Title: Stay Independent of Asthma, Allergies This July 4th
Category: Health News
Created: 7/1/2022 12:00:00 AM
Last Editorial Review: 7/1/2022 12:00:00 AM

Title: Hepatitis C Infection Can Kill, But Less Than a Third of Patients Get Treatment
Category: Health News
Created: 8/10/2022 12:00:00 AM
Last Editorial Review: 8/10/2022 12:00:00 AM

Title: What Is the Main Cause of Leaky Gut, and How Do You Fix It?
Category: Diseases and Conditions
Created: 8/23/2022 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM

Title: How to Get Rid of Mucus in My Chest Fast
Category: Diseases and Conditions
Created: 6/22/2022 12:00:00 AM
Last Editorial Review: 6/22/2022 12:00:00 AM

Title: How Do I Get Rid of Winter Depression?
Category: Diseases and Conditions
Created: 4/27/2022 12:00:00 AM
Last Editorial Review: 4/27/2022 12:00:00 AM

Title: What Are 4 Symptoms of Seasonal Affective Disorder?
Category: Diseases and Conditions
Created: 12/10/2021 12:00:00 AM
Last Editorial Review: 7/6/2022 12:00:00 AM

Title: Study Casts Doubt on 'Chemical Imbalance' Theory of Depression
Category: Health News
Created: 8/9/2022 12:00:00 AM
Last Editorial Review: 8/9/2022 12:00:00 AM

Extract

Living with a respiratory illness requires patients to manage a wide range of symptoms, many of which will worsen as a disease progresses. Breathlessness is a hallmark feature of respiratory conditions, occurring in almost all individuals with COPD and interstitial lung disease (ILD) [1, 2]. Cough is present in 78% of people with ILD and is frequently distressing, with physical, social and emotional impacts [1, 3].

Influenza A virus (IAV) is one of the leading causes of respiratory infections. The lack of efficient anti-influenza therapeutics requires a better understanding of how IAV interacts with host cells. Alveolar macrophages are tissue-specific macrophages that play a critical role in lung innate immunity and homeostasis, yet their role during influenza infection remains unclear. First, our review highlights an active IAV replication within alveolar macrophages, despite an abortive viral cycle. Such infection leads to persistent alveolar macrophage inflammation and diminished phagocytic function, alongside direct mitochondrial damage and indirect metabolic shifts in the alveolar micro-environment. We also discuss the "macrophage disappearance reaction", which is a drastic reduction of the alveolar macrophage population observed after influenza infection in mice but debated in humans, with unclear underlying mechanisms. Furthermore, we explore the dual nature of alveolar macrophage responses to IAV infection, questioning whether they are deleterious or protective for the host. While IAV may exploit immuno-evasion strategies and induce alveolar macrophage alteration or depletion, this could potentially reduce excessive inflammation and allow for the replacement of more effective cells. Despite these insights, the pathophysiological role of alveolar macrophages during IAV infection in humans remains understudied, urging further exploration to unravel their precise contributions to disease progression and resolution.

Background

Severe asthma significantly impacts a minority of children with asthma, leading to frequent symptoms, hospitalisations and potential long-term health consequences. However, accurate global data on severe asthma epidemiology is lacking. This study aims to address this gap, providing data on severe asthma epidemiology, regional differences and associated comorbidities.

Bronchiectasis is a chronic respiratory disease characterised by permanent enlargement of the airways associated with cough, sputum production and a history of pulmonary exacerbations. In the past few years, incidence and prevalence of bronchiectasis have increased worldwide, possibly due to advances in imaging techniques and disease awareness, leading to increased socioeconomic burden and healthcare costs. Consistently, a mortality increase in bronchiectasis patient cohorts has been demonstrated in certain areas of the globe, with mortality rates of 16–24.8% over 4–5 years of follow-up. However, heterogeneity in epidemiological data is consistent, as reported prevalence in the general population ranges from 52.3 to more than 1000 per 100 000. Methodological flaws in the designs of available studies are likely to underestimate the proportion of people suffering from this condition worldwide and comparisons between different areas of the globe might be unreliable due to different assessment methods or local implementation of the same method in different contexts. Differences in disease severity associated with diverse geographical distribution of aetiologies, comorbidities and microbiology might explain an additional quota of heterogeneity. Finally, limited access to care in certain geographical areas is associated with both underestimation of the disease and increased severity and mortality. The aim of this review is to provide a snapshot of available real-world epidemiological data describing incidence and prevalence of bronchiectasis in the general population. Furthermore, data on mortality, healthcare burden and high-risk populations are provided. Finally, an analysis of the geographical distribution of determinants contributing to differences in bronchiectasis epidemiology is offered.

The prognosis of people with cystic fibrosis (pwCF) has improved dramatically with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators (CFTRm). The ageing of the cystic fibrosis (CF) population is changing the disease landscape with the emergence of different needs and increasing comorbidities related to both age and long-term exposure to multiple treatments including CFTRm. Although the number of pwCF eligible for this treatment is expected to increase, major disparities in care and outcomes still exist in this population. Moreover, the long-term impact of the use of CFTRm is still partly unknown due to the current short follow-up and experience with their use, thus generating some uncertainties. The future spread and initiation of these drugs at an earlier stage of the disease is expected to reduce the systemic burden of systemic inflammation and its consequences on health. However, the prolonged life expectancy is accompanied by an increasing burden of age-related comorbidities, especially in the context of chronic disease. The clinical manifestations of the comorbidities directly or indirectly associated with CFTR dysfunction are changing, along with the disease dynamics and outcomes. Current protocols used to monitor slow disease progression will need continuous updates, including the composition of the multidisciplinary team for CF care, with a greater focus on the needs of the adult population.

Background

In adults with serious respiratory illness, fatigue is prevalent and under-recognised, with few treatment options. The aim of this review was to assess the impact of graded exercise therapy (GET) on fatigue in adults with serious respiratory illness.

Background

People living with serious respiratory illness experience a high burden of distressing symptoms. Although opioids are prescribed for symptom management, they generate adverse events, and their benefits are unclear.

Retrotransposable elements (RTEs) are common mobile genetic elements comprising ~42% of the human genome. RTEs play critical roles in gene regulation and function, but how they are specifically involved in complex diseases is largely unknown. Here, we investigate the cellular heterogeneity of RTEs using 12 single-cell transcriptome profiles covering three neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease, and multiple sclerosis. We identify cell type marker RTEs in neurons, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells that are related to these diseases. The differential expression analysis reveals the landscape of dysregulated RTE expression, especially L1s, in excitatory neurons of multiple neurodegenerative diseases. Machine learning algorithms for predicting cell disease stage using a combination of RTE and gene expression features suggests dynamic regulation of RTEs in AD. Furthermore, we construct a single-cell atlas of retrotransposable elements in neurodegenerative disease (scARE) using these data sets and features. scARE has six feature analysis modules to explore RTE dynamics in a user-defined condition. To our knowledge, scARE represents the first systematic investigation of RTE dynamics at the single-cell level within the context of neurodegenerative diseases.

PWAS (proteome-wide association study) is an innovative genetic association approach that complements widely used methods like GWAS (genome-wide association study). The PWAS approach involves consecutive phases. Initially, machine learning modeling and probabilistic considerations quantify the impact of genetic variants on protein-coding genes’ biochemical functions. Secondly, for each individual, aggregating the variants per gene determines a gene-damaging score. Finally, standard statistical tests are activated in the case-control setting to yield statistically significant genes per phenotype. The PWAS Hub offers a user-friendly interface for an in-depth exploration of gene–disease associations from the UK Biobank (UKB). Results from PWAS cover 99 common diseases and conditions, each with over 10,000 diagnosed individuals per phenotype. Users can explore genes associated with these diseases, with separate analyses conducted for males and females. For each phenotype, the analyses account for sex-based genetic effects, inheritance modes (dominant and recessive), and the pleiotropic nature of associated genes. The PWAS Hub showcases its usefulness for asthma by navigating through proteomic-genetic analyses. Inspecting PWAS asthma-listed genes (a total of 27) provide insights into the underlying cellular and molecular mechanisms. Comparison of PWAS-statistically significant genes for common diseases to the Open Targets benchmark shows partial but significant overlap in gene associations for most phenotypes. Graphical tools facilitate comparing genetic effects between PWAS and coding GWAS results, aiding in understanding the sex-specific genetic impact on common diseases. This adaptable platform is attractive to clinicians, researchers, and individuals interested in delving into gene–disease associations and sex-specific genetic effects.

Sequence variation observed in populations of pathogens can be used for important public health and evolutionary genomic analyses, especially outbreak analysis and transmission reconstruction. Identifying this variation is typically achieved by aligning sequence reads to a reference genome, but this approach is susceptible to reference biases and requires careful filtering of called genotypes. There is a need for tools that can process this growing volume of bacterial genome data, providing rapid results, but that remain simple so they can be used without highly trained bioinformaticians, expensive data analysis, and long-term storage and processing of large files. Here we describe split k-mer analysis (SKA2), a method that supports both reference-free and reference-based mapping to quickly and accurately genotype populations of bacteria using sequencing reads or genome assemblies. SKA2 is highly accurate for closely related samples, and in outbreak simulations, we show superior variant recall compared with reference-based methods, with no false positives. SKA2 can also accurately map variants to a reference and be used with recombination detection methods to rapidly reconstruct vertical evolutionary history. SKA2 is many times faster than comparable methods and can be used to add new genomes to an existing call set, allowing sequential use without the need to reanalyze entire collections. With an inherent absence of reference bias, high accuracy, and a robust implementation, SKA2 has the potential to become the tool of choice for genotyping bacteria. SKA2 is implemented in Rust and is freely available as open-source software.

High-throughput sequencing (HTS) technologies have been instrumental in investigating biological questions at the bulk and single-cell levels. Comparative analysis of two HTS data sets often relies on testing the statistical significance for the difference of two negative binomial distributions (DOTNB). Although negative binomial distributions are well studied, the theoretical results for DOTNB remain largely unexplored. Here, we derive basic analytical results for DOTNB and examine its asymptotic properties. As a state-of-the-art application of DOTNB, we introduce DEGage, a computational method for detecting differentially expressed genes (DEGs) in scRNA-seq data. DEGage calculates the mean of the sample-wise differences of gene expression levels as the test statistic and determines significant differential expression by computing the P-value with DOTNB. Extensive validation using simulated and real scRNA-seq data sets demonstrates that DEGage outperforms five popular DEG analysis tools: DEGseq2, DEsingle, edgeR, Monocle3, and scDD. DEGage is robust against high dropout levels and exhibits superior sensitivity when applied to balanced and imbalanced data sets, even with small sample sizes. We utilize DEGage to analyze prostate cancer scRNA-seq data sets and identify marker genes for 17 cell types. Furthermore, we apply DEGage to scRNA-seq data sets of mouse neurons with and without fear memory and reveal eight potential memory-related genes overlooked in previous analyses. The theoretical results and supporting software for DOTNB can be widely applied to comparative analyses of dispersed count data in HTS and broad research questions.

Most studies of genome organization have focused on intrachromosomal (cis) contacts because they harbor key features such as DNA loops and topologically associating domains. Interchromosomal (trans) contacts have received much less attention, and tools for interrogating potential biologically relevant trans structures are lacking. Here, we develop a computational framework that uses Hi-C data to identify sets of loci that jointly interact in trans. This method, trans-C, initiates probabilistic random walks with restarts from a set of seed loci to traverse an input Hi-C contact network, thereby identifying sets of trans-contacting loci. We validate trans-C in three increasingly complex models of established trans contacts: the Plasmodium falciparum var genes, the mouse olfactory receptor "Greek islands," and the human RBM20 cardiac splicing factory. We then apply trans-C to systematically test the hypothesis that genes coregulated by the same trans-acting element (i.e., a transcription or splicing factor) colocalize in three dimensions to form "RNA factories" that maximize the efficiency and accuracy of RNA biogenesis. We find that many loci with multiple binding sites of the same DNA-binding proteins interact with one another in trans, especially those bound by factors with intrinsically disordered domains. Similarly, clustered binding of a subset of RNA-binding proteins correlates with trans interaction of the encoding loci. We observe that these trans-interacting loci are close to nuclear speckles. These findings support the existence of trans-interacting chromatin domains (TIDs) driven by RNA biogenesis. Trans-C provides an efficient computational framework for studying these and other types of trans interactions, empowering studies of a poorly understood aspect of genome architecture.

Asgard archaea are of great interest as the progenitors of Eukaryotes, but little is known about the mobile genetic elements (MGEs) that may shape their ongoing evolution. Here, we describe MGEs that replicate in Atabeyarchaeia, a wetland Asgard archaea lineage represented by two complete genomes. We used soil depth–resolved population metagenomic data sets to track 18 MGEs for which genome structures were defined and precise chromosome integration sites could be identified for confident host linkage. Additionally, we identified a complete 20.67 kbp circular plasmid and two family-level groups of viruses linked to Atabeyarchaeia, via CRISPR spacer targeting. Closely related 40 kbp viruses possess a hypervariable genomic region encoding combinations of specific genes for small cysteine-rich proteins structurally similar to restriction-homing endonucleases. One 10.9 kbp integrative conjugative element (ICE) integrates genomically into the Atabeyarchaeum deiterrae-1 chromosome and has a 2.5 kbp circularizable element integrated within it. The 10.9 kbp ICE encodes an expressed Type IIG restriction-modification system with a sequence specificity matching an active methylation motif identified by Pacific Biosciences (PacBio) high-accuracy long-read (HiFi) metagenomic sequencing. Restriction-modification of Atabeyarchaeia differs from that of another coexisting Asgard archaea, Freyarchaeia, which has few identified MGEs but possesses diverse defense mechanisms, including DISARM and Hachiman, not found in Atabeyarchaeia. Overall, defense systems and methylation mechanisms of Asgard archaea likely modulate their interactions with MGEs, and integration/excision and copy number variation of MGEs in turn enable host genetic versatility.

Somatic mutations arise and accumulate during tissue culture and vegetative propagation, potentially affecting various traits in horticultural crops, but their characteristics are still unclear. Here, somatic mutations in regenerated woodland strawberry derived from tissue culture of shoot tips under different conditions and 12 cultivated strawberry individuals are analyzed by whole genome sequencing. The mutation frequency of single nucleotide variants is significantly increased with increased hormone levels or prolonged culture time in the range of 3.3 x 10^–8–3.0 x 10^–6 mutations per site. CG methylation shows a stable reduction (0.71%–8.03%) in regenerated plants, and hypoCG-DMRs are more heritable after sexual reproduction. A high-quality haplotype-resolved genome is assembled for the strawberry cultivar "Beni hoppe." The 12 "Beni hoppe" individuals randomly selected from different locations show 4731–6005 mutations relative to the reference genome, and the mutation frequency varies among the subgenomes. Our study has systematically characterized the genetic and epigenetic variants in regenerated woodland strawberry plants and different individuals of the same strawberry cultivar, providing an accurate assessment of somatic mutations at the genomic scale and nucleotide resolution in plants.

The poly(A) signal, together with auxiliary elements, directs cleavage of a pre-mRNA and thus determines the 3' end of the mature transcript. In many species, including humans, the poly(A) signal is an AAUAAA hexamer, but we recently found that the deeply branching eukaryote Giardia lamblia uses a distinct hexamer (AGURAA) and lacks any known auxiliary elements. Our discovery prompted us to explore the evolutionary dynamics of poly(A) signals and auxiliary elements in the eukaryotic kingdom. We use direct RNA sequencing to determine poly(A) signals for four protists within the Metamonada clade (which also contains G. lamblia) and two outgroup protists. These experiments reveal that the AAUAAA hexamer serves as the poly(A) signal in at least four different eukaryotic clades, indicating that it is likely the ancestral signal, whereas the unusual Giardia version is derived. We find that the use and relative strengths of auxiliary elements are also plastic; in fact, within Metamonada, species like G. lamblia make use of a previously unrecognized auxiliary element where nucleotides flanking the poly(A) signal itself specify genuine cleavage sites. Thus, despite the fundamental nature of pre-mRNA cleavage for the expression of all protein-coding genes, the motifs controlling this process are dynamic on evolutionary timescales, providing motivation for future biochemical and structural studies as well as new therapeutic angles to target eukaryotic pathogens.

Understanding the evolution of chromatin conformation among species is fundamental to elucidate the architecture and plasticity of genomes. Nonrandom interactions of linearly distant loci regulate gene function in species-specific patterns, affecting genome function, evolution, and, ultimately, speciation. Yet, data from nonmodel organisms are scarce. To capture the macroevolutionary diversity of vertebrate chromatin conformation, here we generate de novo genome assemblies for two cryptodiran (hidden-neck) turtles via Illumina sequencing, chromosome conformation capture, and RNA-seq: Apalone spinifera (ZZ/ZW, 2n = 66) and Staurotypus triporcatus (XX/XY, 2n = 54). We detected differences in the three-dimensional (3D) chromatin structure in turtles compared to other amniotes beyond the fusion/fission events detected in the linear genomes. Namely, whole-genome comparisons revealed distinct trends of chromosome rearrangements in turtles: (1) a low rate of genome reshuffling in Apalone (Trionychidae) whose karyotype is highly conserved when compared to chicken (likely ancestral for turtles), and (2) a moderate rate of fusions/fissions in Staurotypus (Kinosternidae) and Trachemys scripta (Emydidae). Furthermore, we identified a chromosome folding pattern that enables "centromere–telomere interactions" previously undetected in turtles. The combined turtle pattern of "centromere–telomere interactions" (discovered here) plus "centromere clustering" (previously reported in sauropsids) is novel for amniotes and it counters previous hypotheses about amniote 3D chromatin structure. We hypothesize that the divergent pattern found in turtles originated from an amniote ancestral state defined by a nuclear configuration with extensive associations among microchromosomes that were preserved upon the reshuffling of the linear genome.

The transcription factor (TF) cone-rod homeobox (CRX) is essential for the differentiation and maintenance of photoreceptor cell identity. Several human CRX variants cause degenerative retinopathies, but most are variants of uncertain significance. We performed a deep mutational scan (DMS) of nearly all possible single amino acid substitutions in CRX using a cell-based transcriptional reporter assay, curating a high-confidence list of nearly 2000 variants with altered transcriptional activity. In the structured homeodomain, activity scores closely aligned to a predicted structure and demonstrated position-specific constraints on amino acid substitution. In contrast, the intrinsically disordered transcriptional effector domain displayed a qualitatively different pattern of substitution effects, following compositional constraints without specific residue position requirements in the peptide chain. These compositional constraints were consistent with the acidic exposure model of transcriptional activation. We evaluated the performance of the DMS assay as a clinical variant classification tool using gold-standard classified human variants from ClinVar, identifying pathogenic variants with high specificity and moderate sensitivity. That this performance could be achieved using a synthetic reporter assay in a foreign cell type, even for a highly cell type-specific TF like CRX, suggests that this approach shows promise for DMS of other TFs that function in cell types that are not easily accessible. Together, the results of the CRX DMS identify molecular features of the CRX effector domain and demonstrate utility for integration into the clinical variant classification pipeline.

As a major type of structural variants, tandem duplication plays a critical role in tumorigenesis by increasing oncogene dosage. Recent work has revealed that noncoding enhancers are also affected by duplications leading to the activation of oncogenes that are inside or outside of the duplicated regions. However, the prevalence of enhancer duplication and the identity of their target genes remains largely unknown in the cancer genome. Here, by analyzing whole-genome sequencing data in a non-gene-centric manner, we identify 881 duplication hotspots in 13 major cancer types, most of which do not contain protein-coding genes. We show that the hotspots are enriched with distal enhancer elements and are highly lineage-specific. We develop a HiChIP-based methodology that navigates enhancer–promoter contact maps to prioritize the target genes for the duplication hotspots harboring enhancer elements. The methodology identifies many novel enhancer duplication events activating oncogenes such as ESR1, FOXA1, GATA3, GATA6, TP63, and VEGFA, as well as potentially novel oncogenes such as GRHL2, IRF2BP2, and CREB3L1. In particular, we identify a duplication hotspot on Chromosome 10p15 harboring a cluster of enhancers, which skips over two genes, through a long-range chromatin interaction, to activate an oncogenic isoform of the NET1 gene to promote migration of gastric cancer cells. Focusing on tandem duplications, our study substantially extends the catalog of noncoding driver alterations in multiple cancer types, revealing attractive targets for functional characterization and therapeutic intervention.

The human major histocompatibility complex (MHC) is a ~4 Mb genomic segment on Chromosome 6 that plays a pivotal role in the immune response. Despite its importance in various traits and diseases, its complex nature makes it challenging to accurately characterize on a routine basis. We present a novel approach allowing targeted sequencing and de novo haplotypic assembly of the MHC region in heterozygous samples, using long-read sequencing technologies. Our approach is validated using two reference samples, two family trios, and an African-American sample. We achieved excellent coverage (96.6%–99.9% with at least 30x depth) and high accuracy (99.89%–99.99%) for the different haplotypes. This methodology offers a reliable and cost-effective method for sequencing and fully characterizing the MHC without the need for whole-genome sequencing, facilitating broader studies on this important genomic segment and having significant implications in immunology, genetics, and medicine.

Two decades into the era of Electronic Health Records (EHRs), the promise of streamlining clinical care, reducing burden, and improving patient outcomes has yet to be realized. A cross-sectional family physician census conducted by the American Board of Family Medicine in 2022 and 2023 included self-reported physician EHR satisfaction. Of the nearly 10,000 responding family physicians, only one-in-four (26.2%) report being very satisfied and one-in-three (33.8%) were not satisfied. These low levels of satisfaction point to the need for greater transparency in the marketplace and pressure to increase user-centric EHR design.

Background:

The COVID-19 pandemic social distancing requirements encouraged patients to avoid public spaces including in-office health care visits. Ambulatory-care-sensitive conditions (ACSCs) represent conditions that can be managed with quality primary care and when access is limited, these conditions can lead to avoidable emergency department (ED) visits.

Without compromising accuracy, point of care testing (POCT) provides immediate results at the time of in person patient consultation. The purpose of this study was to evaluate time until therapeutic intervention with POCT HbA1c versus venipuncture, where venipuncture was considered standard of care.

The primary outcome was time (hours) to implementation of a therapeutic intervention based on POCT HbA1c result, as compared with most recent venipuncture HbA1c before the study and its associated therapeutic intervention. A total of 94 POCT HbA1c tests were included in the primary analysis.

For the POCT HbA1c, the mean time to therapeutic intervention was 1.6 ± 3.14 hours. For the previous venipuncture HbA1c, the mean time to therapeutic intervention was 1376.66 ± 3356.6 hours (P < .001). Overall, this trial showed that POCT HbA1c results in a significantly faster time to therapeutic intervention than venipuncture in a primary care clinic that serves a rural population.

The rising obesity epidemic is a phenomenon that has gained increasing attention from health providers and health policy makers. This led to recognition of nonalcoholic fatty liver disease (MASLD). The standard for its assessment has been histologic, which is neither practical nor acceptable by patients. Subsequently, a number of noninvasive assessment methods have been developed. However, despite ease of implementation, their confounding variables do hinder their accuracy. Nonetheless, the development of the liver stiffness measurement (LSM) and incorporation of other biological parameters has minimized but not eliminated the need for liver biopsy. Imaging methods are useful in evaluation, estimation, and following the progression of steatosis and fibrosis with particular attention to controlled attenuation parameter (CAP) and MRI–Proton Density Fat Fraction (MRI-PDFF). The choices for the family physician are broad and rely on tests’ availability, cost, and patient acceptance. Great efforts have been undertaken to produce more robust and novel noninvasive markers that indicate fibrinogenesis directly in an implementable and cost-effective way.

Background:

Continuous glucose monitoring (CGM) for patients with type 1 and type 2 diabetes is associated with improved clinical, behavioral, and psychosocial patient health outcomes and is part of the American Diabetes Association’s Standards of Medical Care. CGM prescription often takes place in endocrinology practices, yet 50% of adults with type 1 diabetes and 90% of all people with type 2 diabetes receive their diabetes care in primary care settings. This study examined primary care clinicians’ perceptions of barriers and resources needed to support CGM use in primary care.

Background:

Screening rates for Human Immunodeficiency Virus (HIV) remain low despite guidelines by both the CDC and USPSTF recommending that all adolescents and adults be screened at least once. The aim of this quality improvement study was to increase HIV screening among eligible patients.

Background:

Certain health-related risk factors require legal interventions. Medical-legal partnerships (MLPs) are collaborations between clinics and lawyers that address these health-harming legal needs (HHLNs) and have been shown to improve health and reduce utilization.

Background:

Higher trust in healthcare providers has been linked to better health outcomes and satisfaction. Lower trust has been associated with healthcare-based discrimination.

Objective:

In this study, we sought to comprehensively evaluate GPT-4 (Generative Pre-trained Transformer)’s performance on the 2022 American Board of Family Medicine’s (ABFM) In-Training Examination (ITE), compared with its predecessor, GPT-3.5, and the national family residents’ performance on the same examination.

COPD and asthma are two of the most common chronic lung diseases, affecting over 545 million people globally and 34 million in the United States. Annual health care costs related to chronic lung disease are estimated at €380 billion in the European Union, and $24–$50 billion in the United States averaging to $4,000 in out-of-pocket costs per person in the U.S. A full-text literature search was conducted for English publications between January 1, 2005–March 18, 2024. It returned over 5,000 publications that were further narrowed using key search words, resulting in 172 peer-reviewed articles. Using their experience and subject expertise, the authors further narrowed the peer-reviewed articles to 55 that were in their opinion relevant. Also, 38 recently published industry reports and news articles specific to downstream effects of inhaler market changes and the future impact were included. The literature suggests that individuals with chronic lung disease face increased challenges with access to inhaled medication due to rising medication costs, discontinuation of branded medications, introduction of generic medications not covered by insurance, exclusionary preferred drug list tactics that force health care providers into non-medical switching of medication or devices, and ongoing medication shortages. Providers experience ongoing hurdles in prescribing appropriate inhaled medications for individuals with chronic lung disease, including increased time and costs spent on administrative tasks due to inhaler denials, a loss of patient trust, and limits on their ability to prescribe appropriate inhaled medication for individuals with chronic lung disease.

BACKGROUD:Lung volume measurements are important for monitoring functional aeration and recruitment and may help guide adjustments in ventilator settings. The expiratory phase of airway pressure release ventilation (APRV) may provide physiologic information about lung volume based on the expiratory flow-time slope, angle, and time to approach a no-flow state (expiratory time [TE]). We hypothesized that expiratory flow would correlate with estimated lung volume (ELV) as measured using a modified nitrogen washout/washin technique in a large-animal lung injury model.METHODS:Eight pigs (35.2 ± 1.0 kg) were mechanically ventilated using an Engström Carescape R860 on the APRV mode. All settings were held constant except the expiratory duration, which was adjusted based on the expiratory flow curve. Abdominal pressure was increased to 15 mm Hg in normal and injured lungs to replicate a combination of pulmonary and extrapulmonary lung injury. ELV was estimated using the Carescape FRC INview tool. The expiratory flow-time slope and TE were measured from the expiratory flow profile.RESULTS:Lung elastance increased with induced lung injury from 29.3 ± 7.3 cm H2O/L to 39.9 ± 15.1cm H2O/L, and chest wall elastance increased with increasing intra-abdominal pressures (IAPs) from 15.3 ± 4.1 cm H2O/L to 25.7 ± 10.0 cm H2O/L in the normal lung and 15.8 ± 6.0 cm H2O/L to 33.0 ± 6.2 cm H2O/L in the injured lung (P = .39). ELV decreased from 1.90 ± 0.83 L in the injured lung to 0.67 ± 0.10 L by increasing IAP to 15 mm Hg. This had a significant correlation with a TE decrease from 2.3 ± 0.8 s to 1.0 ± 0.1 s in the injured group with increasing insufflation pressures (ρ = 0.95) and with the expiratory flow-time slope, which increased from 0.29 ± 0.06 L/s2 to 0.63 ± 0.05 L/s2 (ρ = 0.78).CONCLUSIONS:Changes in ELV over time, and the TE and flow-time slope, could be used to demonstrate evolving lung injury during APRV. Using the slope to infer changes in functional lung volume represents a unique, reproducible, real-time, bedside technique that does not interrupt ventilation and may be used for clinical interpretation.

BACKGROUND:Opioids are known to cause respiratory depression, aspiration, and to suppress the immune system. This study aimed to investigate the relationship between short- and long-term opioid use and the occurrence and clinical outcomes of pneumonia in South Korea.METHODS:The data for this population-based retrospective cohort analysis were obtained from the South Korean National Health Insurance Service. The opioid user group consisted of those prescribed opioids in 2016, while the non-user group, who did not receive opioid prescriptions that year, was selected using a 1:1 stratified random sampling method. The opioid users were categorized into short-term (1–89 d) and long-term (≥90 d) users. The primary end point was pneumonia incidence from January 1, 2017–December 31, 2021, with secondary end points including pneumonia-related hospitalizations and mortality rates during the study period.RESULTS:In total, 4,556,606 adults were enrolled (opioid group, 2,070,039). Opioid users had a 3% higher risk of pneumonia and an 11% higher risk of pneumonia requiring hospitalization compared to non-users. Short-term users had a 3% higher risk of pneumonia, and long-term users had a 4% higher risk compared to non-users (P < .001). Additionally, short-term users had an 8% higher risk of hospital-treated pneumonia, and long-term users had a 17% higher risk compared to non-users (P < .001).CONCLUSIONS:Both short- and long-term opioid prescriptions were associated with higher incidences of pneumonia and hospital-treated pneumonia. In addition, long-term opioid prescriptions were linked to higher mortality rates due to pneumonia.

BACKGROUND:Practice on fasting prior to extubation in critically ill patients is variable. Efficacy of fasting in reducing gastric volume has not been well established. The primary objective of this study was to assess the effect of 4 h of fasting on prevalence of empty stomach using gastric ultrasonography in critically ill subjects who are fasted for extubation. The secondary objectives were to evaluate the change in gastric volumes during 4 h of fasting and to determine factors associated with empty stomach after fasting.METHODS:This was a single-center, prospective, observational study on adult ICU subjects who were enterally fed for at least 6 h continuously and mechanically ventilated. Gastric ultrasound was performed immediately prior to commencement of fasting, after 4 h of fasting, and after nasogastric (NG) aspiration after 4 h of fasting. An empty stomach was defined as a gastric volume ≤ 1.5 mL/kg.RESULTS:Forty subjects were recruited, and 38 (95%) had images suitable for analysis. The prevalence of empty stomach increased after 4 h of fasting (25 [65.8%] vs 31 [81.6%], P = .041) and after 4 h of fasting with NG aspiration (25 [65.8%] vs 34 [89.5%], P = .008). There was a significant difference in median (interquartile range) gastric volume per body weight between before fasting and 4 h after fasting (1.0 [0.5–1.8] mL/kg vs 0.4 [0.2–1.0] mL/kg, P < .001). No patient factors were associated with higher prevalence of empty stomach after 4 h of fasting.CONCLUSIONS:Most mechanically ventilated subjects had empty stomachs prior to fasting for extubation. Fasting for 4 h further increased the prevalence of empty stomach at extubation to > 80%.

BACKGROUND:PEEP is a cornerstone treatment for children with pediatric ARDS. Unfortunately, its titration is often performed solely by evaluating oxygen saturation, which can lead to inadequate PEEP level settings and consequent adverse effects. This study aimed to assess the impact of increasing PEEP on hemodynamics, respiratory system mechanics, and oxygenation in children with ARDS.METHODS:Children receiving mechanical ventilation and on pressure-controlled volume-guaranteed mode were prospectively assessed for inclusion. PEEP was sequentially changed to 5, 12, 10, 8 cm H2O, and again to 5 cm H2O. After 10 min at each PEEP level, hemodynamic, ventilatory, and oxygenation variables were collected.RESULTS:A total of 31 subjects were included, with median age and weight of 6 months and 6.3 kg, respectively. The main reasons for pediatric ICU admission were respiratory failure caused by acute viral bronchiolitis (45%) and community-acquired pneumonia (32%). Most subjects had mild or moderate ARDS (45% and 42%, respectively), with a median (interquartile range) oxygenation index of 8.4 (5.8–12.7). Oxygen saturation improved significantly when PEEP was increased. However, although no significant changes in blood pressure were observed, the median cardiac index at PEEP of 12 cm H2O was significantly lower than that observed at any other PEEP level (P = .001). Fourteen participants (45%) experienced a reduction in cardiac index of > 10% when PEEP was increased to 12 cm H2O. Also, the estimated oxygen delivery was significantly lower, at 12 cm H2O PEEP. Finally, respiratory system compliance significantly reduced when PEEP was increased. At a PEEP of 12 cm H2O, static compliance had a median reduction of 25% in relation to the initial assessment (PEEP of 5 cm H2O).CONCLUSIONS:Although it may improve arterial oxygen saturation, inappropriately high PEEP levels may reduce cardiac output, oxygen delivery, and respiratory system compliance in pediatric subjects with ARDS with low potential for lung recruitability.

BACKGROUND:Beneficial effects of breathing at FIO2 < 0.21 on disease outcomes have been reported in previous preclinical and clinical studies. However, the safety and intra-hospital feasibility of breathing hypoxic gas for 5 d have not been established. In this study, we examined the physiologic effects of breathing a gas mixture with FIO2 as low as 0.11 in 5 healthy volunteers.METHODS:All 5 subjects completed the study, spending 5 consecutive days in a hypoxic tent, where the ambient oxygen level was lowered in a stepwise manner over 5 d, from FIO2 of 0.16 on the first day to FIO2 of 0.11 on the fifth day of the study. All the subjects returned to an environment at room air on the sixth day. The subjects' SpO2, heart rate, and breathing frequency were continuously recorded, along with daily blood sampling, neurologic evaluations, transthoracic echocardiography, and mental status assessments.RESULTS:Breathing hypoxia concentration dependently caused profound physiologic changes, including decreased SpO2 and increased heart rate. At FIO2 of 0.14, the mean SpO2 was 92%; at FIO2 of 0.13, the mean SpO2 was 93%; at FIO2 of 0.12, the mean SpO2 was 88%; at FIO2 of 0.11, the mean SpO2 was 85%; and, finally, at an FIO2 of 0.21, the mean SpO2 was 98%. These changes were accompanied by increased erythropoietin levels and reticulocyte counts in blood. All 5 subjects concluded the study with no adverse events. No subjects exhibited signs of mental status changes or pulmonary hypertension.CONCLUSIONS:Results of the current physiologic study suggests that, within a hospital setting, delivering FIO2 as low as 0.11 is feasible and safe in healthy subjects, and provides the foundation for future studies in which therapeutic effects of hypoxia breathing are tested.

BACKGROUND:This study sought to estimate the overall cumulative incidence and odds of Hospital-acquired venous thromboembolism (VTE) among critically ill children with and without exposure to invasive ventilation. In doing so, we also aimed to describe the temporal relationship between invasive ventilation and hospital-acquired VTE development.METHODS:We performed a retrospective cohort study using Virtual Pediatric Systems (VPS) data from 142 North American pediatric ICUs among children < 18 y of age from January 1, 2016–December 31, 2022. After exclusion criteria were applied, cohorts were identified by presence of invasive ventilation exposure. The primary outcome was cumulative incidence of hospital-acquired VTE, defined as limb/neck deep venous thrombosis or pulmonary embolism. Multivariate logistic regression was used to determine whether invasive ventilation was an independent risk factor for hospital-acquired VTE development.RESULTS:Of 691,118 children studied, 86,922 (12.4%) underwent invasive ventilation. The cumulative incidence of hospital-acquired VTE for those who received invasive ventilation was 1.9% and 0.12% for those who did not (P < .001). The median time to hospital-acquired VTE after endotracheal intubation was 6 (interquartile range 3–14) d. In multivariate models, invasive ventilation exposure and duration were each independently associated with development of hospital-acquired VTE (adjusted odds ratio 1.64 [95% CI 1.42–1.86], P < .001; and adjusted odds ratio 1.03 [95% CI 1.02–1.03], P < .001, respectively).CONCLUSIONS:In this multi-center retrospective review from the VPS registry, invasive ventilation exposure and duration were independent risk factors for hospital-acquired VTE among critically ill children. Children undergoing invasive ventilation represent an important target population for risk-stratified thromboprophylaxis trials.

BACKGROUND:Pulmonary function tests (PFTs) have historically used race-specific prediction equations. The recent American Thoracic Society guidelines recommend the use of a race-neutral approach in prediction equations. There are limited studies centering the opinions of practicing pulmonologists on the use of race in spirometry. Provider opinion will impact adoption of the new guideline. The aim of this study was to ascertain the beliefs of academic pulmonary and critical care providers regarding the use of race as a variable in spirometry prediction equations.METHODS:We report data from 151 open-ended responses from a voluntary, nationwide survey (distributed by the Association of Pulmonary Critical Care Medicine Program Directors) of academic pulmonary and critical care providers regarding the use of race in PFT prediction equations. Responses were coded using inductive and deductive methods, and a thematic content analysis was conducted.RESULTS:There was a balanced distribution of opinions among respondents supporting, opposing, or being unsure about the incorporation of race in spirometry prediction equations. Responses demonstrated a wide array of understanding related to the concept and definition of race and its relationship to physiology.CONCLUSIONS:There was no consensus among providers regarding the use of race in spirometry prediction equations. Concepts of race having biologic implications persist among pulmonary providers and will likely affect the uptake of the Global Lung Function Initiative per the American Thoracic Society guidelines.

BACKGROUND:Training in mechanical ventilation is a key goal in critical care fellowship education. Web-based simulators offer a cost-effective and readily available alternative to traditional on-site simulators. However, it is unclear how effective they are as teaching tools. In this study, we evaluated the test scores of fellows who underwent mechanical ventilation training by using a web-based simulator compared with fellows who used an on-site simulator during a mechanical ventilation course.METHODS:This was a nonrandomized controlled trial conducted as part of a mechanical ventilation course that involved 70 first-year critical care fellows. The course was identical except for the simulation technology used. One group of instructors used a traditional on-site simulator, the ASL 5000 Lung Solution (n = 39). The second group was instructed in using a web-based simulator, VentSim (n = 31). Each fellow completed a pre-course test and a post-course test by using a validated, case-based ventilator waveform examination that consisted of 5 questions with a total possible score of 100. The primary outcome was a comparison of the mean scores on the posttest between the 2 groups. The study was designed as a non-inferiority trial with a predetermined margin of 10 points.RESULTS:There was no significant difference in the mean ± SD pretest scores between the web-based and the on-site groups (21.1 ± 12.6 and 26.9 ± 13.6 respectively; P = .11). The mean ± SD posttest scores were 45.6 ± 25.0 for the web-based simulator and 43.4 ± 16.5 for on-site simulator (mean difference 2.2; one-sided 95% CI –7.0 to ∞; Pnon-inferiority = .02 [non-inferiority confirmed]). Changes in mean ± SD scores (posttest – pretest) were 25.9 ± 20.9 for the web-based simulator and 16.5 ± 15.9 for the on-site simulator (mean difference 9.4, one-sided 95% CI 0.9 to ∞; Pnon-inferiority < .001 [non-inferiority confirmed]).CONCLUSIONS:In the education of first-year critical care fellows on mechanical ventilation waveform analysis, a web-based mechanical ventilation simulator was non-inferior to a traditional on-site mechanical ventilation simulator.