Early identification of patients at high risk of deep surgical site infection after open extremity fractures is crucial for timely intervention and improved outcomes. This study aimed to develop and internally validate a clinical prediction model, the BIGB2OSS score, for predicting deep surgical site infection within three months of injury using variables easily obtained in early post-injury phase. A prospective cohort study was conducted at two university hospitals in Japan, including 570 consecutive patients with open extremity fractures. Data on 18 candidate predictors were collected in the early post-injury phase. The primary outcome was the occurrence of deep surgical site infection within three months of injury. A backward stepwise logistic regression model was used to build the prediction model. Model performance was assessed using the area under the curve (AUC) and internal validation with bootstrap methods. The BIGB2OSS score was a 5-point model based on four predictors: BMI ≥ 25 (1 point), Gustilo-Anderson classification IIIA (1 point), Gustilo-Anderson IIIB or IIIC (2 points), OTA-OFC skin = 3 (1 point), and smoking history (1 point). The model showed fair discriminative ability with an AUC of 0.76 (95% CI 0.70-0.83). Internal validation using bootstrap resampling with 1000 repetitions yielded an optimism-adjusted C-statistic of 0.76 (95% CI 0.70-0.83). The estimated probabilities of deep surgical site infection were 2.7% for scores 0-1, 11% for scores 2-3, and 30% for scores 4-5, closely matching the actual prevalence. The BIGB2OSS score is a simple clinical prediction model with fair discrimination for deep surgical site infection in patients with open extremity fractures. It uses early post-injury variables and may support timely risk communication and follow-up planning. Further external validation is needed to confirm its utility in diverse clinical settings.
Benzodiazepines (BZPs) continue to be widely prescribed in non-psychiatric settings, despite clinical guideline recommendations favouring selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) for the treatment of anxiety and depressive disorders. Long-term, hospital-based evidence comparing these prescribing patterns in Japan remains limited. The study aim was to evaluate long-term trends in BZP prescribing relative to SSRI/SNRI use and to identify factors associated with anxiolytic BZP versus SSRI/SNRI prescriptions. We conducted a database study of all 16,886,524 prescriptions issued between April 2001 and March 2022 at a tertiary university hospital in Japan. Anxiolytic and hypnotic BZPs, SSRIs, SNRIs, and related antidepressants were identified. The ratio of anxiolytic BZP to SSRI/SNRI prescriptions (B/S ratio) was calculated according to department group. Factors associated with anxiolytic BZP versus SSRI/SNRI prescribing were examined using multiple logistic regression analysis. Anxiolytic BZP prescriptions accounted for 2.3% of all prescriptions and declined over time, whereas SSRI/SNRI prescriptions (1.4%) remained largely stable throughout the study period. The B/S ratio was consistently higher in internal medicine than in psychiatry, although a gradual reduction was observed over time. Multivariable analysis demonstrated that anxiolytic BZP prescribing was independently associated with the internal medicine department, female sex, outpatient status, younger age, and earlier calendar years. Despite a temporal decline, anxiolytic BZPs continue to be preferentially prescribed over SSRIs/SNRIs in non-psychiatric settings. These findings underscore persistent gaps between evidence-based recommendations and clinical practice and highlight the need for targeted educational and policy interventions to optimise psychotropic prescribing.
Study DesignMulticenter prospective observational study.ObjectivesTo determine the responsiveness, reliability, and construct validity of commonly used clinician-reported and patient-reported outcome measures in surgically treated thoracic myelopathy, a condition for which standardized outcome assessment has not been established.MethodsAdults undergoing surgery for MRI-confirmed thoracic myelopathy were prospectively enrolled at nine tertiary centers. Clinician-reported measures included the Japanese Orthopaedic Association (JOA) score, a thoracic-adapted JOA subtotal (JOAt), and the modified JOA (mJOA). Patient-reported outcomes included the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) and EuroQOL 5-dimension (EQ-5D). Assessments were performed preoperatively and at 3-6 months postoperatively. Internal responsiveness was evaluated using Wilcoxon's r, test-retest reliability using ICC(1,1), and construct validity using Spearman's correlation with EQ-5D.ResultsFifty-one patients were included (mean age 65.6 years; 59% male). Significant postoperative improvement was observed across major clinician-reported and patient-reported outcomes. Large internal responsiveness was demonstrated for JOA (r=0.64), JOAt (0.63), mJOA (0.68), and JOACMEQ lower-extremity function (LF) (0.59). Test-retest reliability was high for JOA, JOAt, mJOA, JOACMEQ-LF, and EQ-5D (ICC range 0.78-0.85). JOACMEQ-LF showed the strongest construct validity with EQ-5D at both baseline (ρ=0.62) and follow-up (ρ=0.72).ConclusionsJOAt, mJOA, and JOACMEQ lower-extremity function demonstrated robust psychometric performance in thoracic myelopathy. These measures represent suitable candidates for standardized outcome assessment and provide a methodological foundation for future clinical studies and guideline development in this under-studied condition.
This study aimed to characterize the spectrum of anatomical variations in the origin and course of the suprascapular artery. We investigated the origin and course of 239 suprascapular arteries from 134 Japanese cadavers donated to Juntendo University School of Medicine for anatomical education. The suprascapular arteries were classified into six types based on their origin and course. Type 1, originating from the thyrocervical trunk, represented the most common and standard morphology (158/239, 66.1%). Type 2 arose from the proximal portion of the internal thoracic artery (15/239, 6.3%), and Type 3 originated directly from the second part of the subclavian artery (10/239, 4.2%). Types 1-3 passed superior to the superior transverse scapular ligament to enter the supraspinous fossa. Type 4 originated directly from the third part of the subclavian artery (50/239, 20.9%), whereas Types 5 and 6 arose from the superior thoracic artery (4/239, 1.7%) and the superficial subscapular artery (2/239, 0.8%), respectively. Types 4-6 traversed the scapular notch inferior to the superior transverse scapular ligament, accompanying the suprascapular nerve, to enter the supraspinous fossa. The brachial plexus sheath, which envelops the brachial plexus and adjacent arteries, was identified as a potential anatomical determinant of the correlation between the origin and course of the suprascapular artery. Type 1 represented the standard morphology of the suprascapular artery. Consistent with previous studies, the suprascapular artery exhibited considerable anatomical variation, with a distinct correlation between origin and course.
Global longitudinal strain (GLS) is a well-established prognostic marker for the early detection of cancer therapy-related cardiac dysfunction (CTRCD). We previously developed machine learning (ML) models to predict reduced GLS (Low-GLS, defined as absolute GLS < 16%) from conventional echocardiographic parameters in patients with cancer. This study aimed to externally validate the performance and generalizability of the previously developed ML models in an independent cohort. This multicenter study included patients from the Tokyo Metropolitan Tama Medical Center (TMC, n = 1484) and Shizuoka Cancer Center (SCC, n = 141) who underwent echocardiography with GLS measurements before or after anticancer chemotherapy. The exclusion criterion was left ventricular ejection fraction < 50%. Low-GLS was predicted using 25 conventional echocardiographic parameters. The previously developed ML models (Random Forest, Extra Trees, and CatBoost) were directly applied, without retraining, to an independent external validation cohort from SCC. A conventional logistic regression model was included as a reference for comparison. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), and other metrics. In the internal validation cohort, the ML models demonstrated discriminative comparable performance (AUCs 0.722-0.748), whereas logistic regression achieved an AUC of 0.729. In the external validation cohort, performance was generally preserved; the Random Forest model demonstrated the highest discriminative ability (AUC 0.772), while the remaining models achieved AUCs of 0.725-0.746. Logistic regression achieved an AUC of 0.738. ML models trained on conventional echocardiographic parameters retained moderate predictive ability for reduced GLS upon external validation.
Severe caffeine intoxication can cause life-threatening complications, yet serum caffeine measurements are rarely available at presentation. We aimed to develop a simple clinical prediction model using readily available clinical parameters to predict severe caffeine intoxication. This retrospective study involved patients with acute caffeine intoxication admitted between April 2016 and March 2022. Data on clinical variables at presentation were collected. Severe intoxication was defined as serum caffeine concentration ≥ 80 mg/L (412 μmol/L). Candidate predictors included heart rate and serum potassium and bicarbonate levels. A ridge logistic regression model was developed and evaluated using the area under the receiver operating characteristic curve, calibration plots, and Hosmer-Lemeshow test. Internal validation was performed using bootstrap resampling and leave-one-out cross-validation. Conventional logistic regression was performed as a sensitivity analysis. Clinical utility was assessed using decision curve analysis. Of 30 patients included, 13 (43%) had serum caffeine concentration ≥ 80 mg/L (412 μmol/L). Patients with severe intoxication had higher ingested doses, shorter time to presentation, higher heart rates and respiratory rates, lower bicarbonate and potassium levels, and more frequent use of hemodialysis and activated charcoal. The ridge model retained heart rate and bicarbonate and potassium levels as predictors. Internal validation demonstrated excellent discrimination and good calibration. Decision curve analysis indicated net clinical benefit across a range of threshold probabilities. Sensitivity analysis using conventional logistic regression revealed consistent results, with heart rate remaining a significant predictor. The selected predictors are biologically plausible and reflect key pathophysiological features of severe caffeine intoxication. Internal validation demonstrated excellent discrimination and calibration, supporting the robustness of the model. We developed a practical bedside prediction model for caffeine intoxication using heart rate and bicarbonate and potassium levels. The model demonstrated excellent discrimination and calibration. It may support early risk stratification and guide intensive monitoring or extracorporeal therapy.
The AirPods Pro 2® (Apple Inc., Cupertino, CA, USA) recently received regulatory approval in Japan as a Class II medical device incorporating a self-administered hearing assessment feature ("Hearing Check") and a hearing assistance program ("Hearing Aid Program"). Unlike conventional prescription hearing aids fitted using prescriptive algorithms such as NAL-NL2 and DSL v5, the amplification characteristics of the AirPods Pro 2 Hearing Aid Program are automatically determined by proprietary algorithms based on device-derived thresholds, and internal processing parameters are not publicly disclosed. To characterize the level-dependent real-ear insertion gain (REIG) generated by the AirPods Pro 2 Hearing Aid Program across representative audiometric profiles and to compare its gain characteristics with NAL-NL2 and DSL v5 prescriptive targets. Five representative audiometric profiles (30-dB flat, 50-dB flat, low-frequency hearing loss, gradually sloping high-frequency loss, and steeply sloping high-frequency loss) were selected from an independent dataset obtained using the AirPods Hearing Check. These profiles were sequentially programmed into the device for real-ear measurements in 10 adult volunteers (10 right ears). REIG was measured using the International Speech Test Signal at input levels of 50, 65, and 80 dB SPL in a calibrated sound-treated booth. Measured REIG was descriptively compared with prescriptive targets calculated from the same device-derived thresholds. REIG varied according to audiometric profile and input level. Gain generally increased toward mid- and high-frequency regions relative to low frequencies. Insertion gain progressively decreased as input level increased, with marked attenuation at 80 dB SPL. Compared with prescriptive targets, measured REIG was generally lower and showed less pronounced frequency-specific gain variation. The AirPods Pro 2 Hearing Aid Program exhibits nonlinear, level-dependent amplification with moderate frequency shaping and attenuation at higher input levels. Its gain characteristics differ from conventional prescriptive targets, suggesting emphasis on listening support and output control rather than strict prescriptive matching. Further studies are needed to clarify the clinical role of consumer-oriented hearing devices.
Influenza A and B viruses are considerable public health threats. Annual seasonal epidemics are driven by antigenic drift and cause an estimated 3-5 million severe cases and 290,000-650,000 deaths annually. The clinical presentation of seasonal influenza is typically an abrupt, uncomplicated acute respiratory illness with full recovery; however, it can lead to severe, life-threatening complications in individuals at high risk. Antigenic shift caused by reassortment of a seasonal influenza A virus with avian and/or swine influenza A viruses has led to unpredictable pandemics. The successful cross-species transmission of influenza A viruses requires key viral adaptations, including changes in receptor specificity and compatibility with host factors such as ANP32A. Host defence involves a layered innate response, which is antagonized by proteins, such as non-structural protein 1, and a robust adaptive immunity comprising cytotoxic CD8+ T cells targeting conserved internal proteins and B cells producing neutralizing antibodies. Diagnosis primarily depends on highly sensitive PCR-based methods and multiplexed rapid antigen tests. Prevention involves annually updated seasonal vaccines (including inactivated, live attenuated and protein-based vaccines), while treatment relies on early use of neuraminidase and polymerase acidic protein inhibitors. Research priorities include the development of improved vaccines and a better understanding of influenza virus transmission from animals to humans.
Remote diffusion-weighted imaging lesions (RDWILs) after intracerebral hemorrhage (ICH) are associated with unfavorable outcomes and reflect secondary microvascular injury in the setting of systemic stress responses and autonomic dysfunction due to ICH. However, association of RDWILs with neuroendocrine stress markers and acute blood pressure (BP) control remain unclear. We evaluated whether stress hormone levels and the duration of intravenous nicardipine infusion, as an index of post-ICH BP management burden, were associated with RDWILs. Patients with ICH enrolled in a prospective study (October 2020-December 2022) were analyzed. RDWILs were defined as diffusion restriction located ≥ 10 mm from the hematoma. Plasma concentrations of the hypothalamic-pituitary-adrenal (HPA) axis markers-adrenocorticotropic hormone and cortisol-and the sympathetic-adrenomedullary (SAM) axis markers-dopamine, adrenaline, noradrenaline, and urinary total metanephrine-were measured in the subacute phase. Post-ICH BP management burden was indexed by days of intravenous nicardipine required to achieve and maintain systolic BP < 140 mmHg. Among 39 patients (median age 54 years; 67% male), 7 (18%) had RDWILs. In unadjusted analyses, dysregulated HPA-axis- (lower adrenocorticotropic hormone and higher cortisol) and higher SAM-axis-related stress markers (higher dopamine, noradrenaline, and urinary total metanephrine), and longer nicardipine duration were significantly associated with RDWILs. These associations were consistent in exploratory adjusted models. Dopamine, noradrenaline, and urinary total metanephrine were also positively associated with nicardipine infusion duration. Dysregulated HPA-axis- and higher SAM-axis-related stress markers, and longer nicardipine duration were each associated with RDWILs. Higher SAM-axis-related stress markers were also associated with post-ICH BP management burden.
SKYSCRAPER-03 (NCT04513925) was a phase III, open-label, randomized, study that evaluated consolidation therapy with tiragolumab plus atezolizumab versus durvalumab in patients with locally advanced, unresectable, stage III, non-small cell lung cancer (NSCLC) after platinum-based concurrent chemoradiation. Eligible patients were randomized (1:1) to receive either atezolizumab (1680 mg every 4 weeks [Q4W]) plus tiragolumab (840 mg Q4W) on day 1 of each cycle, or durvalumab (10 mg/kg every 2 weeks or 1500 mg Q4W for those ≥30 kg body weight) on days 1 and 15 of each cycle, for 13 x 28-day cycles. The primary endpoint was Independent Review Facility (IRF)-assessed progression-free survival (PFS) in patients with programmed cell death ligand-1-positive (PD-L1+; tumor cells [TC] ≥1%) NSCLC. Key secondary endpoints were overall survival (OS) and safety. The PD-L1 all-comers population included 413 patients randomly assigned to tiragolumab plus atezolizumab and 416 to durvalumab; the PD-L1+ population included 209 and 210 patients in each arm, respectively. After a median follow-up of 33.0 months, median IRF-assessed PFS in PD-L1+ patients was 19.4 months with tiragolumab plus atezolizumab versus 16.6 months with durvalumab (stratified hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.75-1.23; p = 0.76); median PFS in PD-L1 all-comers was 14.2 versus 13.8 months, respectively (stratified HR 1.00; 95% CI, 0.84-1.19). Median OS in PD-L1+ patients was not estimable with tiragolumab plus atezolizumab versus 54.8 months with durvalumab (stratified HR 0.99; 95% CI 0.73-1.34); in PD-L1 all-comers, median OS was 45.6 versus 45.8 months, respectively (stratified HR 0.98; 95% CI 0.80-1.20). The safety profile of the combination was consistent with prior observations, and there were no new or unexpected findings. The primary endpoint of the SKYSCRAPER-03 study was not met. Tiragolumab plus atezolizumab was tolerated but did not offer additional benefit over durvalumab.
Wastewater-based epidemiology (WBE) has been widely used to track SARS-CoV-2 transmission using viral RNA, but its capacity to capture population immunity remains poorly defined. Although antibodies can be recovered from wastewater, the relationship between wastewater antibody signals, individual-level shedding dynamics, and community-wide infection and immunity patterns has not been systematically established. We conducted a three-year longitudinal study (2020-2022) across urban and rural communities in Thailand, covering approximately 18 million people. SARS-CoV-2 viral RNA and anti-SARS-CoV-2 IgG concentrations were quantified in wastewater from diverse facility types. To calibrate wastewater signals, faecal viral RNA and IgG shedding kinetics were characterised in 412 individuals from the same communities. Deconvolution models were applied to infer infection incidence from wastewater measurements, and lagged regression analyses assessed associations with confirmed cases, mortality, and vaccination coverage. Faecal viral RNA shedding peaked early after symptom onset and declined rapidly, whereas anti-SARS-CoV-2 IgG exhibited delayed onset, peaked around 50 days, and persisted for several months. These distinct kinetics produced temporally offset wastewater signals, with RNA-based incidence consistently preceding antibody-based estimates. Prior to vaccine rollout, wastewater incidence was dominated by viral RNA signals, while antibody levels remained low. Following widespread vaccination and successive infection waves, antibody-based incidence increased and gradually converged with RNA-based estimates, particularly in highly vaccinated urban areas. Wastewater antibody levels showed strong temporal autocorrelation and positive lagged associations with confirmed cases and vaccination, with weaker associations with mortality. Integrating viral RNA and antibody measurements in wastewater, informed by individual-level shedding dynamics, enables concurrent assessment of infection burden and population immunity.
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General ward nurses increasingly care for patients with advanced cancer; however, the implementation of evidence-based nursing support remains unclear. Multicenter palliative care unit (PCU) surveys quantified nursing practices for major cancer-related symptoms and caregiver burden using systematically developed item sets; however, findings from PCU settings may not directly generalize to general wards, given differences in staffing, patient populations, and resources. To describe the frequency of nonpharmacological nursing for five cancer-related symptoms (pain, dyspnea, nausea/vomiting, constipation, and delirium) and family caregiver burden provided by general ward nurses in Japan. We will conduct a multicenter, cross-sectional, web-based survey (Jan-Mar 2026) in designated cancer care hospitals nationwide. Registered nurses working in general wards will report their opportunities to provide symptom-related support in the past 12 months and the frequency of specific practices on a 5-point Likert scale. Item sets are based on scoping reviews and prior PCU surveys and will be refined through pretesting with general ward nurses. Primary outcomes are proportions reporting frequent use of each item; analyses will summarize overall and symptom-specific distributions, excluding respondents with no opportunity. Target sample size is 1,300-1,500, estimated using dyspnea and accounting for clustering. This study will provide nationally representative evidence on nursing support practices in general wards. The findings will inform targeted educational strategies by identifying potential gaps suggested by the observed frequencies of reported practices and enabling contextual interpretation in relation to prior PCU findings, thereby supporting future interventions, strengthening evidence-based palliative care.
BICSTaR (BICtegravir Single Tablet Regimen) is a multinational observational study assessing the virologic effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (HIV). Previously, the 12-month analysis of the Japan cohort of BICSTaR showed high levels of virologic effectiveness and tolerability with B/F/TAF. Data for 84 treatment-experienced (TE) or 116 treatment-naïve (TN) participants aged ≥20 years receiving B/F/TAF as part of routine clinical care in Japan were collected retrospectively and prospectively. Outcomes analyzed at 24 months included HIV-1 RNA <50 copies/mL, treatment persistence, drug-related adverse events (DRAEs), and patient-reported outcomes (prospective cohort only). At 24 months, 97% of TN and TE participants had HIV-1 RNA <50 copies/mL (missing-equals-excluded analysis), and 96% of participants remained in the study and were receiving B/F/TAF. DRAEs were reported by 14% of participants (TN: 16%; TE: 10%), with diarrhea (TN: 3%; TE: 2%) and weight gain (TN: 4%; TE: 0%) being the most common; the majority of DRAEs occurred in the first 12 months. Participants enrolled prospectively reported stable or improved quality of life through 24 months. Treatment with B/F/TAF in routine HIV clinical care in Japan was associated with high persistence, virologic effectiveness, and was well tolerated through 24 months.
Adverse social determinants of health (SDOH) are associated with higher risk of acute kidney injury (AKI). This study evaluated the association of individual- and neighborhood-level SDOH with incident ESKD among intensive care unit (ICU) survivors of AKI. 30,498 adult ICU survivors of AKI at a major academic medical center between January 1, 2012, and December 31, 2022, were included. Individual-level SDOH (race, ethnicity, and insurance status) were obtained from the hospital electronic health record, whereas neighborhood-level SDOH (Area Deprivation Index (ADI), among others) were derived from census-based indices. ESKD was defined by kidney failure with an estimated glomerular filtration rate <15 mL/min/1.73 m2 or the initiation of kidney replacement therapy, including maintenance dialysis or kidney transplantation. Association of individual- and neighborhood-level SDOH with incident ESKD were evaluated using multivariable cause-specific Cox proportional hazards models adjusting for clinical factors. The median age was 58 years, 40% were women, 31% were Black, and 12% were uninsured. The median follow-up time was 730 days, during which 326 (1%) patients developed ESKD and 2,723 (9%) died. In adjusted models, Black race was associated with a higher hazard of ESKD compared with White race (adjusted hazard ratio [aHR] 1.43, 95% CI 1.05-1.94), whereas having health insurance was associated with a lower hazard of ESKD (aHR 0.60, 95% CI 0.39-0.92). Higher neighborhood-level socioeconomic disadvantage was also independently associated with higher risk of ESKD (ADI tertile 2: aHR 1.42, 95% CI 1.01-2.00; tertile 3: aHR 1.58, 95% CI 1.08-2.33). Black race, lack of health insurance, and residence in socioeconomically deprived neighborhoods were independently associated with a higher hazard of incident ESKD among ICU survivors of AKI. Standardized SDOH assessment in clinical practice may improve risk stratification of ESKD and identify AKI survivors most likely to benefit from post-discharge interventions.
Discrepancies between endoscopic and histological diagnoses occasionally occur after colorectal polypectomy. This study aimed to evaluate the diagnostic impact of additional histological sections on serrated polyps. We conducted a retrospective cross-sectional study of resected colorectal polyps between June 2023 and August 2023. Polyps that were endoscopically suspected to be sessile serrated lesions (SSLs) or hyperplastic polyps and resected en bloc were included. Lesions initially diagnosed as normal mucosa were subjected to deeper sectioning and histopathological re-evaluation. Clinicopathological and endoscopic features, including endoscopic SSL diagnosis score, were analysed. Among the 276 eligible lesions, 117 were initially diagnosed as normal mucosa. Deeper sectioning corrected the histopathological diagnosis in 50% of these cases, identifying 5 SSLs and 53 hyperplastic polyps. The lesions reclassified in deeper sections were significantly smaller than those diagnosed in the first sections (P < 0.001). Compared with the "normal mucosa by first and deeper sections" group, the "SSL by deeper section" group showed significantly higher SSL diagnosis scores, including features such as larger size, mucus cap, and indistinct borders (P < 0.01). Additional histological sectioning significantly improved the diagnostic yield for serrated polyps initially diagnosed as normal mucosa, particularly in small lesions. This effect was most evident in lesions that were ultimately classified as hyperplastic polyps. Endoscopic features suggestive of SSLs were also associated with upgraded diagnoses, although the number of SSL cases was limited.
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The randomised, double-blind, placebo-controlled, phase 3 Program fOr Evaluation of TYK2 inhibitor Psoriatic Arthritis-1 (POETYK PsA-1) trial evaluated the efficacy, safety, and tolerability of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with PsA naïve to biologic disease-modifying antirheumatic drugs. Adults with active PsA, high-sensitivity C-reactive protein concentration ≥ 3 mg/L, and ≥ 1 PsA-related hand and/or foot erosion detectable via radiograph were randomised 1:1 to oral deucravacitinib 6 mg once daily or placebo through week (W) 16. At W16, patients continued receiving deucravacitinib or switched from placebo to deucravacitinib through W52. The primary endpoint was American College of Rheumatology 20% improvement in response (ACR20) at W16. Nonresponder imputation was used for missing data. Efficacy and safety were evaluated through W52. Post hoc rank analysis of covariance was used to evaluate structural damage with no missing data imputation. In 670 patients, a significantly greater proportion of those receiving deucravacitinib vs placebo achieved ACR20 at W16 (54.2% vs 34.1%, P < .001). Responses with deucravacitinib were increased at W52. Patients who switched from placebo to deucravacitinib achieved improvements similar to those in patients who received continuous deucravacitinib. Inhibition of structural damage was observed at W16 and W52. At W16, incidences of serious adverse events (AEs) (deucravacitinib, 1.8%; placebo, 2.4%) and discontinuations due to AEs (2.4%; 1.8%) were low and remained low through W52, without imbalances in cardiovascular events, malignancies, or opportunistic infections. No new safety signals were detected; no deaths occurred. Deucravacitinib demonstrated superiority vs placebo for clinical responses, patient-reported outcomes, and structural damage inhibition in patients with PsA, with favourable tolerability and safety.
Scleroderma renal crisis (SRC) and posterior reversible encephalopathy syndrome (PRES) are rare but severe complications of systemic sclerosis (SSc). We report the case of a 44-year-old patient with SSc who developed SRC and PRES, potentially triggered by non-steroidal anti-inflammatory drugs (NSAIDs). The patient presented with impaired consciousness, renal dysfunction, hemolytic anemia, thrombocytopenia, and occipital white matter lesions on magnetic resonance imaging. Treatment included enalapril, hemodialysis, and plasma exchange. This case highlights the potential role of NSAIDs in the development of SRC, and emphasizes the importance of considering NSAIDs as a significant risk factor for SRC in patients with SSc.
In antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, infection risk exceeds that of the general population, and infection is a leading cause of death. However, the impact of the COVID-19 pandemic on serious infections and mortality in this population remains uncertain. This observational study used data from the nationwide registry in Japan (Japan Collaborative Registry of ANCA-Associated Vasculitis), which includes patients with newly diagnosed and relapsed ANCA-associated vasculitis from 29 sites between January 2017 and March 2023. The primary outcome was serious infection requiring hospitalisation; the secondary outcome was all-cause mortality. The impact of COVID-19 was estimated using an interrupted time-series analysis, with the boundary between April and May 2020 as the change point, following the first declaration of a state of emergency in Japan. Monthly incidence rates were modelled using segmented Poisson regression. Rate ratios (RRs) for level and slope changes with 95% CI were reported. Several sensitivity analyses were performed. Among 1064 patients, total follow-up was 37,535 person-months; 205 serious infections and 96 deaths occurred. For serious infection, the level-change RR was 0.54 (95% CI: 0.31-0.94) and the slope-change RR was 1.01 (0.98-1.04). For all-cause mortality, the level-change RR was 0.35 (0.12-0.98) and the slope-change RR was 1.001 (0.94-1.06). Findings were robust across sensitivity analyses. Immediately after the onset of the COVID-19 pandemic, a clear reduction in serious infections and mortality was observed without major changes in patient characteristics. These findings may reflect the impact of social and personal infection control measures.