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Physical Therapy Provision After COVID-19 in the Netherlands: Retrospective Cohort Study.1 week agoMany patients have been treated by physical therapists after an infection with COVID-19. The policy changes and unique situation of the COVID-19 pandemic necessitate a retrospective analysis.
This study examined physical therapy provision for adult patients recovering from COVID-19 in primary care in the Netherlands over the first 2.5 years of the pandemic. The primary aim was to examine changes in the amount of health care provision and associated factors. Furthermore, we aimed to gain insight into the patient population and changes over time, as well as the use of advised outcome measures in physical therapy after COVID-19.
We conducted a retrospective cohort study using routine health care data from the electronic health records of physical therapy practices in Dutch primary care. In total, 71,152 COVID-19 treatment trajectories initiated between March 1, 2020, and December 18, 2022, were included. Multilevel generalized linear mixed model analyses examined changes over time in the patient population and in the amount of physical therapy within treatment trajectories (ie, duration in weeks and number of consultations). Outcome measures were analyzed using descriptive statistics.
Completed treatment trajectories had an overall duration of 24 weeks with 28 consultations, with a decreasing trend in the amount of physical therapy provided over time (P<.001). Also, a parabolic effect of age (P<.001) was found, showing a maximum number of consultations and duration of the treatment trajectory among older patients aged 60 to 79 years, with smaller quantities for younger and older patients. Treatment trajectories for women were 1.5 weeks longer than those for men (β 1.5, SE 0.12; P<.001) but did not include more consultations (P=.76). In 83% (59,184/71,152) of treatment trajectories, a baseline score on at least one of the included advised outcome measures was registered. Median (IQR) baseline scores were 420 (340-490) m on the 6-minute walking test (n=27,035); 13 (10-17) seconds on the 5-times sit-to-stand test (n=2337); 5.8 (5-6.3) points on the Fatigue Severity Scale (n=995); 8 (7-10) points on the Patient-Specific Functional Scale (PSFS; n=55,074); 10 (9-12) points on the Short Physical Performance Battery (n=4665); and 29 (22-38) and 30 (24-40) kg of grip strength, respectively, on the left (n=12,306) and right (n=12,293) hand. Difference scores could be examined for the 6-minute walking test, grip strength, and the PSFS.
This study demonstrates the potential of routinely collected health care data to describe real-world physical therapy provision for COVID-19 in Dutch primary care. Patients showed severe perceived fatigue, reduced functional capacity, and lower-limb strength at the start of physical therapy. The amount of physical therapy declined over the first 2.5 years of the pandemic, differed by age and gender, and was generally lower than the amount reimbursed by the Dutch government through basic health insurance.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Acute Neurological Manifestations in COVID-19 Are Associated With Complement Activation and Glia-Promoted Neuroinflammation.1 week agoPathophysiological mechanisms of neurological manifestations in COVID-19 are not fully known yet. In this case-control study, proteomic analysis was used to characterize cerebrospinal fluid (CSF) samples from COVID-19 patients with acute neurological manifestations primarily categorized as: isolated refractory headache (n = 12), encephalopathy (n = 24), and inflammatory neurological diseases (IND) (n = 13). Individuals with non-inflammatory, non-infectious neurological conditions (n = 8) were included as controls. Differentially expressed proteins (DEPs) in neuro-COVID-19 were associated with the complement system, function/activation of microglia/macrophages, inflammatory responses, and neuronal function/homeostasis. Functional enrichment analysis of DEPs and/or proteins specifically detected in neuro-COVID-19 groups indicated activation of complement and coagulation cascades, and synapse pruning in encephalopathy and IND. Upregulated complement activation was confirmed by increased CSF levels of C3a and soluble C5b-9. Biological processes of neuroinflammation, migration of immune cells into the central nervous system, activation of glia cells (microglia and astrocytes), and tissue remodeling were also present in IND. In turn, processes associated with disturbed organization/formation of neuron projections were related to encephalopathy and isolated headache. CSF from patients with isolated refractory headache was enriched for proteins related to neurons and to the cerebral cortex, cerebellum, and basal ganglia. Meanwhile, CSF from encephalopathy and IND patients was mostly enriched for proteins mapped to the cerebral cortex, choroid plexus, and thalamus. Moreover, CSF from IND patients had an increased proportion of microglia-related proteins. These findings support a model in which cases of IND and encephalopathy are associated with blood-brain barrier disruption potentially induced by complement activation and glia-promoted neuroinflammation, resulting in the involvement of distinct brain structures in COVID-19.Chronic respiratory diseaseAccessAdvocacy
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Frequency of Radiologic Bronchiolocentric Interstitial Pneumonia Patterns and Associated Factors in Welders.1 week agoBronchiolocentric interstitial pneumonia (BIP) is an airway-centered pattern observed in various interstitial lung diseases. This study aimed to evaluate the clinical, occupational, and radiological factors associated with the frequency of the BIP pattern on HRCT in welders.
In this retrospective cross-sectional study, an operational HRCT-based methodology was used to systematically define the BIP pattern in 73 male welders. The frequency of the BIP pattern and its associations with clinical, demographic, and occupational factors were investigated by comparing cases according to BIP status. Cases were compared according to the presence of BIP, which was defined based on operational radiological criteria. Appropriate parametric and nonparametric tests were used for statistical analyses.
The BIP pattern was detected in 21.9% of welders (n = 16; 13 nonfibrotic and 3 fibrotic). Although BIP frequency did not differ significantly between never-smokers and current smokers (13.3% vs. 16.2%; p = 0.102), cumulative smoking exposure was higher among BIP-positive cases (32.5 vs. 20 pack-years; p = 0.021). DLCO and KCO were significantly lower in BIP-positive cases among the 33 patients with available diffusion capacity measurements (p = 0.007 and p = 0.002, respectively). Cases with the BIP pattern also had higher mMRC dyspnea scores (p = 0.032). The most frequent HRCT findings were bronchiolar wall thickening and centrilobular ground-glass nodules.
The BIP pattern is observed at a notable frequency on HRCT in welders. The findings suggest that BIP is not specific to hypersensitivity pneumonitis and may represent a morphological pattern associated with various inhalational etiologies. Occupational history should be carefully assessed in cases exhibiting the BIP pattern.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
High-Frequency Oscillatory Ventilation Combined With Inhaled Nitric Oxide for Persistent Pulmonary Hypertension of the Newborn: A Single-Center Randomized Clinical Trial.1 week agoPersistent pulmonary hypertension of the newborn (PPHN) may respond incompletely to inhaled nitric oxide (iNO) when poorly recruited lung limits delivery to ventilated alveoli. We evaluated whether high-frequency oscillatory ventilation (HFOV) combined with iNO improved clinical and physiologic outcomes compared with conventional mechanical ventilation (CMV) + iNO or HFOV alone.
In this prospective, single-center, 3-arm, open-label randomized clinical trial, 138 neonates born at 34 weeks of gestation or later with echocardiographically confirmed PPHN and an oxygenation index of 25 or greater were randomized 1:1:1 to HFOV + iNO, CMV + iNO, or HFOV alone. The principal complete-case per-protocol analysis included 126 infants (42 per group) with ascertainable 120-day primary outcomes who completed the assigned strategy without a major protocol deviation. The possible influence of the 12 unavailable primary outcomes was evaluated in post hoc randomized-denominator extreme-case sensitivity analyses. The primary outcome was death or extracorporeal membrane oxygenation (ECMO) within 120 days.
In the complete-case per-protocol population, death or ECMO occurred in 3 of 42 infants (7.1%) assigned to HFOV + iNO, 11 of 42 (26.2%) assigned to CMV + iNO, and 14 of 42 (33.3%) assigned to HFOV alone (overall p = 0.012). For HFOV + iNO versus CMV + iNO, the risk ratio was 0.27 (95% CI, 0.08-0.91), and the risk difference was -19.0 percentage points (95% CI, -34.5 to -3.6; Holm-adjusted p = 0.038). For HFOV + iNO versus HFOV alone, the risk ratio was 0.21 (95% CI, 0.07-0.69) and the risk difference was -26.2 percentage points (95% CI, -42.4 to -9.9; Holm-adjusted p = 0.011). The mean oxygenation index at 72 h was 7.1 (SD, 2.8), 11.0 (SD, 3.8), and 15.9 (SD, 4.5), respectively (group-by-time interaction p < 0.001). The overall primary comparison remained significant under symmetric extreme-case assignments for the unavailable outcomes but not under the differential worst-case assumption for HFOV + iNO (p = 0.222).
In the observed per-protocol population, HFOV + iNO was associated with fewer deaths or ECMO events and faster improvement in oxygenation and right-ventricular echocardiographic measures than either comparator. Because 12 randomized infants were excluded and the overall comparison was not robust to the differential worst-case missing-outcome assumption, confidence in the apparent treatment effect is limited. These findings are exploratory and hypothesis-generating, do not establish efficacy, and require confirmation in a prospectively registered multicenter trial with complete outcome ascertainment.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
How Can Multi-Criteria Portfolio Decision Analysis Help Mitigate Mis/Disinformation?1 week agoIn this paper, we examine and illustrate the relevance of multi-criteria portfolio decision analysis as an approach to addressing mis/disinformation risks. After summarizing representative applications of these methods, we draw on the framework for societal resilience developed in the Finnish COVID-19 Science to Panel to elaborate on the range of capabilities that can be leveraged to mitigate mis/disinformation, for example, by maintaining alertness, implementing risk management actions, and interacting with stakeholders to promote awareness. We then present a numerical case study that illustrates how multi-criteria portfolio decision analysis can be combined with probabilistic approaches for modeling voting behavior and the spread of mis/disinformation to identify cost-efficient strategies consisting of combinations of risk management actions. We conclude by discussing some of the challenges posed by mis/disinformation.Chronic respiratory diseaseAccessAdvocacyEducation
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Patient-Caregiver Dyads in Severe and Advanced COPD: Relationships, Caregiving Burden, and Intervention Support: A Narrative Review.1 week agoInformal caregivers are central to the home management of severe and advanced chronic obstructive pulmonary disease (COPD), particularly when patients have high symptom burden, recurrent exacerbations, respiratory disability, long-term oxygen therapy (LTOT), or home non-invasive ventilation (NIV). This narrative review synthesizes evidence on patient-caregiver relationships, caregiving burden, and intervention support in these high-need COPD phenotypes.
We conducted an iterative narrative review using PubMed as the primary database, citation chaining from included literature, and targeted searches of guideline and organizational sources through March 2026. The synthesis drew on 96 publications spanning quantitative and qualitative studies, systematic and narrative reviews, randomized trials and trial protocols, clinical practice guidelines, and policy reports. Evidence was charted by design, population/phenotype, measures or intervention, main findings and key limitations.
Four dimensions emerged from the evidence: (1) multidimensional caregiver burden; (2) changing patient-caregiver relationship dynamics; (3) evolving caregiver roles across the severe-COPD trajectory, including LTOT, home NIV, exacerbations, hospitalization, and palliative care; and (4) intervention and support-system responses. Caregivers report anxiety, depression, fatigue, social restriction, financial strain, and uncertainty, while patient-caregiver disagreement about symptoms and support can intensify distress. Evidence is strongest for guidelines and systematic reviews confirming high need and for selected rehabilitation and breathlessness interventions; it is weaker for caregiver-specific, long-term, technology-supported, and low-resource interventions. The Zarit Burden Interview is widely used but has limited content validity in COPD caregiving; COPD-specific or caregiver-validated measures such as Informal Caregiver Burden Assessment Questionnaire (QASCI) and the Carer Support Needs Assessment Tool warrant greater use.
For people with severe or advanced COPD who depend on regular home support, care should more consistently recognize the patient-caregiver dyad as an important unit of assessment and intervention. Routine caregiver needs assessment, education for advanced home therapies, family-inclusive rehabilitation, psychological support, and needs-based palliative care are promising components of care.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Impact of the COVID-19 pandemic on long-term trends in psychiatric service utilisation at an accident and emergency department in Hong Kong.1 week agoTo describe trends in psychiatric service utilisation at the accident and emergency department (AED) of the Prince of Wales Hospital, Hong Kong, between July 2017 and June 2024.
This retrospective observational study reviewed medical records of patients who received psychiatric services in the AED of the Prince of Wales Hospital, Hong Kong, between July 2017 and June 2024 encompassing periods before the pandemic (July 2017 to December 2019), during the pandemic (January 2020 to September 2022), and after the pandemic (October 2022 to June 2024). The 'window period' (May 2021 to December 2021), during which no community outbreak was reported, was excluded from the pandemic period. Data collected included patient demographics, psychiatric diagnoses, and management plans. Trends in psychiatric service utilisation during the study period were analysed.
In total, 7441 AED psychiatric consultations (61.1% women) were included in the analysis. The median patient age significantly increased from 45 years in 2017 to 49 years in 2024 (p = 0.007). There was an increasing trend in AED psychiatric service utilisation. Attendance counts decreased during the first two quarters of 2020 (beginning of the pandemic) and substantially surged in 2021 during the window period, followed by a sharp decline in 2022 during the fifth wave driven by the Omicron variant and then rebounded at the beginning of 2023, and the upward trend continued. Daily attendance counts significantly increased from 2017 to 2024 among patients with major neurocognitive disorders, neurodevelopmental disorders, and disorders specifically associated with stress. Discharge to the community was the most common management plan.
The COVID-19 pandemic disrupted access to healthcare services in patients with psychiatric illnesses. Demand for AED psychiatric services rebounded after the pandemic. Between 2017 and 2024, the overall patient age increased, and service utilisation increased among patients with major neurocognitive disorders and neurodevelopmental disorders.Chronic respiratory diseaseMental HealthAccessCare/ManagementAdvocacy -
Pathogen genome enrichment sequencing to support a city-wide Legionnaires' disease outbreak investigation.1 week agoPathogen genomics can provide high-confidence source attribution for epidemiological investigations of Legionnaires' disease (LD) outbreaks. However, the utility of culture-based genomics can be undermined by long lead times for Legionella pneumophila culture or a lack of isolates when dealing with non-culturable bacteria or low-biomass specimens. Here, during a large 2024 LD outbreak in Melbourne, Australia, we compared direct specimen, hybridization-based enrichment sequencing with traditional culture-based whole-genome sequencing of 18 clinical and 5 environmental L. pneumophila specimens. Informed by the L. pneumophila global population structure, the method used 28,061 RNA bait hybridization probes to enrich >170,000 known genome-wide informative SNP sites directly from clinical and environmental specimens. Genome enrichment sequencing detected L. pneumophila with high sensitivity, achieving genome-wide coverage at 100 c.f.u. ml-1. Using sequence enrichment data with phylogenomic and machine learning approaches, we identified that a single cooling tower was likely responsible for the outbreak. Genome enrichment sequencing has the potential to enable faster and more comprehensive source tracking, thereby enhancing public health responses to outbreaks of environmental pathogens, permitting earlier, more confident interventions.Chronic respiratory diseaseCare/ManagementAdvocacy
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SRGAP2-AS1 Regulates RSV Replication and EMT-Associated Changes Through PTBP1 and ZEB1.1 week agoRespiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease, but the contribution of long non-coding RNAs (lncRNAs) to RSV-induced epithelial-mesenchymal transition (EMT)-associated changes remains unclear. We used transcriptomic screening in RSV-exposed BEAS-2B cells to identify candidate lncRNAs and then examined SRGAP2-AS1 in cell and mouse models. Expression was measured by RT-qPCR, and loss- and gain-of-function experiments were combined with RNA immunoprecipitation, co-immunoprecipitation, Western blot analysis, and TCID50 assays. SRGAP2-AS1 was increased in RSV-infected BEAS-2B cells and mouse lung tissue. Silencing SRGAP2-AS1 reduced viral replication, lowered IL-6 and IL-1β mRNA, increased IFN-β mRNA, and attenuated EMT-associated marker changes in RSV-infected BEAS-2B cells. SRGAP2-AS1 was predominantly cytoplasmic and enriched in PTBP1 immunoprecipitates. Reciprocal co-immunoprecipitation showed that PTBP1 and ZEB1 were present in the same endogenous complex, and ZEB1 abundance changed with SRGAP2-AS1 gain and loss of function. ZEB1 knockdown produced parallel changes in viral RNA, immune-related transcripts, and EMT-associated markers. Ectopic ZEB1 expression reversed the E-cadherin change caused by SRGAP2-AS1 depletion, supporting a downstream role for ZEB1 in the epithelial arm of the EMT-associated phenotype. These findings support regulatory relationships among SRGAP2-AS1, PTBP1, and ZEB1 during RSV infection. The causal order of the viral and immune-related changes, and the in vivo relevance of the EMT-associated phenotype, remain unresolved.Chronic respiratory diseaseCare/Management
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Mantis: A foundation model for mechanistic disease forecasting.1 week agoInfectious disease forecasting in novel outbreaks or low-resource settings is hampered by the need for large disease and covariate datasets, bespoke training, and expert tuning, all of which can hinder rapid generation of forecasts for new settings. To address these challenges, we developed Mantis, a foundation model trained entirely on mechanistic simulations, which enables out-of-the-box forecasting across diseases, regions, and outcomes, even in settings with limited historical data. We evaluated Mantis against 78 forecasting models across 16 diseases with diverse transmission modes, assessing both point forecast accuracy [mean absolute error (MAE)] and probabilistic performance (weighted interval score and coverage). Despite using no real-world data during training, Mantis achieved lower MAE than all models in the CDC's COVID-19 Forecast Hub when backtested on early pandemic forecasts which it had not previously seen. Across all other diseases tested, Mantis consistently ranked in the top two models across evaluation metrics. Mantis further generalized to diseases with transmission mechanisms not represented in its training data, demonstrating that it can capture fundamental contagion dynamics rather than memorizing disease-specific patterns. These capabilities illustrate that purely simulation-based foundation models such as Mantis can provide a practical foundation for disease forecasting: general-purpose, accurate, and deployable where traditional models struggle.Chronic respiratory diseaseAdvocacy