bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Unplanned ICU Transfers: Linking a Revised Definition of Deterioration to Patient Outcomes
Authors: Byrd Thomas F. , Phelan Tom A. , Ingraham Nicholas E. , Langworthy Benjamin W. , Bhasin Ajay , Kc Abhinab , Melton-Meaux Genevieve B. , Tignanelli Christopher J.
Published: June 2024

OBJECTIVES:

To develop an electronic descriptor of clinical deterioration for hospitalized patients that predicts short-term mortality and identifies patient deterioration earlier than current standard definitions.

DESIGN:

A retrospective study using exploratory record review, quantitative analysis, and regression analyses.

SETTING:

Twelve-hospital community-academic health system.

PATIENTS:

All adult patients with an acute hospital encounter between January 1, 2018, and December 31, 2022.

INTERVENTIONS:

Not applicable.

MEASUREMENTS AND MAIN RESULTS:

Clinical trigger events were selected and used to create a revised electronic definition of deterioration, encompassing signals of respiratory failure, bleeding, and hypotension occurring in proximity to ICU transfer. Patients meeting the revised definition were 12.5 times more likely to die within 7 days (adjusted odds ratio 12.5; 95% CI, 8.9–17.4) and had a 95.3% longer length of stay (95% CI, 88.6–102.3%) compared with those who were transferred to the ICU or died regardless of meeting the revised definition. Among the 1812 patients who met the revised definition of deterioration before ICU transfer (52.4%), the median detection time was 157.0 min earlier (interquartile range 64.0–363.5 min).

CONCLUSIONS:

The revised definition of deterioration establishes an electronic descriptor of clinical deterioration that is strongly associated with short-term mortality and length of stay and identifies deterioration over 2.5 hours earlier than ICU transfer. Incorporating the revised definition of deterioration into the training and validation of early warning system algorithms may enhance their timeliness and clinical accuracy.
A Review of Terlipressin in Hepatorenal Syndrome: Targeting Endothelial Dysfunction and Subsequent Cardiovascular Adverse Events
Authors: Bielawski Adrienne M. , Frishman William H.
Published: June 2024

Hepatorenal syndrome (HRS) is a serious complication of decompensated liver cirrhosis that results in acute kidney injury (AKI). The mortality rate is high. Endothelial dysfunction secondary to liver cirrhosis is a key driver of the development of portal hypertension, which is eventually complicated by ascites and HRS. Ultimately, splanchnic vasodilation and excess gut lymph production result in ascites, low effective arterial blood volume, and maladaptive compensatory mechanisms that contribute to renal hypoperfusion and injury. While the only curative treatment is liver transplantation, vasoconstrictors and albumin have been the mainstay of treatment for candidates who are ineligible or waiting for transplantation. On September 14, 2022, terlipressin, a V1 vasopressin receptor agonist, was approved by the Food and Drug Administration for the treatment of HRS-AKI. In clinical trials, terlipressin plus albumin have been superior to albumin alone and equivocal to noradrenaline plus albumin in renal function improvement. Terlipressin, however, does not improve survival, is costly, and is associated with severe adverse events—including severe cardiac and vascular complications. The aim of this review is to provide an overview of terlipressin pharmacology, adverse events—with a focus on cardiovascular complications—and comparative randomized controlled trials that resulted in the Food and Drug Administration's approval of terlipressin. New literature since its approval and ongoing clinical trials will also be highlighted.
Enhancing clinical sense in rare disease diagnosis: a cloud computing collaboration approach using google workspace
Authors: Maharjan Leison , Dangol Bhawana , Yadav Dhirendra
Published: June 2024

Rare diseases is a growing global public health priority. Due to their rarity, these diseases frequently go misdiagnosed or go unnoticed, which has a serious negative influence on patients’ and families’ physical and mental health. Currently used methods for enhancing diagnosis include using electronic medical records, conducting longitudinal studies, and compiling data from across the country. But in our opinion, a clinician’s clinical sense is ultimately what determines an accurate diagnosis. The authors discuss the challenges in diagnosing rare diseases and propose a novel strategy to improve clinicians’ clinical sense using cloud computing such as Google Workspace, a free platform that can serve as a noticeboard and especially helpful in developing nations with limited resources. Cloud computing enables real-time reporting, making diseases accessible to a large number of clinicians. As a result, clinicians can gain invaluable experiences and familiarity with rare diseases, which can improve their diagnostic skills in identifying future patients with rare diseases.
The GLAND-IQ Technique for Surgical Correction of Moderate to Severe Gynecomastia
Authors: Gilardino Mirko S. , Vela-Lasagabaster Arturo
Published: June 2024

Surgical correction of gynecomastia currently ranks in the top five cosmetic procedures performed in men in the United States. Although removal of excess gland is relatively straightforward, the combination of glandular/fatty excess, significant skin redundancy, nipple ptosis, and nipple-areolar complex hypertrophy poses a significant challenge in the male patient desiring inconspicuous scars. The latter renders any form of skin and nipple reduction/elevation using traditional mastopexy patterns or breast amputation with free nipple grafting less favorable due to the surgical stigmata and scars produced with these techniques. To that end, we present our experience treating cases of moderate to severe gynecomastia involving significant skin excess (defined as Simon grade IIb and III) with a technique focused on avoiding visible extra-areolar scars, called the glandular excision, liposuction-assisted, areolar mastopexy for nipple repositioning and skin reduction with internal quilting sutures.
Contemporary Parental Leave Policies and Practice Among Obstetrics and Gynecology Trainees and Faculty
Authors: MATTEI LARISSA H. , POLAN ROSA M.
Published: June 2024

This article aims to describe contemporary parental leave among obstetrics and gynecology trainees and early-career faculty. Here, we present results of a survey that collected information about parental leave policies and contemporary practice, as well as beliefs about surgical and clinical experience for those who take leave. Faculty and trainees were equally well represented among respondents, with half of each group self-identifying as a parent. Most reported that childbearing trainees currently take 6 weeks or less of parental leave and believed that childbearing and nonchildbearing residents should be able to take 12 weeks of leave without extending training.
Predictors of Multidimensional Profiles of Participation After Traumatic Brain Injury: A TBI Model Systems Study
Authors: Juengst Shannon B. , Kumar Raj G. , Venkatesan Umesh M. , O'Neil-Pirozzi Therese M. , Evans Emily , Sander Angelle M. , Klyce Daniel , Agtarap Stephanie , Erler Kimberly S. , Rabinowitz Amanda R. , Bushnik Tamara , Kazis Lewis E. , Whiteneck Gale G.
Published: June 2024

Objectives:

To identify personal, clinical, and environmental factors associated with 4 previously identified distinct multidimensional participation profiles of individuals following traumatic brain injury (TBI).

Setting:

Community.

Participants:

Participants (n = 408) enrolled in the TBI Model Systems (TBIMS) Participation Module, all 1 year or more postinjury.

Design:

Secondary data analysis of cross-sectional data from participants in a multicenter TBIMS module study on participation conducted between May 2006 and September 2007. Participants provided responses to questionnaires via a telephone interview at their study follow-up (1, 2, 5, 10, or 15 years postinjury).

Main Measures:

Participants provided responses to personal (eg, demographic), clinical (eg, function), environmental (eg, neighborhood type), and participation measures to create multidimensional participation profiles. Data from measures collected at the time of injury (preinjury questionnaire, injury characteristics) were also included. The primary outcome was assignment to one of 4 multidimensional participation profile groups based on participation frequency, importance, satisfaction, and enfranchisement. The measures used to develop the profiles were: Participation Assessment with Recombined Tools-Objective, Importance, and Satisfaction scores, each across 3 domains (Productivity, Social Relationships, Out and About in the Community) and the Enfranchisement Scale (contributing to one's community, feeling valued by the community, choice and control).

Results:

Results of the multinomial regression analysis, with 4 distinct participation profile groups as the outcome, indicated that education, current employment, current illicit drug use, current driving status, community type, and FIM Cognitive at follow-up significantly distinguished participation profile groups. Findings suggest a trend toward differences in participation profile groups by race/Hispanic ethnicity.

Conclusions:

Understanding personal, clinical, and environmental factors associated with distinct participation outcome profiles following TBI may provide more personalized and nuanced guidance to inform rehabilitation intervention planning and/or ongoing clinical monitoring.
Diagnostic accuracy of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and neutrophil–lymphocyte-to-platelet ratio biomarkers in predicting bacteremia and sepsis in immunosuppressive patients with cancer: literature review
Authors: Martinez Jose Manuel , Espírito Santo Ana , Ramada Diana , Fontes Filipa , Medeiros Rui
Published: June 2024

Background:

This literature review explores the role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil–lymphocyte-to-platelet ratio (NLPR) biomarkers, as potential indicators for predicting bacteremia and sepsis in patients with cancer.

Objective:

Tracing the evolution of interest in this area since 2001, the aim of this review was to report a comprehensive overview of current knowledge and gaps, particularly in patients undergoing immunosuppression.

Summary of Findings:

The literature research indicates the potential of NLR, PLR, and other biomarkers in diagnosing and predicting sepsis, with some studies emphasizing their value in mortality prediction. A specific focus on bacteremia shows the effectiveness of NLR and PLR as early indicators and prognostic tools, though mostly in noncancer patient populations. While NLR and PLR are promising in general cancer patient populations, the review addresses the challenges in applying these biomarkers to patients with neutropenic and lymphopenic cancer. The NLPR could be considered a significant biomarker for inflammation and mortality risk in various medical conditions, yet its diagnostic accuracy in patients with immunosuppressed cancer is not extensively validated.

Conclusion:

This review offers a snapshot of the current research on biomarkers in patients with immunocompromised cancer in the sepsis and bacteremia area. More focused research on their application is necessary. This gap underscores an opportunity for future studies to enhance diagnostic and prognostic capabilities in this high-risk group.
Reporting on Neurological Decline as Identified by Hourly Neuroassessments
Authors: Brazel Marcus , Harris Jennifer , Carroll Dawn , Davidson Judy , Levchak Philip J. , Malhotra Atul , LaBuzetta Jamie Nicole
Published: June 2024

BACKGROUND:Hourly neurological examinations (neuro exam) have been widely used to monitor for a decline in neurological status, allowing for timely intervention. There are, however, limited data behind this common practice. The objective of this study was to identify how frequently neurological decline occurred across various diagnoses and whether that decline (1) was identified by a scheduled neurocheck and (2) altered management.METHODS:A cross-sectional survey was performed in a neurological intensive care unit at a tertiary care academic medical center. Clinical neuroscience nurses caring for patients with hourly neurological assessments completed a brief survey at 12-hour shift completion.RESULTS:Data were collected from 212 nurse's shifts. Neurological changes were identified by nurses in 14% (n = 30) of shifts. The neurological change was identified during a scheduled neurocheck 67% of the time, with the detection of changes more likely to occur during a scheduled neuro exam than at other times (P< .05). There was no change to the care plan in 55% of the cases of neurological decline. Patients with subarachnoid hemorrhage were more likely to have a decline detected.CONCLUSION:Findings suggest that many patients undergo hourly neurological exams without ever identifying a neurological deterioration. In many instances of neurodeterioration, there was no change to the treatment plan pursued. Primary diagnoses and neurological changes may not be entirely independent, and therefore, hourly neuro exams may have greater yield in some diagnoses than others. Replication is warranted with a larger sample to evaluate the risks and benefits of neuroassessments.
The 1-minute preceptor to improve diagnostic reasoning in a primary care nurse practitioner residency program
Authors: Kopelson Kristin , de Peralta Shelly , Pike Nancy A.
Published: June 2024

Background:

The One-Minute Preceptor (OMP) model to teach diagnostic reasoning and Reporter, Interpreter, Manager, and Educator (RIME) framework to measure progress are used in physician training. Little is known about the use of these tools in nurse practitioner (NP) training.

Local problem:

Precepting NP trainees at the Veterans Affairs (VA) is not standardized. A standardized approach to precepting NP residency trainees using the OMP model and RIME scoring was evaluated for improvement and helpfulness.

Methods:

A quality-improvement project with two Plan-Do-Study-Act (PDSA) cycles were conducted over a 12-week period. Mean RIME scores, preceptor self-efficacy, and use of teaching skills were measured preintervention and postintervention. Data were analyzed using a paired sample t-test and descriptive statistics.

Interventions:

A convenience sample of preceptors and trainees was recruited from a large VA medical center. A 1-hour workshop educated preceptors with role playing and return demonstrations on OMP techniques and RIME scoring. The teachings were applied to standardize precepting and assess diagnostic reasoning. Trainee self-scoring and results triggered conversations to fulfil the identified gaps.

Results:

Mean RIME scores improved (1.62 [0.17] vs. 2.23 [0.38], p < .001) post 12-week intervention. Mean RIME scores improved between PDSA cycle 1 and cycle 2 (2.07 [0.25] vs. 2.48 [0.39], p < .001). Preceptors (91%) and trainees (100%) found the OMP model and RIME framework helpful.

Conclusion:

Use of the OMP improved diagnostic reasoning in NP trainees. The OMP and RIME framework provided standardization of precepting and trainee discussions on improvements.
The impact of normothermic machine perfusion and acuity circles on waitlist time, mortality, and cost in liver transplantation: A multicenter experience
Authors: Wehrle Chase J. , Hong Hanna , Gross Abby , Liu Qiang , Ali Khaled , Cazzaniga Beatrice , Miyazaki Yuki , Tuul Munkhbold , Modaresi Esfeh Jamak , Khalil Mazhar , Pita Alejandro , Fernandes Eduardo , Kim Jaekeun , Diago-Uso Teresa , Aucejo Federico , Kwon David C. H. , Fujiki Masato , Quintini Cristiano , Schlegel Andrea , Pinna Antonio , Miller Charles , Hashimoto Koji
Published: June 2024

Ex situ normothermic machine perfusion (NMP) helps increase the use of extended criteria donor livers. However, the impact of an NMP program on waitlist times and mortality has not been evaluated. Adult patients listed for liver transplant (LT) at 2 academic centers from January 1, 2015, to September 1, 2023, were included (n=2773) to allow all patients ≥6 months follow-up from listing. Routine NMP was implemented on October 14, 2022. Waitlist outcomes were compared from pre-NMP pre-acuity circles (n=1460), pre-NMP with acuity circles (n=842), and with NMP (n=381). Median waitlist time was 79 days (IQR: 20–232 d) at baseline, 49 days (7–182) with acuity circles, and 14 days (5–56) with NMP (p<0.001). The rate of transplant-per-100-person-years improved from 61-per-100-person-years to 99-per-100-person-years with acuity circles and 194-per-100-person-years with NMP (p<0.001). Crude mortality without transplant decreased from 18.3% (n=268/1460) to 13.3% (n=112/843), to 6.3% (n=24/381) (p<0.001) with NMP. The incidence of mortality without LT was 15-per-100-person-years before acuity circles, 19-per-100 with acuity circles, and 9-per-100-person-years after NMP (p<0.001). Median Model for End-Stage Liver Disease at LT was lowest with NMP, but Model for End-Stage Liver Disease at listing was highest in this era (p<0.0001). The median donor risk index of transplanted livers at baseline was 1.54 (1.27–1.82), 1.66 (1.42–2.16) with acuity circles, and 2.06 (1.63–2.46) with NMP (p<0.001). Six-month post-LT survival was not different between eras (p=0.322). The total cost of health care while waitlisted was lowest in the NMP era ($53,683 vs. $32,687 vs. $23,688, p<0.001); cost-per-day did not differ between eras (p=0.152). The implementation of a routine NMP program was associated with reduced waitlist time and mortality without compromising short-term survival after liver transplant despite increased use of riskier grafts. Routine NMP use enables better waitlist management with reduced health care costs.
Geographic Variation of Antidementia and Antipsychotic Medication Use Among US Nursing Home Residents With Dementia
Authors: Rataj Alison , Alcusky Matthew , Baek Jonggyu , Ott Brian , Lapane Kate L.
Published: June 2024

Background:

Several antidementia medications have been approved for symptomatic treatment of cognitive and functional impairment due to Alzheimer disease. Antipsychotics are often prescribed off-label for behavioral symptoms.

Objective:

The aim of this study was to describe the basis for regional variation in antidementia and antipsychotic medication use.

Setting:

US nursing homes (n=9735), hospital referral regions (HRR; n=289).

Subjects:

Long-stay residents with dementia (n=273,004).

Methods:

Using 2018 Minimum Data Set 3.0 linked to Medicare data, facility information, and Dartmouth Atlas files, we calculated prevalence of use and separate multilevel logistic models [outcomes: memantine, cholinesterase inhibitor (ChEI), antipsychotic use] estimated adjusted odds ratios (aOR) and 95% CIs for resident, facility, and HRR characteristics. We then fit a series of cross-classified multilevel logistic models to estimate the proportional change in cluster variance (PCV).

Results:

Overall, 20.9% used antipsychotics, 16.1% used memantine, and 23.3% used ChEIs. For antipsychotics, facility factors [eg, use of physical restraints (aOR: 1.08; 95% CI: 1.05–1.11) or poor staffing ratings (aOR: 1.10; 95% CI: 1.06–1.14)] were associated with more antipsychotic use. Nursing homes in HRRs with the highest health care utilization had greater antidementia drug use (aOR memantine: 1.68; 95% CI: 1.44–1.96). Resident/facility factors accounted for much regional variation in antipsychotics (PCVSTATE: 27.80%; PCVHRR: 39.54%). For antidementia medications, HRR-level factors accounted for most regional variation (memantine PCVSTATE: 37.44%; ChEI PCVSTATE: 39.02%).

Conclusion:

Regional variations exist in antipsychotic and antidementia medication use among nursing home residents with dementia suggesting the need for evidence-based protocols to guide the use of these medications.
Biochemical monitoring of 21-hydroxylase deficiency: a clinical utility of overnight fasting urine pregnanetriol
Authors: Hasegawa Yukihiro , Itonaga Tomoyo , Ishii Tomohiro , Izawa Masako , Amano Naoko
Published: June 2024

Purpose of review

21-Hydroxylase deficiency (21-OHD), the most common form of congenital adrenal hyperplasia, is an autosomal recessive disorder caused by pathogenic variants in CYP21A2. Although this disorder has been known for several decades, many challenges related to its monitoring and treatment remain to be addressed. The present review is written to describe an overview of biochemical monitoring of this entity, with particular focus on overnight fasting urine pregnanetriol.

Recent findings

We have conducted a decade-long research project to investigate methods of monitoring 21-OHD in children. Our latest studies on this topic have recently been published. One is a review of methods for monitoring 21-OHD. The other was to demonstrate that measuring the first morning PT level may be more practical and useful for biochemical monitoring of 21-OHD. The first morning pregnanetriol (PT), which was previously reported to reflect a long-term auxological data during the prepubertal period, correlated more significantly than the other timing PT in this study, with 17-OHP, before the morning medication.

In conclusion, although the optimal method of monitoring this disease is still uncertain, the use of overnight fasting urine pregnanetriol (P3) as a marker of 21-OHD is scientifically sound and may be clinically practical.
Neonatal skin health and associated dermatological conditions
Authors: Rezaei Shawheen J. , Linggonegoro Danny , Admani Shehla
Published: June 2024

Purpose of review

This review describes recent developments in neonatal skincare management and situates these findings within the preexisting literature on neonatal dermatology.

Recent findings

The studies included in this review expand research methods evaluating skincare management to different contexts across the world. Several studies explore the roles of emollient therapy, disinfection, and skin-to-skin contact on improving neonates’ long-term health outcomes. Recent findings also assess the impact of neonatal interventions on atopic dermatitis risk later in life as well as epidemiological and microbiome variables that may predict this risk. Additionally, updates on various dermatological conditions unique to neonates are discussed in further detail.

Neonatal skincare management differs in notable ways from that of other age groups. The presentation of dermatologic diseases as well as the rare conditions that affect neonates make their clinical management unique. The recent literature on neonatal dermatology can help inform clinicians regarding important considerations in treating their neonatal population.
Development and Validation of a Ready-to-Talk Measure for Use in Adolescents and Young Adults Living With Advanced Cancer
Authors: Bell Cynthia J. , Spruit Jessica L. , Deatrick Janet A. , Weaver Meaghann S. , Dickens David S. , Hinds Pamela S. , Kavanaugh Karen L.
Published: June 2024

Background

In the era of evolving and emerging therapies, adolescents and young adults (AYAs) living with advanced cancer experience a high degree of uncertainty, making palliative care and end-of-life (PCEOL) discussions difficult. Clinical conversations determine values/preferences that guide shared decision-making and goals of treatment, including end-of-life care when cancer progresses. Initiating PCEOL conversations is challenging for clinicians.

Objective

This study describes the development and validation of an instrument that measures AYA readiness to engage in PCEOL clinical conversations.

Methods

A Ready-to-Talk Measure (R-T-M) was developed, guided by the revised conceptual model of readiness across 3 domains (awareness, acceptance, and willingness). Content experts evaluated validity, and 13 AYAs with advanced cancer participated in cognitive interviews. Acceptability (item applicability, clarity, interpretation, sensitivity, missingness) and experiences (benefit, burden) were analyzed.

Results

The scale content validity index was ≥0.90 for each domain. Forty-two of the 55 R-T-M items were acceptable without any change. Three items were deleted. Ten items were modified, and 3 were added. Adolescents and young adults wanted more items about friends/siblings and about AYA unique qualities for clinicians to know them better. Adolescents and young adults acknowledged benefit through talking about difficult, relevant topics.

Conclusion

Ready-to-Talk Measure validity was strengthened by deleting or modifying unclear or misinterpreted items and by adding items. Next steps include psychometric analysis to determine reliability/dimensionality and stakeholder input to make the R-T-M a clinically useful tool.

Implications for Practice

Ready-to-Talk Measure assessment of readiness to engage in PCEOL conversations while identifying unique preferences of AYAs holds promise for facilitating ongoing discussions.
The Effect of the COVID-19 Pandemic on Suicide Trends in Pretoria, South Africa
Authors: Robinson Kay-Leigh , Pretorius Candice , Blumenthal Ryan , Meyer Pieter
Published: June 2024

Suicide is one of the worldwide leading causes of unnatural death. Pretoria is a capital city of South Africa and is the fourth most populated city in South Africa. Between 16 and 22 suicide cases are recorded daily in South Africa.

Case files from the Pretoria Medico-Legal Laboratory were reviewed between 1 January 2015 to 31 December 2021, which spanned the COVID-19 pandemic. All cases of possible and probable suicides were included. One-way analysis of variance and Pearson chi2 tests were conducted to determine statistical significance in the observed trends.

A total of 1820 possible and probable suicide cases were identified. The year following the outbreak of the COVID-19 pandemic accounted for the largest number of suicides. White males were the most heavily represented population, followed by Black males. Hanging was the most common method for males, whereas poisoning via ingestion and/or overdose was more commonly used by females.

Suicides in Pretoria have increased since previous studies from 9.74% and 10.2% to 13.32%. Methods used have changed among various population groups over the past two decades. This paper examined changes in suicide trends in Pretoria compared to previous studies and highlighted correlations between suicide trends and COVID-19 lockdown measures.
Gender Identity in Forensic Death Investigation
Authors: Fedor Juniper , Krywanczyk Alison , Redgrave Anthony
Published: June 2024

In the current body of forensic literature, there is little guidance available regarding death investigations of transgender, intersex, and gender diverse individuals. An increase in the prevalence of gender diverse identifying people and the frequency in which these individuals experience a premature death makes it more likely these deaths will fall under the jurisdiction of the medical examiner's office. The inability to navigate these diverse cases due to a lack of training, education, and support may leave forensic professionals without the tools needed to accurately represent these deaths.

This narrative review is intended to provide the foundational knowledge needed by forensic death investigators when investigating gender identity in death, including suggested guidelines for a more effective and empathetic death investigation. A better understanding of the implications and applications of this information when included in reports will bolster the quality and quantity of the data reported and collected. This will lead to more accurate monitoring and reporting of violent, suicidal, and homicidal deaths of transgender, intersex, and other gender diverse individuals, and a higher identification rate of unidentified remains with gender diverse markers.
Pediatric Acute Respiratory Distress Syndrome Severity and Health-Related Quality of Life Outcomes: Single-Center Retrospective Cohort, 2011–2017*
Authors: Killien Elizabeth Y. , Ohman Robert T. , Dervan Leslie A. , Smith Mallory B. , Rivara Frederick P. , Watson R. Scott
Published: June 2024

OBJECTIVES:

To determine factors associated with health-related quality of life (HRQL) decline among pediatric acute respiratory distress syndrome (PARDS) survivors.

DESIGN:

Retrospective cohort study.

SETTING:

Academic children’s hospital.

PATIENTS:

Three hundred fifteen children 1 month to 18 years old with an unplanned PICU admission from December 2011 to February 2017 enrolled in the hospital’s Outcomes Assessment Program.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Pre-admission baseline and median 6-week post-discharge HRQL were assessed using the Pediatric Quality of Life Inventory or the Functional Status II-R. Patients meeting retrospectively applied Second Pediatric Acute Lung Injury Consensus Conference criteria for PARDS were identified, and PARDS severity was classified using binary (mild/moderate, severe) and trichotomous (mild, moderate, severe) categorization for noninvasive ventilation and invasive mechanical ventilation (IMV). PARDS occurred in 41 of 315 children (13.0%). Clinically important HRQL decline (≥ 4.5 points) occurred in 17 of 41 patients (41.5%) with PARDS and 64 of 274 without PARDS (23.4%). On multivariable generalized linear regression adjusted for age, baseline Pediatric Overall Performance Category, maximum nonrespiratory Pediatric Logistic Organ Dysfunction score, diagnosis, length of stay, and time to follow-up, PARDS was associated with HRQL decline (adjusted relative risk [aRR], 1.70; 95% CI, 1.03–2.77). Four-hour and maximum PARDS severity were the only factors associated with HRQL decline. HRQL decline occurred in five of 18 patients with mild PARDS at 4 hours, five of 13 with moderate PARDS (aRR 2.35 vs. no PARDS [95% CI, 1.01–5.50]), and seven of ten with severe PARDS (aRR 2.56 vs. no PARDS [95% CI, 1.45–4.53]). The area under the receiver operating characteristic curve for discrimination of HRQL decline for IMV patients was 0.79 (95% CI, 0.66–0.91) for binary and 0.80 (95% CI, 0.69–0.93) for trichotomous severity categorization.

CONCLUSIONS:

HRQL decline is common among children surviving PARDS, and risk of decline is associated with PARDS severity. HRQL decline from baseline may be an efficient and clinically meaningful endpoint to incorporate into PARDS clinical trials.
NYC Care: A Large Health Care Access Program for Uninsured New York City Residents
Authors: Jiménez Jonathan , Kress Marielle , Long Ted , Katz Mitchell
Published: June 2024

Context:

Millions of people living in the United States are excluded from health insurance due to income or immigration status. These 2 groups are more likely to lack access to health care or a regular source of care.

Program:

NYC Health + Hospitals is addressing this need with NYC Care, a health care access program. The program is designed to be the single point of access for uninsured care citywide and includes a membership card, a 24-hour customer service line, and direct access to primary care medical homes. Health care is coordinated across NYC Health + Hospitals using integrated electronic referrals and a medical record system.

Implementation:

The program uses a single enrollment process across safety net health care resources of NYC Health + Hospitals. A 24-hour call center was established to answer questions, make primary care appointments, and make warm handoffs to enrollment staff. Once eligibility is confirmed and patients are enrolled, they are mailed a membership card, a member handbook, and offered a primary care appointment. A multipronged public awareness campaign including citywide, multilingual marketing and outreach via community-based organizations was essential to build trust.

Outcomes:

NYC Care had 119 203 members at the end of June 2023. Fifty-eight percent had not seen a primary care doctor in the NYC Health + Hospitals system in the prior 36 months. In total, 76 439 had completed 1 or more primary care visits; 53.1% of enrollees with diabetes had improved hemoglobin A1c, and 73.4% of enrollees with hypertension had improved blood pressure control after 6 months of enrollment.

Discussion:

NYC Care demonstrates that municipalities can improve access to care for the uninsured by simplifying steps to affordable health care services, connecting patients directly to patient-centered medical homes, and improving the patient experience. A comprehensive public awareness campaign is also crucial.
Valleix's Sign
Authors: Gohritz Andreas , Dellon A. Lee
Published: June 2024

Some patients present with clinical symptoms of localized tenderness and pain associated with a specific peripheral nerve, such as the ulnar nerve at the elbow or the sciatic nerve, which has been called, although rarely, "Valleix point” or “Valleix phenomenon”. The purpose of this article was to translate and research the 719-page book “Traité des névralgies ou affections douloureuses des nerfs” dated 1841, dedicated solely to nerve pain (neuralgia), written by the French physician François Louis Isidore Valleix (1807–1855). He may have been the first person to observe and describe this phenomenon of localized pain, but he was probably also the first to describe distal nerve radiation, which he called “élancement” or lancinating, or stabbing. He described the phenomenon of a nerve producing pain at points along its course that we now understand to be sites of compression, clearly describing cubital and fibular tunnel syndromes, which he called neuralgias. He also described some rarer sites of compression, such as supraorbital and occipital neuralgia, notalgia paresthetica, and ACNES, but he did not describe the most common site of compression today, the median nerve at the wrist. Valleix's descriptions are clear and precede the classic 1915 reports of Hoffmann's and Tinel's signs by 74 years.
Compression therapy in patients with venous leg ulcers: a best practice implementation project
Authors: Ruiz María Jesús Samaniego , Moll Nieves Valero , Gálvez Miguel Muñoz , Jiménez Marina Gallego , Muñoz Laura Albornos
Published: June 2024

Introduction and objectives:

Venous leg ulcers are the most common ulcerations of the lower extremities. Compression is the most important consideration and the gold standard treatment for venous leg ulcers. This implementation project aimed to promote best practices in the management of venous leg ulcers in a rural community-care setting.

Methods:

This project was guided by the JBI Evidence Implementation Framework, which is grounded in audit and feedback processes, along with a structured approach to identifying and managing barriers to compliance with recommended best practices.

Results:

Compliance with best practices increased for most audit criteria. The use of compression therapy increased from 16.7% to 60%, documentation increased from 6.7% to 50%, replacement of compression bandages from 6.7% to 60%, patient education from 0% to 46.7%, and holistic assessment from 0% to 13%. However, compliance for individualized interventions to promote adherence remained at 0%.

Conclusions:

This project succeeded in introducing compression therapy as a basic treatment for venous ulcers. However, continued improvement in the care for venous ulcers and guarantee of long-term implementation of evidence are necessary.

Spanish abstract:

http://links.lww.com/IJEBH/A212
Roseinatronobacter alkalisoli sp. nov., an alkaliphilic bacterium isolated from soda soil, and genome-based reclassification of the genera Rhodobaca and Roseinatronobacter
Authors: Hu Xinyu , Yang Fan , Yang Shujing , Guo Wenjun , Ren Jiangtao , Liu Shenkui , Xiao Xiang , Zhu Lin , Wei Wei
Published: June 2024

The genera Rhodobaca and Roseinatronobacter are phylogenetically related genera within the family Paracoccaceae. Species of these genera were described using 16S rRNA gene-based phylogeny and phenotypic characteristics. However, the 16S rRNA gene identity and phylogeny reveal the controversy of the taxonomic status of these two genera. In this work, we examined the taxonomic positions of members of both genera using 16S rRNA gene phylogeny, phylogenomic analysis and further validated using overall genome-related indexes, including digital DNA–DNA hybridization, average nucleotide identity, average amino acid identity and percentage of conserved proteins. Based on phylogenetic and phylogenomic results, the current four species of the two genera clustered tightly into one clade with high bootstrap values, suggesting that the genus Rhodobaca should be merged with Roseinatronobacter. In addition, a novel species isolated from a soda soil sample collected from Anda City, PR China, and designated as HJB301T was also described. Phenotypic, chemotaxonomic, genomic and phylogenetic properties suggested that strain HJB301T (=CCTCC AB 2021113T=KCTC 82977T) represents a novel species of the genus Roseinatronobacter, for which the name Roseinatronobacter alkalisoli sp. nov. is proposed.
Paraburkholderia largidicola sp. nov., a gut symbiont of the bordered plant bug Physopelta gutta
Authors: Yashima Reona , Terata Yuan , Sakamoto Kaoru , Watanabe Miho , Takeshita Kazutaka
Published: June 2024

Gram-negative, aerobic, rod-shaped, non-spore-forming, motile bacteria, designated strains F2T and PGU16, were isolated from the midgut crypts of the bordered plant bug Physopelta gutta, collected in Okinawa prefecture, Japan. Although these strains were derived from different host individuals collected at different times, their 16S rRNA gene sequences were identical and showed the highest similarity to Paraburkholderia caribensis MWAP64T (99.3 %). The genome of strain F2T consisted of two chromosomes and two plasmids, and its size and G+C content were 9.28 Mb and 62.4 mol% respectively; on the other hand, that of strain PGU16 consisted of two chromosomes and three plasmids, and its size and G+C content were 9.47 Mb and 62.4 mol%, respectively. Phylogenetic analyses revealed that these two strains are members of the genus Paraburkholderia. The digital DNA–DNA hybridization value between these two strains was 92.4 %; on the other hand, the values between strain F2T and P. caribensis MWAP64T or phylogenetically closely related Paraburkholderia species were 44.3 % or below 49.1 %. The predominant fatty acids of both strains were C16 : 0, C17 : 0 cyclo, summed feature 8 (C18 : 1
 ω7c/C18 : 1
 ω6c), and C19 : 0 cyclo ω8c, and their respiratory quinone was ubiquinone 8. Based on the above genotypic and phenotypic characteristics, strains F2T and PGU16 represent a novel species of the genus Paraburkholderia for which the name Paraburkholderia largidicola sp. nov. is proposed. The type strain is F2T (=NBRC 115765T=LMG 32765T).
FGF21 reflects a responsive adipose tissue-liver axis in both cardiometabolic burden and following metabolic surgery
Authors: Patt Marie , Karkossa Isabel , Krieg Laura , Massier Lucas , Makki Kassem , Tabei Shirin , Karlas Thomas , Dietrich Arne , Gericke Martin , Stumvoll Michael , Blüher Matthias , von Bergen Martin , Schubert Kristin , Kovacs Peter , Chakaroun Rima M.
Published: June 2024

Objective

This research aims to uncover the factors associated with circulating FGF21 levels in a cohort mimicking metabolic disease progression, examining its relationship with adipose tissue (AT) morphology and function. It also investigates FGF21 level changes post-metabolic surgery, predictive factors, and their links to metabolic adjustments.

Design

In this observational study, serum FGF21 was measured in 678 individuals cross-sectionally and longitudinally in 189 undergoing metabolic surgery. We explored links between FGF21, AT histology, cardiometabolic risk factors, weight loss, glucose metabolism changes using feature selection algorithms, univariate/multivariate models, and transcriptome/proteome network analyses in subcutaneous and visceral AT.

Results

FGF21 levels track closely with central adiposity, subclinical inflammation, insulin resistance, and cardiometabolic risk, with circulating leptin emerging as the top predictor. Visceral AT inflammation was associated with liver dysfunction and FGF21 elevation. Post-surgery, FGF21 peaked transitorily at 3 months and predicted fat mass loss at 12 months but not HOMA-IR improvements. Mediation analysis indicated an increased catabolic and AT-lipolytic state associated with higher liver enzyme and FGF21 levels (total effect 0.38, p<0.01; proportion mediation 32%, p<0.01). AT fibrosis was related to a blunted transitory FGF21 increase, and lower fat loss, and hence linked with a reduced surgical effect (FFA and visceral AT fibrosis: rho=-0.31, p=0.030; FFA and fat-mass loss: rho=0.17, p=0.020).

Conclusion

FGF21 reflects the liver’s metabolic response to AT characteristics in both central adiposity and after metabolic surgery, with its dynamics reflecting AT-liver crosstalk.
Induction of the inflammasome by the SARS-CoV-2 accessory protein ORF9b, abrogated by small-molecule ORF9b homodimerization inhibitors
Authors: Zodda Erika , Pons Mònica , DeMoya-Valenzuela Natàlia , Calvo-González Cristina , Benítez-Rodríguez Cristina , López-Ayllón Blanca Díes , Hibot Achraf , Cascante Marta , Montoya María , Dolors Pujol María , Rubio-Martínez Jaime , Thomson Timothy M.
Published: June 2024

Viral accessory proteins play critical roles in viral escape form host innate immune responses and in viral inflammatory pathogenesis. Here we show that the SARS-CoV-2 accessory protein, ORF9b, but not other SARS-CoV-2 accessory proteins (ORF3a, ORF3b, ORF6, ORF7, ORF8, ORF9c, ORF10), strongly activates inflammasome-dependent caspase-1 in A549 lung carcinoma cells and THP-1 monocyte-macrophage cells. Exposure to lipopolysaccharide (LPS) and ATP additively enhanced the activation of caspase-1 by ORF9b, suggesting that ORF9b and LPS follow parallel pathways in the activation of the inflammasome and caspase-1. Following rationalin silicoapproaches, we have designed small molecules capable of inhibiting the homodimerization of ORF9b, which experimentally inhibited ORF9b-ORF9b homotypic interactions, caused mitochondrial eviction of ORF9b, inhibited ORF9b-induced activation of caspase-1 in A549 and THP-1 cells, cytokine release in THP-1 cells, and restored type I interferon (IFN-I) signaling suppressed by ORF9b in both cell models. These small molecules are first-in-class compounds targeting a viral accessory protein critical for viral-induced exacerbated inflammation and escape from innate immune responses, with the potential of mitigating the severe immunopathogenic damage induced by highly pathogenic coronaviruses and restoring antiviral innate immune responses curtailed by viral infection.
iHDSel software: The Price equation and the population stability index to detect genomic patterns compatible with selective sweeps. An example with SARS-CoV-2.
Authors: Carvajal-Rodriguez Antonio
Published: June 2024

A large number of methods have been developed and continue to be developed for detecting the signatures of selective sweeps in genomes. Significant advances have been made, including the combination of different statistical strategies and the incorporation of artificial intelligence (machine learning) methods. Despite these advances, several common problems persist, such as the unknown null distribution of the statistics used, necessitating simulations and resampling to assign significance to the statistics. Additionally, it is not always clear how deviations from the specific assumptions of each method might affect the results. In this work, allelic classes of haplotypes are used along with the informational interpretation of the Price equation to design a statistic with a known distribution that can detect genomic patterns caused by selective sweeps. The statistic consists of Jeffreys divergence, also known as the population stability index, applied to the distribution of allelic classes of haplotypes in two samples. Results with simulated data show optimal performance of the statistic in detecting divergent selection. Analysis of real SARS-CoV-2 genome data also shows that some of the sites playing key roles in the virus's fitness and immune escape capability are detected by the method. The new statistic, called JHAC, is incorporated into the iHDSel (informed HacDivSel) software available at https://acraaj.webs.uvigo.es/iHDSel.html.
Urban wastewater contains a functional human antibody repertoire of mucosal origin
Authors: Stephenson Sean , Eid Walaa , Wong Chandler Hayyin , Mercier Elisabeth , D’Aoust Patrick M. , Kabir Md Pervez , Baral Stefan , Gilbride Kimberly A. , Oswald Claire , Straus Sharon E. , Mackenzie Alex , Delatolla Robert , Graber Tyson E.
Published: June 2024

Wastewater-based surveillance of human disease offers timely insights to public health, helping to mitigate infectious disease outbreaks and decrease downstream morbidity and mortality. These systems rely on nucleic acid amplification tests for monitoring disease trends, while antibody-based seroprevalence surveys gauge community immunity. However, serological surveys are resource-intensive and subject to potentially long lead times and sampling bias. We identified and characterized a human antibody repertoire, predominantly secretory IgA, isolated from a central wastewater treatment plant and building-scale wastewater collection points. These antibodies partition to the solids fraction and retain immunoaffinity for SARS-CoV-2 and Influenza A virus antigens. This stable pool could enable real-time tracking of correlates of vaccination, infection, and immunity, aiding in establishing population-level thresholds for immune protection and assessing the efficacy of future vaccine campaigns, particularly those that are designed to induce humoral mucosal immunity.
Genome-wide association study of anterior uveitis
Authors: Koskimäki Fredrika , Ahokas Oona ,   FinnGen, Estonian Biobank Research Team, Elnahas Abdelrahman , Reigo Anu , Reis Kadri , Esko Tõnu , Palta Priit , Leinonen Sanna , Kettunen Johannes , Liinamaa Johanna , Karjalainen Minna K. , Saarela Ville
Published: June 2024

Importance

Anterior uveitis is an intraocular disease characterized by inflammation of the iris and the ciliary body and known to co-occur with autoimmune diseases. This is the largest genome-wide association study (GWAS) meta-analysis specifically for anterior uveitis to date.

Objective

The purpose of this study is to define genetic factors associated with anterior uveitis through genome-wide association study.

Design, setting and participants

In this GWAS meta-analysis we combined data from the FinnGen, Estonian Biobank and UK Biobank with a total of 12 205 anterior uveitis cases and 917 145 controls. We performed a phenome-wide association study to investigate associations across phenotypes and traits. We also evaluated genetic correlations of anterior uveitis.

Main outcomes and measures

Genetic variants associated with anterior uveitis.

Results

We identified six anterior uveitis associated loci. Genome-wide significant (p< 5 × 10−8) associations were identified for the first time at three loci (INAVA, NLRP3andNOS2). We detected associations at three loci previously reported to be associated with uveitis (ERAP1, TNRC18and theHLAregion) and also replicated associations at two loci previously associated with acute anterior uveitis (IL23RandHDAC2-AS2). In phenome-wide association study, we further detected that lead single nucleotide polymorphism, SNPs, at three of the anterior uveitis associated loci (ERAP1, INAVAandTNRC18) are associated with other immunity-related phenotypes, including ankylosing spondylitis and inflammatory bowel disease. Additionally, we detected a moderate genetic correlation between anterior uveitis and inflammatory bowel disease (rg=0.39,p= 8 × 10−5).

Conclusions and relevance

We identified six anterior uveitis associated loci including three novel loci with genome-wide significance. Our findings deepen our understanding of the genetic basis of anterior uveitis and the genetic connections between anterior uveitis and immune related disorders, providing a foundation for further research and potential therapeutic interventions.