bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of Antimicrobial Stewardship Programs Using Therapeutic Drug Monitoring and Pharmacokinetics–Pharmacodynamics Protocols: A Cost-Benefit Review
Authors: Telles João Paulo , Morales Ronaldo , Yamada Carolina Hikari , Marins Tatiana A. , D'Amaro Juodinis Vanessa , Sztajnbok Jaques , Silva Moacyr , Bassetti Bil Randerson , Albiero James , Tuon Felipe Francisco 
Published: January 2023

Purpose:
Antimicrobial stewardship programs are important for reducing antimicrobial resistance because they can readjust antibiotic prescriptions to local guidelines, switch intravenous to oral administration, and reduce hospitalization times. Pharmacokinetics–pharmacodynamics (PK-PD) empirically based prescriptions and therapeutic drug monitoring (TDM) programs are essential for antimicrobial stewardship, but there is a need to fit protocols according to cost benefits. The cost benefits can be demonstrated by reducing toxicity and hospital stay, decreasing the amount of drug used per day, and preventing relapses in infection. Our aim was to review the data available on whether PK-PD empirically based prescriptions and TDM could improve the cost benefits of an antimicrobial stewardship program to decrease global hospital expenditures.

Methods:
A narrative review based on PubMed search with the relevant studies of vancomycin, aminoglycosides, beta-lactams, and voriconazole.

Results:
TDM protocols demonstrated important cost benefit for patients treated with vancomycin, aminoglycosides, and voriconazole mainly due to reduce toxicities and decreasing the hospital length of stay. In addition, PK-PD strategies that used infusion modifications to meropenem, piperacillin-tazobactam, ceftazidime, and cefepime, such as extended or continuous infusion, demonstrated important cost benefits, mainly due to reducing daily drug needs and lengths of hospital stays.

Conclusions:
TDM protocols and PK-PD empirically based prescriptions improve the cost-benefits and decrease the global hospital expenditures.
Automated Detection of Patient Harm: Implementation and Prospective Evaluation of a Real-Time Broad-Spectrum Surveillance Application in a Hospital With Limited Resources
Authors: Saikali Melody , Békarian Gariné , Khabouth José , Mourad Charbel , Saab Antoine 
Published: January 2023

Objectives
This study aimed to prospectively validate an application that automates the detection of broad categories of hospital adverse events (AEs) extracted from a basic hospital information system, and to efficiently mobilize resources to reduce the level of acquired patient harm.

Methods
Data were collected from an internally designed software, extracting results from 14 triggers indicative of patient harm, querying clinical and administrative databases including all inpatient admissions (n = 8760) from October 2019 to June 2020. Representative samples of the triggered cases were clinically validated using chart review by a consensus expert panel. The positive predictive value (PPV) of each trigger was evaluated, and the detection sensitivity of the surveillance system was estimated relative to incidence ranges in the literature.

Results
The system identified 394 AEs among 946 triggered cases, associated with 291 patients, yielding an overall PPV of 42%. Variability was observed among the trigger PPVs and among the estimated detection sensitivities across the harm categories, the highest being for the healthcare-associated infections. The median length of stay of patients with an AE showed to be significantly higher than the median for the overall patient population.

Conclusions
This application was able to identify AEs across a broad spectrum of harm categories, in a real-time manner, while reducing the use of resources required by other harm detection methods. Such a system could serve as a promising patient safety tool for AE surveillance, allowing for timely, targeted, and resource-efficient interventions, even for hospitals with limited resources.
Factors Associated With Household Work Limitations in Mexican Patients With Rheumatoid Arthritis
Authors: Ortiz-Haro Ana Belén , Contreras-Yáñez Irazú , Guaracha-Basáñez Guillermo , Pascual-Ramos Virginia 
Published: January 2023

Background
Little attention has been given to the impact of rheumatoid arthritis (RA) on domestic work, which remains the domain of women, particularly in the Latin American region. The study identified factors associated with RA-related household work limitations (HOWL) in Mexican for women with long-standing disease.

Methods
This cross-sectional study was performed between September 2020 and April 2022, in patients from the recent-onset RA cohort (initiated in 2004). At study entry, patients had standard rheumatic assessments and were administered the HOWL questionnaire, a survey to assess family responsibilities, household work characteristics, and the patient's economic dependency, and the family APGAR index to assess family function. Multiple logistic regression analysis identified variables associated with RA-related HOWL.

Results
Data from 114 female RA patients were analyzed. Overall, at cohort entry, patients were middle-aged (median, 37.5 years), with 12 years of education, and the minority (n = 42 [39.3%]) were married or living together. Patients were representative of typical patients with recent-onset disease and had significant disease activity. At study entry, the patients had 12 (7–16) years of disease duration, and their disease was under control. The median (interquartile range) HOLW-Q score was 0.67 (0–3.33), and 33 patients (28.9%) had RA-related HOWL. Receiving financial support for family living expenses, requiring assistance for activities of daily living, and DAS28 (Disease Activity Score, 28 joints evaluated) were associated with RA-related HOWL; meanwhile, a better Short-Form 36 score at disease onset was protective.

Conclusions
Domestic work in Mexican RA women might be impacted by social determinants, health-related quality of life at disease onset, and current disease activity status.
Insurance churn after adult traumatic injury: A national evaluation among a large private insurance database
Authors: Fu Sue J. , Arnow Katherine , Barreto Nicolas B. , Aouad Marion , Trickey Amber W. , Spain David A. , Morris Arden M. , Knowlton Lisa M. 
Published: January 2023

BACKGROUND
Traumatic injury leads to significant disability, with injured patients often requiring substantial health care resources to return to work and baseline health. Temporary disability or inability to work can result in changes or loss of employer-based private insurance coverage, which may significantly impact health care access and outcomes. Among privately insured patients, we hypothesized increased instability in insurance coverage for patients with higher severity of injury.

METHODS
Adults 18 years and older presenting to a hospital with traumatic injury were evaluated for insurance churn using Clinformatics Data Mart private-payer claims. Insurance churn was defined as cessation of enrollment in the patient's private health insurance plan. Using Injury Severity Score (ISS), we compared insurance churn over the year following injury between patients with mild (ISS, <9), moderate (ISS, 9–15), severe (ISS, 16–24), and very severe (ISS, >24) injuries. Kaplan-Meier analysis was used to compare time with insurance churn by ISS category. Flexible parametric regression was used to estimate hazard ratios for insurance churn.

RESULTS
Among 750,862 privately insured patients suffering from a traumatic injury, 50% experienced insurance churn within 1 year after injury. Compared with patients who remained on their insurance plan, patients who experienced insurance churn were younger and more likely male and non-White. The median time to insurance churn was 7.7 months for those with mild traumatic injury, 7.5 months for moderately or severely injured, and 7.1 months for the very severely injured. In multivariable analysis, increasing injury severity was associated with higher rates of insurance churn compared with mild injury, up to 14% increased risk for the very severely injured.

CONCLUSION
Increasing severity of traumatic injury is associated with higher levels of health coverage churn among the privately insured. Lack of continuous access to health services may prolong recovery and further aggravate the medical and social impact of significant traumatic injury.

LEVEL OF EVIDENCE
Economic and Value Based Evaluations; Level III.
Long-term health-related quality of life and independence among older survivors of serious injury
Authors: Pollack Lauren R. , Liao Joanna , Powelson Elisabeth B. , Gause Emma , Robinson Bryce R. H. , Vavilala Monica S. , Engelberg Ruth A. , Reed May J. , Arbabi Saman , O’Connell Kathleen M. 
Published: January 2023

BACKGROUND
Little is known about the recovery experiences of older trauma intensive care unit (TICU) survivors and the relationship between geriatric trauma care and long-term functional ability and health-related quality of life (HRQOL).

METHODS
We conducted a prospective cohort study of 218 patients (age, ≥65 years) admitted to a Level 1 regional trauma center TICU before versus after implementation of a geriatric care bundle with protocolized geriatrics consultations (Geri-T). Survivors or their proxies were interviewed approximately 1 year after hospitalization. Outcomes included the Katz Index of Independence in Activities of Daily Living (ADLs), Lawton Instrumental Activities of Daily Living (IADLs), and EQ-5D-5L HRQOL survey. Two investigator-developed questions regarding recovery experiences were included. Differences in outcomes among survivors admitted before versus after Geri-T were analyzed using multivariable linear regression. Responses to questions about recovery experiences were qualitatively assessed using content analysis.

RESULTS
We reached 67% (146/218) of hospital survivors or their proxies across both groups; 126 patients were still alive and completed the survey. Mean age was 76 (SD, 8), 36% were female, and 90% were independent with ADLs preinjury. At follow-up, independence with ADLs was 76% and IADLs was 63%. The mean EQ-5D-5L index score was 0.78 (SD, 0.18). Most patients (65%) reported having not returned to preinjury functional status. Neither functional ability or HRQOL differed significantly among patients admitted before versus after Geri-T. Content analysis of open-ended questions revealed themes of activity limitations, persistent pain, and cognitive dysfunction.

CONCLUSION
Nearly one-fifth of TICU survivors experienced loss of ADL function 1 year after injury, and most reported having not returned to preinjury functional status. Nonetheless, patient-reported HRQOL was comparable to age-adjusted norms. Geri-T was not associated with differences in HRQOL or functional ability. Survivors reported persistent difficulty with activities beyond those of daily living, pain, and cognition.

LEVEL OF EVIDENCE
Prognostic and Epidemiologic, Level III.
Accuracy of Surgeon and Patient Estimated Cost and Reimbursement for Common General Surgical Operations and Benefit of Centers for Medicare and Medicaid Services Price Transparency Rules
Authors: Frazier Grant D , Turrentine Florence E , Williams Michael D 
Published: January 2023

Introduction:
January 1, 2021, the Centers for Medicare and Medicaid Services (CMS) implemented a Hospital Price Transparency Rule. Consumerism as a means of reducing healthcare expenditures is predicated on informed consumers making discrete choices.

Methods:
For 10 months, immediately following an academic medical center preoperative clinic visit, patients and their surgeons were surveyed regarding their estimation of hospital cost and hospital reimbursement for the upcoming surgery. Responses were compared to average FY 2019 institutional Cost for Medicare patients undergoing a laparoscopic approach for each operation. We calculated the difference between actual reimbursements and costs with patients’ estimates and actual reimbursements and costs with surgeons’ estimates.

Results:
66 questionnaires were collected from patients who underwent laparoscopic: cholecystectomy (n=20), inguinal hernia (n=17), umbilical hernia repair (n=6), ventral hernia repair (n=6), incisional hernia (n=6), hiatal hernia repair (n=1), and lipoma or cyst excision (n=10). Patients’ estimates for hospital costs exceeded actual hospital costs by a median of $4502 and were less than hospital reimbursements by a median of $1834. Surgeon estimates for direct costs were $825 less than hospital direct costs and $1659 less than hospital reimbursement.

Conclusion:
Patients as well as their surgeons do not estimate healthcare costs or remuneration accurately and therefore will be ineffective change agents in reducing surgical spending based on price transparency without further education of both parties. Patients consistently overestimated surgical costs while surgeons consistently underestimated surgical costs and reimbursements. Better-informed surgeons and patients are likely necessary prerequisites for CMS Price Transparency Rules to be effective in reducing Medicare expenditures in surgery.
Identification of rare missense mutations in the glutamate ionotropic receptor AMPA type subunit genes in schizophrenia
Authors: Lin Ko-Huan , Hu Tsung-Ming , Hsu Shih-Hsin , Tsai Hsin-Yao , Cheng Min-Chih 
Published: January 2023

Objective
The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors significantly regulate the synaptic transmission and functions of various synaptic receptors. This study aimed to identify single nucleotide mutations in the glutamate receptor, ionotropic, AMPA type (GRIA) gene family, which is associated with schizophrenia.

Methods
The exon regions of four genes (GRIA1, GRIA2, GRIA3, and GRIA4) encoding glutamate ionotropic receptor AMPA type proteins were resequenced in 516 patients with schizophrenia. We analyzed the protein function of the identified rare mutants via immunoblotting.

Results
A total of 24 coding variants were detected in the GRIA gene family, including six missense mutations, 17 synonymous mutations, and one frameshift insertion. Notably, three ultra-rare missense mutations (GRIA1
p.V182A, GRIA2
p.P123Q, and GRIA4
p.Y491H) were not documented in the single nucleotide polymorphism database, gnomAD genomes, and 1517 healthy controls available from Taiwan BioBank. Immunoblotting revealed GRIA4
p.Y491H mutant with altered protein expressions in cultured cells compared with the wild type.

Conclusion
Our findings suggest that, in some patients affected by schizophrenia, the GRIA gene family harbors rare functional mutations, which support rare coding variants that could contribute to the genetic architecture of this illness. The in-vitro impacts of these rare pathological mutations on the pathophysiology of schizophrenia are worthy of future investigation.
Mediating effect of genome-wide DNA methylation on suicidal ideation induced by stressful events
Authors: De Luca Vincenzo , Al-Chalabi Nzaar , Chaudhary Zanib , Qian Jessica , Borlido Carol , Chintoh Araba , Gerretsen Philip , Graff Ariel , Remington Gary , Sanches Marcos , Battaglia Marco 
Published: January 2023

Objective
Schizophrenia is a debilitating disease that is associated with higher rates of death by unnatural causes including suicide. Exposure to stressful events is an important risk factor for suicidal ideation (SI); however, the mechanisms that link stress, SI, and suicide remain unclear. Epigenetic processes are involved in both vulnerability to suicidal behavior and stress. Therefore, we sought to study the relationship between epigenetic modifications and suicidal behavior and stress.

Methods
This pilot study was conducted on 39 patients diagnosed with schizophrenia (54% men and age 45.5 ± 12.7). We analyzed the effects of (a) stress exposure and (b) the mediation of DNA methylation [via an epigenetic wide association study (EWAS) of more than 450 000 CpG sites across the genome] on SI severity.

Results
The top CpG site mediating the effect of global stress exposure on SI was cg27660192 located in an intergenic region on chromosome 11, exerting a facilitating effect on worsening SI through DNA hypomethylation.

Conclusion
These preliminary results indicate that DNA methylation in peripheral tissues can shed light on the complex relationship between stress and SI in schizophrenia.
Molecular Epidemiology of Antimicrobial Resistance in Central Africa: A Systematic Review
Authors: DIKOUMBA Annicet-Clotaire , ONANGA Richard , MANGOUKA Laurette G. , BOUNDENGA Larson , NGOUNGOU Edgard-Brice , GODREUIL Sylvain 
Published: January 2023

Background: In Central Africa, it is difficult to fight against antibiotic resistance, because of a lack of data and information on bacterial resistance, due to the low number of studies carried out in the field. To fill this gap, we carried out a systematic review of the various studies, and devise a molecular epidemiology of antimicrobial resistance from humans, animals and the environmental samples.Method: A systematic search of all publications from 2005 to 2020 on bacterial resistance in Central Africa was performed on Pubmed, Google scholar and African journals online. All circulating resistance genes, prevalence and genetic carriers of these resistances were collected. The study area was limited to the 9 countries of Central Africa. Results: Five hundred seventeen studies were identified through a literature search, and sixty studies carried out in 8 countries were included. Among all articles included, 43 articles were from human. Our study revealed not only the circulation of beta-lactamase and carbapenemase genes, but also several other types of resistance genes. To finish, we noticed that some studies reported mobile genetic elements such as integrons, transposons, plasmids, or chromosomes.Conclusion: The scarcity of data poses difficulties in the implementation of effective strategies in the fight against antibiotic resistance, which requires a health policy in a "One Health" approach.
A genomic blueprint of the healthy human oesophageal microbiome
Authors: Gilroy Rachel , Adam Mina E. , Kumar Bhaskar , Pallen Mark J. 
Published: January 2023

Background. The oesophageal microbiome is thought to contribute to the pathogenesis of oesophageal cancer. However, investigations using culture and molecular barcodes have provided only a low-resolution view of this important microbial community. We therefore exploited culturomics and metagenomic binning to generate a catalogue of reference genomes from the healthy human oesophageal microbiome, alongside a comparison set from saliva.
Results. Twenty-two distinct colonial morphotypes from healthy oesophageal samples were genome-sequenced. These fell into twelve species clusters, eleven of which represented previously defined species. Two isolates belonged to a novel species, which we have named Rothia gullae. We performed metagenomic binning of reads generated from UK samples from this study alongside reads generated from Australian samples in a recent study. Metagenomic binning generated 136 medium or high-quality metagenome-assembled genomes (MAGs). MAGs were assigned to 56 species clusters, eight representing novel Candidatus species, which we have named Ca.Granulicatella gullae, Ca. Streptococcus gullae, Ca. Nanosynbacter quadramensis, Ca. Nanosynbacter gullae, Ca.Nanosynbacter colneyensis, Ca. Nanosynbacter norwichensis, Ca. Nanosynococcus oralis and Ca. Haemophilus gullae. Five of these novel species belong to the recently described phylum Patescibacteria. Although members of the Patescibacteria are known to inhabit the oral cavity, this is the first report of their presence in the oesophagus. Eighteen of the metagenomic species were, until recently, identified only by hard-to-remember alphanumeric placeholder designations. Here we illustrate the utility of a set of recently published arbitrary Latinate species names in providing user-friendly taxonomic labels for microbiome analyses.
Our non-redundant species catalogue contained 63 species derived from cultured isolates or MAGs. Mapping revealed that these species account for around half of the sequences in the oesophageal and saliva metagenomes. Although no species was present in all oesophageal samples, 60 species occurred in at least one oesophageal metagenome from either study, with 50 identified in both cohorts.
Conclusions. Recovery of genomes and discovery of new species represents an important step forward in our understanding of the oesophageal microbiome. The genes and genomes that we have released into the public domain will provide a base line for future comparative, mechanistic and intervention studies
Content Analysis of YouTube Videos Related to E-cigarettes and COVID-19
Authors: Lee Juhan , Murthy Dhiraj , Kong Grace 
Published: January 2023

ABSTRACTINTRODUCTIONE-cigarettes are frequently promoted on social media and portrayed in ways that are attractive to youth. While COVID-19 pandemic significantly affected people’s lives, less known is how the pandemic influenced e-cigarette-related marketing and information on social media. This study identifies how e-cigarettes are portrayed during the COVID-19 pandemic on YouTube, one of the most popular social media platforms.METHODSWe searched for combinations of search terms related to e-cigarettes (i.e., “electronic cigarette”, “e-cigarette”, “e-cig”, “vape” and “vaping”) and COVID-19 (i.e., “corona”, “COVID”, “lockdown” and “pandemic”). To be included in the analysis, the video must be: uploaded after February 1, 2020, in English, related to e-cigarettes and COVID-19 and less than 30 minutes in length. We assessed video themes related to e-cigarettes and COVID-19, uploader characteristics, and featured e-cigarette products.RESULTSWe examined N=307 videos and found that N=220 (73.6%) were related to the health effects of e-cigarette use on COVID-19, followed by videos of how COVID-19 affects e-cigarette access/sales (N=40, 12.9%), and face mask-related videos (N=16, 5.1%) which included content regarding masks and e-cigarette use. Instructional videos on how to modify e-cigarettes to use with masks had the highest number of likes (Median=23; IQR=32) and comments (Median=10; IQR=7).CONCLUSIONSThis study identified various e-cigarette contents on YouTube during the COVID-19 pandemic. Our findings support the need for continuous surveillance on novel vaping-related content in reaction to policies and events such as the global pandemic on social media is needed.