaling plays multiple roles in plant development under abiotic and biotic stress conditions and is regulated by a plethora of plant physiological as well as external factors. Here, our study was conducted to evaluate the role of an ACC deaminase-producing endophytic bacteria in regulating ethylene-induced PR signaling in red pepper plants under salt stress. We also evaluated the efficiency of the bacteria in down-regulating the PR signaling for efficient colonization and persistence in the plant endosphere. We used a characteristic endophyte, Methylobacterium oryzae CBMB20 and its ACC deaminase knockdown mutant (acdS- ). The wild-type M. oryzae CBMB20 was able to decrease ethylene emission by 23% compared to the noninoculated and acdS- M. oryzae CBMB20 inoculated plants under salt stress. The increase in ethylene emission resulted in enhanced hydrogen peroxide concentration, phenylalanine ammonia-lyase activity, ß-1,3 glucanase activity, and expression profiles of WRKY, CaPR1, and CaPTI1 genes that are typical salt stress and PR signaling factors. Furthermore, the inoculation of both the bacterial strains had shown induction of PR signaling under normal conditions during the initial inoculation period. However, wild-type M. oryzae CBMB20 was able to down-regulate the ethylene-induced PR signaling under salt stress and enhance plant growth and stress tolerance. Collectively, ACC deaminase-producing endophytic bacteria down-regulate the salt stress-mediated PR signaling in plants by regulating the stress ethylene emission levels and this suggests a new paradigm in efficient colonization and persistence of ACC deaminase-producing endophytic bacteria for better plant growth and productivity.

Identification and Characterization of HEPN-MNT Type II TA System from Methanothermobacter thermautotrophicus ΔH.

Toxin-antitoxin (TA) systems are widespread in bacteria and archaea plasmids and genomes to regulate DNA replication, gene transcription, or protein translation. Higher eukaryotic and prokaryotic nucleotide-binding (HEPN) and minimal nucleotidyltransferase (MNT) domains are prevalent in prokaryotic genomes and constitute TA pairs. However, three gene pairs (MTH304/305, 408/409, and 463/464) of Methanothermobacter thermautotropicus ΔH HEPN-MNT family have not been studied as TA systems. Among these candidates, our study characterizes the MTH463/MTH464 TA system. MTH463 expression inhibited Escherichia coli growth, whereas MTH464 did not and blocked MTH463 instead. Using site-directed MTH463 mutagenesis, we determined that amino acids R99G, H104A, and Y106A from the R[ɸX]4-6H motif are involved with MTH463 cell toxicity. Furthermore, we established that purified MTH463 could degrade MS2 phage RNA, whereas purified MTH464 neutralized MTH463 activity in vitro. Our results indicate that the endonuclease toxin MTH463 (encoding a HEPN domain) and its cognate antitoxin MTH464 (encoding the MNT domain) may act as a type II TA system in M. thermautotropicus ΔH. This study provides initial and essential information studying TA system functions, primarily archaea HEPN-MNT family.

The Effect of Task-Oriented Activities Training on Upper-Limb Function, Daily Activities, and Quality of Life in Chronic Stroke Patients: A Randomized Controlled Trial.

This randomized controlled study aimed to investigate the effects of 8-week task-oriented activities of daily living (T-ADL) training on upper limb functions, activities of daily living (ADL), and quality of life (QoL) in chronic stroke patients. The 33 patients were randomly assigned to the T-ADL training or conventional occupational therapy (OT) group. The respective interventions were provided for 45-min a day, five times a week for eight weeks. To compare the upper-limb function before and after the intervention, the manual function test (MFT), box and block test (BBT), and grasp power test were performed; to compare the level of ADL performance, the modified-Barthel index (MBI) was measured. To evaluate QoL, stroke-specific QoL was measured. There was a significant group-by-time interaction in the affected side MFT score and both sides of BBT scores, but no significant interaction was found in the unaffected side MFT score, ADL, and QoL. Both groups showed a significant main effect of time in their ADL and QoL after the intervention (p < 0.001). The results of this study indicate that the eight-week T-ADL training has a positive effect on upper limb functions and gross manual dexterity, and both T-ADL training and conventional OT are effective in improving ADL and QoL in chronic stroke patients.

Atomic Layer Deposition of Sb2 Te3 /GeTe Superlattice Film and Its Melt-Quenching-Free Phase-Transition Mechanism for Phase-Change Memory.

Atomic layer deposition (ALD) of Sb2 Te3 /GeTe superlattice (SL) film on planar and vertical sidewall areas containing TiN metal and SiO2 insulator is demonstrated. The peculiar chemical affinity of the ALD precursor to the substrate surface and the 2D nature of the Sb2 Te3 enable the growth of an in situ crystallized SL film with a preferred orientation. The SL film shows a reduced reset current of ≈1/7 of the randomly oriented Ge2 Sb2 Te5 alloy. The reset switching is induced by the transition from the SL to the (111)-oriented face-centered-cubic (FCC) Ge2 Sb2 Te5 alloy and subsequent melt-quenching-free amorphization. The in-plane compressive stress, induced by the SL-to-FCC structural transition, enhances the electromigration of Ge along the [111] direction of FCC structure, which enables such a significant improvement. Set operation switches the amorphous to the (111)-oriented FCC structure.

The Medical Needs and Characteristics of Cancer and Progressive Neurologic Disease Patients Who Use Home-Based Medical Care in Korea: A Retrospective Study for 2011-2020.

OBJECTIVES: To investigate the needs and characteristics of patients with cancer and neurologic disorders requiring home-based medical care (HBMC). DESIGN: Retrospective observational study. SETTING AND PARTICIPANTS: Patients receiving HBMC on discharge from a tertiary hospital in Korea during 2011-2020. METHODS: Patients were classified into 3 disease groups: cancer, progressive neurologic disorders (NR), and others. Characteristics and medical needs were assessed in each disease group. Medical needs were categorized based on functional items requiring support or management at the time of registration: respiratory, feeding, urinary system, drain tube, central catheter, wound, medication, and other. Patients with multiple medical needs were assigned to multiple categories. Patients who used HBMC for more than 3 months were defined as long-term users; their characteristics were evaluated in the same way. RESULTS: Of the total 655 patients, 47.0% (308) had cancer and 17.3% (113) were NR patients. Among all patients, 78.8% were partially dependent (44.0%) or completely dependent (34.8%) in daily activities, and there were more dependent patients in the NR group (80.5%) than cancer (26.6%). Patients with cancer needed central catheter management the most (43.5%), followed by wound care (36.7%), feeding support (35.1%), and drain tube management (22.1%). NR patients required feeding support the most (80.5%), followed by respiratory support (43.4%), wound care (41.6%), and urinary system support (19.5%). Of all patients, 30.2% (198) were long-term users (NR, 37.9%; cancer, 35.4%). Long-term users were common among patients who needed respiratory support (59.4%), feeding support (48.75), and urinary system support (34.6%). CONCLUSIONS AND IMPLICATIONS: Homebound patients with cancer and progressive neurologic disorders need medical services at home after discharge. Patients who need feeding and respiratory support usually use HBMC for more than 3 months. Further studies are needed to design an optimal HBMC that continuously provides medical services to patients with serious illnesses living at home.

Expression of Inflammatory Markers in the Muscles of Patients with Idiopathic Inflammatory Myopathy According to the Presence of Interstitial Lung Disease.

BACKGROUND: Several studies have identified factors associated with the development of interstitial lung disease (ILD) in patients with idiopathic inflammatory myopathies (IIMs). However, few have assessed the association between ILD and muscle biopsy findings, including inflammatory marker expressions analyzed using immunohistochemistry (IHC). METHODS: Muscle biopsies from patients who were newly diagnosed with IIMs between 2000 and 2017 were reviewed. ILD was diagnosed based on chest computed tomography findings at the time of diagnosis of IIMs. IHC staining was performed for CD3, CD4, CD8, CD20, CD68, CD163, MX1, MHC class I, and HLA-DR. The factors associated with the presence of ILD were evaluated by logistic regression analysis. RESULTS: Of the 129 patients with IIM, 49 (38%) had ILD. In the muscle biopsy findings, CD4 expression, MX1 expression on immune cells, and expression of MHC class I and HLA-DR on myofibers were more common in patients with ILD than those without. In the logistic regression analysis, the HLA-DR expression on myofibers was significantly associated with the risk of ILD (OR, 2.39; 95% CI, 1.24-4.90, p = 0.012) after adjusting for pathologic findings, clinical features, and autoantibodies. CONCLUSION: The expression of HLA-DR on myofibers was associated with the presence of ILD in patients with IIM.

Aggressiveness of care in the last days of life in the emergency department of a tertiary hospital in Korea.

BACKGROUND: High-quality end-of-life (EOL) care requires both comfort care and the maintenance of dignity. However, delivering EOL in the emergency department (ED) is often challenging. Therefore, we aimed to investigate characteristics of EOL care for dying patients in the ED. METHODS: We conducted a retrospective cohort study of patients who died of disease in the ED at a tertiary hospital in Korea between January 2018 and December 2020. We examined medical care within the last 24 h of life and advance care planning (ACP) status. RESULTS: Of all 222 disease-related mortalities, 140 (63.1%) were men, while 141 (63.5%) had cancer. The median age was 74 years. As for critical care, 61 (27.5%) patients received cardiopulmonary resuscitation, while 80 (36.0%) received mechanical ventilation. The absence of serious illness (p = 0.011) and the lack of an advance statement (p < 0.001) were both independently associated with the receipt of more critical care. Only 70 (31.5%) patients received comfort care through opioids. Younger patients (< 75 years) (p = 0.002) and those who completed life-sustaining treatment legal forms (p = 0.001) received more comfort care. While EOL discussions were initiated in 150 (67.6%) cases, the palliative care team was involved only in 29 (13.1%). CONCLUSIONS: Patients in the ED underwent more aggressive care and less comfort care in a state of imminent death. To ensure better EOL care, physicians should minimize redundant evaluations and promptly introduce ACP.

Effects of Robot-Assisted Gait Training with Body Weight Support on Gait and Balance in Stroke Patients.

This study investigated the effects of robot-assisted gait training with body weight support on gait and balance in stroke patients. The study participants comprised 24 patients diagnosed with stroke. Patients were randomly assigned to four groups of six: robot A, B, C, and non-robot. The body weight support (BWS) for the harness of the robot was set to 30% of the patient's body weight in robot group A, 50% in robot group B, and 70% in robot group C. All experimental groups received robot-assisted gait training and general physical therapy. The non-robot group underwent gait training using a p-bar, a treadmill, and general physical therapy. The intervention was performed for 30 min a day, five times a week, for 6 weeks. All participants received the intervention after the pre-test. A post-test was performed after all of the interventions were completed. Gait was measured using a 10 m Walking test (10MWT) and the timed up and go (TUG) test. Balance was assessed using the Berg Balance Scale (BBS). Robot groups A, B, and C showed significantly better 10MWT results than did the non-robot group (p < 0.5). TUG was significantly shorter in robot groups A, B, and C than in the non-robot group (p < 0.5). The BBS scores for robot group A improved significantly more than did those for robot groups B and C and the non-robot group (p < 0.5), indicating that robot-assisted gait training with body weight support effectively improved the gait of stroke patients.

The Effect of Task-Oriented Training on Upper-Limb Function, Visual Perception, and Activities of Daily Living in Acute Stroke Patients: A Pilot Study.

This pilot study aimed to investigate the effects of task-oriented training on upper-limb functioning, visual perception, and activities of daily living (ADL) in acute stroke patients. Of 20 participants, 10 were randomly assigned in a 1:1 ratio to experimental and control groups. Task-oriented training and table-top activity training were implemented for 6 weeks. Change in upper-limb functioning was assessed with the Manual Function Test (MFT); visual perceptual skill and ADL performance were evaluated using the Motor-Free Visual Perception Test­Vertical (MVPT-V) and Korean Modified Barthel Index (K-MBI), respectively. There was a significant interaction in the MFT and MBI score between the group and time (p < 0.05), but the group effect was not significant (p > 0.05). The MFT and MBI score significantly increased in both groups after the intervention (p < 0.001), but the effect size was greater in the task-oriented training group than the table-top activity training group. No significant interaction with MVPT-V score was found between the group and time (p > 0.05), and no statistical group difference was found either (p > 0.05). Both groups showed significant improvement in their MVPT-V score after the intervention (p < 0.001). The pilot study findings demonstrate that both task-oriented training and table-top activity training are effective in recovering upper-limb function, visual perception, and ADL in acute stroke patients.

Effects of Cognitive Exercise Therapy on Upper Extremity Sensorimotor Function and Activities of Daily Living in Patients with Chronic Stroke: A Randomized Controlled Trial.

This study investigated the effects of cognitive exercise therapy on upper extremity sensorimotor function and daily activity in patients with chronic stroke and compared these effects to those of conventional occupational therapy. The 30 patients with chronic stroke (mean age: 63.6 ± 12.7 years; height: 162.8 ± 8.1 cm; weight: 60.6 ± 7.6 kg; body mass index: 22.8 ± 1.9 kg/m2) were divided into two treatment groups with 15 patients in each. The respective interventions were provided for 30 min per day, five times weekly for 4 weeks. Manual and sensory function tests were conducted to evaluate the sensorimotor function, while the Korean-Modified Barthel Index was used to assess daily activities. All outcome variables were assessed before and after the interventions. A significant interaction was observed in sensory function (p = 0.001) but not motor function or daily activities (p > 0.05). No significant main group effects were found for any outcome variables (p > 0.05). The experimental group showed significant improvements in motor function (p < 0.001), sensory function (p < 0.001), and daily life activities (p = 0.001) after cognitive exercise therapy, whereas the control group showed significant improvement only in daily life activities post-intervention (p = 0.012). These results demonstrated the positive effects of cognitive exercise therapy on upper extremity sensorimotor function and daily life activities and the lack of improvement in motor and sensory function following conventional occupational therapy in patients with chronic stroke. Thus, the combination of cognitive exercise and conventional occupational therapies may be an effective way to improve sensory function and upper extremity motor function in patients with chronic stroke.

Safety of JAK inhibitor use in patients with rheumatoid arthritis who developed herpes zoster after receiving JAK inhibitors.

INTRODUCTION: To determine the safety of Janus kinase inhibitor (JAKi) use following herpes zoster (HZ) reactivation in patients with rheumatoid arthritis (RA). METHODS: Medical records of all patients who received JAKi at a tertiary referral center between August 2015 and June 2021 were retrospectively reviewed. Data from patients who developed HZ reactivation were collected, and the HZ-related safety of those who continued JAKis after reactivation was evaluated. RESULTS: Of the 416 patients who received JAKis, 33 (7.9%) developed HZ reactivation during treatment (tofacitinib, n = 22; baricitinib, n = 11). The mean age of the patients was 60.2 ± 11.8 years. Fourteen patients (42.4%) received glucocorticoids with a median dose of 3.75 mg of prednisone (IQR, 2.5-5.0). The median duration of JAKi administration before HZ reactivation was 11 months (IQR, 4-29). JAKi was continued in 24 (72.7%) patients during the HZ episode, while it was temporarily discontinued and then resumed after the HZ episode in 5 (15.2%) patients. Three (9.1%) patients had acute complications, such as encephalitis with HZ ophthalmicus. Four (12.1%) patients, including the 3 with complications, permanently discontinued JAKis. Of the 29 patients who were observed for a median of 12 months (IQR, 6-21) after the initial HZ reactivation episode, reactivation recurred in one (3.4%); this patient maintained JAKi treatment for a further 18 months without additional HZ recurrence. CONCLUSION: JAKis were commonly continued or re-administered in patients with HZ reactivation, and the majority of these patients did not experience significant complications or recurrence of HZ reactivation. Thus, the use of JAKi after HZ reactivation episode seems to be tolerated.