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Persistent-relapsing SARS-CoV-2 infection following rituximab treatment for autoimmune rheumatic diseases: diagnosis and outcomes.3 months agoCOVID-19 may persist or relapse in patients on B-cell depleting biologic therapies.
To examine the rate and outcome of persistent-relapsing COVID-19 (prCOVID-19) in patients with autoimmune rheumatic diseases (AIRD) treated with rituximab (RTX).
Single-centre, retrospective cohort study of patients diagnosed with prCOVID-19 (June 2021 to January 2025). prCOVID-19 was defined as persistence of symptoms and lung imaging findings for >30 days, along with persistently positive or PCR-based conversion in upper or lower respiratory tract samples.
26 out of 225 (11.6%) AIRD patients, previously diagnosed with COVID-19 during RTX treatment period, developed 27 prCOVID-19 events (females: 20 (76.9%), median age: 61 years, median disease duration: 5.5 years, ≥3 COVID-19 vaccine doses: 20 (76.9%)). No prCOVID-19 infection in a control sample of 661 patients treated with other biologic/targeted synthetic/conventional synthetic disease-modifying antirheumatic drugs was documented. Median cumulative RTX dose was 12 g, while in 17 (68%) prCOVID-19 events, IgG levels were below 700 mg/L. Median duration of prCOVID-19 infection was 65 (IQR 74) days and median duration of hospitalisation 10.5 (IQR 14) days. 11 patients (42.3%) had ≥2 hospitalisations, 3 patients needed mechanical ventilation and 4 deaths were recorded. 59 of 113 (52.2%) nasopharyngeal PCR samples (NPS) and 12/17 (70.6%) bronchoalveolar lavage (BAL) PCR samples were positive during prCOVID-19. Bronchoscopy established the diagnosis of prCOVID-19 in 33% of events.
AIRD patients treated with RTX are at risk for prCOVID-19. In such patients, the diagnostic accuracy of NPS PCR is suboptimal, necessitating PCR testing in BAL when prCOVID-19 is highly suspected.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
How to culturally adapt the pulmonary rehabilitation programme for people living with COPD in Sri Lanka: a qualitative study.3 months agoPulmonary rehabilitation (PR) is a low-cost, high-impact intervention for people living with chronic obstructive pulmonary disease (COPD). Despite the high prevalence of COPD, there are currently very limited facilities to provide PR in Sri Lanka. The views of people living with COPD, their caregivers and relevant healthcare professionals (HCPs) are essential to develop culturally appropriate PR, acceptable in a Sri Lankan setting.
We aimed to explore the lived experiences of key stakeholders on the development and implementation of culturally appropriate PR in Sri Lanka.
A qualitative study was conducted at the Central Chest Clinic (CCC), Sri Lanka. Focus group discussions (FGDs) and semistructured interviews (SSIs) were conducted with the three populations: people living with COPD, their caregivers and relevant HCPs. After audio recording, transcribing and translating, the data were analysed using thematic analysis.
Three FGDs comprising 11 adults with COPD (9 males, age range 39-83 years), three FGDs comprising five family caregivers (three females), three FGDs comprising 14 nurses and 12 SSIs with doctors and physiotherapists were conducted, representing diverse ethnic groups. Two overarching themes were generated: 'PR adaptations' and 'Barriers to PR implementation and adherence'. Within 'PR adaptations', four subthemes were generated: the educational component of PR, nutritional support, psychological support and the use of music during PR sessions. Under 'Barriers to PR implementation and adherence', three subthemes were generated: barriers and issues in participating, need for better medical facilities and difficulty in conducting exercises.
Culturally tailoring PR for people living with COPD in Sri Lanka should include the integration of singing, music and nutritional support, as it may enhance acceptability. Barriers, including a lack of resources to deliver PR, difficulties encountered by patients attending PR sessions and perceived difficulties in performing standardised PR exercises, need to be addressed when developing a culturally appropriate programme in Sri Lanka.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Determining what patients admitted with a chronic obstructive pulmonary disease (COPD) exacerbation will use for remote clinical monitoring: a patient engagement survey.3 months agoRemote monitoring may improve the health of people with chronic obstructive pulmonary disease (COPD) through earlier detection and intervention before conditions worsen, but there are major challenges in recruitment and retention in these research studies. There are also increasing technologies and the uptake of specific technologies in people with COPD is not well known.
The objective of this study was to identify remote monitoring interventions that people admitted to hospital with an exacerbation of COPD would be willing to use upon discharge and to identify factors that influenced their preferences.
We surveyed consecutive patients admitted to hospital with acute exacerbations of COPD. We asked participants how likely they would be willing to use 15 remote monitoring interventions and to explain the reasoning behind their preferences. We correlated demographic factors with willingness to use interventions.
Out of the 88 people with COPD approached, we recruited 50 (57%). The average age was 72.5 years, and 48% were women. Patients were most willing to use in-home visits by nurses, remote monitoring of vital signs and reporting oximeter values through an app or a website. Least popular interventions were in-home cough, speech and activity monitoring. Perceived usefulness and previous positive experiences were reasons why participants would accept various interventions. Increased willingness to use remote monitoring was seen in women (p=0.02), people who spoke English as a primary language (p=0.005), people who did not rely on others for support (p=0.04) and those followed by a respirologist (p=0.02).
Our survey of patients admitted with COPD exacerbations provides insight into the types of remote monitoring interventions patients will accept and who are more interested in participating. We also provide insight into equity concerns of remote monitoring technology by identifying demographic factors that may influence intervention use that could widen the digital divide.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
[Clinical features and prognosis of children with influenza-associated encephalopathy: an analysis of 23 cases].3 months agoTo study the clinical and imaging features of children with influenza-associated encephalopathy (IAE), and to investigate the influencing factors for prognosis.
A retrospective analysis was conducted on the medical data (clinical data, laboratory examinations, imaging data, and prognosis) of 23 children with IAE who were diagnosed and treated in Children's Hospital of Nanjing Medical University from May 2022 to April 2023.
Among the 23 patients, 18 (78%) had influenza A and 5 (22%) had influenza B. All patients had fever and encephalopathy, and 20 patients (87%) had seizures, while 11 patients (48%) had persistent convulsions. There were 10 patients (43%) with an increase in alanine aminotransferase, 14 (61%) with an increase in aspartate aminotransferase, and 18 (78%) with an increase in lactate dehydrogenase. Abnormal imaging findings were observed in 20 patients (87%), among whom 10 (43%) had acute necrotizing encephalopathy. All 23 patients received peramivir or oseltamivir. Of all patients, 12 (52%) achieved complete recovery, 5 (22%) had varying degrees of neurological dysfunction, and 6 (26%) died. Compared with the good prognosis group, the poor prognosis group had significantly higher levels of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase (P<0.05).
Fever and convulsions are the most common symptoms of children with IAE, and acute necrotizing encephalopathy is the most common clinical imaging syndrome. Increases in alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase have a certain value in predicting poor prognosis.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Stochastic modeling and analysis of the mutual influence between respiratory diseases and air quality.3 months agoRespiratory viruses can be transmitted through both human contact and airborne particles. Air pollution exacerbates the spread of airborne diseases, while the societal burden imposed by these diseases drives efforts to improve air quality. This study proposes a stochastic bidirectionally coupled model to capture the mutual influence between respiratory disease transmission and air pollution. It incorporates dual transmission routes and accounts for stochastic factors influencing both disease dynamics and air quality fluctuations. Conditions for the elimination and persistence of both air pollutants and respiratory diseases are derived, with numerical simulations validating the conclusions. When both respiratory diseases and air pollution persist, the stochastic model exhibits a stationary distribution. The findings suggest that stochasticity can promote the elimination of respiratory diseases and contribute to mitigating air pollution. Data fitting validates the accuracy and effectiveness of the coupled model, and numerical results confirm that incorporating coupling relationships provides a more comprehensive understanding of disease transmission dynamics and air quality variations.Chronic respiratory diseaseAccessAdvocacy
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Persistent Postictal Central Apnea in Focal Seizures: Incidence, Features, and Imaging Findings.3 months agoPostconvulsive central apnea has emerged as a contributor to sudden unexplained death in epilepsy. The aim of this study was to evaluate the incidence and characteristics of postictal central apnea (PICA) in focal seizures. The secondary aim was to analyze morphometric features of the amygdala and other subcortical structures involved in autonomic control.
We prospectively enrolled consecutive patients admitted to the Epilepsy Monitoring Unit at Modena Academic Hospital (Italy) from April 2020 to December 2023. Inclusion criteria were as follows: (1) age older than 13 years; (2) at least 1 focal-onset seizure recorded during long-term video-EEG monitoring (LTVEM) with cardiorespiratory polygraphy. For each seizure, the presence of ictal central apnea (ICA) and/or PICA and its features were evaluated. Amygdala, hippocampus, thalamus, brainstem, and cerebellum volumetry were compared in patients with ICA/PICA with respect to healthy controls and patients with focal seizures without peri-ictal breathing disorders.
A total of 69 patients (mean age 35.7 years; 42% female) with 406 focal-onset seizures were analyzed. ICA was recorded in 71 seizures (17%) in 27 patients. PICA was recorded in 24 seizures in 12 patients (10 with temporal lobe epilepsy) corresponding to 5.9% of all recorded seizures. Notably, PICA was observed only in seizures showing ictal apnea (in 33.8%). In 11 seizures with PICA, a single apneic event starting in the ictal and extending to the postictal period was observed. In 13 seizures, multiple apneic events were present in the postictal period (range 2-8). Seizures with PICA showed a longer peri-ictal apnea time (mean 75 seconds vs 40 seconds; p = 0.007) and a longer time to restore a regular rhythmic breathing after seizure termination (mean 173 seconds vs 42 seconds; p < 0.001) than seizures with self-limiting ictal apnea. Amygdala volumes ipsilateral to the epileptogenic zone were larger in patients with ICA/PICA compared with controls and patients without seizure-related apnea.
PICA occurs in approximately 6% of focal seizures and is associated with extended apnea time and an enlarged amygdala ipsilaterally to the epileptogenic zone. Our data support the existence of a continuum from ictal to PICA and highlight the importance of cardiorespiratory recordings in LTVEM.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Identification and validation of oxidative stress-related genes for the diagnosis of sepsis-induced acute lung injury.3 months agoSepsis-induced acute lung injury (ALI) is an inflammatory pulmonary condition characterized by a complex pathophysiological mechanism. The development and progression of sepsis-induced ALI are accompanied by significant oxidative damage. This study aimed to identify key oxidative stress-related genes associated with sepsis-induced ALI. Samples, including sepsis, sepsis-induced ALI, and control groups, were obtained from the Gene Expression Omnibus database. Key oxidative stress-related genes in sepsis-induced ALI were identified using Weighted Gene Co-expression Network Analysis (WGCNA), Protein-Protein Interaction (PPI) network analysis, logistic regression, and LASSO regression analysis. Functional information regarding these genes was explored through Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA). A logistic regression model was constructed based on the identified hub oxidative stress-related genes. The diagnostic value of this model for sepsis-induced ALI was assessed using the receiver operating characteristic (ROC) curve. The relative abundance of 22 human immune cell types was calculated using CIBERSORT software. The expression levels of hub genes in the blood samples of sepsis-induced ALI patients were analyzed through RT-PCR and ELISA. A total of 1,055 genes associated with sepsis-induced ALI were identified via WGCNA, of which 145 genes were linked to oxidative stress. GSVA revealed that these 145 genes were significantly enriched in 79 biological pathways, while GSEA indicated a strong association with immune-related signaling pathways. Additionally, the top 20 genes were selected through PPI network analysis. The logistic regression model was constructed using VDAC1, HSPA8, SOD1, HSPA9, TXN, and SNCA. In the training set and the validation set, the AUC values of logistic regression model were 0.9091 and 0.8279, respectively, suggesting good discriminability when distinguishing normal from sepsis-induced ALI. Notably, these six genes were correlated with immune cell infiltration in sepsis-induced ALI, with HSPA8, SOD1, and HSPA9 showing downregulation in sepsis-induced ALI. In conclusion, VDAC1, HSPA8, SOD1, HSPA9, TXN, and SNCA have been identified as oxidative stress-related genes associated with sepsis-induced ALI. The logistic regression model developed using these six genes could identify patients with sepsis-induced ALI. Our findings might provide novel research strategies for the molecular therapeutic target of sepsis-induced ALI.Chronic respiratory diseaseAccessAdvocacy
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Participant engagement in a national longitudinal study of COVID-19: Insights from the INSPIRE study.3 months agoTo examine participants' motivations and their experiences throughout a decentralized, longitudinal COVID-19 study in the U.S.
We recruited 355 participants from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) between November 2022 - March 2023 to answer five qualitative survey questions anonymously. We used an inductive content analysis approach to analyze the data.
We identified five key themes from the analysis, which reflected participants' a) motivations to join the study, b) study benefits, c) perceptions of survey questions, d) experiences with the research process, and e) preferences for disseminating research findings. Participants were motivated to learn with researchers about COVID-19. They expressed divided opinions about the relevance of INSPIRE research questions. They reported difficulties navigating the virtual research platform and the need for making survey participation less cognitively demanding. They sought more regular feedback on study findings.
Our findings offered insights into incorporating decentralized participatory methods in longitudinal research, strengthening reciprocal research communications, making virtual research platforms user-friendly, and employing strategies to reduce participants' cognitive burden in research.
Longitudinal studies should focus on optimizing these aspects of participant engagement to produce rigorous findings that inform policy and practice on lasting effects of COVID-19 including Long COVID.Chronic respiratory diseaseCardiovascular diseasesAccessCare/ManagementAdvocacy -
Hybrid Immunity in a Mozambican Cohort After 1 or 2 Doses of the BBIBP-CorV Vaccine.3 months agoMore than half of the BBIBP-CorV vaccines, outside of Pacific Asia, were distributed in Africa. Nevertheless, there are limited data on the immunogenicity of BBIBP-CorV from Africa. We compared the antibody response, after 1 and 2 doses of the BBIBP-CorV vaccine, in individuals seropositive or seronegative to severe acute respiratory syndrome coronavirus 2 prior to vaccination.
From March to May 2021, blood samples were obtained at first and second doses of the BBIBP-CorV, and 2 weeks later. Antibody titers against the full-length spike, receptor binding domain and nucleocapsid protein (anti-NC) of severe acute respiratory syndrome coronavirus 2 were measured. Pseudovirus neutralization assays and antibody-dependent cellular cytotoxicity (ADCC) against the D614G, BA.2, and BA.4 variants were also evaluated.
At the second dose, the immunoglobulin G titers for full-length spike and anti-nucleocapsid protein, the ADCC against BA-2, and the neutralizing activity against the D614G and BA.2 were higher in individuals seropositive to any of the epitopes at the first dose (n = 26) compared to the levels observed 2 weeks later in the seronegative group (n = 25). We did not observe an increase on magnitude of binding antibodies, ADCC, and neutralizing activities, in those seropositive, after the second homologous dose of the BBIBP-CorV vaccine.
We suggest that 1 dose of the BBIBP-CorV vaccine in seropositive individuals induced better antibodies response including against variant of concerns compared to that observed after 2 doses in seronegative individuals. A further homologous dose of the BBIBP-CorV vaccine, in those who are seropositive, does not improve the antibody response observed after the first dose.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Enhancing Clinical Trial Sites in Low- and Middle-Income Countries to Facilitate Product Development in Response to the COVID-19 Pandemic.3 months agoThe swift development of coronavirus disease 2019 (COVID-19) vaccines marked a monumental effort in global coordination and collaboration; however, there remained major disparities in vaccine access and research capacity across countries. Unequal participation in vaccine development studies from low- and middle- income countries (LMICs) clearly signaled an urgent need to strengthen health research infrastructure in those regions.
With funding from the Gates Foundation (GF), this site readiness initiative carried out rapid capacity enhancement activities to enable large-scale, Phase 3 pivotal clinical trial conduct in LMICs. The International Vaccine Institute (IVI) worked with site partners in four countries (Mozambique, Ghana, Nepal, and the Philippines) after conducting feasibility assessments for site selection. Site-specific gaps were identified, and capacity building activities focused on staff training, site infrastructure, and resource mobilization were carried out over roughly 7 months from October 2020 to May 2021.
Despite pandemic-related challenges such as supply chain shortages, by the end of the capacity building efforts all sites were either contracted to or in discussions with trial sponsors to conduct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine studies. This article provides an overview of the site selection process, critical components of site establishment, and final site readiness evaluations carried out amidst a global health emergency.
This experience illustrates the value of research capacity enhancement as essential to both pandemic preparedness and global health equity. The lessons learned are being carried into an ongoing initiative across West Africa, currently underway as the "Advancing Research Capabilities in West Africa (ARC-WA)."Chronic respiratory diseaseAccessCare/ManagementPolicyAdvocacy