bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenethyl-4-ANPP: A Marginally Active Byproduct Suggesting a Switch in Illicit Fentanyl Synthesis Routes
Authors: Vandeputte Marthe M , Krotulski Alex J , Hulpia Fabian , Van Calenbergh Serge , Stove Christophe P 
Published: April 2021

Abstract
Profiling of the illicit fentanyl supply is invaluable from surveillance and intelligence perspectives. An important strategy includes the study of chemical attribution signatures (e.g., trace amounts of synthesis precursors, impurities/byproducts in seized material and metabolites in biological samples). This information provides valuable insight into the employed synthesis routes at the heart of illicit fentanyl manufacture (previously mainly the so-called Janssen or Siegfried methods), allowing to track and ultimately regulate crucial precursors. This report focuses on phenethyl-4-anilino-N-phenethylpiperidine (phenethyl-4-ANPP), a formerly unknown compound that was identified for the first time in a fentanyl powder sample seized in April 2019, followed by its identification in a biological sample in December 2019. Between 2019-Q4 and 2020-Q3, phenethyl-4-ANPP was detected in 25/1,054 fentanyl cases in the USA. There are currently no reports on how this compound may have ended up in illicit drug preparations and whether its presence may have potential in vivo relevance. We propose three possible fentanyl synthesis routes that, when badly executed in a single reaction vessel, may involve the formation of phenethyl-4-ANPP. We hypothesize that the presence of the latter is the result of a shift in fentanyl synthesis routes in an attempt to circumvent restrictions on previously used precursors. Using a cell-based µ-opioid receptor recruitment assay, we show that the extent of MOR activation caused by 100 µM phenethyl-4-ANPP is comparable to that exerted by a roughly 100,000-fold lower concentration of fentanyl (0.001 µM or 0.336 ng/mL). Negligible in vitro opioid activity, combined with its low abundance in fentanyl preparations, most likely renders phenethyl-4-ANPP biologically irrelevant in vivo. However, as clandestine operations are constantly changing shape, monitoring of fentanyl attributions remains pivotal in our understanding and control of illicit fentanyl manufacture and supply.
T4 Impact of Opioid-Minimizing Pain Protocols after Burn Injury
Authors: Donthula Deepanjli , Conner Christopher R , Truong Van Thi Thanh , Green Charles , Jiang Chuantao , Wandling Michael W , Komak Spogmai , Huzar Todd F , Adams Sasha D , Freet Daniel J , Wainwright David J , Wade Charles E , Kao Lillian S , Harvin John A 
Published: April 2021

Abstract

Introduction
Traditionally, opioids have been the mainstay of treatment for background, breakthrough, procedural, and postoperative pain after burns. However, in addition to an impetus to reduce provider-driven opioid exposure, there is increasing evidence that opioids can worsen acute pain through induction of hyperalgesia. In 2019, we implemented a pill-based, opioid-minimizing pain protocol and protocolized moderate sedation for dressing changes. We hypothesized that these protocols would reduce inpatient opioid exposure without increasing acute pain scores.

Methods
Two groups of consecutive patients admitted to the burn service were compared: Pre (01/2018 to 07/2019) and Post (01/2020 to 06/2020) implementation of the protocols (08/2019 to 12/2019). Patient demographics, burn characteristics, and lengths of stay were abstracted from the burn registry. Opioid exposure and pain scale scores were obtained from the electronic medical record. The primary outcome was total morphine milligram equivalents (MME). Secondary outcomes included MME/day, pain domain specific MME, pain scores, and lengths of stay. Pain was estimated by creating a normalized pain score (range 0–1) from three different pain scales (Numeric Rating Scale, Behavioral Pain Scale, and Behavioral Pain Assessment Scale). Groups were compared using Wilcoxon Rank Sum and Chi Square. Treatment effect was estimated using Bayesian generalized linear models.

Results
There were no differences in demographics or burn characteristics between the Pre (n=495) and Post groups (n=174), including TBSA burn (Pre 4% [2, 10] versus Post 5% [2, 10], p=0.898). The Post group had significantly lower total MME (IRR 0.72, 95% CrI 0.57–0.93, posterior probability 99%), MME/day (IRR 0.76, 95% CrI 0.65–0.90, posterior probability 99%), and domain-specific total MME (Table). No difference in average normalized pain scores was seen. The Pre group were hospitalized longer than the Post group (5 days [2, 14] versus 4 days [1, 9], p=0.012).

Conclusions
Implementation of opioid-minimizing protocols for acute burn pain were associated with a significant reduction in inpatient opioid exposure without increased pain scores. More information is needed to understand the association with reduced hospital days.
11 Vitamin D Deficiency on Admission and the Association with Length of Stay in Patients with Thermal Injury: A Multi-center Analysis
Authors: Zavala Sarah , Pape Kate , Walroth Todd A , Reger Melissa A , Garner Katelyn , Kiracofe Brittany , Thomas Wendy L , Adams Beatrice , Hill David M 
Published: April 2021

Abstract

Introduction
In burn patients, vitamin D deficiency has been associated with increased incidence of sepsis. The objective of this study was to assess the impact of vitamin D deficiency in adult burn patients on hospital length of stay (LOS).

Methods
This was a multi-center retrospective study of adult patients at 7 burn centers admitted between January 1, 2016 and July 25, 2019 who had a 25-hydroxyvitamin D (25OHD) concentration drawn within the first 7 days of injury. Patients were excluded if admitted for a non-burn injury, total body surface area (TBSA) burn less than 5%, pregnant, incarcerated, or made comfort care or expired within 48 hours of admission. The primary endpoint was to compare hospital LOS between burn patients with vitamin D deficiency (defined as 25OHD &lt; 20 ng/mL) and sufficiency (25OHD ≥ 20 ng/mL). Secondary endpoints include in-hospital mortality, ventilator-free days of the first 28, renal replacement therapy (RRT), length of ICU stay, and days requiring vasopressors. Additional data collected included demographics, Charlson Comorbidity Index, injury characteristics, form of vitamin D received (ergocalciferol or cholecalciferol) and dosing during admission, timing of vitamin D initiation, and form of nutrition provided. Dichotomous variables were compared via Chi-square test. Continuous data were compared via student t-test or Mann-Whitney U test. Univariable linear regression was utilized to identify variables associated with LOS (p &lt; 0.05) to analyze further. Cox Proportional Hazard Model was utilized to analyze association with LOS, while censoring for death, and controlling for TBSA, age, presence of inhalation injury, and potential for a center effect.

Results
Of 1,147 patients screened, 412 were included. Fifty-seven percent were vitamin D deficient. Patients with vitamin D deficiency had longer LOS (18.0 vs 12.0 days, p &lt; 0.001), acute kidney injury (AKI) requiring RRT (7.3 vs 1.7%, p = 0.009), more days requiring vasopressors (mean 1.24 vs 0.58 days, p = 0.008), and fewer ventilator free days of the first 28 days (mean 22.9 vs 25.1, p &lt; 0.001). Univariable analysis identified burn center, AKI, TBSA, inhalation injury, admission concentration, days until concentration drawn, days until initiating supplementation, and dose as significantly associated with LOS. After controlling for center, TBSA, age, and inhalation injury, the best fit model included only deficiency and days until vitamin D initiation.

Conclusions
Patients with thermal injuries and vitamin D deficiency on admission have increased length of stay and worsened clinical outcomes as compared to patients with sufficient vitamin D concentrations.
13 Utilization of a Burn Sepsis Algorithm: A Five-Year Analysis
Authors: Williams Jeffrey W , Saraswat Anju , Bailey John K , Craig Christopher K , Holmes James H 
Published: April 2021

Abstract

Introduction
After the first 24 hours, the major cause of death in burn patients is multiple organ dysfunction/failure syndrome. It is preceded by an infection in 83% of burn patients, with reported septic mortality up to 65%. Since the early recognition and treatment of infection has been shown to decrease mortality from sepsis, we implemented a multidisciplinary algorithm designed to rapidly identify septic adult burn patients.

Methods
Adult (≥18 y) admissions between 7/1/2014 – 6/30/2019 were identified from our registry, and all initial sepsis screens were evaluated in the EMR. Patients were screened clinically at least twice daily and were considered a “positive” screen if MAP &lt; 65 mmHg (SBP&lt; 90 mmHg) or if 2 of the 3 occurred: Temp &gt;102.2F; HR &gt;120; RR &gt;28 (or RR &gt;10% of ventilator set rate if set rate is &gt;24 bpm). A positive screen prompted lab work to include CBC, BMP, procalcitonin (PCT), and lactic acid (LA), per protocol. If PCT &gt;3.0 ng/ml or LA &gt;2.0 mmol/L, or both thrombocytopenia and hyperglycemia were present, a “Burn Code Sepsis” was initiated and included cultures, a CXR, and empiric antibiotics. A patient was then formally considered “septic” (i.e. infected) if the cultures were positive or the CXR demonstrated an infectious process.

Results
There were 1,523 admissions during the 5-year period, and 228 initial positive screens. Of the 228 patients with positive screens, 159 (70%) were infected. There was a significant difference in PCT level between patients with and without infections, while no difference was noted for LA, WBC, platelets, temperature, glucose, age, %TBSA burned, or time to triggering a positive screen between the groups (Table). Defining PCT ≥3.0 ng/mL as being positive for sepsis demonstrated a 76% PPV and a 36% NPV for PCT alone. Our initial sepsis screening algorithm had a sensitivity of 64.8% and a specificity of 40.6% over the five-year period.

Conclusions
Recognition of sepsis remains difficult in burn patients. PCT and the use of a sepsis screening algorithm may have a role in the early detection of sepsis. Further research is warranted.
49 Comparing Intravenous & Subcutaneous Insulin Regimens for Management of Hyperglycemia in Adult Burn Patients
Authors: Walroth Todd A , Luty Cole D , Brown Michelle E , Deodhar Karishma , Foster David , McIntire Allyson M , Grooms Cortni , Hartman Brett C 
Published: April 2021

Abstract

Introduction
Burn patients are at an increased risk of hyperglycemia due to metabolic, anabolic, and treatment-related factors. Studies in burn patients have targeted goal blood glucose (BG) values ranging from 80–140 mg/dL. Our study aimed to evaluate current management of hyperglycemia in burn patients and to develop a treatment protocol in this population.

Methods
A retrospective study of patients admitted between 10/2016 - 8/2019 was conducted. Eligible patients were at least 18 years old, admitted within 48 hours following injury, and admitted for either thermal, chemical, or electrical burn, frostbite, or inhalation injury. The primary outcome was glycemic control, defined as percent of time spent within our predefined BG goal range of 90–130 mg/dL using a time-weighted BG (TWBG) level. Insulin regimens were compared to determine the most effective modality for achieving this goal. Additional secondary outcomes included consequences of hypoglycemia, complications of poor glycemic control, length of stay, and in-hospital mortality.

Results
A total of 68 patients were evaluated, and 48 met inclusion criteria. Majority of patients were male (73%), with a mean (SD) age 60 (16) years, median (IQR) TBSA 10% (4,19), and median (IQR) baseline HbA1c 6.6% (5.6,8.2). Twenty-four (50%) patients did not have a history of diabetes. Patients spent a median (IQR) 38% (20,61) of days in goal range. Twelve patients (25%) had a TWBG level between 90–130 mg/dL. Overall, the median (IQR) TWBG level for all 48 patients was 140 mg/dL (132,160). Majority of patients were either on an insulin infusion (60%) or basal + sliding scale insulin (SSI) (51%). Patients that were on insulin infusions were controlled for a median (IQR) 75% (50,83) of days compared to patients treated using basal + SSI 20% (0,40) of days (p&lt; 0.01). Other regimens are included in the table below. No patients were hypoglycemic (BG less than 70 mg/dL) based on TWBG.

Conclusions
The majority of patients in this study were not within goal BG range during their hospitalization. Patients were primarily managed by an insulin infusion or basal + SSI. However, the most appropriate regimen appears to be an insulin infusion or basal + bolus + SSI.
63 Risk Factors Associated with Lack of Patient Outpatient Follow Up at a Regional Burn Center
Authors: Moore Allison N , Carmichael Heather , Duffy Patrick S , Lambert Wagner Anne L , Wiktor Arek J 
Published: April 2021

Abstract

Introduction
Burn patients are a vulnerable population at risk for poor follow up after injury. With few burn centers throughout the country, there is often limited access to specialized care. We investigated barriers to patient compliance with recommended outpatient burn care at a single ABA-verified burn center after presentation at referring Emergency Departments (ED).

Methods
A retrospective review was performed on patients who presented at two EDs located 60–75 miles from our burn center over a two-year period. Recommendation for follow up was made by a burn surgeon at our regional burn center after telephone consultation. Medical record review was performed to determine what specific follow up occurred. Data on patient demographics, burn size/location/etiology were also recorded.

Results
Out of 135 consults from the two EDs, a total of 60 patients were recommended for outpatient follow up (vs. transfer, local management, or no follow up). Median age was 35 years [IQR 27–38] and most patients were male (n=40, 66%). Most patients had burns measuring &lt; 1% total body surface area (TBSA) (n=43, 72%). Half scheduled a follow up appointment (n=31, 52%) and fewer came to that appointment (n=26, 43%). Median time from initial presentation to burn clinic follow up was 2 days (range 1–8 days). Of patients who did not attend recommended follow up, 24% (n=8/34) presented for additional visits to the ED or another local provider. Patients who did not follow up were more likely to be male (79% vs. 50%, p=0.03), lack insurance (27% vs. 4%, p=0.05), be homeless/institutionalized (18% vs. 0%, p=0.03) and have facial burns as compared to other body regions (32% vs. 8%, p=0.05). Patients who followed up were more likely to have scald burns versus flash/flame/contact burns (69% vs. 18%, p&lt; 0.001) and were more likely to have been injured at home/work as opposed to outdoors/other location (100% vs. 38% p&lt; 0.001). Age, marital status, race/ethnicity, having a primary care physician, %TBSA, and other comorbidities were not associated with follow up. Although reasons for not following up were rarely noted in the medical record, anecdotal reasons included lack of transportation (n=4), incarceration (n=3), and feeling that burns were healing (n=1).

Conclusions
Less than half of patients followed up at the regional burn center as recommended, while nearly a quarter followed up at local EDs/clinics. Barriers to follow up include patient gender, insurance, and resources (transportation).
95 Growing Up with Burn Injuries - Has the Experience Changed Over Time?
Authors: Brubaker Ruth B , Bay Curt , Kalil Emile , Chacon Daniel W , Wise Dustin K , Milem Mik , Esker Mark , Duke Desiree , Foster Kevin N 
Published: April 2021

Abstract

Introduction
Growing up with disfigurement and functional limitations resulting from childhood burns can be challenging. Initial stages of care involve painful surgeries/dressing changes, strenuous physical & occupational therapy, pressure garments and time away from family/school activities. Few studies have examined the voiced issues faced by youth while maturing with burns. This study’s purpose was to determine if experiences in the post-injury phase differed between currently burn-injured youth vs. young adults burned as children.

Methods
A prior study asked Child Burn Survivors (CBS -10–16 yrs.) and Young Adults (YAs -17-25yrs.) to answer the statement: “The hardest thing about being burned is…” The most common issues included: People Staring, Getting Unwanted Questions, Being Bullied, Remembering When I Was Burned, Having Additional Surgeries and My Scars. The current study asked participants to rate items on a 4-point scale from (1) Not at all to (4) Really a lot. The YAs were asked to consider issues they encountered maturing with burns.

Results
Child Survivors (CBS, n=147) mean age 13.4 years, male (n=46%) female (n=54%), and YA Survivors (YA, n = 81) male(n=39%) female (n=61%) mean age =19.1 yrs. and were predominately racial/ethnic minorities (CBS=67%; YA = 58%). No differences existed for age burned (CBS=6 yrs. vs. YA = 6.4 yrs.) hidden & visible scars (CBS=55% vs. YA=68%) and TBSA &gt; 50% (CBS=19% vs. YA =20%). Top mean scores for CBS’s included: Remembering the Burn (2.05) & Getting Unwanted Questions (2.0). The YA group’s top mean scores included Being Bullied (2.10) & People Staring (2.0). The CBS group reported that Getting Unwanted Questions was more problematic than the YA Group (p =003). YAs shared that Being Bullied was their biggest problem vs. CVS, significantly more so (p=.01).

Conclusions
Bullying appears to be less of a problem for current child burn survivors than those previously burned. The difference may be due to a recent emphasis placed on anti-bullying in US schools. Findings highlight an ongoing need to address the psycho/social issues related to burns. Teaching interventions like the Phoenix Society’s Rehearse Your Response can help youth address unwanted questions and staring. Providing children an opportunity to process the injury event may also improve their ability to cope with burn stressors.
97 Major Psychiatric Illness and Substance Use Disorder Influence Mortality in Major Burn Injury: A Secondary Analysis of the Transfusion Requirement in Burn Care Evaluation (TRIBE) Study
Authors: Andre John A , Sen Soman , Greenhalgh David G , Palmieri Tina L , Romanowski Kathleen S 
Published: April 2021

Abstract

Introduction
Prior studies of burn patients with &lt; 20% total body surface area (TBSA) burns have found that 15.4% of patients have major psychiatric illness (MPI) and 27.6% have Substance Use Disorder (SUD). In patients with small burns, SUD is associated with larger burn size and secondarily with longer length of stay while MPI is associated with longer lengths of stay while not increasing burn size. The purpose of this study was to determine whether MPI or SUD dependence affects outcomes such as mortality in patients with major burn injuries (≥20% TBSA).

Methods
A secondary analysis from the prospective, randomized, multicenter Transfusion Requirement in Burn Care Evaluation (TRIBE) study was conducted. Patients with MPI and SUD were compared with patients without these disorders. Statistical analysis with chi-square for categorical variables and student’s t-test for continuous variables was conducted. Mortality between those with and without MPI and SUD were analyzed with a multivariable regression analysis.

Results
A total of 347 patients with a mean age of 43±17 years, 274 men and 73 women, were analyzed. The mean total body surface area burn (TBSA) was 38±18%, and 23% had inhalation injury. In this study population, 29.1% had SUD, 7.5% had MPI, and 2.3% had both. There was no difference with respect to age, gender, TBSA, frailty, or assignment to the liberal or restrictive transfusion strategy based on the presence of MPI, SUD, or both. Inhalation injury was more common in patients with MPI (27%) or SUD (35%) when compared with patients without these comorbidities (18%) or those who have both (11%) (p=0.006). Patients with MPI were more likely to die of their burn injuries (27%) when compared with those with SUD (17%), both (11%), or neither (8%) (p=0.014). On multivariate analysis for mortality controlling for TBSA and inhalation injury, MPI was found to be an independent predictor of death with an odds ratio of 5 (95% confidence interval 1.7–15, p=0.003).

Conclusions
In burns &gt;20% TBSA, both MPI and SUD influence patient’s likelihood of sustaining inhalation injury. MPI is also independently associated with mortality in the study. Further work must be done to mitigate the effects of mental illness on burn outcomes.
98 The Epidemiology of Acute Stress Disorder Among Inpatient Adult Patients with Burn Injury
Authors: Schneider Daniel M , Keyloun John W , Travis Taryn E , Johnson Laura S , Tejiram Shawn , Shupp Jeffrey W 
Published: April 2021

Abstract

Introduction
Burn injured patients are at high risk for developing Acute Stress Disorder (ASD) and Posttraumatic Stress Disorder (PTSD) following injury. ASD itself is a reliable predictor for the development of PTSD, which usually persists once established. Injury-related characteristics in burn patients (TBSA and anatomic location of burn) do not predict the development of psychological trauma. There is a paucity of literature examining acute psychosocial evaluations of patients with burn injury to address the need for early interventions. Behavioral health assessment and treatment in burn centers may foster improved detection and management of ASD among a variety of other mental health conditions. The goal of this study is to investigate the demographic and injury characteristics associated with new ASD diagnoses in a cohort of inpatient burn survivors.

Methods
Burn injured patients who were admitted to a regional burn center between June 2019 and June 2020 and referred for burn psychology evaluation were retrospectively reviewed. Minors, non-burn injured patients, and those with incomplete evaluations were excluded. Demographic, injury characteristic, health history, and psychologic evaluation results were collected from the medical record. ASD diagnosis was defined by criteria outlined in the PTSD Checklist for DSM-5 (PCL-5). Demographic and injury characteristic were compared between patients with and without ASD diagnoses. Statistical analysis was performed with Mann-Whitney, Chi-square, and Fisher’s Exact test as appropriate. Significance was set at a p=0.05.

Results
Fifty-two patients with median age of 49.5 (IQR, 29–62) years and median TBSA of 6 (2.8–14.4) % met inclusion criteria. Of these, 11 (21%) patients were diagnosed with ASD. Patients with ASD were more often female, (73% vs. 29%, p=0.01), younger (38.5 years vs. 46 years, p=0.05), involved in a structural fire (45.5% vs. 10%, p=0.01), and employed at the time of injury (63% vs. 14.6%, p=0.002). There were no significant differences between groups in TBSA, hospital length of stay, ICU admission, or proportion of patients requiring operative intervention. Among patients who required operative intervention, those in the ASD group underwent fewer total procedures (1 vs. 4, p=0.05).

Conclusions
Patients who developed ASD were younger, more likely female, more often involved in structural fires, and employed. Markers of injury severity such as TBSA, need for operative intervention, ICU admission and hospital length of stay were not associated with the development of ASD.