Factors Underlying Vaccine Hesitancy and Their Mitigations in Saudi Arabia: Protocol for a Systematic Review.

BACKGROUND: Vaccine hesitancy is a growing concern in Saudi Arabia, impacting even well-educated parents. The decision-making process involves various factors such as accessibility, trustworthy information, and the influence of social networks, reflecting a complex interplay of emotional, cultural, social, spiritual, and political dimensions. OBJECTIVE: This review seeks to evaluate the prevalence and trends of vaccine hesitancy, identify contributing factors, and explore potential solutions to enhance immunization rates. This review aligns with global concerns, as the World Health Organization has identified vaccine hesitancy as a top global health threat. METHODS: Our systematic review will follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and PICOS (Population, Intervention, Comparison, Outcomes, and Study) criteria for comprehensive assessment. We will conduct a thorough search across various databases, encompassing a wide range of vaccines, and pay special attention to vaccination campaigns and refusals. Inclusion criteria involve descriptive, observational, and analytical studies focusing on factors influencing vaccine acceptance or hesitancy. The study will use the Crowe Critical Appraisal Tool for quality assessment and perform a narrative synthesis to summarize findings thematically. RESULTS: This systematic review is expected to unveil the prevalence and trends of vaccine hesitancy in diverse populations in Saudi Arabia, shedding light on cultural, religious, and social factors contributing to hesitancy. It aims to assess the effectiveness of implemented strategies, enable regional and global comparisons, and provide implications for tailored vaccination policies. Additionally, the review may pinpoint research gaps, guiding future investigations to address and mitigate vaccine hesitancy effectively. CONCLUSIONS: The findings are expected to have direct policy implications and guide interventions to strengthen vaccination programs and improve public health outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54680.

Mild airways obstruction: spirometric diagnostic pitfalls and solutions.

PURPOSE OF REVIEW: Spirometry is a validated tool in the diagnosis of obstructive airways disease. However, it may be insufficiently sensitive in detecting airflow limitation in the small airways. This review highlights common clinical scenarios wherein airflow limitation may be missed or overlooked. RECENT FINDINGS: This article covers recent literature on the interpretation of lung function test, focusing on detection of mild obstructive airways disease. It also sheds light on the contextual difficulties of defining mild airflow limitation on spirometry. SUMMARY: We highlight the consensus definition of mild obstructive airways disease and emphasize that this definition does not necessarily mean mild in certain disease-specific contexts. Several spirometric findings outside of a reduced forced expiratory volume in one second/forced vital capacity ratio should raise suspicion of mild obstruction.

Investigation of natural compounds as methyltransferase inhibitors against dengue virus: an in silico approach.

The global challenge posed by Dengue virus (DENV) infection persists, exacerbated by the absence of specific antiviral therapies. The viral methyltransferase (MTase) enzyme, crucial for viral RNA methylation and immune system evasion, has emerged as a promising drug target for combating Dengue fever. In this study, a comprehensive exploration of natural compounds derived from the COCONUT database was conducted, selecting 224 compounds based on their structural similarity to the native substrate of the MTase enzyme, S-adenosyl-L-methionine (SAM). Employing virtual screening techniques, four natural compounds (CNP0307160, CNP0082902, CNP0449158, and CNP0296775) with acceptable docking scores were selected for further re-docking after geometry optimization by the DFT method. Re-docking analyses unveiled significant interactions, including hydrogen bonds and hydrophobic interactions, between these selected ligands and the MTase protein. To gain deeper insights into the dynamic stability of these complexes, we conducted molecular dynamics simulations which showed lower RMSD values for CNP0307160, CNP0082902, and CNP0296775 when compared to the reference molecule. Furthermore, we assessed the structural and dynamic stability of the protein-ligand complexes through free binding energy calculations and Principal Component Analysis (PCA) of the simulation trajectories. In these analyses, the CNP0296775 compound exhibited promising results compared to the other three compounds. The cumulative findings of these investigations underscore the potential of CNP0296775 as a strong inhibitor of DENV MTase, thus offering a promising starting point for its further experimental validation and optimization.Communicated by Ramaswamy H. Sarma.

Role of Three-Dimensional Printing in Treatment Planning for Orthognathic Surgery: A Systematic Review.

Three-dimensional (3D) printing refers to a wide range of additive manufacturing processes that enable the construction of structures and models. It has been rapidly adopted for a variety of surgical applications, including the printing of patient-specific anatomical models, implants and prostheses, external fixators and splints, as well as surgical instrumentation and cutting guides. In comparison to traditional methods, 3D-printed models and surgical guides offer a deeper understanding of intricate maxillofacial structures and spatial relationships. This review article examines the utilization of 3D printing in orthognathic surgery, particularly in the context of treatment planning. It discusses how 3D printing has revolutionized this sector by providing enhanced visualization, precise surgical planning, reduction in operating time, and improved patient communication. Various databases, including PubMed, Google Scholar, ScienceDirect, and Medline, were searched with relevant keywords. A total of 410 articles were retrieved, of which 71 were included in this study. This article concludes that the utilization of 3D printing in the treatment planning of orthognathic surgery offers a wide range of advantages, such as increased patient satisfaction and improved functional and aesthetic outcomes.

The Psychological Impact of Vitiligo in Saudi Arabia.

Background Vitiligo, the most common pigment disorder, impacts 0.5-2% of the global population, often causing psychological distress due to appearance changes and potential discrimination. Existing data on depressive symptoms and quality of life (QoL) effects in Saudi Arabian vitiligo patients are limited and inconsistent. Hence, this multi-center investigation was conducted in Saudi Arabia to determine the prevalence of depressive symptoms and quality of life (QoL) impairment in patients with vitiligo and to identify factors linked to increased psychological distress in this population. Methods We conducted a multi-center cross-sectional study in Saudi Arabia, employing two validated Arabic questionnaires, the Dermatology Life Quality Index (DLQI) and the Patient Health Questionnaire-9 items (PHQ-9), along with demographic information. Appropriate statistical analyses were performed. Results In total, 204 patients completed the survey. The median DLQI was 4 (range: 25), while the median PHQ-9 was 5 (range: 27). Factors associated with worse QoL included an early age of onset (under 18 years) and a disease duration exceeding five years. Conversely, only disease duration correlated with worse PHQ-9 scores. Vitiligo lesions on the lower extremities, feet, and genitalia were linked to poorer DLQI scores, while only genitalia were associated with worse PHQ-9 scores. We recommend further social awareness campaigns emphasizing the role of supportive families to improve the well-being of vitiligo patients.

Nanotechnology-Based Drug Delivery Approaches of Mangiferin: Promises, Reality and Challenges in Cancer Chemotherapy.

Mangiferin (MGF), a xanthone derived from Mangifera indica L., initially employed as a nutraceutical, is now being explored extensively for its anticancer potential. Scientists across the globe have explored this bioactive for managing a variety of cancers using validated in vitro and in vivo models. The in vitro anticancer potential of this biomolecule on well-established breast cancer cell lines such as MDA-MB-23, BEAS-2B cells and MCF-7 is closer to many approved synthetic anticancer agents. However, the solubility and bioavailability of this xanthone are the main challenges, and its oral bioavailability is reported to be less than 2%, and its aqueous solubility is also 0.111 mg/mL. Nano-drug delivery systems have attempted to deliver the drugs at the desired site at a desired rate in desired amounts. Many researchers have explored various nanotechnology-based approaches to provide effective and safe delivery of mangiferin for cancer therapy. Nanoparticles were used as carriers to encapsulate mangiferin, protecting it from degradation and facilitating its delivery to cancer cells. They have attempted to enhance the bioavailability, safety and efficacy of this very bioactive using drug delivery approaches. The present review focuses on the origin and structure elucidation of mangiferin and its derivatives and the benefits of this bioactive. The review also offers insight into the delivery-related challenges of mangiferin and its applications in nanosized forms against cancer. The use of a relatively new deep-learning approach to solve the pharmacokinetic issues of this bioactive has also been discussed. The review also critically analyzes the future hope for mangiferin as a therapeutic agent for cancer management.

Repurposing Anti-Dengue Compounds against Monkeypox Virus Targeting Core Cysteine Protease.

The monkeypox virus (MPXV) is an enveloped, double-stranded DNA virus belonging to the genus Orthopox viruses. In recent years, the virus has spread to countries where it was previously unknown, turning it into a worldwide emergency for public health. This study employs a structural-based drug design approach to identify potential inhibitors for the core cysteine proteinase of MPXV. During the simulations, the study identified two potential inhibitors, compound CHEMBL32926 and compound CHEMBL4861364, demonstrating strong binding affinities and drug-like properties. Their docking scores with the target protein were -10.7 and -10.9 kcal/mol, respectively. This study used ensemble-based protein-ligand docking to account for the binding site conformation variability. By examining how the identified inhibitors interact with the protein, this research sheds light on the workings of the inhibitors' mechanisms of action. Molecular dynamic simulations of protein-ligand complexes showed fluctuations from the initial docked pose, but they confirmed their binding throughout the simulation. The MMGBSA binding free energy calculations for CHEMBL32926 showed a binding free energy range of (-9.25 to -9.65) kcal/mol, while CHEMBL4861364 exhibited a range of (-41.66 to -31.47) kcal/mol. Later, analogues were searched for these compounds with 70% similarity criteria, and their IC50 was predicted using pre-trained machine learning models. This resulted in identifying two similar compounds for each hit with comparable binding affinity for cysteine proteinase. This study's structure-based drug design approach provides a promising strategy for identifying new drugs for treating MPXV infections.

Clinical Characteristics and Treatment Strategies for Group B Streptococcus (GBS) Infection in Pediatrics: A Systematic Review.

Background and Objectives: Group B streptococcus (GBS) is the leading cause of infections in neonates with high fatality rates. GBS is caused by the streptococcus bacterium known as streptococcus agalactiae, which is highly contagious and can be transmitted from pregnant women to infants. GBS infection can occur as an early onset or late-onset infection and has different treatment strategies. Antibiotics are effective in treating GBS infections at early stages. The aim of this systematic review was to summarize the clinical characteristics and treatment strategies for GBS, with a focus on antibiotics. Material and Methods: The findings of this review were reported in accordance with the PRISMA 2020 guidelines and a flow diagram of the study selection process, a summary of the included studies, a description of the study characteristics, a summary of the results, a discussion of the implications of the findings, and a conclusion are included. Overall, the authors followed a rigorous methodology to ensure that this review is comprehensive and inclusive of relevant studies on GBS infection and its treatment. Results: Overall, 940 studies were reviewed and only the most relevant 22 studies were included in the systematic review. This review describes the characteristics of patients in different studies related to early onset GBS disease and presents various treatment strategies and outcomes for GBS infection in pediatrics. The studies suggest that preventive measures, risk-based intrapartum antibiotic prophylaxis, and maternal vaccination can significantly reduce the burden of GBS disease, but late-onset GBS disease remains a concern, and more strategies are required to decrease its rate. Improvement is needed in the management of the risk factors of GBS. A conjugate vaccine with a serotype (Ia, Ib, II, III, and V) has been proven effective in the prevention of GBS in neonates. Moreover, penicillin is an important core antibiotic for treating early onset GBS (EOD). Conclusions: This systematic review summarizes the treatment comparison for GBS infections in neonates, with a primary focus on antibiotics. IAP (intrapartum antibiotic prophylaxis) according to guidelines, antenatal screening, and the development of a conjugate vaccine may be effective and could lower the incidence of the disease.

Global Advancement in Pharmacy Services for Mental Health: A Review for Evidence-Based Practices.

The symptoms of psychiatric infirmities have variability, and selected drug regimens for mental illness are comparatively complex and individualized; therefore, pharmacy services vary with respect to patients, diseases, healthcare settings, community structures, and countries. Clinical pharmacy services for mental health (MH) are continuously being upgraded. A structured search of the literature was performed in the Cochrane, PubMed (Medline), PsycINFO, Google scholar, Scopus, Science Direct, and Springer Links databases. The title and abstract of each retrieved article were evaluated for relevance. To remove uncertainty and ambiguity, the full-text articles were retrieved and examined for relevance. The articles were further assessed on the basis of inclusion and exclusion criteria. Narrative synthesis was performed, creating new categories and relevant subcategories and further subsections. The articles and the results were assessed for quality and bias. Pharmacists have a range of expertise in psychiatric care. The services can be classified as conventional, extended, and advanced pharmacy services. Conventional services include the quality use of medicines in healthcare settings and medication support services in communities that ensure medication adherence. Pharmacists perform extended roles in collaborative medication therapy management, multidisciplinary community mental health teams, collaborative care, patient education, home medication review, hospital-to-home transit, and screening services. In the USA, the role of pharmacists was advanced by prescribing as collaborative and interim prescribers. Australia launched an accredited program for psychiatric first-aid pharmacists. Pharmacists can provide mental care to rural populations using health technology. The role of pharmacists in MH is appreciated either independently or as a team member. Patients and healthcare providers rank the services of pharmacists in MH highly. Still, there is a margin for improvement in the training of pharmacists. Pharmacists cannot provide sufficient time to their patients. Public awareness about the role of pharmacists in MH needs more attention. Moreover, the training of psychiatric pharmacists should be standardized around the world.

QcrB inhibition as a potential approach for the treatment of tuberculosis: A review of recent developments, patents, and future directions.

The unmet medical need for drug-resistant tuberculosis (DRTB) is a significant concern. Accordingly, identifying new drug targets for tuberculosis (TB) treatment and developing new therapies based on these drug targets is one of the strategies to tackle DRTB. QcrB is an innovative drug target to create treatments for DRTB. This article highlights QcrB inhibitors and their therapeutic compositions for treating TB. The literature for this article was gathered from PubMed and free patent databases utilizing different keywords related to QcrB inhibitor-based inventions. The data was collected from the conceptualization of telacebec (2010) QcrB to December 2022. A little interesting and encouraging research has been performed on QcrB inhibitors. Telacebec and TB47 are established QcrB inhibitors in the clinical trial. The inventive QcrB inhibitor-based drug combinations can potentially handle DRTB and reduce the TB therapy duration. The authors anticipate great opportunities in fostering QcrB inhibitor-based patentable pharmaceutical inventions against TB. Drug repurposing can be a promising strategy to get safe and effective QcrB inhibitors. However, developing drug resistance, drug tolerance, and selectivity of QcrB inhibitors for Mtb will be the main challenges in developing effective QcrB inhibitors. In conclusion, QcrB is a promising drug target for developing effective treatments for active, latent, and drug-resistant TB. Many inventive and patentable combinations and compositions of QcrB inhibitors with other anti-TB drugs are anticipated as future treatments for TB.

Computer-assisted discovery of safe and effective DprE1/ aaRSs Inhibitors against TB utilizing Drug Repurposing approach.

BACKGROUND: The emergence of various drug-resistant strains of Mycobacterium tuberculosis compelled medicinal chemists to expedite the discovery of novel, safer alternatives to present regimens. Decaprenylphosphoryl-ß-d-ribose 2'-epimerase (DprE1), an essential component of arabinogalactan biosynthesis, has been considered a novel target for developing new inhibitors against Tuberculosis. We aimed to discover DprE1 inhibitors utilizing the drug repurposing approach. METHODS: A structure-based virtual screening of FDA and world-approved drugs database was carried out, and initially, 30 molecules were selected based on their binding affinity. These compounds were further analyzed by molecular docking with extra-precision mode, MMGBSA binding free energy estimation, and prediction of ADMET profile. RESULTS: Based on the docking results and MMGBSA energy values- ZINC000006716957, ZINC000011677911, and ZINC000022448696 were identified to be the top three hit molecules with good binding interactions inside the active site of DprE1. These hit molecules were subjected to molecular dynamics (MD) simulation for a period of 100 ns to study the dynamic nature of the binding complex. MD results were in accordance with molecular docking and MMGBSA analysis showing protein-ligand contacts with key amino acid residues of DprE1. CONCLUSION: Based on their stability throughout the 100 ns simulation, ZINC000011677911 was the best in silico hit with an already known safety profile. This molecule could lead to future optimization and development of new DprE1 inhibitors.

Novel Therapeutic Approach in PEGylated Chitosan Nanoparticles of Apigenin for the Treatment of Cancer via Oral Nanomedicine.

The goal of this study was to optimize and formulate apigenin (APG)-loaded pegylated chitosan nanoparticles (PEGylated-CNPs) via ionic gelation techniques using the Box-Behnken design (BBD). Three individual variables, X1(chitosan: TPP concentration), X2 (PEG-400 concentration), and X3 (sonication time), were investigated for their influence on response variables (Y1-particle size (PS); Y2-drug entrapment efficiency (DEE); and Y3-zeta potential (ZP). The optimized formula of APG-PEGylated CNPs was picked from the statistical design and was then examined for physical, morphological, release characterization, anti-oxidant, and anti-tumor potential. The average PS, PDI, %DEE, and ZP were found to be 139.63 ± 5.67 nm, 0.296 ± 0.014, 79.55 ± 3.12%, and 24.68 ± 1.84 mV, respectively. The optimized APG formulation was chosen and reformulated based on the desirability function. Results of the observed and predicted values of responses through the BBD process were found to be nearly identical. The resulting APG-PEGylated CNPs were spherical and smooth, according to surface morphology studies. The release study revealed that PEGylated-CNPs exhibited biphasic release patterns distinguished by an initial burst release of APG only at early phases accompanied by a delayed release near 24 h. Furthermore, APG-PEGylated CNPs demonstrated statistically increased antioxidant activities and cytotoxicity against MCF-7 cells compared to pure APG. Based on the findings, it is possible to conclude that BBD was efficient in optimizing the PEGylated CNPs formulation and recognizing the impacts of formulation variables. In conclusion, the developed formulation has a significant potential for anticancer therapy.

Nanoplatform for the Delivery of Topotecan in the Cancer Milieu: An Appraisal of its Therapeutic Efficacy.

Chemotherapy has been the predominant treatment modality for cancer patients, but its overall performance is still modest. Difficulty in penetration of tumor tissues, a toxic profile in high doses, multidrug resistance in an array of tumor types, and the differential architecture of tumor cells as they grow are some of the bottlenecks associated with the clinical usage of chemotherapeutics. Recent advances in tumor biology understanding and the emergence of novel targeted drug delivery tools leveraging various nanosystems offer hope for developing effective cancer treatments. Topotecan is a topoisomerase I inhibitor that stabilizes the transient TOPO I-DNA cleavable complex, leading to single-stranded breaks in DNA. Due to its novel mechanism of action, TOPO is reported to be active against various carcinomas, namely small cell lung cancer, cervical cancer, breast cancer, and ovarian cancer. Issues of cross-resistance with numerous drugs, rapid conversion to its inactive form in biological systems, appended adverse effects, and higher water solubility limit its therapeutic efficacy in clinical settings. Topotecan nanoformulations offer several benefits for enhancing the therapeutic action of this significant class of chemotherapeutics. The likelihood that the target cancer cells will be exposed to the chemotherapeutic drug while in the drug-sensitive s-phase is increased due to the slow and sustained release of the chemotherapeutic, which could provide for a sustained duration of exposure of the target cancer cells to the bioavailable drug and result in the desired therapeutic outcome. This article explores nanoenabled active and passive targeting strategies and combinatorial therapy employing topotecan to ameliorate various cancers, along with a glimpse of the clinical studies utilizing the said molecule.

Risk Factors Associated with Mortality Among Patients with Novel Coronavirus Disease (COVID-19) in Africa.

BACKGROUND: The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in China and later spread rapidly to other parts of the world, including Africa. Africa was projected to be devastated by COVID-19. There is currently limited data regarding regional predictors of mortality among patients with COVID-19. This study aimed to evaluate the independent risk factors associated with mortality among patients with COVID-19 in Africa. METHODS: A total of 1028 confirmed cases of COVID-19 from Africa with definite survival outcomes were identified retrospectively from an open-access individual-level worldwide COVID-19 database. The live version of the dataset is available at https://github.com/beoutbreakprepared/nCoV2019 . Multivariable logistic regression was conducted to determine the risk factors that independently predict mortality among patients with COVID-19 in Africa. RESULTS: Of the 1028 cases included in study, 432 (42.0%) were females with a median (interquartile range, IQR) age of 50 (24) years. Older age (adjusted odds ratio {aOR} 1.06; [95% confidence intervals {95% CI}, 1.04-1.08]), presence of chronic disease (aOR 9.63; [95% CI, 3.84-24.15]), travel history (aOR 2.44; [95% CI, 1.26-4.72]), as well as locations of Central Africa (aOR 0.14; [95% CI, 0.03-0.72]) and West Africa (aOR 0.12; [95% CI, 0.04-0.32]) were identified as the independent risk factors significantly associated with increased mortality among the patients with COVID-19. CONCLUSIONS: The COVID-19 pandemic is evolving gradually in Africa. Among patients with COVID-19 in Africa, older age, presence of chronic disease, travel history, and the locations of Central Africa and West Africa were associated with increased mortality. A regional response should prioritize strategies that will protect these populations. Also, conducting a further in-depth study could provide more insights into additional factors predictive of mortality in COVID-19 patients.

Pharmacological appraisal of ligustrazine based cyclohexanone analogs as inhibitors of inflammatory markers.

The targeting of pro-inflammatory enzymes becomes a therapeutic intervention when acute inflammation is proliferating in pathological conditions. This research is intended to carry out an evaluation of inhibiting and inducing enzymes with inflammatory associations with 28 cyclohexanone analogs based on the ligustrazine. Tests were undertaken with inhibitor screening assay kits using a range of synthetic compounds to investigate how they could inhibit the activity of cyclooxygenase (COX) enzymes, secretory phospholipase A2 (sPLA2), and lipoxygenase (LOX) enzyme. Significant and similar inhibitory activities against sPLA2 with were noted with synthetic compounds which included 1f and 1g (IC50 = 2.2 µM). The optimal inhibitory activity regarding LOX enzyme was shown with compounds 1d (IC50 = 8.1 µM) and 1e (IC50 = 7.5 µM). Additionally, the compounds 1b, 1d, 1e, 2n, and 2o were shown to be significant inhibitors of COX-1 activity with IC50 values 0.09 to 0.7 µM. The outcomes of assays for COX inhibition demonstrated that the same compounds had a further strong inhibitive influence on the COX-2 enzyme, and certain compounds such as 1d, 1e, and 2n demonstrated enhanced potency compared with positive controls.

Impact of Healthcare Expenditures on Healthcare Outcomes in the Middle East and North Africa (MENA) Region: A Cross-Country Comparison, 1995-2015.

The association between healthcare expenditures and outcomes, mainly mortality and life expectancy, is complex. The real explanation for this association is not clear, especially in the Middle East and North Africa (MENA) region. This study assesses the impact of health expenditures on improving healthcare systems and health status and finds a relationship between health expenditures and health outcomes across different region. Annual time series data on healthcare spending and outcomes from 1995 to 2015 were used for MENA region in comparison to developed and developing countries. Health expenditure was adjusted by the consumer price index equation to the 2015 US dollar eliminate the impact of inflation on our results. For many countries, spending on healthcare continues to rise, Among MENA countries, we found that the United Arab Emirates and Kuwait spent more per capita on health, $1,711 and $1,420, respectively, than any other countries in the region. Although this study demonstrated a relationship between total healthcare expenditure and outcomes, some countries spend more on healthcare but have shorter life expectancy. In most countries, efficient and effective utilization of healthcare resources is the key strategy for improving health outcomes in any country. The lack of a positive correlation between healthcare spending and life expectancy may indicate that health resources are not allocated effectively. In those cases, increasing health spending does not guarantee that there is any kind of improvement in healthcare.

Phenotyping and outcomes of hospitalized COPD patients using rapid molecular diagnostics on sputum samples.

BACKGROUND: Etiologies of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are heterogeneous. We phenotyped severe AECOPD based on molecular pathogen detection of sputum samples collected at hospitalization of COPD patients and determined their outcomes. METHODS: We phenotyped 72 sputum samples of COPD patients who were hospitalized with a primary diagnosis of AECOPD using a molecular array that detected common bacterial and viral respiratory pathogens. Based on these results, the patients were classified into positive or negative pathogen groups. The pathogen-positive group was further divided into virus or bacteria subgroups. Admission day 1 blood samples were assayed for N-terminal prohormone brain natriuretic peptide, CRP, and complete blood counts. RESULTS: A total of 52 patients had a positive result on the array, while 20 patients had no pathogens detected. The most common bacterial pathogen detected was Haemophilus influenzae and the most common virus was rhinovirus. The pathogen-negative group had the worse outcomes with longer hospital stays (median 6.5 vs 5 days for bacteria-positive group, P=0.02) and a trend toward increased 1-year mortality (P=0.052). The bacteria-positive group had the best prognosis, whereas the virus-positive group had outcomes somewhere in between the bacteria-positive and pathogen-negative groups. CONCLUSION: Molecular diagnostics on sputum can rapidly phenotype serious AECOPD into bacteria-, virus-, or pathogen-negative groups. The bacteria-positive group appears to have the best prognosis, while pathogen-negative group has the worst. These data suggest that AECOPD is a heterogeneous event and that accurate phenotyping of AECOPD may lead to novel management strategies that are personalized and more precise.

Sputum Microbiome Is Associated with 1-Year Mortality after Chronic Obstructive Pulmonary Disease Hospitalizations.

Rationale: Lung dysbiosis promotes airway inflammation and decreased local immunity, potentially playing a role in the pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Objectives: We sought to determine the relationship between sputum microbiome at the time of AECOPD hospitalization and 1-year mortality in a COPD cohort. Methods: We used sputum samples from 102 patients hospitalized because of AECOPD. All subjects were followed for 1 year after discharge. The microbiome profile was assessed through sequencing of 16S rRNA gene. Microbiome analyses were performed according to 1-year mortality status. To investigate the effect of α-diversity measures and taxon features on time to death, we applied Cox proportional hazards regression models and obtained hazard ratios (HRs) associated with these variables. Measurements and Main Results: We observed significantly lower values of α-diversity (richness, Shannon index, evenness, and Faith's Phylogenetic Diversity) among nonsurvivors (n = 19, 18.6%) than survivors (n = 83, 81.4%). ß-Diversity analysis also demonstrated significant differences between both groups (adjusted permutational multivariate ANOVA, P = 0.010). The survivors had a higher relative abundance of Veillonella; in contrast, nonsurvivors had a higher abundance of Staphylococcus. The adjusted HRs for 1-year mortality increased significantly with decreasing α-diversity. We also observed lower survival among patients in whom sputum samples were negative for Veillonella (HR, 13.5; 95% confidence interval, 4.2-43.9; P < 0.001) or positive for Staphylococcus (HR, 7.3; 95% confidence interval, 1.6-33.2; P = 0.01). Conclusions: The microbiome profile of sputum in AECOPD is associated with 1-year mortality and may be used to identify subjects with a poor prognosis at the time of hospitalization.