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The Journal of Allergy and Clinical... Jul 2023Benralizumab is an mAb therapy for severe eosinophilic asthma. Real-world data on its clinical impact in various patient populations such as patients with varying...
BACKGROUND
Benralizumab is an mAb therapy for severe eosinophilic asthma. Real-world data on its clinical impact in various patient populations such as patients with varying eosinophil levels, previous biologic use, and extended follow-up in the United States are limited.
OBJECTIVE
To determine the effectiveness of benralizumab in different asthmatic patient cohorts and its long-term clinical impact.
METHODS
Patients with asthma treated with benralizumab from November 2017 to June 2019 with 2 or more exacerbations in the 12 months before benralizumab initiation (index) were included in this pre-post cohort study that used medical, laboratory, and pharmacy US insurance claims. Asthma exacerbation rates in the 12 months pre and post index were compared. Nonmutually exclusive patient cohorts were defined by blood eosinophil counts (<150, ≥150, 150-<300, <300, and ≥300 cells/μL), a switch from another biologic, or follow-up for 18 or 24 months post index.
RESULTS
There were 429 patients in the eosinophil cohort, 349 in the biologic-experienced cohort, and 419 in the extended follow-up cohort. In all eosinophil cohort subgroups, the asthma exacerbation rate decreased from 3.10-3.55 per patient-year (PPY) pre index to 1.11-1.72 PPY post index (52%-64% decrease; P < .001). Similar decreases were observed in patients switching from omalizumab (3.25 to 1.25 PPY [62%]) or mepolizumab (3.81 to 1.78 PPY [53%]) to benralizumab and those followed up for 18 months (3.38 to 1.18 PPY [65%]) or 24 months (3.38 to 1.08 PPY [68%]) (all P < .001). In the extended follow-up cohort, 39% and 49% had no exacerbations in the 0 to 12 months and the 12 to 24 months post index, respectively.
CONCLUSIONS
Benralizumab achieved significantly improved asthma control in real-world patients with different blood eosinophil counts, including eosinophil counts ranging from less than 150 to greater than or equal to 300 cells/μL, switching from other biologics, or treated for up to 24 months.
Topics: Humans; Anti-Asthmatic Agents; Cohort Studies; Disease Progression; Double-Blind Method; Asthma; Eosinophils; Pulmonary Eosinophilia
PubMed: 37146880
DOI: 10.1016/j.jaip.2023.04.029 -
Virology Journal Nov 2023In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence.
OBJECTIVES
To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19.
METHODS
We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms.
RESULTS
The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported.
INTERPRETATION
LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .
Topics: Adult; Humans; COVID-19; Double-Blind Method; Drugs, Chinese Herbal; Treatment Outcome
PubMed: 38017515
DOI: 10.1186/s12985-023-02144-6 -
Movement Disorders : Official Journal... Aug 2023Rescue of mitochondrial function is a promising neuroprotective strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has shown considerable promise as a... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Rescue of mitochondrial function is a promising neuroprotective strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has shown considerable promise as a mitochondrial rescue agent across a range of preclinical in vitro and in vivo models of PD.
OBJECTIVES
To investigate the safety and tolerability of high-dose UDCA in PD and determine midbrain target engagement.
METHODS
The UP (UDCA in PD) study was a phase II, randomized, double-blind, placebo-controlled trial of UDCA (30 mg/kg daily, 2:1 randomization UDCA vs. placebo) in 30 participants with PD for 48 weeks. The primary outcome was safety and tolerability. Secondary outcomes included 31-phosphorus magnetic resonance spectroscopy ( P-MRS) to explore target engagement of UDCA in PD midbrain and assessment of motor progression, applying both the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) and objective, motion sensor-based quantification of gait impairment.
RESULTS
UDCA was safe and well tolerated, and only mild transient gastrointestinal adverse events were more frequent in the UDCA treatment group. Midbrain P-MRS demonstrated an increase in both Gibbs free energy and inorganic phosphate levels in the UDCA treatment group compared to placebo, reflecting improved ATP hydrolysis. Sensor-based gait analysis indicated a possible improvement of cadence (steps per minute) and other gait parameters in the UDCA group compared to placebo. In contrast, subjective assessment applying the MDS-UPDRS-III failed to detect a difference between treatment groups.
CONCLUSIONS
High-dose UDCA is safe and well tolerated in early PD. Larger trials are needed to further evaluate the disease-modifying effect of UDCA in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Humans; Parkinson Disease; Ursodeoxycholic Acid; Double-Blind Method
PubMed: 37246815
DOI: 10.1002/mds.29450 -
BMC Genomics Jun 2023The last decade has seen advancements in sequencing technologies and laboratory preparation protocols for ancient DNA (aDNA) that have rapidly been applied in multiple...
The last decade has seen advancements in sequencing technologies and laboratory preparation protocols for ancient DNA (aDNA) that have rapidly been applied in multiple research areas thus enabling large-scale scientific research. Future research could also refine our understanding of the evolution of humans, non-human animals, plants, invertebrate specimens, and microorganisms.
Topics: Animals; DNA, Ancient; Sequence Analysis, DNA; Plants; Laboratories
PubMed: 37291482
DOI: 10.1186/s12864-023-09396-0 -
Mathematical Biosciences and... Aug 2023Social media contains useful information about people and society that could help advance research in many different areas of health (e.g. by applying opinion mining,...
Social media contains useful information about people and society that could help advance research in many different areas of health (e.g. by applying opinion mining, emotion/sentiment analysis and statistical analysis) such as mental health, health surveillance, socio-economic inequality and gender vulnerability. User demographics provide rich information that could help study the subject further. However, user demographics such as gender are considered private and are not freely available. In this study, we propose a model based on transformers to predict the user's gender from their images and tweets. The image-based classification model is trained in two different methods: using the profile image of the user and using various image contents posted by the user on Twitter. For the first method a Twitter gender recognition dataset, publicly available on Kaggle and for the second method the PAN-18 dataset is used. Several transformer models, i.e. vision transformers (ViT), LeViT and Swin Transformer are fine-tuned for both of the image datasets and then compared. Next, different transformer models, namely, bidirectional encoders representations from transformers (BERT), RoBERTa and ELECTRA are fine-tuned to recognize the user's gender by their tweets. This is highly beneficial, because not all users provide an image that indicates their gender. The gender of such users could be detected from their tweets. The significance of the image and text classification models were evaluated using the Mann-Whitney U test. Finally, the combination model improved the accuracy of image and text classification models by 11.73 and 5.26% for the Kaggle dataset and by 8.55 and 9.8% for the PAN-18 dataset, respectively. This shows that the image and text classification models are capable of complementing each other by providing additional information to one another. Our overall multimodal method has an accuracy of 88.11% for the Kaggle and 89.24% for the PAN-18 dataset and outperforms state-of-the-art models. Our work benefits research that critically require user demographic information such as gender to further analyze and study social media content for health-related issues.
Topics: Humans; Social Media; Electric Power Supplies; Research Design
PubMed: 37919997
DOI: 10.3934/mbe.2023711 -
Lancet (London, England) Feb 2024Recently, we found that a new malaria vaccine, R21/Matrix-M, had over 75% efficacy against clinical malaria with seasonal administration in a phase 2b trial in Burkina... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Recently, we found that a new malaria vaccine, R21/Matrix-M, had over 75% efficacy against clinical malaria with seasonal administration in a phase 2b trial in Burkina Faso. Here, we report on safety and efficacy of the vaccine in a phase 3 trial enrolling over 4800 children across four countries followed for up to 18 months at seasonal sites and 12 months at standard sites.
METHODS
We did a double-blind, randomised, phase 3 trial of the R21/Matrix-M malaria vaccine across five sites in four African countries with differing malaria transmission intensities and seasonality. Children (aged 5-36 months) were enrolled and randomly assigned (2:1) to receive 5 μg R21 plus 50 μg Matrix-M or a control vaccine (licensed rabies vaccine [Abhayrab]). Participants, their families, investigators, laboratory teams, and the local study team were masked to treatment. Vaccines were administered as three doses, 4 weeks apart, with a booster administered 12 months after the third dose. Half of the children were recruited at two sites with seasonal malaria transmission and the remainder at standard sites with perennial malaria transmission using age-based immunisation. The primary objective was protective efficacy of R21/Matrix-M from 14 days after third vaccination to 12 months after completion of the primary series at seasonal and standard sites separately as co-primary endpoints. Vaccine efficacy against multiple malaria episodes and severe malaria, as well as safety and immunogenicity, were also assessed. This trial is registered on ClinicalTrials.gov, NCT04704830, and is ongoing.
FINDINGS
From April 26, 2021, to Jan 12, 2022, 5477 children consented to be screened, of whom 1705 were randomly assigned to control vaccine and 3434 to R21/Matrix-M; 4878 participants received the first dose of vaccine. 3103 participants in the R21/Matrix-M group and 1541 participants in the control group were included in the modified per-protocol analysis (2412 [51·9%] male and 2232 [48·1%] female). R21/Matrix-M vaccine was well tolerated, with injection site pain (301 [18·6%] of 1615 participants) and fever (754 [46·7%] of 1615 participants) as the most frequent adverse events. Number of adverse events of special interest and serious adverse events did not significantly differ between the vaccine groups. There were no treatment-related deaths. 12-month vaccine efficacy was 75% (95% CI 71-79; p<0·0001) at the seasonal sites and 68% (61-74; p<0·0001) at the standard sites for time to first clinical malaria episode. Similarly, vaccine efficacy against multiple clinical malaria episodes was 75% (71-78; p<0·0001) at the seasonal sites and 67% (59-73; p<0·0001) at standard sites. A modest reduction in vaccine efficacy was observed over the first 12 months of follow-up, of similar size at seasonal and standard sites. A rate reduction of 868 (95% CI 762-974) cases per 1000 children-years at seasonal sites and 296 (231-362) at standard sites occurred over 12 months. Vaccine-induced antibodies against the conserved central Asn-Ala-Asn-Pro (NANP) repeat sequence of circumsporozoite protein correlated with vaccine efficacy. Higher NANP-specific antibody titres were observed in the 5-17 month age group compared with 18-36 month age group, and the younger age group had the highest 12-month vaccine efficacy on time to first clinical malaria episode at seasonal (79% [95% CI 73-84]; p<0·001) and standard (75% [65-83]; p<0·001) sites.
INTERPRETATION
R21/Matrix-M was well tolerated and offered high efficacy against clinical malaria in African children. This low-cost, high-efficacy vaccine is already licensed by several African countries, and recently received a WHO policy recommendation and prequalification, offering large-scale supply to help reduce the great burden of malaria in sub-Saharan Africa.
FUNDING
The Serum Institute of India, the Wellcome Trust, the UK National Institute for Health Research Oxford Biomedical Research Centre, and Open Philanthropy.
Topics: Child, Preschool; Female; Humans; Infant; Male; Antibodies, Viral; Burkina Faso; Double-Blind Method; Immunization; Malaria; Malaria Vaccines; Nanoparticles; Saponins
PubMed: 38310910
DOI: 10.1016/S0140-6736(23)02511-4 -
The Lancet. Healthy Longevity Jun 2023Physical exercise is effective at attenuating ageing-related physical decline in general, but evidence of its benefits for older adults in residential care, who often... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Physical exercise is effective at attenuating ageing-related physical decline in general, but evidence of its benefits for older adults in residential care, who often have functional dependency, multimorbidity, and polypharmacy, is inconclusive. We aimed to establish the effects of exercise interventions on the physical function of this population.
METHODS
For this systematic review and network meta-analysis, we searched PubMed, Web of Science, Cochrane Library, Rehabilitation & Sports Medicine Source, and SPORTDiscus to identify randomised controlled trials assessing the effects of exercise interventions (vs usual care) on physical function (ie, functional independence, physical performance, and other related measures, such as muscle strength, balance, or flexibility) in adults aged 60 years or older living in residential care. Relevant studies published in English or Spanish up to Jan 12, 2023, were included in the systematic review. The quality of studies was assessed using the Tool for the Assessment of Study Quality and Reporting in Exercise (TESTEX) score. A network meta-analysis was performed for physical function-related outcomes reported in at least ten studies, with subanalyses for specific intervention (ie, exercise type, training volume, and study duration) and participant (eg, having cognitive impairment or dementia, pre-frail or frail status, and being functionally dependent) characteristics. The study protocol was registered on PROSPERO (CRD42021247809).
FINDINGS
147 studies (11 609 participants, with mean ages ranging from 67 years [SD 9] to 92 years [2]) were included in the systematic review, and were rated as having overall good quality (median TESTEX score 9 [range 3-14]). In the meta-analysis (including 105 studies, n=7759 participants), exercise interventions were associated with significantly improved overall physical function, with a standardised mean difference [SMD] of 0·13 (95% credible interval [CrI] 0·04-0·21), which was confirmed in all analysed subpopulations. The strongest association was observed with 110-225 min per week of exercise, and the greatest improvements were observed with 170 min per week (SMD 0·36 [95% CrI 0·20-0·52]). No significant differences were found between exercise types. Subanalyses showed significant improvements for almost all analysed physical function-related outcomes (Barthel index, five-times sit-to-stand test, 30-s sit-to-stand test, knee extension, hand grip strength, bicep curl strength, Short Physical Performance Battery, 6-min walking test, walking speed, Berg balance scale, and sit-and-reach test). Large heterogeneity was found between and within studies in terms of population and intervention characteristics.
INTERPRETATION
Exercise interventions are associated with improved physical function in older adults in residential care, and should, therefore, be routinely promoted in long-term care facilities.
FUNDING
None.
TRANSLATION
For the Spanish translation of the abstract see Supplementary Materials section.
Topics: Aged; Humans; Exercise; Exercise Therapy; Hand Strength; Muscle Strength; Network Meta-Analysis; Randomized Controlled Trials as Topic; Aged, 80 and over
PubMed: 37182530
DOI: 10.1016/S2666-7568(23)00057-0 -
Clinical Chemistry and Laboratory... Aug 2023C-reactive protein (CRP) is an acute-phase protein which is synthesized by the liver in response to the secretion of several inflammatory cytokines including interleukin... (Review)
Review
C-reactive protein (CRP) is an acute-phase protein which is synthesized by the liver in response to the secretion of several inflammatory cytokines including interleukin 6 (IL-6), IL-1 and tumor necrosis factor (TNF). CRP was the first acute-phase protein to be described and adopted in clinical laboratories as an exquisitely sensitive systemic marker of inflammation and tissue damage. The measurement of CRP is widely used for the diagnosis and monitoring of inflammatory conditions, including sepsis, trauma, and malignancies. In the last decades, impressive advances in analytical methods (from qualitative to high-sensitivity assays), automation and availability of results in a short time, not only translated in an increasing demand for the right management of systemic inflammatory diseases, but also in evaluating subclinical inflammatory processes underlying atherothrombotic events. CRP measurement is one of the most requested laboratory tests for both the wide range of clinical conditions in which it may assure a valuable information and some analytical advantages due to the evidence that it is a "robust biomarker". Even recently, the measurement of CRP received new interest, particularly as a biomarker of severity of Coronavirus disease 2019 (COVID-19), and it deserves further concern for improving demand appropriateness and result interpretation.
Topics: Humans; C-Reactive Protein; Laboratories, Clinical; COVID-19; Biomarkers; Acute-Phase Proteins
PubMed: 36745137
DOI: 10.1515/cclm-2023-0086 -
Survey of Ophthalmology 2023Descemet membrane endothelial keratoplasty (DMEK) is a partial-thickness corneal transplantation procedure that involves selective transplantation of the Descemet... (Review)
Review
Descemet membrane endothelial keratoplasty (DMEK) is a partial-thickness corneal transplantation procedure that involves selective transplantation of the Descemet membrane and endothelium. DMEK offers significant advantages over other keratoplasty techniques, such as faster visual rehabilitation, better final visual acuity due to minimal optical interface effects, lower risk of allograft rejection, and less long-term dependence on topical steroids. Despite all its advantages, DMEK has been found to be more challenging than other corneal transplantation techniques, and its steep learning curve appears to be an obstacle to its widespread use and adoption by corneal surgeons worldwide. DMEK surgical training laboratories (wet labs) provide a window of opportunity for surgeons to learn, prepare, manipulate, and deliver these grafts in a risk-free environment. Wet labs are a significant learning tool, especially for those institutions that have limited tissue availability in their local centers. We provide a step-by-step guide for preparing DMEK grafts using different techniques on human and nonhuman models with instructional videos. This article should eventually help the trainees and the educators understand the requirements for performing DMEK and conducting a DMEK wet lab and develop their skills and interests from a wide variety of available techniques.
Topics: Humans; Descemet Membrane; Laboratories; Descemet Stripping Endothelial Keratoplasty; Cornea; Endothelium, Corneal; Corneal Diseases
PubMed: 37392969
DOI: 10.1016/j.survophthal.2023.06.008 -
Frontiers in Public Health 2023Metagenomic next-generation sequencing (mNGS) has been gradually applied to the diagnosis of tuberculosis (TB) due to its rapid and highly sensitive characteristics.... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Metagenomic next-generation sequencing (mNGS) has been gradually applied to the diagnosis of tuberculosis (TB) due to its rapid and highly sensitive characteristics. Despite numerous studies on this subject, their results vary significantly. Thus, the current meta-analysis was performed to assess the performance of the mNGS on tuberculosis.
METHODS
PubMed, Embase, Web of Science, and The Cochrane Library were searched up to June 21, 2023. Studies utilizing the mNGS for tuberculosis detection were included. The risk of bias was assessed by QUADAS-2, and a meta-analysis was performed with STATA14.0 software.
RESULTS
Seventeen studies comprising 3,205 specimens were included. The combined sensitivity and specificity of mNGS for clinical specimens were 0.69[0.58-0.79] and 1.00[0.99-1.00], respectively. Subgroup analysis identified sequencing platform, diagnostic criteria, study type, sample size, and sample types as potential sources of heterogeneity. Cerebrospinal Fluid (CSF) has a lower sensitivity of 0.58 (0.39-0.75). In a population with a 10% prevalence rate, the accuracy of sensitivity reached 94%.
CONCLUSION
Metagenomic next-generation sequencing technology exhibits high sensitivity and speed in diagnosing . Its application in mono and mixed infections peoples shows promise, and mNGS is likely to be increasingly used to address challenges posed by complexes in the future.
Topics: Humans; Mycobacterium tuberculosis; High-Throughput Nucleotide Sequencing; Coinfection; Research Design; Technology
PubMed: 37637815
DOI: 10.3389/fpubh.2023.1224993