bluuebunny/crossref_metadata_2025 huggingface dataset:
Queensland Pediatric Sepsis Breakthrough Collaborative: Multicenter Observational Study to Evaluate the Implementation of a Pediatric Sepsis Pathway Within the Emergency Department
Authors: Harley Amanda , Lister Paula , Gilholm Patricia , Rice Michael , Venkatesh Bala , Johnston Amy N.B. , Massey Debbie , Irwin Adam , Gibbons Kristen , Schlapbach Luregn J. ,   on behalf of the Queensland Statewide Sepsis Collaborative
Published: November 2021

OBJECTIVES:

To evaluate the implementation of a pediatric sepsis pathway in the emergency department as part of a statewide quality improvement initiative in Queensland, Australia.

DESIGN:

Multicenter observational prospective cohort study.

SETTING:

Twelve emergency departments in Queensland, Australia.

PATIENTS:

Children less than 18 years evaluated for sepsis in the emergency department. Patients with signs of shock, nonshocked patients with signs of organ dysfunction, and patients without organ dysfunction were assessed.

INTERVENTIONS:

Introduction of a pediatric sepsis pathway.

MEASUREMENTS AND MAIN RESULTS:

Process measures included compliance with and timeliness of the sepsis bundle, and bundle components. Process and outcome measures of children admitted to the ICU with sepsis were compared with a baseline cohort. Five-hundred twenty-three children were treated for sepsis including 291 with suspected sepsis without organ dysfunction, 86 with sepsis-associated organ dysfunction, and 146 with septic shock. Twenty-four (5%) were admitted to ICU, and three (1%) died. The median time from sepsis recognition to bundle commencement for children with septic shock was 56 minutes (interquartile range, 36–99 min) and 47 minutes (interquartile range, 34–76 min) for children with sepsis-associated organ dysfunction without shock; 30% (n = 44) and 40% (n = 34), respectively, received the bundle within the target timeframe. In comparison with the baseline ICU cohort, bundle compliance improved from 27% (n = 45) to 58% (n = 14) within 60 minutes of recognition and from 47% (n = 78/167) to 75% (n = 18) within 180 minutes of recognition (p < 0.05).

CONCLUSIONS:

Our findings on the introduction of protocolized care in a large and diverse state demonstrate ongoing variability in sepsis bundle compliance. Although bundle compliance improved compared with a baseline cohort, continued efforts are required to ensure guideline targets and sustainability are achieved.
Elucidation of obstructive sleep apnoea related blood pressure surge using a novel continuous beat-to-beat blood pressure monitoring system
Authors: Kwon Younghoon , Baruch Martin , Stafford Patrick L. , Bonner Heather , Cho Yeilim , Mazimba Sula , Logan Jeongok G. , Shimbo Daichi , Park Sung-Ha , Lin Gen-Min , Azarbarzin Ali , Calhoun David A. , Berry Richard , Carey Robert M.
Published: November 2021

Background:

Obstructive sleep apnoea (OSA) episode related blood pressure (BP) surge may mediate the association of OSA with cardiovascular disease. However, BP is not measured during a clinical sleep study.

Method:

We tested the feasibility of incorporating the Caretaker physiological monitor, which utilizes a novel continuous beat-to-beat (b-b) BP monitoring technology, into polysomnography (PSG) and aimed to characterize BP surges related to obstructive respiratory events. B-b BP was concurrently collected and merged with PSG data on a posthoc basis. We compared BP surge between mean respiratory (apnoea, hypopnea and desaturation-alone events) and nonrespiratory events (spontaneous or leg movement-related arousals). We examined the association of the degree of oxygen desaturation with BP surge in a given respiratory event combining all events. A total of 17 consecutive patients (12 men, mean 52 years old, nine diagnostic and eight split-night PSGs) undergoing clinically indicated PSG were included after excluding one patient with poor signal quality due to excessive movement.

Results:

Caretaker was well tolerated. Mean respiratory BP surge ranged from 5 to 19 mmHg [Median (IQR) = 13.9 (9.5--16.2)]. Mean BP surge between the respiratory and nonrespiratory events was similar [13.8 (4.5) vs. 14.9 (5.3) mmHg, P = 0.13]. Accounting for the count distribution of desaturation/BP surge data pair events, there was a linear correlation between the degree of oxygen desaturation and BP surge (R = 0.57, P < 0.001). In eight patients undergoing split-night sleep studies, the number of BP surge events (≥10 mmHg/h) decreased during continuous positive airway pressure in all but one patient.

Conclusion:

We demonstrated highly variable OSA-related BP surge patterns using the Caretaker's b-b BP monitoring technology that has the potential to be integrated into sleep studies.
Phakomatous Choristomas: A Case Report and Review of Literature
Authors: Jung Emily H. , Avila Sarah A. , Gordon Abigail A. , de la Garza Adam G. , Grossniklaus Hans E.
Published: November 2021

Purpose:

To document a case of phakomatous choristoma (PC), a rare benign periocular tumor, and to review the literature on previously reported cases.

Methods:

The authors describe a case of PC and its clinical, histopathological, immunohistochemical, and radiological features, and present findings from a comprehensive review of all previously reported cases of this rare pediatric tumor.

Results:

This case report and review highlights the benign clinical nature of PC. It typically presents at birth as a lower eyelid mass involving the orbit. Definitive diagnosis is made with hematoxylin and eosin stain showing the tumor’s histological similarities to lenticular tissue.

Conclusion:

PC remains a rare entity that should be included in the differential of pediatric eyelid lesions. Surgical excision is curative, and the postoperative clinical course is unremarkable as there have been no reports of recurrence. Prompt recognition and surgical intervention may be warranted due to astigmatism and anisometropia induced by mass effect.
Patient-specific Implants for Orbital Fractures: A Systematic Review
Authors: Maher Dominic I. , Hall Anthony J. , Gwini StellaMay , Ben Artsi Elad
Published: November 2021

Purpose:

Orbital fractures are common facial fractures that can be challenging to repair and require careful attention to avoid unacceptable ophthalmic complications. Customized implants that are unique to an individual patient, or patient-specific implants (PSIs), have been increasingly used to repair orbital wall fractures. This systematic review summarizes the current evidence regarding custom-made orbital wall implants.

Methods:

A keyword search of published literature from January 2010 to September 2021 was performed using Ovid MEDLINE, PubMed, and the Cochrane Library databases. Original articles that included more than 3 human subjects with an orbital fracture repaired with a PSI were included. The search results were reviewed, duplicates were removed and relevant articles were included for analysis.

Results:

Fifteen articles meeting the inclusion criteria. The articles were categorized into 3 separate groups based on the method of PSI fabrication: manual molding of a PSI on a 3D-printed orbital model (53%), directly from a 3D printer (27%), or via a template fabricated from a 3D printer (20%). Three primary postoperative outcomes were assessed: rates of diplopia, enophthalmos, and orbital volume. Postoperative rates of diplopia and enophthalmos improved regardless of the PSI technique, and postoperative orbital volumes were reduced compared with their preoperative state. When PSIs were compared to conventional implants, patient outcomes were comparable.

Conclusions:

This review of existing PSI orbital implant literature highlights that while PSI can accurately and safely repair orbital fractures, patient outcomes are largely comparable to orbital fractures repaired by conventional methods, and PSI do not offer a definitive benefit over conventional implants.
Assessment of Reflux From Needleless Connectors: Blinded Comparison of Category Designation to Benchtop Function Using a Venous Simulator
Authors: Gorzek Sarah , LaDisa John F.
Published: November 2021

Needleless connectors (NCs) for vascular access have limited needlestick injuries, but complications including occlusion, thrombosis, and infections have increased despite reduced needlestick injuries. These complications relate to the ability of an NC design to limit volume fluctuations that can lead to fluid reflux with potential for microbial contamination. Different NC designs requiring specific usage protocols and training, a lack of clarity in NC function relative to manufacturer-designated categories, and confounding results from a limited number of studies comparing different NCs have resulted in confusion, ultimately leading to complications from undesirable fluid movement within the vascular access. The authors therefore quantified the magnitude of reflux with current commercially available NCs using a venous stimulator. Thirteen blinded NC designs spanning the categories of negative and positive displacement, neutral, and antireflux were tested to quantify fluid movement upon disconnection and reconnection from a representative intravenous pressure (3 NCs per design; 10 trials per NC). Trials for each NC tested followed consistent displacement trends leading to tight error bars. Blinded NCs were then characterized according to their function and compared with their category designation after unblinding. All positive and negative NCs functioned in a manner consistent with their respective category designations. Conversely, all NCs categorized as neutral actually functioned with negative displacement (ie, reflux upon disconnection; 4/5 NCs) or positive displacement (1/5 NCs). Only NCs classified as antireflux functioned as neutral, which was confirmed in a blinded bidirectional flow test. These results suggest that the neutral NC-marketed category may be confusing to users unless the particular NC design has an integrated antireflux component.
Incidence of Pediatric Eosinophilic Esophagitis and Characterization of the Stricturing Phenotype in Alberta, Canada
Authors: Burnett David , Persad Rabin , Huynh Hien Quoc
Published: November 2021

Introduction:

Limited work has been done to characterize the stricturing pediatric eosinophilic esophagitis (EoE) phenotype. We aimed to determine, in pediatric EoE: the local incidence, the frequency of esophageal stricturing, and the safety of mechanical dilations.

Methods:

We retrospectively identified all new cases of EoE at our center from 2015 to 2018 using esophageal biopsy reports, EoE clinic lists, and a local OR database of esophageal dilatations. Electronic medical records (EMRs) were reviewed to confirm EoE diagnosis. Clinical data were captured from the outpatient EMR and gastroscopy/pathology reports. Scope adverse event data were captured from multiple sources. The 2016 census data were used to calculate incidence rates.

Results:

One hundred eighty-five new cases of EoE were diagnosed during the study period. For patients <15 years old living in Edmonton, the incidence over the 4 years was 11.1 cases per 100,000 person years. Eight of 185 (4%) patients had endoscopically confirmed esophageal strictures, 4 of which required mechanical dilation. Eleven of 185 (5.9%) patients had more subtle signs of esophageal narrowing, but no focal strictures. No perforations or episodes of significant bleeding were reported. Pain was reported after 15% of all scopes, including 50% of the 28 scopes with focal strictures. No unexpected admissions or emergency department visits occurred within 72 hours of a gastroscope with esophageal narrowing.

Conclusions:

Edmonton zone has one of the highest incidences of pediatric EoE reported. In this cohort, 4% had focal esophageal strictures, and 6% had more subtle narrowing. Mechanical dilation of esophageal strictures was associated with no significant adverse events.
Infantile Adenomyomatosis of the Gallbladder in a 3-Month-Old
Authors: Sparks Chelsea , Fagen Kimberly , Wilsey Michael , Condino Adria , Kucera Jennifer Neville
Published: November 2021

Adenomyomatosis of the gallbladder is an acquired condition of the gallbladder with epithelial, mucosal, and muscular hypertrophy. The result is usually gallbladder wall thickening with associated diverticula known as Rokitansky-Aschoff’s sinuses. These mucosal invaginations of the gallbladder wall may extend beyond the muscular layer. The condition is typically asymptomatic and is predominantly diagnosed in adults between 50 and 60 years of age, usually with concomitant cholelithiasis, motility disorders, or chronic inflammation. Few cases within the literature have been described in the pediatric population and even fewer within this subset have been diagnosed in infants. We describe a case of a 3-month-old male with failure to thrive, persistent nonbilious, nonbloody emesis, and elevated transaminases with ultrasound evidence of gallbladder adenomyomatosis. The patient was managed with outpatient laboratory monitoring and follow-up imaging.
Liraglutide with Lifestyle Intervention in Adolescents with Overweight/Obesity, Nonalcoholic Fatty Liver Disease, and Type II Diabetes Mellitus
Authors: Kohut Taisa , Panganiban Jennifer
Published: November 2021

There is a strong interplay between nonalcoholic fatty liver disease (NAFLD), obesity, insulin resistance, and type II diabetes mellitus (T2DM). Liraglutide, a glucagon-like-peptide-1 (GLP-1) analogue, is FDA approved for T2DM in children 10 years or older and more recently approved for chronic weight management in children 12 years or older with obesity. GLP-1 analogues have also been shown to reduce liver enzymes and improve liver histology. We report two adolescent females with T2DM and biopsy proven nonalcoholic steatohepatitis (NASH) refractory to lifestyle intervention who were safety treated with liraglutide with associated weight loss and liver enzyme improvement. This is the first case series reporting use of liraglutide in pediatric NASH. Liraglutide should be considered in pediatric patients with overweight/obesity, NAFLD, and T2DM.
Growth deficits in antiretroviral and HIV-exposed uninfected versus unexposed children in Malawi and Uganda persist through 60 months of age
Authors: Fowler Mary Glenn , Aizire Jim , Sikorskii Alla , Atuhaire Patience , Ogwang Lillian Wambuzi , Mutebe Alex , Katumbi Chaplain , Maliwichi Limbika , Familiar Itziar , Taha Taha , Boivin Michael J.
Published: November 2021

Objective:

To compare childhood physical growth among antiretroviral drug and maternal HIV-exposed uninfected (AHEU) compared with HIV-unexposed uninfected (HUU) children.

Design:

Longitudinal follow-up of PROMISE trial (NCT01061151) AHEU and age-matched and sex-matched HUU children, enrolled (September 2013 to October 2014) in Malawi and Uganda.

Method:

We compared WHO population standardized z-scores [height-for-age (HAZ), weight-for-age (WAZ), weight-for-height (WHZ), head-circumference-for-age (HCAZ) at 12, 24, 36, 48, and 60 months of age]. We evaluated HUU versus AHEU [in-utero combination antiretroviral treatment (cART) versus Zidovudine (ZDV) alone]; stratified by country, using longitudinal linear and generalized linear mixed models.

Results:

Of 466 Malawian and 477 Ugandan children, median maternal age at enrollment was 24.5 years (Malawi) and 27.8 years (Uganda); more than 90% were breastfed through 12 months except Uganda AHEU (64.0%). HAZ scores (adjusted for maternal age, breastfed, and socioeconomic status) were lower among AHEU versus HUU children at every time point, significant (P < 0.05) among Ugandan but not Malawian children. Similar patterns were seen for WAZ but not for WHZ or HCAZ scores. High stunting was observed in both countries, significantly higher in Malawi; and higher among AHEU versus HUU children through 48 months of age, significantly (P < 0.05) among Ugandan but not Malawian children. We found no differences in childhood growth trajectories with in-utero exposures to ZDV compared with cART.

Conclusion:

AHEU versus HUU children had lower median LAZ and WAZ scores persisting through 60 months of age. However, proportions of children with stunting or underweight decreased after 24 months of age.
Using computer-assisted content analysis to advance anal dysplasia natural history research
Authors: Cachay Edward R. , Hasteh Farnaz , Mathews William Christopher
Published: November 2021

Objective:

Our study aim was to validate the use of computer-aided narrative content analysis in the extraction of standard diagnostic categories using an archived cytology database that included individually overread reference classification.

Design:

A retrospective analysis of narrative anal cytology results collected on HIV-infected patients at the University of California, San Diego between January and December 2001.

Methods:

We used computer-assisted content analysis extraction methodology using Wordstat 8.0 (Provalis Research) that operated using a classification dictionary that we developed for the following diagnostic categories: NAMC, ASCUS, LSIL, HSIL. We compared its accuracy to a physician overread manually extracted method: that classified each report into the most severe diagnostic category referenced in the narrative report. Agreement between content analysis mapped diagnostic categories and the reference category was evaluated using kappa agreement.

Results:

During 2001, 901 patients underwent 997 anal cytological examinations as routine screening. By reference diagnostic category: 54 (5.4%) were unsatisfactory, 460 (46.1%) were NAMC, 291 (29.2%) were ASCUS, 131 (13.1%) were LSIL, and 61 (6.1%) were HSIL. Computer-aided content analysis extracted a single diagnosis from each report in 963 (96.2%) cases and two diagnoses in 38 (3.8%) cases. The Kappa agreement was 0.96 (0.019 s.e.). There were 29 cases classified ASCUS by reference category but LSIL by adjudicated content analysis. A focused review indicated that the over reader assigned reference category was in error.

Conclusion:

Computer-aided narrative content analysis of anal cytology results yielded accurate and time-efficient classification into meaningful diagnostic categories that can be used to evaluate screening programs and modeling natural history.
Higher prevalence of stunting and poor growth outcomes in HIV-exposed uninfected than HIV-unexposed infants in Kenya
Authors: Neary Jillian , Langat Agnes , Singa Benson , Kinuthia John , Itindi Janet , Nyaboe Edward , Ng’anga’ Lucy W. , Katana Abraham , John-Stewart Grace C. , McGrath Christine J.
Published: November 2021

Background:

With the growing population of HIV-exposed uninfected (HEU) children globally, it is important to determine population-level growth differences between HEU and HIV-unexposed uninfected (HUU) children.

Methods:

We analyzed data from a population-level survey enrolling mother–infant pairs attending 6-week and 9-month immunizations in 140 clinics across Kenya. Weight-for-age (WAZ), length-for-age (LAZ), head circumference-for-age (HCAZ) z-scores and underweight (WAZ < −2), stunting (LAZ < −2), and microcephaly (HCAZ < −2), were compared between HEU and HUU. Correlates of growth faltering and poor growth were assessed using generalized Poisson and linear regression models.

Results:

Among 2457 infants, 456 (19%) were HEU. Among mothers living with HIV, 64% received antiretroviral therapy (ART) and 22% were on antiretroviral prophylaxis during pregnancy. At 9 months, 72% of HEU and 98% of HUU were breastfeeding. At 6 weeks, HEU had lower mean WAZ (−0.41 vs. −0.09; P < 0.001) and LAZ (−0.99 vs. −0.31; P = 0.001) than HUU. Stunting was higher in HEU than HUU at 6 weeks (34% vs. 18%, P < 0.001) and 9 months (20% vs. 10%, P < 0.001). In multivariable analyses, HEU had lower mean LAZ at 6 weeks (−0.67, 95% confidence interval [CI]: −1.07, −0.26) and 9 months (−0.57, 95% CI: −0.92, −0.21) and HEU had higher stunting prevalence (week-6 adjusted prevalence ratio [aPR]: 1.88, 95% CI: 1.35, 2.63; month-9 aPR: 2.10, 95% CI: 1.41, 3.13). HEU had lower mean head circumference (−0.49, 95% CI: −0.91, −0.07) and higher prevalence of microcephaly (aPR: 2.21, 95% CI: 1.11, 4.41) at 9 months.

Conclusion:

Despite high maternal ART coverage, HEU had poorer growth than HUU in this large population-level comparison. Optimizing breastfeeding practices in HEU may be useful to improve growth.
Safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in adults living with HIV
Authors: Mohapi Lerato , Pinedo Yvett , Osiyemi Olayemi , Supparatpinyo Khuanchai , Ratanasuwan Winai , Molina Jean-Michel , Dagan Ron , Tamms Gretchen , Sterling Tina , Zhang Ying , Pedley Alison , Hartzel Jon , Kan Yanqing , Hurtado Kim , Musey Luwy , Simon Jakub K. , Buchwald Ulrike K.
Published: November 2021

Objectives:

To evaluate safety and immunogenicity of V114 [15-valent pneumococcal conjugate vaccine (PCV) containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F], followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 8 weeks later, in adults living with HIV.

Design:

In this phase 3 study (V114-018; NCT03480802), pneumococcal vaccine-naive adults with HIV (CD4+ cell count ≥50 cells/μl, plasma HIV RNA <50 000 copies/ml, receiving antiretroviral therapy) were randomized 1 : 1 to receive one dose of V114 or licensed 13-valent PCV (PCV13) on day 1; participants received PPSV23 at week 8.

Methods:

Adverse events and serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) antibodies were evaluated after each vaccination.

Results:

Of 302 participants enrolled, 292 (96.7%) completed the study. Proportions of participants experiencing at least one adverse event were 73.0 and 62.7% in the V114 and PCV13 groups following PCV and 60.7 and 71.6% following PPSV23. Most solicited adverse events were of mild or moderate severity and short duration. OPA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) were generally comparable between groups for shared serotypes at day 30 and maintained at week 12. OPA and IgG responses for additional serotypes in V114 (22F, 33F) were higher following V114 than PCV13 at day 30 but comparable at week 12, 30 days post-PPSV23.

Conclusion:

In pneumococcal vaccine-naive adults living with HIV, V114 was well tolerated and induced immune responses for all 15 pneumococcal serotypes. V114 can be followed by PPSV23 8 weeks later to broaden serotype coverage.
Association of HIV infection with outcomes among adults hospitalized with COVID-19
Authors: Durstenfeld Matthew S. , Sun Kaiwen , Ma Yifei , Rodriguez Fatima , Secemsky Eric A. , Parikh Rushi V. , Hsue Priscilla Y.
Published: November 2021

Objective:

The aim of this study was to evaluate the association of HIV infection with outcomes among people hospitalized with COVID-19.

Design:

A prospectively planned analysis of the American Heart Association's COVID-19 Cardiovascular Disease Registry.

Setting:

One hundred and seven academic and community hospitals in the United States from March through December 2020

Participants:

Consecutive sample of 21 528 adults hospitalized with COVID-19 at participating hospitals

Main outcome and measure:

Primary outcome was predefined as in-hospital mortality. We used hierarchical mixed effects models to assess the association of HIV with in-hospital mortality accounting for patient demographics, comorbidities, and clustering by hospital. Secondary outcomes included major adverse cardiac events (MACE), severity of illness, and length of stay (LOS).

Results:

The registry included 220 people with HIV (PWH). PWH were younger and more likely to be male, Non-Hispanic Black, on Medicaid, and active tobacco users. Of the study population, 36 PWH (16.4%) died compared with 3290 (15.4%) without HIV [risk ratio 1.06; 95% confidence interval (95% CI) 0.79–1.43; P = 0.71]. After adjustment for age, sex, race, and insurance, HIV was not associated with in-hospital mortality (aOR 1.12; 95% CI 0.76–1.64; P = 0.58) with no change in effect after adding BMI and comorbidities (aOR 1.14; 95% CI 0.78–1.68; P = 0.51). HIV was not associated with MACE (aOR 0.99; 95% CI 0.69–1.44, P = 0.91), COVID severity (aOR 0.96; 95% CI 0.62–1.50; P = 0.86), or LOS (aOR 1.03; 95% CI 0.76–1.66; P = 0.21).

Conclusion:

In the largest study of PWH hospitalized with COVID-19 in the United States to date, we did not find significant associations between HIV and adverse outcomes including in-hospital mortality, MACE, or severity of illness.
Heterogeneity in Surgical Quality Improvement in Michigan
Authors: Lussiez Alisha , Eton Ryan , Anderson Maia , Valbuena Valeria , Campbell Darrell , Englesbe Michael , Howard Ryan
Published: November 2021

Objective:

The aim of this study was to evaluate changes in 30-day postoperative outcomes and individual hospital variation in outcomes from 2012 to 2019 in a collaborative quality improvement network.

Summary Background Data:

Collaborative quality improvement efforts have been shown to improve postoperative outcomes overall; however, heterogeneity in improvement between participating hospitals remains unclear. Understanding the distribution of individual hospital-level changes is necessary to inform resource allocation and policy design.

Methods:

We performed a retrospective cohort study of 51 hospitals in the Michigan Surgical Quality Collaborative (MSQC) from 2012 to 2019. Risk-and reliability-adjusted hospital rates of 30-day mortality, complications, serious complications, emergency department (ED) visits, readmissions, and reoperations were calculated for each year and compared between the last 2 years and the first 2 years of the study period.

Results:

There was a significant decrease in the rates of all 5 adverse outcomes across MSQC hospitals from 2012 to 2019. Of the 51 individual hospitals, 31 (61%) hospitals achieved a decrease in mortality (range –1.3 percentage points to +0.6 percentage points), 40 (78%) achieved a decrease in complications (range –8.5 percentage points to +2.9 percentage points), 26 (51%) achieved a decrease in serious complications (range –3.2 percentage points to +3.0 percentage points), 29 (57%) achieved a decrease in ED visits (range 5.0 percentage points to +2.2 percentage points), 46 (90%) achieved a decrease in readmissions (range –3.1 percentage points to +0.4 percentage points) and 39 (76%) achieved a decrease in reoperations (range 3.3 percentage points to +1.0 percentage points).

Conclusions:

Despite overall improvement in surgical outcomes across hospitals participating in a quality improvement collaborative, there was substantial variation in improvement between hospitals, highlighting opportunities to better understand hospital-level barriers and facilitators to surgical quality improvement.
Development and Validation of an Electronic Health Record-based Score for Triage to Perioperative Medicine
Authors: Le Sidney T. , Corbin J. Dalton , Myers Laura C. , Kipnis Patricia , Cohn Bradley , Liu Vincent X.
Published: November 2021

Objective:

To develop an electronic health record-based risk model for perioperative medicine (POM) triage and compare this model with legacy triage practices that were based on clinician assessment.

Summary of Background Data:

POM clinicians seek to address the increasingly complex medical needs of patients prior to scheduled surgery. Identifying which patients might derive the most benefit from evaluation is challenging.

Methods:

Elective surgical cases performed within a health system 2014– 2019 (N = 470,727) were used to develop a predictive score, called the Comorbidity Assessment for Surgical Triage (CAST) score, using split validation. CAST incorporates patient and surgical case characteristics to predict the risk of 30-day post-operative morbidity, defined as a composite of mortality and major NSQIP complications. Thresholds of CAST were then selected to define risk groups, which correspond with triage to POM appointments of different durations and modalities. The predictive discrimination CAST score was compared with the surgeon’s assessments of patient complexity and the American Society of Anesthesiologists class.

Results:

The CAST score demonstrated a significantly higher discrimination for predicting post-operative morbidity (area under the receiver operating characteristic curve 0.75) than the surgeon’s complexity designation (0.63; P < 0.001) or the American Society of Anesthesiologists (0.65; P < 0.001) (Fig. 1). Incorporating the complexity designation in the CAST model did not significantly alter the discrimination (0.75; P = 0.098). Compared with the complexity designation, classification based on CAST score groups resulted a net reclassification improvement index of 10.4% (P < 0.001) (Table 1).

Conclusion:

A parsimonious electronic health record-based predictive model demonstrates improved performance for identifying pre-surgical patients who are at risk than previously-used assessments for POM triage.
Microbiota-targeted interventions for mental health
Authors: Berding Kirsten , Cryan John F.
Published: November 2021

Purpose of review

The gut microbiota has emerged as a key conduit in mental health and is a promising target for interventions. This review provides an update on recent advances in using microbiota-targeted approaches for the management of mental health.

Recent findings

Approaches that have emerged as microbiota-targeted interventions in the management of mental health include probiotics, prebiotics, synbiotics, fecal microbiota transplant as well as diet. Among these approaches, probiotic supplementation has been investigated most prominently, providing promising evidence for its use in improving mood and anxiety. There is also growing interest in the use of multistrain probiotics, whole dietary interventions or combined approaches, with encouraging results emerging from recent studies.

Although the current literature preliminarily supports targeting the microbiota to manage mental health and use as adjuvant therapies for certain brain disorders, large gaps remain and especially data including clinical cohorts remains scarce. Research studies including larger cohorts, well-characterized clinical populations and defined duration and dosage of the intervention are required to develop evidence-based guidelines for microbiota-targeted strategies.
Quality Improvement in Clinical Research: ESA Utilization to improve Patient Safety Monitoring, time management, and Research Compliance
Authors: Del Pino Maria , Bonmati Ana , Mendoza Patricia
Published: November 2021

We analyzed the capabilities of Electronic Signature Administrators (ESA) in reporting adverse and serious adverse events (AE/SAE) in clinical trials to improve Principal Investigator (PI) oversight. The current and most conventional way to sing on AE/SAE reports, by wet ink paper signatures, faces long report completion times, miscommunications, and a high rate of error that can put the study and the patient at risk. We demonstrate here that ESAs can easily take over this task, speeding up the process and enhancing patient’s safety and research compliance. Our results show that the average of 31 days to obtain wet-signatures on AE/SAE reports is reduced to merely 3 days after the implementation of ESA. We also found that research professionals spend more than half an hour in commuting each time they need to get PI signatures, while this time is zero if ESAs are used. Finally, an anonymous survey distributed to coordinators shows that ESAs can be well received when implemented since 86% have used an ESA and are satisfied with it or are interested in using it, while only 14% of the participants are either not interested or not satisfied.
Lipid Alterations in African American Prostate Cancer
Authors: Ravindran Anindita , Badrajee Piyarathna Danthasinghe Waduge , Gohlke Jie , Putluri Vasanta , Soni Tanu , Lloyd Stacy , Castro Patricia , Pennathur Subramaniam , Jones Jeffrey A , Ittmann Michael , Putluri Nagireddy , Michailidis George , Rajendiran Thekkelnaycke M , Sreekumar Arun
Published: November 2021

African-American (AA) men are more than twice as likely to die of prostate cancer (PCa) than European American (EA) men. Previous in-silico analysis revealed enrichment of altered lipid metabolic pathways in pan-cancer AA tumors. Here, we performed global unbiased lipidomics profiling on 48 matched localized PCa and benign adjacent tissues (30 AA, 24 ancestry-verified, and 18 EA, 8 ancestry verified) and quantified 429 lipids belonging to 15 lipid classes. Significant alterations in long chain polyunsaturated lipids was observed between PCa and benign adjacent tissues, low and high Gleason tumors, as well as associated with early biochemical recurrence, both in the entire cohort, and within AA patients. Altered levels of cholesteryl esters, and phosphatidyl inositols delineated AA and EA PCa, while levels of triglycerides, phosphatidyl glycerol, phosphatidyl choline, phosphatidic acid and cholesteryl esters distinguished AA and EA PCa patients with biochemical recurrence. These first-in-field results implicate lipid alterations as biological factors for prostate cancer disparities.
Trends in Homeschooling Rates Following Elimination of Nonmedical Exemptions to Childhood Immunizations, 2012-2020
Authors: Patel Kavin M. , McFadden SarahAnn M. , Mohanty Salini , Joyce Caroline M. , Delamater Paul L. , Klein Nicola P. , Salmon Daniel A , Omer Saad B. , Buttenheim Alison M.
Published: November 2021

STRUCUTRED ABSTRACT

Introduction

In 2015 California passed Senate Bill No. 277 (SB 277) and became the first state in over 30 years to eliminate nonmedical exemptions to mandatory childhood immunizations for school entry. One concern that emerged was that the law created an incentive for parents to remove children from brick-and-mortar schools to bypass the immunization requirements.

Objective

To assess the impact of eliminating nonmedical exemptions to childhood immunizations on homeschooling rates.

Design

Pre-Post Intervention study. We calculated homeschooling rates as the number of K-8 students enrolled through each of California’s three homeschooling mechanisms (Independent Study Program, Private School Affidavit, and Private School Satellite Program) divided by all K-8 students enrolled in the same academic year. Data on homeschooling rates was obtained from the California Department of Education. We then conducted an interrupted time series analyses in which the outcome variable was percent of students enrolled in a homeschool program pre- and post-SB 277.

Setting

California homeschools

Participants

K-8 students enrolled through each of the state’s three homeschooling mechanisms (Independent Study Program, Private School Affidavit, and Private School Satellite Program)

Intervention

Passage of SB 277 which eliminated nonmedical exemptions to childhood immunizations for school entry

Main Outcome

K-8 homeschooling rates

Results

The homeschooling enrollment for K-8 students in California increased from 0.8% (35,122 students) during SY 2012-13 to 1.9% (86,574 students) during SY 2019-20; however, we found no significant increase in the percent of students enrolled in homeschooling programs in California following the implementation of SB 277 beyond the secular trend.

Conclusions and Relevance

Legislative action to limit nonmedical exemptions to compulsory vaccination for school entry is not associated with removal from classroom-based instruction in brick- and-mortar institutions.

KEY POINTS

Question

What is effect of California Senate Bill No. 277, which eliminated nonmedical exemptions to childhood immunizations for school entry, on the homeschooling rates?

Finding

We found no evidence that elimination of nonmedical exemptions to mandatory childhood immunizations for school entry was associated with an increase in homeschooling rates for K-8 in California.

Meaning

Legislative action to limit nonmedical exemptions to compulsory vaccination for school entry is not associated with removal from classroom-based instruction in brick-and-mortar institutions.
Phage-like particle vaccines are highly immunogenic and protect against pathogenic coronavirus infection and disease
Authors: Davenport Bennett J. , Catala Alexis , Weston Stuart M. , Johnson Robert M. , Ardunay Jeremy , Hammond Holly L. , Dillen Carly , Frieman Matthew B. , Catalano Carlos E. , Morrison Thomas E.
Published: November 2021

The response by vaccine developers to the COVID-19 pandemic has been extraordinary with effective vaccines authorized for emergency use in the U.S. within one year of the appearance of the first COVID-19 cases. However, the emergence of SARS-CoV-2 variants and obstacles with the global rollout of new vaccines highlight the need for platforms that are amenable to rapid tuning and stable formulation to facilitate the logistics of vaccine delivery worldwide. We developed a “designer nanoparticle” platform using phage-like particles (PLPs) derived from bacteriophage lambda for multivalent display of antigens in rigorously defined ratios. Here, we engineered PLPs that display the receptor binding domain (RBD) protein from SARS-CoV-2 and MERS-CoV, alone (RBDSARS-PLPs, RBDMERS-PLPs) and in combination (hCoV-RBD PLPs). Functionalized particles possess physiochemical properties compatible with pharmaceutical standards and retain antigenicity. Following primary immunization, BALB/c mice immunized with RBDSARS- or RBDMERS-PLPs display serum RBD-specific IgG endpoint and live virus neutralization titers that, in the case of SARS-CoV-2, were comparable to those detected in convalescent plasma from infected patients. Further, these antibody levels remain elevated up to 6 months post-prime. In dose response studies, immunization with as little as one microgram of RBDSARS-PLPs elicited robust neutralizing antibody responses. Finally, animals immunized with RBDSARS-PLPs, RBDMERS-PLPs, and hCoV-RBD PLPs were protected against SARS-CoV-2 and/or MERS-CoV lung infection and disease. Collectively, these data suggest that the designer PLP system provides a platform for facile and rapid generation of single and multi-target vaccines.
Feasibility evaluation of transtympanic laser stimulation of the cochlea from the outer ear
Authors: Uenaka Miku , Nagamura Hidekazu , Hiryu Shizuko , Kobayasi Kohta I. , Tamai Yuta
Published: November 2021

Infrared laser stimulation has been studied as an alternative approach to auditory prostheses. This study evaluated the feasibility of infrared laser stimulation of the cochlea from the outer ear bypassing the middle ear function. An optic fiber was inserted into the ear canal and a laser was used to irradiate the cochlea through the tympanic membrane in Mongolian gerbil. A pulsed infrared laser (10.1 mJ/cm2) and clicking sound (70 peak-to-peak equivalent sound pressure level) were presented to the animals. The amplitude of the laser-evoked cochlear response was systematically decreased following insertion of a filter between the tympanic membrane and cochlea; however, the auditory-evoked cochlear response did not decrease. The filter was removed and the laser-evoked response returned to around the original level. The amplitude ratio and the relative change in response amplitude before and during filter insertion significantly decreased as the absorbance of the infrared filter increased. These results indicate that laser irradiation could bypass the function of the middle ear and directly activate the cochlea. Therefore, an auditory prosthesis based on laser stimulation represents a possible noninvasive alternative to conventional auditory prostheses requiring surgical implants.
Paradoxical excitation of lateral habenula neurons by propofol involves enhanced presynaptic release of glutamate
Authors: Shepard Ryan David , Wu Kunwei , Lu Wei
Published: November 2021

Sleep is a fundamental physiological process conserved across most species. As such, deficits in sleep can result in a myriad of psychological and physical health issues. However, the mechanisms underlying the induction of sleep are relatively unknown. Interestingly, general anesthetics cause unconsciousness by positively modulating GABA-A receptors (GABAARs). Based on this observation, it is hypothesized that GABAARs play a critical role in modulating circuits involved in sleep to promote unconsciousness. Recently, the lateral habenula (LHb) has been demonstrated to play a role in sleep physiology and sedation. Specifically, propofol has been shown to excite LHb neurons to promote sedation. However, the mechanism by which this occurs is unknown. Here, we utilize whole-cell voltage and current clamp recordings from LHb neurons obtained from 8-10 week old male mice to determine the physiological mechanisms for this phenomenon. We show that bath application of 1.5μM propofol is sufficient to increase LHb neuronal excitability involving synaptic transmission, but not through modulation of intrinsic properties. Additionally, although there is increased LHb neuronal excitability, GABAARs localized postsynaptically on LHb neurons are still responsive to propofol, as indicated by an increase in the decay time. Lastly, we find that propofol increases the synaptic drive onto LHb neurons involving enhanced presynaptic release of both glutamate and GABA. However, the greatest contributor to the potentiated synaptic drive is the increased release of glutamate which shifts the balance of synaptic transmission towards greater excitation. Taken together, this study is the first to identify the physiological basis for why LHb neurons are excited by propofol, rather than inhibited, and as a result promote sedation.
Macrophage proliferation machinery leads to PDAC progression, but susceptibility to innate immunotherapy
Authors: Zuo Chong , Baer John M. , Knolhoff Brett L. , Belle Jad I. , Liu Xiuting , Hogg Graham D. , Fu Christina , Kingston Natalie L. , Brenden Marcus A. , De La Lastra Angela Alarcon , Dodhiawala Paarth B. , Zhou Cui , James C. Alston , Ding Li , Lim Kian-Huat , Fields Ryan C. , Hawkins William G. , Zhao Guoyan , Weber Jason D. , DeNardo David G.
Published: November 2021

Tumor-associated macrophages (TAMs) are involved in many aspects of cancer progression and correlate with poor clinical outcomes in many cancer types, including pancreatic ductal adenocarcinomas (PDACs). Previous studies have shown that TAMs can populate PDAC tumors not only by monocyte recruitment but also by local proliferation. However, the impact local proliferation might have on macrophage phenotype and cancer progression is unknown. Here, we utilized genetically engineered cancer models, single-cell RNA-sequencing data, andin vitrosystems to show that proliferation of TAMs was driven by colony stimulating factor-1 (CSF1) produced by cancer-associated fibroblasts. CSF1 induced high levels of p21 in macrophages, which regulated both TAM proliferation and phenotype. TAMs in human and mouse PDACs with high levels of p21 had more inflammatory and immunosuppressive phenotypes. The p21 expression in TAMs was induced by both stromal interaction and/or chemotherapy treatment. Finally, by modeling p21 expression levels in TAMs, we found that p21-driven macrophage immunosuppressionin vivodrove tumor progression. Serendipitously, the same p21-driven pathways that drive tumor progression, also drive response to CD40 agonist. These data suggest that stromal or therapy-induced regulation of cell cycle machinery can regulate both macrophage-mediated immune suppression and susceptibility to innate immunotherapy.

TAMs are indicative of poor clinical outcomes and in PDAC their number is sustained in part by local proliferation. This study shows that stromal desmoplasia drives local proliferation of TAMs, and induces their immunosuppressive ability through altering cell cycle machinery, including p21 expression. Serendipitously, these changes in p21 in TAMs also potentially render tumors more sensitive to CD40 agonist therapy.
CCK-A and CCK-B receptors enhance olfactory recognition via distinct neuronal pathways.
Authors: Lemaire M , Barnéoud P , Böhme G A , Piot O , Haun F , Roques B P , Blanchard J C
Published: November 2021

We have previously reported that CCK-A receptor agonists and CCK-B receptor antagonists both enhance memory in an olfactory recognition test. Here, we report that the memory-enhancing effect of the CCK-B receptor antagonist L-365,260 (1 mg/kg i.p.), but not that of the CCK-A receptor agonist caerulein (0.03 mg/kg i.p.), was dramatically decreased following a bilateral transection of the perforant path, a principal source of input to the hippocampal formation. We further confirmed that a significant memory deficit occurred subsequent to this deafferentation of the hippocampus in untreated animals. In contrast, the effect of caerulein, but not that of L-365,260, was abolished following a bilateral subdiaphragmatic vagotomy. These results demonstrate that the hippocampal system plays a role in olfactory recognition and indicate that distinct neuronal pathways underlie the memory-enhancing effects of CCK-A and CCK-B drugs observed in the olfactory recognition test. The former effects (CCK-A) appear to involve a peripheral relay to the brain via the vagus nerve, whereas the latter (CCK-B) are directly central and involve, at least in part, the hippocampal system.
Overstraining international climate finance: when conflicts of objectives threaten its success
Authors: Buchholz Wolfgang , Rübbelke Dirk
Published: November 2021

Purpose

Climate finance is regularly not only seen as a tool to efficiently combat global warming but also to solve development problems in the recipient countries and to support the attainment of sustainable development goals. Thereby, conflicts between distributive and allocative objectives arise, which threaten the overall performance of such transfer schemes. Given the severity of the climate change problem, this study aims to raise concerns about whether the world can afford climate transfer schemes that do not focus on prevention of (and adaptation to) climate change but might be considered as a vehicle of rent-seeking by many agents.

Design/methodology/approach

Future designs of international transfer schemes within the framework of the Paris Agreement are to be based on experience gained from existing mechanisms. Therefore, the authors examine different existing schemes using a graphical technique first proposed by David Pearce and describe the conflicts between allocative and distributional goals that arise.

Findings

In line with the famous Tinbergen rule, the authors argue that other sustainability problems and issues of global fairness should not be primarily addressed by climate finance but should be mainly tackled by other means.

Research limitations/implications

As there is still ongoing, intense discussion about how the international transfer schemes addressed in Article 6 of the Paris Agreement should be designed, the research will help to sort some of the key arguments.

Practical implications

There are prominent international documents (like the Paris Agreement and the UN 2030 Agenda for Sustainable Development) seeking to address different goals simultaneously. While synergies between policies is desirable, there are major challenges for policy coordination. Addressing several different goals using fewer policy instruments, for example, will not succeed as the Tinbergen Rule points out.

Social implications

The integration of co-benefits in the analysis allows for taking into account the social effects of climate policy. As the authors argue, climate finance approaches could become overstrained if policymakers would consider them as tools to also solve local sustainability problems.

Originality/value

In this paper, the authors will not only examine what can be learnt from the clean development mechanism (CDM) for future schemes under Article 6 of the Paris Agreement but also observe the experiences gained from a non-CDM scheme. So the authors pay attention to the Trust Fund of the Global Environment Facility (GEF) which was established with global benefit orientation, i.e. – unlike the CDM – it was not regarded as an additional goal to support local sustainable development. Yet, despite its disregard of local co-benefits, the authors think that it is of particular importance to include the GEF in the analysis, as some important lessons can be learnt from it.