bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic Effect of Ketamine and Buprenorphine Observed in the Treatment of Buprenorphine Precipitated Opioid Withdrawal in a Patient With Fentanyl Use
Authors: Hailozian Christian , Luftig Joshua , Liang Amy , Outhay Melena , Ullal Monish , Anderson Erik S. , Kalmin Mariah , Shoptaw Steve , Greenwald Mark K. , Herring Andrew A. 
Published: November 2021

Background
Optimal treatment of buprenorphine precipitated opioid withdrawal (BPOW) is unclear. Full agonist treatment of BPOW is limited by buprenorphine’s high-affinity blockade at mu-opioid receptors (μORs). Buprenorphine’s partial agonism (low intrinsic efficacy) at μORs can limit the effectiveness of even massive doses once BPOW has begun. Adjunct medications, such as clonidine, are rarely effective in severe BPOW. Ketamine is an N-methyl-D-aspartate receptor antagonist with a potentially ideal pharmacologic profile for treatment of BPOW. Ketamine reduces opioid withdrawal symptoms independently of direct μOR binding, synergistically potentiates the effectiveness of buprenorphine μOR signaling, reverses (resensitizes) fentanyl induced μOR receptor desensitization, and inhibits descending pathways of hyperalgesia and central sensitization. Ketamine’s rapid antidepressant effects potentially address depressive symptoms and subjective distress that often accompanies BPOW. Ketamine is inexpensive, safe, and available in emergency departments. To date, neither ketamine as treatment for BPOW nor to support uncomplicated buprenorphine induction has been described.

Case Description
We report a case of an illicit fentanyl-using OUD patient who experienced severe BPOW during an outpatient low-dose cross taper buprenorphine induction (ie, “microdose”). The BPOW was successfully treated in the emergency department with a combination of ketamine (0.6 mg/kg intravenous over 1 hour) combined with high-dose buprenorphine (16 mg sublingual single dose); 3 days later he was administered a month-long dose of extended-release subcutaneous buprenorphine which was repeated monthly (300 mg). At 90 days the patient remained in treatment and reported continuous abstinence from fentanyl use.

Conclusions
This single case observation raises important questions about the potential therapeutic role of ketamine as a treatment for BPOW. BPOW is an important clinical problem for which there is currently only limited guidance and no universally accepted approach. Prospective study comparing the effectiveness of differing pharmacologic approaches to treat BPOW is urgently needed.
Racial-ethnic Differences in Reasons for Misuse of Prescription Medications Among US Adults
Authors: Cury James D. , Sharma Vinita , Falise Alyssa M. , Terry Ellen L. , Lopez-Quintero Catalina 
Published: November 2021

Objectives
This study aims to investigate racial-ethnic differences in reasons for misuse of prescription medications among a nationally representative sample of US adults.

Methods
We analyzed data from the 2015–2019 National Surveys on Drug Use and Health. The study population includes US adults (18–49 years old) who reported misuse of 3 types of prescription drugs (stimulants [n = 6139], sedatives and tranquilizers [n = 5643], and pain relievers [n = 8780]) for 3 reasons: medical-only (eg, to help with pain), recreational-only (eg, to get high), or combined medical and recreational reasons. Multinomial logistic regressions assessed the association between reasons of misuse of prescription medications and self-identified race-ethnicity.

Results
Misuse of the 4 types of prescription medications was primarily motivated by medical reasons (63%–80%). Compared to non-Hispanic Whites, non-Hispanic Blacks (nHB), and Hispanics (H) were less likely to report misuse of pain relievers for combined (nHB: adjusted relative risk ratio [aRRR] = 0.6, 95% confidence interval [CI]: 0.4, 0.7; H; aRRR = 0.7, 95% CI: 0.5, 0.9) or recreational reasons (nHB: aRRR = 0.8, 95% CI: 0.6, 1.0; H; aRRR = 0.7, 95% CI: 0.6, 0.9) rather than medical-only reasons. The odds of misuse of sedatives and tranquilizers for recreational-only reasons as opposed to medical-only reasons were higher among nHB (aRRR = 1.9, 95% CI: 1.3, 2.7) and H (aRRR = 1.9, 95% CI: 1.4, 2.4) than among non-Hispanic Whites.

Conclusions
The increased misuse of prescription pain relievers for medical reasons among racial-ethnic minority groups demonstrates a continued need to investigate underlying structural factors driving these behaviors. The higher odds of sedative and tranquilizer misuse for recreational purposes among racial-ethnic minority groups warrant further investigation.
Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock—A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study)
Authors: Bauer Michael , Weyland Andreas , Marx Gernot , Bloos Frank , Weber Stephan , Weiler Norbert , Kluge Stefan , Diers Anja , Simon Tim Philipp , Lautenschläger Ingmar , Gründling Matthias , Jaschinski Ulrich , Simon Philipp , Nierhaus Axel , Moerer Onnen , Reill Lorenz , Jörres Achim , Guo Renfeng , Loeffler Markus , Reinhart Konrad , Riedemann Niels ,   for the SepNet-Study Group
Published: November 2021

IMPORTANCE:
Anaphylatoxin C5a, a proinflammatory complement split product, plays a central role in mediating organ dysfunction.

OBJECTIVES:
This phase II clinical trial was conducted to study safety, tolerability, pharmacokinetics, and pharmacodynamics of vilobelimab, a recombinant monoclonal antibody against C5a, in patients with severe sepsis or septic shock.

DESIGN:
Multicenter, randomized, and placebo-controlled study.

SETTING AND PARTICIPANTS:
Eleven multidisciplinary ICUs across Germany. Adult patients with severe sepsis or septic shock and with early onset of infection-associated organ dysfunction.

MAIN OUTCOMES AND MEASURES:
Patients were randomly assigned in a ratio of 2:1 to three subsequent dosing cohorts for IV vilobelimab or placebo receiving either 2 × 2 mg/kg (0 and 12 hr), 2 × 4 mg/kg (0 and 24 hr), and 3 × 4 mg/kg (0, 24, and 72 hr). Co-primary endpoints were pharmacodynamics (assessed by C5a concentrations), pharmacokinetics (assessed by vilobelimab concentrations), and safety of vilobelimab. Preliminary efficacy was evaluated by secondary objectives.

RESULTS:
Seventy-two patients were randomized (16 patients for each vilobelimab dosing cohort and eight patients for each placebo dosing cohort). Vilobelimab application was associated with dosing dependent decrease in C5a compared with baseline (p < 0.001). Duration of C5a decrease increased with more frequent dosing. Membrane attack complex lysis capacity measured by 50% hemolytic complement was not affected. Vilobelimab was well tolerated with similar safety findings in all dose cohorts. No vilobelimab-specific adverse events emerged. For vilobelimab-treated patients, investigators attributed less treatment-emergent adverse events as related compared with placebo. Dosing cohorts 2 and 3 had the highest ICU-free and ventilator-free days. There was no difference in mortality, vasopressor-free days, or renal replacement therapy-free days between the groups.

CONCLUSIONS AND RELEVANCE:
Administration of vilobelimab in patients with severe sepsis and septic shock selectively neutralizes C5a in a dose-dependent manner without blocking formation of the membrane attack complex and without resulting in detected safety issues. The data warrant further investigation of C5a inhibition in sepsis.
Assessing Occupational Stressors in Restaurant Work Prior to and During the COVID-19 Pandemic
Authors: Lippert Julia F. , Hofman Nila Ginger , Reyes Teofilo 
Published: November 2021

Objective:
This exploratory study investigated occupational stress in restaurant work prior to and during the COVID-19 pandemic.

Methods:
The study was a mixed methods design conducted in two phases with biomarker data for stress, questionnaire data, and semi-structured interviews.

Results:
Results indicated elevated stressors elevated stress during normal shift conditions (P < 0.05), low job satisfaction, an effort to reward imbalance (P < 0.05), and the majority (72%, n = 28) of participants reporting discrimination at least a “few times a year.” Interview data revealed four interrelated occupational stressors including: (1) financial hardships; (2) increased exposure to occupational health risks during the reopening phases; (3) increased workloads due to inadequate staffing and fewer hours; and (4) social and psychological pressures and ill treatment.

Conclusion:
These elements were reported prior to the COVID-19 pandemic and have persisted throughout with heightened impacts.
The Impact of COVID-19
Authors: Abuatiq Alham , Borchardt Carla 
Published: November 2021

OBJECTIVE
The aim of this study was to explore the occupational stress perception of nurses and how they manage it during the COVID-19 pandemic.

BACKGROUND
The management of occupational stress is a key factor in promoting nurses' well-being.

METHODS
A descriptive cross-sectional study was conducted.

RESULTS
The top occupational stressors from the nurses' perspectives (N = 236) as measured by using an updated version of the Nursing Stress Scale (NSS) included wearing a face mask at all times in the hospital, unpredictable staffing and scheduling, not enough staff to adequately cover the unit, feeling helpless in the case a patient fails to improve, and being assigned to a COVID-19 patient. The mean stress score was 31.87. The updated NSS Cronbach's α was 0.92, and the interclass interclass correlation coefficient was 0.914.

CONCLUSION
Nurse administrators are in a strategic position to develop interventions (eg, open door policy, meetings, and employee assistance programs) to assist nurses in effectively managing stress.
Outcomes and Their State-level Variation in Patients Undergoing Surgery With Perioperative SARS-CoV-2 Infection in the USA
Authors:   COVIDSurg Collaborative
Published: November 2021

Objective:To report the 30-day outcomes of patients with perioperative SARS-CoV-2 infection undergoing surgery in the USA.Background:Uncertainty regarding the postoperative risks of patients with SARS-CoV-2 exists.Methods:As part of the COVIDSurg multicenter study, all patients aged ≥17 years undergoing surgery between January 1 and June 30, 2020 with perioperative SARS-CoV-2 infection in 70 hospitals across 27 states were included. The primary outcomes were 30-day mortality and pulmonary complications. Multivariable analyses (adjusting for demographics, comorbidities, and procedure characteristics) were performed to identify predictors of mortality.Results:A total of 1581 patients were included; more than half of them were males (n = 822, 52.0%) and older than 50 years (n = 835, 52.8%). Most procedures (n = 1261, 79.8%) were emergent, and laparotomies (n = 538, 34.1%). The mortality and pulmonary complication rates were 11.0 and 39.5%, respectively. Independent predictors of mortality included age ≥70 years (odds ratio 2.46, 95% confidence interval [1.65–3.69]), male sex (2.26 [1.53–3.35]), ASA grades 3–5 (3.08 [1.60–5.95]), emergent surgery (2.44 [1.31–4.54]), malignancy (2.97 [1.58–5.57]), respiratory comorbidities (2.08 [1.30–3.32]), and higher Revised Cardiac Risk Index (1.20 [1.02–1.41]). While statewide elective cancelation orders were not associated with a lower mortality, a sub-analysis showed it to be associated with lower mortality in those who underwent elective surgery (0.14 [0.03–0.61]).Conclusions:Patients with perioperative SARS-CoV-2 infection have a significantly high risk for postoperative complications, especially elderly males. Postponing elective surgery and adopting non-operative management, when reasonable, should be considered in the USA during the pandemic peaks.
Assessment of Duration of Smoking Cessation Prior to Surgical Treatment of Non-small Cell Lung Cancer
Authors: Heiden Brendan T. , Eaton Daniel B. , Chang Su-Hsin , Yan Yan , Schoen Martin W. , Chen Li-Shiun , Smock Nina , Patel Mayank R. , Kreisel Daniel , Nava Ruben G. , Meyers Bryan F. , Kozower Benjamin D. , Puri Varun 
Published: November 2021

Objective:
To define the relationship between the duration of smoking cessation and postoperative complications for patients with lung cancer undergoing surgical treatment.

Background:
Smoking increases the risk of postoperative morbidity and mortality in patients with lung cancer undergoing surgical treatment. Although smoking cessation before surgery can mitigate these risks, the ideal duration of preoperative smoking cessation remains unclear.

Methods:
Using a uniquely compiled Veterans Health Administration dataset, we performed a retrospective cohort study of patients with clinical stage I non-small cell lung cancer undergoing surgical treatment between 2006 and 2016. We characterized the relationship between duration of preoperative smoking cessation and risk of postoperative complications or mortality within 30-days using multivariable restricted cubic spline functions.

Results:
The study included a total of 9509 patients, of whom 6168 (64.9%) were smoking at the time of lung cancer diagnosis. Among them, only 662 (10.7%) patients stopped smoking prior to surgery. Longer duration between smoking cessation and surgery was associated with lower odds of major complication or mortality (adjusted odds ratio [aOR] for every additional week, 0.919; 95% confidence interval [CI], 0.850-0.993; P = 0.03). Compared to nonsmokers, patients who quit at least 3 weeks before surgery had similar odds of death or major complication (aOR, 1.005; 95% CI, 0.702–1.437; P = 0.98) whereas those who quit within 3 weeks of surgery had significantly higher odds of death or major complication (aOR, 1.698; 95% CI, 1.203–2.396; P = 0.003).

Conclusion:
Smoking cessation at least 3 weeks prior to the surgical treatment of lung cancer is associated with reduced morbidity and mortality. Providers should aggressively encourage smoking cessation in the preoperative period, since it can disproportionately impact outcomes in early-stage lung cancer.
Life over limb: Arterial access-related limb ischemic complications in 48-hour REBOA survivors
Authors: Laverty Robert B. , Treffalls Rebecca N. , McEntire Shane E. , DuBose Joseph J. , Morrison Jonathon J. , Scalea Thomas M. , Moore Laura J. , Podbielski Jeanette M. , Inaba Kenji , Piccinini Alice , Kauvar David S. 
Published: November 2021

BACKGROUND
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is increasingly used in some trauma settings. Arterial access-related limb ischemic complications (ARLICs) resulting from the femoral arterial access required for REBOA are largely under reported. We sought to describe the incidence of these complications and the clinical, technical, and device factors associated with their development.

METHODS
This was a retrospective cohort study of records of adult trauma patients from the American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute care surgery registry between October 2013 and September 2020 who had REBOA and survived at least 48 hours. The primary outcome was ARLIC, defined as clinically relevant extremity ischemia or distal embolization. Relevant factors associated with ARLIC were also analyzed.

RESULTS
Of 418 identified patients, 36 (8.6%) sustained at least one ARLIC; 22 with extremity ischemia, 25 with distal embolism, 11 with both. Patient demographics and injury characteristics were similar between ARLIC and no ARLIC groups. Access-related limb ischemic complication was associated with larger profile devices (p = 0.009), cutdown access technique (p = 0.02), and the presence of a pelvic external fixator/binder (p = 0.01). Patients with ARLIC had higher base deficit (p = 0.03) and lactate (p = 0.006). One hundred fifty-six patients received tranexamic acid (TXA), with 22 (14%) ARLICs. The rate of TXA use among ARLIC patients was 61% (vs. 35% TXA for non-ARLIC patients, p = 0.002). Access-related limb ischemic complication did not result in additional in-hospital mortality, however, ARLIC had prolonged hospital LOS (31 vs. 24 days, p = 0.02). Five ARLIC required surgical intervention, three patch angioplasty (and two with associated bypass), and four ARLIC limbs were amputated.

CONCLUSION
Femoral artery REBOA access carries a risk of ARLIC, which is associated with unstable pelvis fractures, severe shock, and strongly with the administration of TXA. Use of lower-profile devices and close surveillance for these complications is warranted in these settings and caution should be exercised when using TXA in conjunction with REBOA.

LEVEL OF EVIDENCE
Prognostic and Epidemiologic, Level III
Developing a National Trauma Research Action Plan: Results from the prehospital and mass casualty research Delphi survey
Authors: Newgard Craig D. , Braverman Maxwell A. , Phuong Jimmy , Shipper Edward S. , Price Michelle A. , Bixby Pamela J. , Goralnick Eric , Daya Mohamud R. , Lerner E. Brooke , Guyette Francis X. , Rowell Susan , Doucet Jay , Jenkins Peter , Mann N. Clay , Staudenmayer Kristan , Blake David P. , Bulger Eileen 
Published: November 2021

BACKGROUND
The National Academies of Sciences, Engineering, and Medicine 2016 trauma system report recommended a National Trauma Research Action Plan to strengthen and guide future trauma research. To address this recommendation, 11 expert panels completed a Delphi survey process to create a comprehensive research agenda, spanning the continuum of trauma care. We describe the gap analysis and high-priority research questions generated from the National Trauma Research Action Plan panel on prehospital and mass casualty trauma care.

METHODS
We recruited interdisciplinary national experts to identify gaps in the prehospital and mass casualty trauma evidence base and generate prioritized research questions using a consensus-driven Delphi survey approach. We included military and civilian representatives. Panelists were encouraged to use the Patient/Population, Intervention, Compare/Control, and Outcome format to generate research questions. We conducted four Delphi rounds in which participants generated key research questions and then prioritized the questions on a 9-point Likert scale to low-, medium-, and high-priority items. We defined consensus as ≥60% agreement on the priority category and coded research questions using a taxonomy of 118 research concepts in 9 categories.

RESULTS
Thirty-one interdisciplinary subject matter experts generated 490 research questions, of which 433 (88%) reached consensus on priority. The rankings of the 433 questions were as follows: 81 (19%) high priority, 339 (78%) medium priority, and 13 (3%) low priority. Among the 81 high-priority questions, there were 46 taxonomy concepts, including health systems of care (36 questions), interventional clinical trials and comparative effectiveness (32 questions), mortality as an outcome (30 questions), prehospital time/transport mode/level of responder (24 questions), system benchmarks (17 questions), and fluid/blood product resuscitation (17 questions).

CONCLUSION
This Delphi gap analysis of prehospital and mass casualty care identified 81 high-priority research questions to guide investigators and funding agencies for future trauma research.
Case Series of Thrombosis with Thrombocytopenia Syndrome following COVID-19 vaccination—United States, December 2020–August 2021
Authors: See Isaac , Lale Allison , Marquez Paige , Streiff Michael B. , Wheeler Allison P. , Tepper Naomi K. , Woo Emily Jane , Broder Karen R. , Edwards Kathryn M. , Gallego Ruth , Geller Andrew I. , Jackson Kelly A. , Sharma Shashi , Talaat Kawsar R. , Walter Emmanuel B. , Akpan Imo J. , Ortel Thomas L. , Walker Shannon C. , Yui Jennifer C. , Shimabukuro Tom T. , Mba-Jonas Adamma , Su John R. , Shay David K. 
Published: November 2021

AbstractBackgroundThrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. TTS presents similarly to autoimmune heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis following Janssen/Johnson & Johnson (Ad26.COV2.S) COVID-19 vaccination have been described.ObjectiveDescribe surveillance data and reporting rates of TTS cases following COVID-19 vaccination.DesignCase series.SettingUnited StatesPatientsCase-patients reported to the Vaccine Adverse Event Reporting System (VAERS) receiving COVID-19 vaccine from December 14, 2020 through August 31, 2021, with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction). If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for anti-platelet factor 4 antibody was required.MeasurementsReporting rates (cases/million vaccine doses) and descriptive epidemiology.Results52 TTS cases were confirmed following Ad26.COV2.S (n=50) or mRNA-based COVID-19 (n=2) vaccination. TTS reporting rates were 3.55 per million (Ad26.COV2.S) and 0.0057 per million (mRNA-based COVID-19 vaccines). Median age of patients with TTS following Ad26.COV2.S vaccination was 43.5 years (range: 18–70); 70% were female. Both TTS cases following mRNA-based COVID-19 vaccination occurred in males aged >50 years. All cases following Ad26.COV2.S vaccination involved hospitalization including 32 (64%) with intensive care unit admission. Outcomes of hospitalizations following Ad26.COV2.S vaccination included death (12%), discharge to post-acute care (16%), and discharge home (72%).LimitationsUnder-reporting and incomplete case follow-up.ConclusionTTS is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the two cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate.Funding SourceCDC
Novel protein markers of androgen activity in humans: proteomic study of plasma from young chemically castrated men
Authors: Giwercman Aleksander , Sahlin K Barbara , Pla Indira , Pawłowski Krzysztof , Fehniger Carl , Lundberg Giwercman Yvonne , Leijonhufvud Irene , Appelqvist Roger , Marko-Varga György , Sanchez Aniel , Malm Johan 
Published: November 2021

AbstractBackgroundReliable biomarkers ofv androgen activity in humans are lacking. The aim of this study was, therefore, to identify new protein markers of biological androgen activity and test their predictive value in relation to low vs. normal testosterone values and some androgen deficiency linked pathologies.MethodsBlood samples from 30 healthy GnRH-antagonist treated males were collected at three time points: a) before GnRH antagonist administration; b) 3 weeks later, just before testosterone undecanoate injection, and c) after additional 2 weeks. Subsequently they were analysed by mass spectrometry to identify potential protein biomarkers of testosterone activity. Levels of proteins most significantly associated with testosterone fluctuations were further tested in a cohort of 75 hypo- and eugonadal males suffering from infertility. Associations between levels of those markers and cardio-metabolic parameters, bone mineral density as well as androgen receptor CAG repeat lengths, were explored.ResultsUsing ROC analysis, 4-hydroxyphenylpyruvate dioxygenase (4HPPD), insulin-like growth factor-binding protein 6 (IGFBP6) and fructose-bisphosphate aldolase (ALDOB), as well as a Multi Marker Algorithm, based on levels of 4HPPD and IGFBP6, were shown to be best predictors of low (< 8 nmol/L) vs. normal (> 12 nmol/L) testosterone. They were also more strongly associated with metabolic syndrome and diabetes than testosterone levels. Levels of ALDOB and 4HPPD levels also showed association with AR CAG-repeat lengths.ConclusionsWe identified potential new protein biomarkers of testosterone action. Further investigations to eluciadate their clinical potential are warranted.