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RMD Open May 2024To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
PERFECTRA: a pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs.
OBJECTIVE
To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting.
METHODS
Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) <2.6, changes in PROMs and radiographic progression.
RESULTS
A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP <2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients.
CONCLUSION
Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.
Topics: Humans; Purines; Sulfonamides; Arthritis, Rheumatoid; Pyrazoles; Azetidines; Male; Female; Middle Aged; Antirheumatic Agents; Aged; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Treatment Failure; Adult; Patient Reported Outcome Measures; Severity of Illness Index
PubMed: 38816210
DOI: 10.1136/rmdopen-2024-004291 -
The Lancet. Microbe May 2024Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of...
Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study.
BACKGROUND
Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune dysregulation. We aimed to characterise biomarker trajectories and their associations with clinical outcomes.
METHODS
In this international, prospective cohort study, patients admitted to hospital with COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 platform trial within the Accelerating COVID-19 Therapeutic Interventions and Vaccines programme between Aug 5, 2020 and Sept 30, 2021 were included. Participants were included from 108 sites in Denmark, Greece, Poland, Singapore, Spain, Switzerland, Uganda, the UK, and the USA, and randomised to placebo or one of four neutralising monoclonal antibodies: bamlanivimab (Aug 5 to Oct 13, 2020), sotrovimab (Dec 16, 2020, to March 1, 2021), amubarvimab-romlusevimab (Dec 16, 2020, to March 1, 2021), and tixagevimab-cilgavimab (Feb 10 to Sept 30, 2021). This trial included an analysis of 2149 participants with plasma nucleocapsid antigen, anti-nucleocapsid antibody, C-reactive protein (CRP), IL-6, and D-dimer measured at baseline and day 1, day 3, and day 5 of enrolment. Day-90 follow-up status was available for 1790 participants. Biomarker trajectories were evaluated for associations with baseline characteristics, a 7-day pulmonary ordinal outcome, 90-day mortality, and 90-day rate of sustained recovery.
FINDINGS
The study included 2149 participants. Participant median age was 57 years (IQR 46-68), 1246 (58·0%) of 2149 participants were male and 903 (42·0%) were female; 1792 (83·4%) had at least one comorbidity, and 1764 (82·1%) were unvaccinated. Mortality to day 90 was 172 (8·0%) of 2149 and 189 (8·8%) participants had sustained recovery. A pattern of less favourable trajectories of low anti-nucleocapsid antibody, high plasma nucleocapsid antigen, and high inflammatory markers over the first 5 days was observed for high-risk baseline clinical characteristics or factors related to SARS-CoV-2 infection. For example, participants with chronic kidney disease demonstrated plasma nucleocapsid antigen 424% higher (95% CI 319-559), CRP 174% higher (150-202), IL-6 173% higher (144-208), D-dimer 149% higher (134-165), and anti-nucleocapsid antibody 39% lower (60-18) to day 5 than those without chronic kidney disease. Participants in the highest quartile for plasma nucleocapsid antigen, CRP, and IL-6 at baseline and day 5 had worse clinical outcomes, including 90-day all-cause mortality (plasma nucleocapsid antigen hazard ratio (HR) 4·50 (95% CI 3·29-6·15), CRP HR 3·37 (2·30-4·94), and IL-6 HR 5·67 (4·12-7·80). This risk persisted for plasma nucleocapsid antigen and CRP after adjustment for baseline biomarker values and other baseline factors.
INTERPRETATION
Patients admitted to hospital with less favourable 5-day biomarker trajectories had worse prognosis, suggesting that persistent viral burden might drive inflammation in the pathogenesis of COVID-19, identifying patients that might benefit from escalation of antiviral or anti-inflammatory treatment.
FUNDING
US National Institutes of Health.
PubMed: 38815595
DOI: 10.1016/S2666-5247(24)00015-6 -
Blood Transfusion = Trasfusione Del... May 2024Several countries have recently reassessed the international risk of variant Creutzfeldt-Jakob disease (vCJD) transmission through transfusion of blood and blood...
Several countries have recently reassessed the international risk of variant Creutzfeldt-Jakob disease (vCJD) transmission through transfusion of blood and blood components (red blood cells, platelets and plasma) and relaxed donor deferrals based on geographic and transfusion exposure in countries formerly considered to be high risk, such as the UK. In this regard, the European Blood Alliance organised a consensus meeting of experts and involved professionals to discuss current knowledge, epidemiological data, prevention and various methods for assessing the risk of transfusion-transmitted vCJD, as well as to develop an appropriate position on possible approaches to address these challenges in Europe. Participants reached a consensus that the current risk of transfusion-transmitted vCJD associated with blood donors who either travelled to or received transfusions in the UK during the vCJD outbreak is minimal. In addressing such risks, it would be pragmatic that assessments and guidelines are developed by European expert bodies, rather than individual assessments by Member States. Regardless of the approach used, European or national, a qualitative risk assessment based on a review and analysis of available data, considering all the uncertainties and experiences of other countries, would provide crucial information to reassess blood donation strategies regarding the transfusion-associated vCJD risk.
PubMed: 38814884
DOI: 10.2450/BloodTransfus.778 -
Blood Transfusion = Trasfusione Del... May 2024Anaphylaxis after blood transfusion is a feared complication accounting for severe morbidity. A retrospective study was performed at Haukeland University Hospital,...
BACKGROUND
Anaphylaxis after blood transfusion is a feared complication accounting for severe morbidity. A retrospective study was performed at Haukeland University Hospital, Bergen, Norway, to investigate the rate and features of transfusion-associated anaphylaxis (TAA) occurring between 2002-2021.
MATERIALS AND METHODS
Identified cases of TAA were studied by an immunologist and an allergist to extract information about general characteristics, amplifying factors, co-morbidity, treatment, and treatment responses. TAA was reported as perioperative or non-perioperative.
RESULTS
We identified 29 cases of TAA: 13 perioperative and 16 non-perioperative. Allergic transfusion reaction had an incidence rate of 34/100,000 transfusions and TAA a rate of 7/100,000 transfusions. The incidence of allergic reactions and TAA increased 2.6- and 6.4-fold during the study period. The first perioperative TAA was discovered 12 years into the study period but was equally frequent as non-perioperative transfusion-associated anaphylaxis in the last five years of the study period. 52% of the TAA cases had relevant co-morbidity and 100% of them had amplifying factors. Although only 38% of the non-perioperative patients received epinephrine as treatment, 94% of them had a good treatment response to their total treatment regimen. Poorer treatment response was observed with higher age, more cardiovascular- and respiratory disease, higher use of amplifying and sedating medications and a higher severity score.
DISCUSSION
Our findings indicate that TAA, especially in the perioperative setting, is underdiagnosed. The increased incidence of TAA in our study is temporally related to the introduction of a national hemovigilance program, introduction of standardized laboratory testing for anaphylaxis and increased multidisciplinary focus on the condition. In conclusion, increased awareness of TAA, and especially in the perioperative setting, is needed. A multidisciplinary approach is necessary to improve identification and reporting of TAA.
PubMed: 38814882
DOI: 10.2450/BloodTransfus.738 -
JAMA Network Open May 2024The decision for surgical vs nonsurgical treatment for hip fracture can be complicated among community-dwelling people living with dementia.
IMPORTANCE
The decision for surgical vs nonsurgical treatment for hip fracture can be complicated among community-dwelling people living with dementia.
OBJECTIVE
To compare outcomes of community-dwelling people living with dementia treated surgically and nonsurgically for hip fracture.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cross-sectional study undertook a population-based analysis of national Medicare fee-for-service data. Participants included community-dwelling Medicare beneficiaries with dementia and an inpatient claim for hip fracture from January 1, 2017, to June 30, 2018. Analyses were conducted from November 10, 2022, to October 17, 2023.
EXPOSURE
Surgical vs nonsurgical treatment for hip fracture.
MAIN OUTCOMES AND MEASURES
The primary outcome was mortality within 30, 90, and 180 days. Secondary outcomes consisted of selected post-acute care services.
RESULTS
Of 56 209 patients identified with hip fracture (73.0% women; mean [SD] age, 86.4 [7.0] years), 33 142 (59.0%) were treated surgically and 23 067 (41.0%) were treated nonsurgically. Among patients treated surgically, 73.3% had a fracture of the femoral head and neck and 40.2% had moderate to severe dementia (MSD). Among patients with MSD and femoral head and neck fracture, 180-day mortality was 31.8% (surgical treatment) vs 45.7% (nonsurgical treatment). For patients with MSD treated surgically vs nonsurgically, the unadjusted odds ratio (OR) of 180-day mortality was 0.56 (95% CI, 0.49-0.62; P < .001) and the adjusted OR was 0.59 (95% CI, 0.53-0.66; P < .001). Among patients with mild dementia and femoral head and neck fracture, 180-day mortality was 26.5% (surgical treatment) vs 34.9% (nonsurgical treatment). For patients with mild dementia who were treated surgically vs nonsurgically for femoral head and neck fracture, the unadjusted OR of 180-day mortality was 0.67 (95% CI, 0.60-0.76; P < .001) and the adjusted OR was 0.71 (95% CI, 0.63-0.79; P < .001). For patients with femoral head and neck fracture, there was no difference in admission to a nursing home within 180 days when treated surgically vs nonsurgically.
CONCLUSIONS AND RELEVANCE
In this cohort study of community-dwelling patients with dementia and fracture of the femoral head and neck, patients with MSD and mild dementia treated surgically experienced lower odds of death compared with patients treated nonsurgically. Although avoiding nursing home admission is important to persons living with dementia, being treated surgically for hip fracture did not necessarily confer a benefit in that regard. These data can help inform discussions around values and goals with patients and caregivers when determining the optimal treatment approach.
Topics: Humans; Dementia; Hip Fractures; Female; Male; Aged, 80 and over; Cross-Sectional Studies; Retrospective Studies; Independent Living; Aged; United States; Medicare; Treatment Outcome
PubMed: 38814642
DOI: 10.1001/jamanetworkopen.2024.13878 -
The Turkish Journal of Pediatrics May 2024Hyaline fibromatosis syndrome is a rare autosomal recessive disorder caused by ANTXR2 pathogenic variants. The disorder is characterized by the deposition of amorphous...
BACKGROUND
Hyaline fibromatosis syndrome is a rare autosomal recessive disorder caused by ANTXR2 pathogenic variants. The disorder is characterized by the deposition of amorphous hyaline material in connective tissues. The hallmarks of the disease are joint contractures, generalized skin stiffness, hyperpigmented papules over extensor surfaces of joints, fleshy perianal masses, severe diarrhea, and gingival hypertrophy. The severity of the disease varies and prognosis is poor. No specific treatment is yet available. Most patients with the severe form of the condition pass away before the second year of age. In this study, we describe the clinical and molecular findings of a cohort of seven hyaline fibromatosis syndrome patients who were diagnosed and followed up at a single tertiary reference center in Turkey.
METHODS
Genomic DNA was extracted by standard salting out method from peripheric blood samples of three patients. In one patient DNA extraction was performed on pathology slides since peripheric blood DNA was not available. All coding exons of the ANTXR2 were amplified and sequenced on ABI Prism 3500 Genetic Analyser.
RESULTS
Sanger sequencing was performed in 3 patients and homozygous c.945T>G p.(Cys315Trp), c.1073dup p.(Ala359CysfsTer13), and c.1074del p.(Ala359HisfsTer50) variants were identified in ANTXR2. All patients passed away before the age of five years.
CONCLUSIONS
HFS is a rare, progressive disorder with a broad phenotypic spectrum. HFS can be recognized easily with distinctive clinical features. Nevertheless, it has poor prognosis with increased mortality due to severe clinical decompensation.
Topics: Humans; Hyaline Fibromatosis Syndrome; Male; Female; Infant; Child, Preschool; Receptors, Peptide; Turkey; Child
PubMed: 38814306
DOI: 10.24953/turkjpediatr.2024.4511 -
Aging May 2024Osteoarthritis (OA), a degenerative joint disease, involves synovial inflammation, subchondral bone erosion, and cartilage degeneration. Ferroptosis, a regulated...
Osteoarthritis (OA), a degenerative joint disease, involves synovial inflammation, subchondral bone erosion, and cartilage degeneration. Ferroptosis, a regulated non-apoptotic programmed cell death, is associated with various diseases. This study investigates ferroptosis-related molecular subtypes in OA to comprehend underlying mechanisms. The Gene Expression Omnibus datasets GSE206848, GSE55457, GSE55235, GSE77298 and GSE82107 were used utilized. Unsupervised clustering identified the ferroptosis-related gene (FRG) subtypes, and their immune characteristics were assessed. FRG signatures were derived using LASSO and SVM-RFE algorithms, forming models to evaluate OA's ferroptosis-related immune features. Three FRG clusters were found to be immunologically heterogeneous, with cluster 1 displaying robust immune response. Models identified nine key signature genes via algorithms, demonstrating strong diagnostic and prognostic performance. Finally, qRT-PCR and Western blot validated these genes, offering consistent results. In addition, some of these genes may have implications as new therapeutic targets and can be used to guide clinical applications.
PubMed: 38814177
DOI: 10.18632/aging.205875 -
Frontiers in Pediatrics 2024The study aims to analyze the clinical characteristics of acute phase of SARS-CoV-2 infection in children aged 0-17 years with the Omicron variant, and summarize the...
OBJECTIVE
The study aims to analyze the clinical characteristics of acute phase of SARS-CoV-2 infection in children aged 0-17 years with the Omicron variant, and summarize the persistent symptoms or new-onset clinical manifestations from 4 to 12 weeks after acute COVID. Explore the association between the vaccination status and SARS-CoV-2 neutralizing antibody levels post infection among preschool-aged children. The comprehensive study systematically describes the clinical characteristics of children infected with SARS-CoV-2, providing a foundation for diagnosis and evaluating long-term COVID in pediatric populations.
METHODS
The study enrolled children who were referred to the Children's Hospital, Capital Institute of Pediatrics, (Beijing, China) from January 10, 2023 to March 31, 2023. Participants were classified as infant and toddlers, preschool, school-age, and adolescent groups. Children or their legal guardians completed survey questionnaires to provide information of previous SARS-CoV-2 infection history, as well as clinical presentation during the acute phase and long-term symptoms from 4 to 12 weeks following infection. Furthermore, serum samples were collected from children with confirmed history of SARS-CoV-2 infection for serological testing of neutralizing antibodies.
RESULTS
The study recruited a total of 2,001 children aged 0-17 years who had previously tested positive for SARS-CoV-2 through nucleic acid or antigen testing. Fever emerged as the predominant clinical manifestation in 1,902 (95.1%) individuals with body temperature ranging from 37.3 to 40.0°C. Respiratory symptoms were identified as secondary clinical manifestations, with cough being the most common symptom in 777 (38.8%) children, followed by sore throat (22.1%), nasal congestion (17.8%), and runnning nose (17.2%). Fatigue (21.6%), headache (19.8%) and muscle-joint pain (13.5%) were frequently reported systemic symptoms in children. The proportion of children with symptoms of SARS-CoV-2 infection varied across age groups. 1,100 (55.0%) children experienced persistent symptoms from 4 to 12 weeks post the acute phase of infection. Trouble concentrating (22.1%), cough (22.1%), and fatigue (12.1%) were frequently reported across age groups in the extended period. A limited number of children exhibited cardiovascular symptoms with chest tightness, tachycardia, and chest pain reported by 3.5%, 2.5%, and 1.8% of children, respectively. Among 472 children aged 3-5 years, 208 children had received two doses of SARS-CoV-2 vaccine at least 6 months prior to infection, and no association was found between the incidence of long-term COVID and pre-infection vaccination statuses among the 3-5 years age groups ( = 1.136, = 0.286).
CONCLUSIONS
In children aged 0-17 years infected with SARS-CoV-2 Omicron variant, fever was the primary clinical manifestation in the acute phase, followed by respiratory symptoms, systemic non-specific and digestive presentations. In particular, respiratory and digestive system symptoms were more frequent in children aged above 6 years. Regarding the long-term symptoms from 4 to 12 weeks post-infection, the most common presentations were concentrating difficulty, cough, and fatigue. The incidence of persistent symptoms of SARS-CoV-2 did not exhibit a significant correlation with vaccination status, which was attributed to the waning efficacy of the vaccine-induced humoral immune response after 6 months.
PubMed: 38813546
DOI: 10.3389/fped.2024.1332020 -
Frontiers in Aging Neuroscience 2024Age-related motor impairments often cause caregiver dependency or even hospitalization. However, comprehensive investigations of the different motor abilities and the...
Age-related motor impairments often cause caregiver dependency or even hospitalization. However, comprehensive investigations of the different motor abilities and the changes thereof across the adult lifespan remain sparse. We, therefore, extensively assessed essential basic and complex motor functions in 444 healthy adults covering a wide age range (range 21 to 88 years). Basic motor functions, here defined as simple isolated single or repetitive movements in one direction, were assessed by means of maximum grip strength (GS) and maximum finger-tapping frequency (FTF). Complex motor functions, comprising composite sequential movements involving both proximal and distal joints/muscle groups, were evaluated with the Action Research Arm Test (ARAT), the Jebsen-Taylor Hand Function Test (JTT), and the Purdue Pegboard Test. Men achieved higher scores than women concerning GS and FTF, whereas women stacked more pins per time than men during the Purdue Pegboard Test. There was no significant sex effect regarding JTT. We observed a significant but task-specific reduction of basic and complex motor performance scores across the adult lifespan. Linear regression analyses significantly predicted the participants' ages based on motor performance scores ( = 0.502). Of note, the ratio between the left- and right-hand performance remained stable across ages for all tests. Principal Component Analysis (PCA) revealed three across all tests that represented dexterity, force, and speed. These components were consistently present in young (21-40 years), middle-aged (41-60 years), and older (61-88 years) adults, as well as in women and men. Based on the three , -means clustering analysis differentiated high- and low-performing participants across the adult life span. The rich motor data set of 444 healthy participants revealed age- and sex-dependent changes in essential basic and complex motor functions. Notably, the comprehensive assessment allowed for generating robust across the adult lifespan. Our data may serve as a reference for future studies of healthy subjects and patients with motor deficits. Moreover, these findings emphasize the importance of comprehensively assessing different motor functions, including dexterity, force, and speed, to characterize human motor abilities and their age-related decline.
PubMed: 38813530
DOI: 10.3389/fnagi.2024.1368052 -
Frontiers in Neuroergonomics 2024The emerging integration of Brain-Computer Interfaces (BCIs) in human-robot collaboration holds promise for dynamic adaptive interaction. The use of electroencephalogram...
Advancing passive BCIs: a feasibility study of two temporal derivative features and effect size-based feature selection in continuous online EEG-based machine error detection.
The emerging integration of Brain-Computer Interfaces (BCIs) in human-robot collaboration holds promise for dynamic adaptive interaction. The use of electroencephalogram (EEG)-measured error-related potentials (ErrPs) for online error detection in assistive devices offers a practical method for improving the reliability of such devices. However, continuous online error detection faces challenges such as developing efficient and lightweight classification techniques for quick predictions, reducing false alarms from artifacts, and dealing with the non-stationarity of EEG signals. Further research is essential to address the complexities of continuous classification in online sessions. With this study, we demonstrated a comprehensive approach for continuous online EEG-based machine error detection, which emerged as the winner of a competition at the 32nd International Joint Conference on Artificial Intelligence. The competition consisted of two stages: an offline stage for model development using pre-recorded, labeled EEG data, and an online stage 3 months after the offline stage, where these models were tested live on continuously streamed EEG data to detect errors in orthosis movements in real time. Our approach incorporates two temporal-derivative features with an effect size-based feature selection technique for model training, together with a lightweight noise filtering method for online sessions without recalibration of the model. The model trained in the offline stage not only resulted in a high average cross-validation accuracy of 89.9% across all participants, but also demonstrated remarkable performance during the online session 3 months after the initial data collection without further calibration, maintaining a low overall false alarm rate of 1.7% and swift response capabilities. Our research makes two significant contributions to the field. Firstly, it demonstrates the feasibility of integrating two temporal derivative features with an effect size-based feature selection strategy, particularly in online EEG-based BCIs. Secondly, our work introduces an innovative approach designed for continuous online error prediction, which includes a straightforward noise rejection technique to reduce false alarms. This study serves as a feasibility investigation into a methodology for seamless error detection that promises to transform practical applications in the domain of neuroadaptive technology and human-robot interaction.
PubMed: 38813519
DOI: 10.3389/fnrgo.2024.1346791