bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrochemical skin conductance by Sudoscan®: a new tool to predict intradialytic hypotension
Authors: Reach Pauline , Touzot Maxime , Lombardi Yannis , Maheas Catherine , Sacco Emmanuelle , Fels Audrey , Beaussier Hélène , Ureña-Torres Pablo , Chatellier Gilles , Ridel Christophe , Zuber Mathieu
Published: May 2021

Background

Intradialytic hypotension (IDH), a common complication in haemodialysis (HD) patients, is associated with multiple risk factors including cardiac dysfunction and alterations of the peripheral autonomic nervous system. To what extent dysautonomia may contribute to the occurrence of IDH remains elusive. We sought to investigate the clinical utility of Sudocan®, a device that quantifies dysautonomia, in the prediction of IDH.

Methods

We conducted a prospective monocentric study in adult HD patients from July 2019 to February 2020. Dysautonomia was assessed by the measurements of hand and foot electrochemical skin conductance (ESC) using Sudocan®, before HD. The primary endpoint was the incidence of IDH (The National Kidney Foundation/Kidney-Dialysis Outcome Quality Initiative definition), according to the presence of a pathological hand and/or foot ESC value, during the 3-month study period.

Results

A total of 176 HD patients (64 ± 14 years old) were enrolled. Mean pre-dialysis HD hand and foot ESC was 45 ± 20 and 54 ± 22 µS, respectively. About 35% and 40% of patients had a pathological ESC at the hand and foot, respectively. IDH occurred in 46 patients. Logistic regression showed that pathologic pre-dialysis HD hand ESC was associated with an increased risk of IDH [odds ratio = 2.56, 95% CI (1.04–6.67), P = 0.04]. The cumulative risk incidence of IHD during the study was 5.65 [95% CI (2.04–15.71), P = 0.001] and 3.71 [95% CI (1.41–9.76), P = 0.008], with a pathological hand and foot ESC, respectively.

Conclusions

A pathological hand ESC, as assessed by a non-invasive Sudoscan® test, is associated with an increased risk of IDH.
Effect of a very low-carbohydrate ketogenic diet vs recommended diets in patients with type 2 diabetes: a meta-analysis
Authors: Rafiullah Mohamed , Musambil Mohthash , David Satish Kumar
Published: May 2021

Context

There is renewed interest in using very low-carbohydrate ketogenic (VLCK) diets to manage diabetes. Many clinical trials have been published, often with mixed results.

Objective

This meta-analysis compares the effect of a VLCK diet on glycemic control, body weight, lipid profile, medication use, and dropouts with that of recommended diets for 12 weeks or longer in people with type 2 diabetes.

Data Sources

Ovid MEDLINE, Ovid Embase, CENTRAL, and CINAHL databases were searched (January 1980 through September 2019).

Study Selection

Two authors independently reviewed search results to select randomized controlled trials (RCTs) comparing a VLCK diet (carbohydrate intake < 50 g/d or < 10% of total energy) with any recommended diet for type 2 diabetes in adults. Discrepancies were resolved after consulting with the third author.

Data Extraction

Eight RCTs with 648 participants were identified.

Results

Compared with control diets, the VLCK diet resulted in a greater decrease in hemoglobin A1c after 3 months (weighted mean difference[WMD]: −6.7 mmol/mol; 95%CI, −9.0 to −4.4) (WMD: −0.61%; 95%CI, −0.82 to −0.40; P < 0.001; moderate-certainty evidence) and after 6 months (WMD: −6.3 mmol/mol; 95%CI, −9.3 to −3.5) (WMD: −0.58%; 95%CI, −0.85 to −0.32; low-certainty evidence). There was a significantly greater weight loss with the VLCK diet after 3 months (WMD: −2.91 kg; 95%CI, −4.88 to −0.95; low-certainty evidence) and after 6 months (WMD: −2.84 kg; 95%CI, −5.29 to −0.39; low-certainty evidence). The VLCK diet was not better than a control diet after 12 months. It was superior in decreasing triglyceride levels, increasing high-density lipoprotein cholesterol levels, and reducing the use of antidiabetic medications for up to 12 months.

Conclusion

The VLCK diet appears to control glycemia and decrease body weight for up to 6 months in people with obesity and diabetes. Beneficial changes in serum triglycerides and high-density lipoprotein cholesterol, along with reductions in antidiabetic medications, continued in the VLCK group until 12 months. However, the quality of currently available evidence is not sufficient to recommend VLCK diets. A major limitation of the VLCK diet is patients’ lack of adherence to carbohydrate restriction.

Systematic Review Registration

PROSPERO registration number CRD42020154700
Diagnostic Accuracy of Health Care Administrative Diagnosis Codes to Identify Nontuberculous Mycobacteria Disease: A Systematic Review
Authors: Mejia-Chew Carlos , Yaeger Lauren , Montes Kevin , Bailey Thomas C , Olsen Margaret A
Published: May 2021

Background

Health care administrative database research frequently uses standard medical codes to identify diagnoses or procedures. The aim of this review was to establish the diagnostic accuracy of codes used in administrative data research to identify nontuberculous mycobacterial (NTM) disease, including lung disease (NTMLD).

Methods

We searched Ovid Medline, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to April 2019. We included studies assessing the diagnostic accuracy of International Classification of Diseases, 9th edition, Clinical Modification (ICD-9-CM) diagnosis codes to identify NTM disease and NTMLD. Studies were independently assessed by 2 researchers, and the Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess bias and quality.

Results

We identified 5549 unique citations. Of the 96 full-text articles reviewed, 7 eligible studies of moderate quality (3730 participants) were included in our review. The diagnostic accuracy of ICD-9-CM diagnosis codes to identify NTM disease varied widely across studies, with positive predictive values ranging from 38.2% to 100% and sensitivity ranging from 21% to 93%. For NTMLD, 4 studies reported diagnostic accuracy, with positive predictive values ranging from 57% to 64.6% and sensitivity ranging from 21% to 26.9%.

Conclusions

Diagnostic accuracy measures of codes used in health care administrative data to identify patients with NTM varied across studies. Overall the positive predictive value of ICD-9-CM diagnosis codes alone is good, but the sensitivity is low; this method is likely to underestimate case numbers, reflecting the current limitations of coding systems to capture NTM diagnoses.
CE: Psychedelic-Assisted Therapy
Authors: Penn Andrew , Dorsen Caroline G. , Hope Stephanie , Rosa William E.
Published: May 2021

Psychedelics are a class of psychoactive substances that were studied extensively between 1943 and 1970 as potential therapies for treating a host of mental health disorders, including addiction. Despite promising early results, U.S. psychedelic research was halted in the early 1970s with the enactment of the Controlled Substances Act. As the field of psychedelic-assisted therapy develops, nurses can decide the role they will play in the continuing clinical and scholarly research of these substances, which may soon be used in controlled settings to treat some of the most widespread mental health disorders. To prepare for this task, this article proposes that nurses

become familiar with the history, relevant language, and scientific findings related to the field of psychedelic research.

learn about existing psychedelic-assisted therapy and research resources.

examine their thoughts, judgments, and opinions about therapeutic psychedelic use.

consider the potential role of nursing in psychedelic-assisted therapies going forward.
Assessing proviral competence: current approaches to evaluate HIV-1 persistence
Authors: Cicilionytė Aurelija , Berkhout Ben , Pasternak Alexander O.
Published: May 2021

Purpose of review

Despite decades of suppressive antiretroviral therapy (ART), HIV-1 reservoirs persist and fuel viral rebound if therapy is interrupted. The persistence of viral reservoirs in infected individuals is the main obstacle to achieving HIV-1 eradication or a long-term remission. Accurate assessment of the viral reservoir size is necessary for monitoring the effectiveness of the curative interventions. Here, we review the recent progress in the development of assays to measure HIV-1 persistence, highlighting their key advantages and limitations.

Recent findings

To estimate the viral reservoir size, a number of assays have been developed that assess different aspects of HIV-1 persistence in ART-treated individuals. These include viral outgrowth assays to measure proviral replication competence, sequencing-based assays to measure genetic intactness of HIV-1 proviruses, and diverse techniques that measure the ability of proviruses to produce viral RNA and/or proteins (transcription and translation competence), with or without ex vivo stimulation. Recent years have seen the development of next-generation reservoir assays that, in addition to measuring viral persistence markers, assess the proviral integration sites and characterize the HIV-1 reservoir cells on the single-cell level.

Although no assay yet can measure the HIV-1 reservoir with 100% accuracy, recent technical advances allow reliable estimation of its size and composition.
Firearm Safety
Authors: Hoskins Nina , Joseph Rachel , Akers Shanna W.
Published: May 2021

Firearm-related injuries to children are reported as one of the top 10 causes of death for all age groups of children. Over 250 children are shot unintentionally each year, with 150 deaths per annum. Accidental shootings occur when a child has access to a family member's weapon and ammunition in the home. This article summarizes the literature on accidental shootings in the home, not including intentional homicides, suicides, or mass shootings. The pediatric surgical nurse can attempt to decrease this tragedy by providing prevention education at every pediatric visit.
Necrotizing fasciitis: The bounce-back patient case report
Authors: Jauregui Jean E. , Seward Kimberly D.
Published: May 2021

Necrotizing fasciitis (NF) is a complicated skin and soft tissue infection that has a high mortality rate and often requires surgical debridement, intravenous antibiotics, and wound care. The nurse practitioner needs to be aware of the common characteristics of NF and depending on their clinical environment, know when to refer the patient to a local emergency department (ED) for further evaluation and treatment and/or consult for hospital admission from an ED.
Early Trauma Is Associated With Suicidal Ideation in Patients With Panic Disorder
Authors: Kim Hyun-Ju , Kim Ji Eun , Lee Sang-Hyuk
Published: May 2021

There are several predictors of suicidality in patients with panic disorder (PD). Being a woman, younger age, low education level, unmarried status, and symptom severity have been suggested. This study aimed to examine whether early trauma is associated with suicidal ideation in patients with PD. Our study included 267 patients with PD and 105 controls. Data on sociodemographic variables and data from the Early Trauma Inventory Self Report–Short Form, Beck Depression Inventory, Panic Disorder Severity Scale, Anxiety Sensitivity Inventory–Revised, Coping Scales, and Scale for Suicide Ideation were collected, and correlation and regression analyses were performed. This study suggests that clinicians should consider early trauma when assessing suicidal ideation in patients with PD. Clinicians could consider alternative treatments, such as trauma-focused cognitive-behavioral therapy, eye movement desensitization, reprocessing approaches, and classical pharmacological and psychological treatments for patients with PD who have a history of early trauma and are expected to be at high risk for suicide.
Genital Herpes Zoster: A Rare Location That Can Mimic Genital Herpes
Authors: Magdaleno-Tapial Jorge , Hernández-Bel Pablo , Ortiz-Salvador José María , López-Martí Cristina , Martínez-Doménech Álvaro , García-Legaz-Martínez Marta , Pérez-Ferriols Amparo
Published: May 2021

Herpes zoster is an acute, cutaneous viral infection caused by the reactivation of varicella-zoster virus. Genital dermatomes are involved in only up to 2% of cases and are probably underrecognized. We present a series of 7 genital herpes zoster cases diagnosed in our Unit of Sexually Transmitted Diseases. None of our patients were positive for HIV test, and only one was taking immunosuppressive medication. We recommend the use of molecular testings to confirm the diagnosis of varicella-zoster virus or herpes simplex virus infection in all cases of genital herpes–like lesions.
Predicting the Probability of Chlamydia Reinfection in African American Women Using Immunologic and Genetic Determinants in a Bayesian Model
Authors: Olson Kristin M. , Geisler William M. , Bakshi Rakesh K. , Gupta Kanupriya , Tiwari Hemant K.
Published: May 2021

Background

African Americans have the highest rates of Chlamydia trachomatis (CT) infection in the United States and also high reinfection rates. The primary objective of this study was to develop a Bayesian model to predict the probability of CT reinfection in African American women using immunogenetic data.

Methods

We analyzed data from a cohort of CT-infected African American women enrolled at the time they returned to a clinic in Birmingham, AL, for the treatment of a positive routine CT test result. We modeled the probability of CT reinfection within 6 months after treatment using logistic regression in a Bayesian framework. Predictors of interest were presence or absence of an HLA-DQB1*06 allele and CT-specific CD4+ IFN-γ response, both of which we had previously reported were independently associated with CT reinfection risk.

Results

Among 99 participants evaluated, the probability of reinfection for those with a CT-specific CD4+ IFN-γ response and no HLA-DQB1*06 alleles was 14.1% (95% credible interval [CI], 3.0%–45.0%), whereas the probability of reinfection for those without a CT-specific CD4+ IFN-γ response and at least one HLA-DQB1*06 allele was 61.5% (95% CI, 23.1%–89.7%).

Conclusions

Our model demonstrated that presence or absence of an HLA-DQB1*06 allele and CT-specific CD4+ IFN-γ response can have an impact on the predictive probability of CT reinfection in African American women.
Race Differences in Reported “Near Miss” Patient Safety Events in Health Care System High Reliability Organizations
Authors: Thomas Angela D. , Pandit Chinmay , Krevat Seth A.
Published: May 2021

Objectives

This study aimed to determine if race differences exist in voluntarily reported near-miss patient safety events in a large integrated, 10-hospital health care system on its journey to become a high reliability organization.

Methods

From July 1, 2015, to June 30, 2017, employees in a mid-Atlantic health care system voluntarily reported near-miss events by type using an occurrence reporting system referred to as the Patient Safety Event Management System. Inpatients, outpatients, and observation patients were identified as “Black,” “White,” or “other” (n = 39,390). Using retrospective analysis and χ2 goodness of fit, comparisons of race proportions were conducted to determine differences at the health system level, by hospital, and by event type.

Results

Significant race differences existed: (1) overall across the health care system with higher proportions of events reported for Whites and lower proportions of events reported for Blacks in the Patient Safety Event Management System, (2) by site in 9 of 10 hospitals, and (3) by type. All differences were significant at P < 0.05.

Conclusions

Race differences in near-miss patient safety events exist in voluntary reporting systems by type. Health care organizations, particularly health care high reliability organizations, can use these findings to help to identify areas of further study and investigation. Further study and investigation should include efforts to understand the root cause of the differences found in this study, including the role of reporting bias by race.
Optimizing Hospital Electronic Prescribing Systems: A Systematic Scoping Review
Authors: Williams Jac , Malden Stephen , Heeney Catherine , Bouamrane Matt , Holder Mike , Perera Uditha , Bates David W. , Sheikh Aziz
Published: May 2021

Objective

Considerable international investment in hospital electronic prescribing (ePrescribing) systems has been made, but despite this, it is proving difficult for most organizations to realize safety, quality, and efficiency gains in prescribing. The objective of this work was to develop policy-relevant insights into the optimization of hospital ePrescribing systems to maximize the benefits and minimize the risks of these expensive digital health infrastructures.

Methods

We undertook a systematic scoping review of the literature by searching MEDLINE, Embase, and CINAHL databases. We searched for primary studies reporting on ePrescribing optimization strategies and independently screened and abstracted data until saturation was achieved. Findings were theoretically and thematically synthesized taking a medicine life-cycle perspective, incorporating consultative phases with domain experts.

Results

We identified 23,609 potentially eligible studies from which 1367 satisfied our inclusion criteria. Thematic synthesis was conducted on a data set of 76 studies, of which 48 were based in the United States. Key approaches to optimization included the following: stakeholder engagement, system or process redesign, technological innovations, and education and training packages. Single-component interventions (n = 26) described technological optimization strategies focusing on a single, specific step in the prescribing process. Multicomponent interventions (n = 50) used a combination of optimization strategies, typically targeting multiple steps in the medicines management process.

Discussion

We identified numerous optimization strategies for enhancing the performance of ePrescribing systems. Key considerations for ePrescribing optimization include meaningful stakeholder engagement to reconceptualize the service delivery model and implementing technological innovations with supporting training packages to simultaneously impact on different facets of the medicines management process.
High conversion of tuberculin skin tests during the first year of antiretroviral treatment among South African adults in primary care
Authors: Van Ginderdeuren Eva , Bassett Jean , Hanrahan Colleen F. , Mutunga Lillian , Van Rie Annelies
Published: May 2021

Objectives:

Anergy reduces the sensitivity of the tuberculin skin test (TST) to detect Mycobacterium tuberculosis infection in people living with HIV. Antiretroviral treatment (ART) can reverse TST anergy, but data is scarce.

Methods:

To estimate TST conversion rates and factors associated with TST conversion, TST was placed at ART initiation, and 6 and 12 months thereafter (if TST negative at prior assessment).

Results:

Of 328 ART-eligible participants, 70% (231/328) had a valid TST result of whom 78% (180/231) were TST negative. At 6-month follow-up, 22% (24/109, 95% confidence interval [CI] 15%, 31%) of participants on ART, without incident tuberculosis (TB), and with a valid TST result converted to a positive TST. Of these 109 individuals, those with baseline CD4+ cell count >250 cells/μl were more likely to TST convert compared to those with baseline CD4+ cell count ≤250 cells/μl (odds ratio [OR] 3.54, 95% CI 1.29, 11.47). At 12 months post-ART initiation, an additional 12% (9/78, 95% CI 6, 20) of participants on ART, without incident TB and with a valid TST result experienced TST conversion. After 1 year on ART, TST conversion rate was 38 per 100 person-years (95% CI 26, 52), and lower in individuals with baseline CD4+ cell count ≤250 cells/μl (23/100 person-years, 95% CI 11, 41) compared to those with baseline CD4+ cell count >250 cells/μl (50/100 person-years, 95% CI 32, 73).

Conclusions:

TST conversion rate in the first year of ART is high, especially among people with CD4+ cell count >250 cells/μl. A TST-based eligibility strategy at ART initiation may underestimate eligibility for preventive therapy for tuberculosis.
Clinical Ultrasound Education for Medical Students
Authors: Rosenfeldt Nielsen Mathias , Kristensen Erik Qvist , Jensen Rune Overgaard , Mollerup Anne Milther , Pfeiffer Thorbjørn , Graumann Ole
Published: May 2021

The primary aim was to evaluate the effect of immersive virtual reality learning for training medical students in basic clinical ultrasound. Secondary outcomes were to explore if virtual reality learning had an effect on hand-eye coordination skills and if the medical students wanted more virtual reality learning.

This pilot study was a double-blind, parallel-group, block-randomized, controlled trial. Participants (n = 20) were blinded and randomized to virtual reality or e-learning for basic ultrasound education. Medical students with no previous ultrasound education were recruited voluntarily from the University of Southern Denmark. Data were collected during introductory courses on ultrasound from March to May 2019. Participants were assessed with Objective Structured Assessment on Ultrasound Skills. Assessing supervisors were blinded.

The virtual reality group (n = 11) scored a significantly higher Objective Structured Assessment on Ultrasound Skills score (143 [95% confidence interval {CI}, 135 to 151]) compared with the e-learning group (n = 9; 126 [95% CI, 113 to 138]; mean difference, 17 points [95% CI, 4 to 30]; P < 0.01). No significant effect on the hand-eye score was found (mean difference, 3 points [95 % CI, −3 to 9]; P = 0.32). Ninety-one percent of the virtual reality group wanted more virtual reality learning.

Immersive virtual reality learning improved medical students’ ultrasound skills significantly compared with e-learning. The hand-eye score was higher in the virtual reality group, although not at a significant level. Students wanted more virtual reality learning. Further research is needed to clarify immersive virtual reality's educational role in the future.
Comparison of the Effectiveness of Shear Wave Elastography and Superb Microvascular Imaging in the Evaluation of Breast Masses
Authors: Uysal Emine , Öztürk Mehmet , Kilinçer Abidin , Koplay Mustafa
Published: May 2021

This study aims to determine the diagnostic performance of superb microvascular imaging (SMI) and shear wave elastography methods in evaluating breast lesions. We will also compare the effectiveness of the stiffness, velocity, and vascular index (VI) parameters in distinguishing malignancy.

From January to June 2019, 121 patients with 121 solid breast masses (category 4 and 5 lesions according to the Breast Imaging-Reporting and Data System) detected during the routine grayscale sonographic examination were included in the study. Stiffness and velocity values were obtained using shear wave elastography for all lesions, and VI was obtained using SMI. The receiver operating characteristic curves were obtained to set the best cutoff values for the stiffness, velocity, and VI to differentiate patients with malignant breast lesions.

All 121 lesions were pathologically verified by US-guided core needle biopsy. Forty-seven (38.9%) of the lesions were malignant, and 74 (61.1%) were benign. Median stiffness, velocity, and VI values were significantly lower in benign masses compared with malignant masses (P < 0.001). The optimum cutoff values for the stiffness, velocity, and VI were determined to be 58.3 kPa, 4.5 m/s, and 1.1%, respectively. The areas under the curves were 0.897 for stiffness, 0.884 for velocity, and 0.687 for VI.

Shear wave elastography and SMI are noninvasive methods that may be used to evaluate breast masses. Although both methods' quantitative data are beneficial in differentiating malignant from benign masses, stiffness is the best parameter to be used.
Toward Ergonomic Design in Ultrasound Scanning
Authors: Kliewer Mark , Walker Tim , Bagley Anjuli R.
Published: May 2021

Sonographers experience stress-related musculoskeletal injuries at alarming rates. The magnitude of the problem has resulted in substantial economic and human costs. Early efforts, such as the transposition of office ergonomic models to the ultrasound suite, have been only marginally successful because of the vast difference between clerical and sonography work demands. In addition, although the issue has attracted the attention of professional sonographer societies, equipment manufacturers, and governmental agencies, such as the OSHA (Occupational Safety and Health), the causative mechanisms by which sonographers are injured remain inadequately addressed. A definitive ergonomic solution has been elusive.

With the help of occupational therapists and biomechanical engineers, we have developed a number of possible ergonomic modifications of ultrasound equipment. We explain the rationale behind these approaches to transducer design and assess the strengths and deficiencies of each.
Craniofacial Injuries From Personal Watercraft Accidents
Authors: Mirsky Nicholas , Kim Minji , Plotsker Ethan , Thaller Seth R.
Published: May 2021

Personal watercraft (PWC) use is a popular leisure activity. Although injuries associated with PWCs have been examined broadly, there is a lack of investigation into craniofacial injuries within this setting. This paper reviews the literature discussing PWC incidents and PWC-related craniofacial injuries. A comprehensive literature search of the MEDLINE, EMBASE, Google Scholar, and National Library of Medicine databases was conducted for studies published through January 2021. Articles were selected if they contained information on PWC accidents and related craniofacial injuries. We also examined 3 patient cases of PWC-related craniofacial injuries. Overall, our review suggests that over the past 20 years, injuries and accidents have decreased significantly whereas fatalities have decreased to a lesser extent. Most PWC-related craniofacial injuries result from blunt trauma and a notable number of deaths and traumatic brain injuries occur in adolescents. Given the increasing number of PWC sales, PWC-related craniofacial injuries may be more prevalent, which prompts improved regulations and protective gears. Existing state laws on PWCs vary dramatically. As of now, there is no uniform policy that requires protective equipment use like helmets or instruction before PWC use. There also should be limitations on alcohol consumption as well as age of the riders. Overall, our review indicates that more research is needed to reduce the number of craniofacial injuries among PWC riders.
An Ovine Model of Hemorrhagic Shock and Resuscitation, to Assess Recovery of Tissue Oxygen Delivery and Oxygen Debt, and Inform Patient Blood Management
Authors: Dyer Wayne B. , Tung John-Paul , Li Bassi Gianluigi , Wildi Karin , Jung Jae-Seung , Colombo Sebastiano Maria , Rozencwajg Sacha , Simonova Gabriela , Chiaretti Sara , Temple Fergal T. , Ainola Carmen , Shuker Tristan , Palmieri Chiara , Shander Aryeh , Suen Jacky Y. , Irving David O. , Fraser John F.
Published: May 2021

Background:

Aggressive fluid or blood component transfusion for severe hemorrhagic shock may restore macrocirculatory parameters, but not always improve microcirculatory perfusion and tissue oxygen delivery. We established an ovine model of hemorrhagic shock to systematically assess tissue oxygen delivery and repayment of oxygen debt; appropriate outcomes to guide Patient Blood Management.

Methods:

Female Dorset-cross sheep were anesthetized, intubated, and subjected to comprehensive macrohemodynamic, regional tissue oxygen saturation (StO2), sublingual capillary imaging, and arterial lactate monitoring confirmed by invasive organ-specific microvascular perfusion, oxygen pressure, and lactate/pyruvate levels in brain, kidney, liver, and skeletal muscle. Shock was induced by stepwise withdrawal of venous blood until MAP was 30 mm Hg, mixed venous oxygen saturation (SvO2) < 60%, and arterial lactate >4 mM. Resuscitation with PlasmaLyte® was dosed to achieve MAP > 65 mm Hg.

Results:

Hemorrhage impacted primary outcomes between baseline and development of shock: MAP 89 ± 5 to 31 ± 5 mm Hg (P < 0.01), SvO2 70 ± 7 to 23 ± 8% (P < 0.05), cerebral regional tissue StO2 77 ± 11 to 65 ± 9% (P < 0.01), peripheral muscle StO2 66 ± 8 to 16 ± 9% (P < 0.01), arterial lactate 1.5 ± 1.0 to 5.1 ± 0.8 mM (P < 0.01), and base excess 1.1 ± 2.2 to −3.6 ± 1.7 mM (P < 0.05). Invasive organ-specific monitoring confirmed reduced tissue oxygen delivery; oxygen tension decreased and lactate increased in all tissues, but moderately in brain. Blood volume replacement with PlasmaLyte® improved primary outcome measures toward baseline, confirmed by organ-specific measures, despite hemoglobin reduced from baseline 10.8 ± 1.2 to 5.9 ± 1.1 g/dL post-resuscitation (P < 0.01).

Conclusion:

Non-invasive measures of tissue oxygen delivery and oxygen debt repayment are suitable outcomes to inform Patient Blood Management of hemorrhagic shock, translatable for pre-clinical assessment of novel resuscitation strategies.
End-tidal Carbon Dioxide as an Indicator of Partial REBOA and Distal Organ Metabolism in Normovolemia and Hemorrhagic Shock in Anesthetized Pigs
Authors: Sadeghi Mitra , Hurtsén Anna Stene , Tegenfalk Josephine , Skoog Per , Jansson Kjell , Hörer Tal M. , Nilsson Kristofer F.
Published: May 2021

Introduction:

It is difficult to estimate the ischemic consequences when using partial resuscitative endovascular balloon occlusion of the aorta (REBOA). The aim was to investigate if end-tidal carbon dioxide (ETCO2) is correlated to degree of aortic occlusion, measured as distal aortic blood flow, and distal organ metabolism, estimated as systemic oxygen consumption (VO2), in a porcine model of normovolemia and hemorrhagic shock.

Materials and methods:

Nine anesthetized pigs (25–32 kg) were subjected to incremental steps of zone 1 aortic occlusion (reducing distal aortic blood flow by 33%, 66%, and 100%) during normovolemia and hemorrhagic grade IV shock. Hemodynamic and respiratory variables, and blood samples, were measured. Systemic VO2 was correlated to ETCO2 and measures of partial occlusion previously described.

Results:

Aortic occlusion gradually lowered distal blood flow and pressure, whereas ETCO2, VO2 and carbon dioxide production decreased at 66% and 100% aortic occlusion. Aortic blood flow correlated significantly to ETCO2 during both normovolemia and hemorrhage (R = 0.84 and 0.83, respectively) and to femoral mean pressure (R = 0.92 and 0.83, respectively). Systemic VO2 correlated strongly to ETCO2 during both normovolemia and hemorrhage (R = 0.91 and 0.79, respectively), blood flow of the superior mesenteric artery (R = 0.77 and 0.85, respectively) and abdominal aorta (R = 0.78 and 0.78, respectively), but less to femoral blood pressure (R = 0.71 and 0.54, respectively).

Conclusion:

ETCO2 was correlated to distal aortic blood flow and VO2 during incremental degrees of aortic occlusion thereby potentially reflecting the degree of aortic occlusion and the ischemic consequences of partial REBOA. Further studies of ETCO2, and potential confounders, in partial REBOA are needed before clinical use.
Targeted Regional Optimization: Increasing the Therapeutic Window for Endovascular Aortic Occlusion In Traumatic Hemorrhage
Authors: Ronaldi Alley E. , Madurska Marta J. , Bozzay Joseph D. , Polcz Jeanette E. , Baer David G. , Burmeister David M. , White Paul W. , Rasmussen Todd E. , White Joseph M.
Published: May 2021

Resuscitative endovascular balloon occlusion of the aorta (REBOA) allows for effective temporization of exsanguination from non-compressible hemorrhage (NCTH) below the diaphragm. However, the therapeutic window for aortic occlusion is time-limited given the ischemia-reperfusion injury generated. Significant effort has been put into translational research to develop new strategies to alleviate the ischemia-reperfusion injury and extend the application of endoaortic occlusion. Targeted regional optimization (TRO) is a partial REBOA strategy to augment proximal aortic and cerebral blood flow while targeting minimal threshold of distal perfusion beyond the zone of partial aortic occlusion. The objective of TRO is to reduce the degree of ischemia caused by complete aortic occlusion while providing control of distal hemorrhage. This review provides a synopsis of the concept of TRO, pre-clinical, translational experiences with TRO and early clinical outcomes. Early results from TRO strategies are promising; however, further studies are needed prior to large-scale implementation into clinical practice.
Homelessness: care for the most vulnerable – a narrative review of risk factors, health needs, stigma, and intervention strategies
Authors: Schreiter Stefanie , Speerforck Sven , Schomerus Georg , Gutwinski Stefan
Published: May 2021

Purpose of review

To summarize the most recent literature on risk factors of homelessness, mental, and somatic health needs, healthcare use, stigma as well as intervention strategies for people experiencing homelessness.

Recent findings

Studies identified adverse life events as well as mental health problems like drug use or suicidality as significant predictors of becoming homeless. Prevalence rates of mental disorders, especially substance use disorders, psychotic disorders, and depression are high. Barriers of healthcare use are financial resources and insurance status as well as experiences of discrimination. Aspects of trust and safety as well as age and gender were identified of high importance in the design of interventions. Strategies of permanent supportive housing like Housing First have shown a stable positive effect on housing stability, but not mental health outcomes. Peer support, forms of intensive case management, and harm reduction strategies are the most promising approaches to address these further needs.

Exploration into the relationship of homelessness and mental health as well as adequate intervention strategies is far from being conclusive. Especially, the development of effective interventions addressing issues of trauma, stigma and discrimination, community integration, and mental health needs is still in its infancy.
Opioids in the United Kingdom: safety and surveillance during COVID-19
Authors: Osborne Vicki
Published: May 2021

Purpose of review

Opioid use is prevalent in the United Kingdom and prior to the COVID-19 pandemic it had been recognized that the safety of opioids was an important issue to be monitored by the UK medicines regulatory agency. With the emergence of COVID-19, this requirement has been even greater. This review was undertaken to determine the impact of the pandemic on safety and surveillance of opioids in the United Kingdom.

Recent findings

During the COVID-19 pandemic, the surveillance of opioids in the United Kingdom continued, although primary research was often conducted with data prior to the pandemic. Of those studies that were conducted while the pandemic was ongoing, access to opioids (or opioid substitution therapy) and the subsequent effect on patient safety was the main theme.

In the United Kingdom, changes in accessibility to the healthcare system and how healthcare providers operated during the COVID-19 pandemic may have had unintended consequences on use and safety of opioids, due to the shift in focus to preventing COVID-19 from overwhelming the healthcare system. The findings from this review support the need to continue surveillance in the United Kingdom, including the impact of the COVID-19 pandemic on opioid utilization and safety.
The cultural evolution of cultural evolution
Authors: Birch Jonathan , Heyes Cecilia
Published: May 2021

What makes fast, cumulative cultural evolution work? Where did it come from? Why is it the sole preserve of humans? We set out a self-assembly hypothesis: cultural evolution evolved culturally. We present an evolutionary account that shows this hypothesis to be coherent, plausible, and worthy of further investigation. It has the following steps: (0) in common with other animals, early hominins had significant capacity for social learning; (1) knowledge and skills learned by offspring from their parents began to spread because bearers had more offspring, a process we call CS1 (or Cultural Selection 1); (2) CS1 shaped attentional learning biases; (3) these attentional biases were augmented by explicit learning biases (judgements about what should be copied from whom). Explicit learning biases enabled (4) the high-fidelity, exclusive copying required for fast cultural accumulation of knowledge and skills by a process we call CS2 (or Cultural Selection 2) and (5) the emergence of cognitive processes such as imitation, mindreading and metacognition—‘cognitive gadgets' specialized for cultural learning. This self-assembly hypothesis is consistent with archaeological evidence that the stone tools used by early hominins were not dependent on fast, cumulative cultural evolution, and suggests new priorities for research on ‘animal culture'.

This article is part of the theme issue ‘Foundations of cultural evolution’.
Drosophila Evolution over Space and Time (DEST) - A New Population
Genomics Resource
Authors: Kapun Martin , Nunez Joaquin C. B. , Bogaerts-Márquez María , Murga-Moreno Jesús , Paris Margot , Outten Joseph , Coronado-Zamora Marta , Tern Courtney , Rota-Stabelli Omar , Guerreiro Maria P. García , Casillas Sònia , Orengo Dorcas J. , Puerma Eva , Kankare Maaria , Ometto Lino , Loeschcke Volker , Onder Banu S. , Abbott Jessica K. , Schaeffer Stephen W. , Rajpurohit Subhash , Behrman Emily L , Schou Mads F. , Merritt Thomas J.S. , Lazzaro Brian P , Glaser-Schmitt Amanda , Argyridou Eliza , Staubach Fabian , Wang Yun , Tauber Eran , Serga Svitlana V. , Fabian Daniel K. , Dyer Kelly A. , Wheat Christopher W. , Parsch John , Grath Sonja , Veselinovic Marija Savic , Stamenkovic-Radak Marina , Jelic Mihailo , Buendía-Ruíz Antonio J. , Gómez-Julián M. Josefa , Espinosa-Jimenez M. Luisa , Gallardo-Jiménez Francisco D. , Patenkovic Aleksandra , Eric Katarina , Tanaskovic Marija , Ullastres Anna , Guio Lain , Merenciano Miriam , Guirao-Rico Sara , Horváth Vivien , Obbard Darren J. , Pasyukova Elena , Alatortsev Vladimir E. , Vieira Cristina P. , Vieira Jorge , Torres J. Roberto , Kozeretska Iryna , Maistrenko Oleksandr M. , Montchamp-Moreau Catherine , Mukha Dmitry V. , Machado Heather E. , Barbadilla Antonio , Petrov Dmitri , Schmidt Paul , Gonzalez Josefa , Flatt Thomas , Bergland Alan O.
Published: May 2021

Drosophila melanogaster is a leading model in
population genetics and genomics, and a growing number of whole-genome datasets
from natural populations of this species have been published over the last 20
years. A major challenge is the integration of these disparate datasets, often
generated using different sequencing technologies and bioinformatic pipelines,
which hampers our ability to address questions about the evolution and
population structure of this species. Here we address these issues by developing
a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from
D. melanogaster to a hologenome consisting of fly
and symbiont genomes and estimates allele frequencies using either a heuristic
(PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline
to generate the largest data repository of genomic data available for
D. melanogaster to date, encompassing 271
population samples from over 100 locations in >20 countries on four
continents based on a combination of 121 unpublished and 150 previously
published genomic datasets. Several of these locations have been sampled at
different seasons across multiple years. This dataset, which we call
Drosophila Evolution over Space and Time (DEST),
is coupled with sampling and environmental meta-data. A web-based genome browser
and web portal provide easy access to the SNP dataset. Our aim is to provide
this scalable platform as a community resource which can be easily extended via
future efforts for an even more extensive cosmopolitan dataset. Our resource
will enable population geneticists to analyze spatio-temporal genetic patterns
and evolutionary dynamics of D. melanogaster
populations in unprecedented detail.
Opioid Prescribing Mediating State Policy Intervention Effects on Drug Overdose Mortality
Authors: Rich Jacob James , Capodilupo Robert
Published: May 2021

The Centers for Disease Control and Prevention reported 70 630 drug overdose deaths for 2019 in the United States, 70.5% of which were opioid-related. Preliminary estimates now warn that drug overdose deaths likely surpassed 86 000 during 2020. Despite a 57.4% decrease in opioid prescribing since a peak in 2012, the opioid death rate has increased 105.8% through 2019, as the share of those deaths involving fentanyl increased from 16.4% to 72.9%. This letter seeks to determine whether the opioid prescribing and mortality paradox is robust to accepted methods of causal policy analysis and if prescribing rates mediate the effects of policy interventions on overdose deaths. Using loge-loge ordinary least squares with three different specifications as sensitivity analyses for all 50 states and Washington, DC for the period 2001-2019, the elasticities from the regressions with all control variables report operational prescription drug monitoring programs (PDMPs) reduce prescribing rates 8.7%, while mandatory PDMPs increase death rates from opioids 16.6%, heroin and fentanyl 19.0%, cocaine 17.3% and all drugs 10.5%. There is also weak evidence that recreational marijuana laws reduce prescribing, increases in prescribing increase pain reliever deaths, pill mill laws increase cocaine deaths, and medical marijuana laws increase total overdose deaths, with demographic variables suggesting states with more male, less non-Hispanic white, and older citizens experience more overdoses. Weak mediation effects were observed for pain reliever, cocaine, and illicit opioid deaths, while broad reductions in prescribing have failed to reduce opioid overdoses.
Transcriptional landscape of human microglia reveals robust gene expression signatures that implicates age, sex and APOE-related immunometabolic pathway perturbations
Authors: Patel Tulsi , Carnwath Troy P. , Wang Xue , Allen Mariet , Lincoln Sarah J. , Lewis-Tuffin Laura J. , Quicksall Zachary S. , Lin Shu , Tutor-New Frederick Q. , Ho Charlotte C.G. , Min Yuhao , Malphrus Kimberly G. , Nguyen Thuy T. , Martin Elizabeth , Garcia Cesar A. , Alkharboosh Rawan M. , Grewal Sanjeet , Chaichana Kaisorn , Wharen Robert , Guerrero-Cazares Hugo , Quinones-Hinojosa Alfredo , Ertekin-Taner Nilüfer
Published: May 2021

Microglia have fundamental roles in health and disease, however effects of age, sex and genetic factors on human microglia have not been fully explored. We applied bulk and single cell approaches to comprehensively characterize human microglia transcriptomes and their associations with age, sex and APOE. We identified a novel microglial signature, characterized its expression in bulk tissue and single cell microglia transcriptomes. We discovered microglial co-expression network modules associated with age, sex and APOE-ε4 that are enriched for lipid and carbohydrate metabolism genes. Integrated analyses of modules with single cell transcriptomes revealed significant overlap between age-associated module genes and both pro-inflammatory and disease-associated microglial clusters. These modules and clusters harbor known neurodegenerative disease genes including APOE, PLCG2 and BIN1. Meta-analyses with published bulk and single cell microglial datasets further supported our findings. Thus, these data represent a well-characterized human microglial transcriptome resource; and highlight age, sex and APOE-related microglial immunometabolism perturbations with potential relevance in neurodegeneration.
Durability of mRNA-1273-induced antibodies against SARS-CoV-2 variants
Authors: Pegu Amarendra , O’Connell Sarah , Schmidt Stephen D , O’Dell Sijy , Talana Chloe A. , Lai Lilin , Albert Jim , Anderson Evan , Bennett Hamilton , Corbett Kizzmekia S. , Flach Britta , Jackson Lisa , Leav Brett , Ledgerwood Julie E. , Luke Catherine J. , Makowski Mat , Roberts Paul C. , Roederer Mario , Rebolledo Paulina A. , Rostad Christina A. , Rouphael Nadine G. , Shi Wei , Wang Lingshu , Widge Alicia T. , Yang Eun Sung ,   the mRNA-1273 Study Group, Beigel John H. , Graham Barney S. , Mascola John R , Suthar Mehul S. , McDermott Adrian , Doria-Rose Nicole A.
Published: May 2021

SARS-CoV-2 mutations may diminish vaccine-induced protective immune responses, and the durability of such responses has not been previously reported. Here, we present a comprehensive assessment of the impact of variants B.1.1.7, B.1.351, P.1, B.1.429, and B.1.526 on binding, neutralizing, and ACE2-blocking antibodies elicited by the vaccine mRNA-1273 over seven months. Cross-reactive neutralizing responses were rare after a single dose of mRNA-1273. At the peak of response to the second dose, all subjects had robust responses to all variants. Binding and functional antibodies against variants persisted in most subjects, albeit at low levels, for 6 months after the primary series of mRNA-1273. Across all assays, B.1.351 had the greatest impact on antibody recognition, and B.1.1.7 the least. These data complement ongoing studies of clinical protection to inform the potential need for additional boost vaccinations.

One-Sentence Summary

Most mRNA-1273 vaccinated individuals maintained binding and functional antibodies against SARS-CoV-2 variants for 6 months.
A large majority of awake hippocampal sharp-wave ripples feature spatial trajectories with momentum
Authors: Krause Emma L. , Drugowitsch Jan
Published: May 2021

During periods of rest, hippocampal place cells feature bursts of activity called sharp-wave ripples (SWRs). Heuristic approaches to their analysis have revealed that a small fraction of SWRs appear to “simulate” trajectories through the environment—called awake hippocampal replay—while the functional role of a majority of these SWRs remains unclear. Applying a novel probabilistic approach to characterize the spatio-temporal dynamics embedded in SWRs, we instead show that almost all SWRs of foraging rodents simulate such trajectories through the environment. Furthermore, these trajectories feature momentum, that is, inertia in their velocities, that mirrors the animals’ natural movement. This stands in contrast to replay events during sleep which seem to follow Brownian motion without such momentum. Lastly, interpreting the replay trajectories in the context of navigational planning revealed that similar past analyses were biased by the heuristic SWR sub-selection. Overall, our approach provides a more complete characterization of the spatio-temporal dynamics within SWRs, highlights qualitative differences between sleep and awake replay, and ought to support future, more detailed, and less biased analysis of the role of awake replay in navigational planning.