bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Mobile App-Based Self-care Health Diary for Heart Transplant Recipients
Authors: Yoo Hye Jin , Suh Eunyoung E.
Published: April 2021

Self-care is an essential concept in health maintenance for patients with heart problems. Mobile applications have received significant attention for their efficacy in facilitating lifestyle management. This study aimed to develop a practical mobile application for Android smartphones to aid in the self-care of heart transplant recipients. Development followed the five stages of the ADDIE model (analysis, design, development, implementation, and evaluation). The developed self-care health diary application provides users with a detailed guide to information and behaviors necessary for self-care through two main components: “Health information” and “Health diary.” We conducted a 5-day pilot test with six subject experts and four heart transplant recipients. The participants were unanimously satisfied with the application's content, but experienced difficulty with its functionality, such as screen display and button operation. The feedback was used to revise and update the application, leading to the development of the final version. This study and application significantly contribute to the creation of a sustainable healthcare environment for the growing number of heart transplant recipients by enabling them to perform daily self-care. In future, education and promotion are required for encouraging heart transplant recipients to use the application regularly and proactively.
Sarcoid-like reaction in a BRAF V600E-mutated metastatic melanoma patient during treatment with BRAF/MEK-targeted therapy
Authors: Tijtgat Jens , Schwarze Julia Katharina , Awada Gil , Neyns Bart , Aspeslagh Sandrine
Published: April 2021

Treatment with combined BRAF and MEK inhibition is widely accepted as a first-line treatment option for patients with advanced BRAF V600E mutant melanoma. It is generally well-tolerated and has limited side-effects. However, we report a case of a sarcoid-like syndrome induced by treatment with dabrafenib/trametinib (D/T) in a patient with stage IV-M1d melanoma. Sarcoid-like syndrome is a known side-effect of immune checkpoint-inhibition therapy but has only rarely been described in BRAF/MEK inhibition. However, recognizing this side-effect is important because of potential misinterpretation as progressive disease and influence on treatment. We describe a 48-year-old female patient who initially presented with solitary brain metastasis and diffuse lung lesions. She was treated with D/T to which she had an initial response in all lesions. One year later, new hilar and mediastinal lymphadenopathies were detected. Imaging was suggestive of the sarcoid-like syndrome. An endoscopic biopsy of the enlarged lymph node showed no melanoma cells. Treatment was continued. Three months later, the patient experienced a drop in hemoglobin, which prompted further investigations into possible occult intestinal metastasis. Video capsule examination revealed a metastatic lesion in the small intestine. A treatment switch to the combination of checkpoint inhibitors nivolumab and ipilimumab successfully treated both lung and small intestine lesions. After the third dose of this combination therapy, she developed an immune-related pneumonitis. Treatment with corticosteroids resolved the pneumonitis and decreased metabolism in the sarcoid-like syndrome. The treatment was not restarted afterward. She remains free of the disease up to today, 2.5 years after diagnosis.
Impact of the development of immune related adverse events in metastatic melanoma treated with PD -1 inhibitors
Authors: Holstead Ryan G. , Kartolo Baskoro A. , Hopman Wilma M. , Baetz Tara D.
Published: April 2021

Some clinical trials have described improved outcomes in patients who develop immune-related adverse events (irAEs) while receiving immune checkpoint inhibitors for advanced melanoma. It is unknown if this effect would be seen in a real-world population. This is a single-center retrospective analysis of all patients receiving single-agent PD-1 inhibitor for unresectable stage III or stage IV melanoma between 2012 and 2018. The majority of patients had cutaneous melanoma and were elderly (put in median and range). Totally 33.3% were BRAF mutated and 66.7% had PD-1 inhibitor as first-line treatment for metastatic disease. Also, 22% of patients had brain metastases at presentation. Of the 87 patients included in this analysis, 48 (55%) developed at least one irAE. Dermatologic toxicities were the most common irAE. The median time to develop any irAE was 12 weeks. Only one patient died of immune-related toxicity. Overall survival in the population of patients that had an irAE was significantly greater than those that did not have any toxicity (21.1 vs. 7.5 months; P < 0.001). The development of endocrine toxicity had the strongest correlation with survival as did patient with grade 1 (NCI V.5) toxicity. The development of multiple toxicities did not correlate with survival. In patients with multiple toxicities, the type of irAE that presented initially did not impact the outcome. These findings add to the growing body of literature suggesting an association between irAEs and immune-checkpoint inhibitor efficacy while suggesting that this benefit may depend on the type of toxicity and severity.
Prognostic impact of thyroid dysfunctions on progression-free survival in patients with metastatic melanoma treated with anti-PD-1 antibodies
Authors: Frelau Alexandra , Jali Eva , Campillo-Gimenez Boris , Pracht Marc , Porneuf Marc , Dinulescu Monica , Edeline Julien , Boussemart Lise , Lesimple Thierry
Published: April 2021

This study aimed to assess the prognostic value of thyroid dysfunctions in metastatic melanoma patients on anti-programmed death-1 (anti-PD-1). A total of 110 stage IV or inoperable stage III melanoma patients treated with anti-PD-1 alone or in association with anti-CTLA-4 (T-lymphocyte antigen-4) antibody from January 2015 to December 2017 at our institution were enrolled in this retrospective study. Median follow-up was 32.8 months. Transitory thyroid dysfunctions and permanent thyroid dysfunctions were distinguished. The main criterion was progression-free survival. Secondary criteria were best response and overall survival. Survival curves were compared with log-rank tests and a cox proportional hazard ratio model was used to adjust patients and melanoma characteristics. Thirty-eight (35%) thyroid dysfunctions were observed during the follow-up, including 25 transitory thyroid dysfunctions (23%) and 13 permanent thyroid dysfunctions (12%). Progression-free survival was longer in patients with thyroid dysfunction (18.1 months) than in patients without thyroid dysfunction (3.9 months, P = 0.0085). In multivariate analysis, thyroid dysfunctions were not an independent predictive factor for progression-free survival. Patients with thyroid dysfunction had a longer overall survival (P = 0.0021), and thyroid dysfunctions were associated with a lower mortality risk (hazard ratio = 0.40; P = 0.005). Best response was positively associated with thyroid dysfunctions (P = 0.048). Thyroid dysfunctions induced by anti-PD-1 were not an independent predictive factor for progression-free survival in metastatic melanoma patients but seemed associated with a better response and increased overall survival.
Comparison of Horizontal Corneal Diameter Measurements Using Orbscan IIz, OPD Scan III, and IOLMaster 700
Authors: Cruz Sebastian , Valenzuela Felipe , Stoppel Juan , Maul Eugenio , Gibbons Allister
Published: April 2021

Purpose:

To compare three automated devices for measuring the horizontal corneal diameter (white to white [WTW]).

Methods:

In 65 eyes of 38 patients, the WTW distance was measured independently by three examiners using the following techniques: Orbscan IIz tomography system (Bausch & Lomb), IOLMaster 700 (Carl Zeiss Meditec), and OPD Scan III (NIDEK). We tested for systematic differences in measurements and estimated the limits of agreement (LoA) using linear mixed-effects models.

Results:

The mean WTW distance was 11.8±0.40 mm with Orbscan IIz, 12.1±0.5 mm with IOLMaster 700 and 12.0±0.4 mm with OPD Scan III. The mean difference between IOLMaster 700 and Orbscan IIz was 0.33 (95% CI, 0.28 to 0.38; P<0.001), between OPD Scan III and Orbscan IIz was 0.24 mm (95% CI, 0.21 to 0.28; P<0.001), and between IOL Master 700 and OPD Scan III was 0.09 (95% CI, 0.05 to 0.12; P<0.001). The 95% LoA for Orbscan IIz versus IOLMaster 700 was −0.69 to 0.03 mm, Orbscan IIz versus OPD Scan III was −0.52 to −0.03 mm, and OPD versus IOLMaster 700 was −0.39 to 0.22 mm.

Conclusions:

The data suggest that these devices are not interchangeable for usual clinical practice. Adjustments based on mean differences were not enough to compensate for interinstrument discrepancy in WTW measurements.
Video Viewing Blink Rate in Normal and Dry Eyes
Authors: Mitchell Travis , Murri Michael , Pflugfelder Stephen C.
Published: April 2021

Objectives:

Decreased blink rate during video display viewing (VDV) has been reported; however, patients with tear dysfunction often complain of more frequent blinking. The objectives were to compare blink rates during conversation and VDV in normal and dry eyes and correlate blink rates with signs and symptoms.

Methods:

Blink rate was measured with an infrared blink sensor for 2 minutes during conversation and for 2 minutes while watching a video clip (VDV) in patients without dry eye disease (control, n=18) and in patients with tear dysfunction from meibomian gland dysfunction (MGD, n=23), conjunctivochalasis (CCh, n=19), and aqueous tear deficiency (n=34; non-Sjögren syndrome n=18 and Sjögren syndrome n=16). Patients completed visual analogue questionnaires assessing irritation frequency and severity and blink frequency and underwent an ocular surface evaluation. Group comparisons and correlations were calculated.

Results:

Compared with control, conversational and VDV blink rates were significantly higher in CCh and aqueous tear deficiency (P≤0.005). Self-reported blink frequency was higher in all tear dysfunction groups compared with control. The VDV blink rate was significantly lower than the conversation blink rate in the control group (P=0.006) but not in any of the tear dysfunction groups. Conversational and VDV blink rates were significantly correlated with irritation frequency and severity.

Conclusions:

Blink rate decreases during VDV in normal eyes; however, this blink rate suppression was not observed in patients with tear dysfunction, perhaps because of their irritation symptoms or tear instability.
The Contemporary Epidemiology, Microbiology and Management of Chronic Osteomyelitis in US Children
Authors: McNeil J. Chase , Joseph Marritta , Sommer Lauren M. , Vallejo Jesus G.
Published: April 2021

Background:

While the majority of pediatric osteomyelitis cases are acute in nature, a significant subset present with prolonged symptoms often associated with substantial morbidity. Little data exist to guide clinicians in the management of these infections. We sought to describe the epidemiology, clinical features and management of chronic osteomyelitis (CO) in children.

Methods:

We reviewed hospital admissions for CO from 2011 to 2018 at Texas Children’s Hospital. Cases were included if symptoms lasted ≥28 days on presentation. Cases were classified as those associated with: (1) a contiguous focus of infection; (2) penetrating trauma; (3) orthopedic hardware; (4) postacute CO (PACO, those occurring after ≥28 days of therapy for acute osteomyelitis); and (5) primary hematogenous CO.

Results:

One hundred fourteen cases met inclusion criteria. The median patient age was 11.8 years and 35.9% had comorbidities. 70.2% of patients underwent ≥1 surgical procedure. A microbiologic etiology was identified in 72.8% of cases and Staphylococcus aureus was most common (39.4%). Contiguous focus of infection was more often associated with polymicrobial disease with or without Pseudomonas. Postacute CO was caused by S. aureus in 95%. The median duration of total therapy was 210 days. 26.3% of patients experienced treatment failure of which 46% underwent repeat hospital admission/surgery. There was no association between duration of intravenous therapy for CO and treatment failure.

Conclusions:

Children with CO represent a diverse group both in terms of pathogenesis and microbiology. Pathogenesis and clinical presentation can provide clues to microbiologic etiology. Prolonged intravenous therapy does not appear to improve outcomes in CO.
Concurrent Longitudinally Extensive Transverse Myelitis and Guillain-Barré Syndrome in a Child Secondary to COVID-19 Infection
Authors: Khera Daisy , Didel Siyaram , Panda Samhita , Tiwari Sarbesh , Singh Kuldeep
Published: April 2021

Neurologic manifestation of coronavirus disease 2019 (COVID-19) in children is evolving with time. We are reporting a young girl who presented to us with acute febrile illness followed by acute onset severe flaccid paralysis requiring prolonged intensive care unit stay and ventilator support. She was evaluated extensively and found to be positive for COVID serology, and neuroimaging revealed features of longitudinally extensive transverse myelitis (LETM) with enhancing cauda equina nerve roots, suggesting Guillain-Barré Syndrome (GBS). She failed to respond to immune suppressive therapy and needed plasma exchange for recovery. Like other common viral illnesses, COVID-19 can also act as a trigger for GBS-like illness and LETM, and we need to suspect these diagnoses in the cases with COVID-19 infection in compatible cases. This is probably the first pediatric case with concurrent GBS and LETM secondary to COVID-19 infection.
Descriptive Study of Employee Engagement With Workplace Wellness Interventions in the UK
Authors: Mulaney Bianca , Bromley-Dulfano Rebecca , McShane Erin K. , Stepanek Martin , Singer Sara J.
Published: April 2021

Objective:

To explore sequential steps of employee engagement in wellness interventions and the impact of wellness interventions on employee health.

Methods:

Using previously collected survey data from 23,667 UK employees, we tabulated intervention availability, awareness, participation, and associated health improvement and compared engagement by participation and risk status.

Results:

Employees’ awareness of wellness interventions at their workplaces was often low (mean 43.3%, range 11.6%–82.3%). Participation was highest in diet/nutrition initiatives (94.2%) and lowest in alcohol counseling and smoking cessation interventions (2.1%). Employees with health risks were less likely than lower-risk employees to report awareness, participation, and health improvements from wellness interventions addressing the relevant health concern.

Conclusion:

Employers and policymakers should consider variation in intervention engagement as they plan and implement wellness interventions. Engaging employee populations with higher health risks requires a more targeted approach.
Variation in Employment in Healthcare Occupations and County-Level Differences in COVID-19 Cases in the United States of America
Authors: Le Dong , Hawkins Devan
Published: April 2021

Objective:

To study how county-level differences in employment in healthcare occupations contributes to county-level differences in COVID-19 cases.

Method:

The number of active COVID-19 cases were gathered from the Johns Hopkins University Coronavirus Resource Center weekly between April 22, 2020 and July 1, 2020. Data for the number of workers employed in healthcare occupations were collected at the county-level from the American Community Survey. These data were combined to explore the association between employment patterns and rates of COVID-19 cases.

Result:

Counties with more employment in healthcare-related occupations experienced higher rate of COVID-19. This association was strongest in April and May compared to later months of the pandemic.

Conclusion:

Employment in healthcare occupations may contribute to the spread of COVID-19. Intervention to protect workers may help to prevent the spread of COVID-19 and other infectious diseases.
Treatment of Sinusoidal Obstruction Syndrome With Defibrotide in Pediatric Cancer Patients Following Nontransplant-associated Chemotherapy: A Case Report and Review of the Literature
Authors: Lawrence Marc R. , Bassal Mylène , Ramphal Raveena , Johnston Donna L.
Published: April 2021

Sinusoidal obstruction syndrome (SOS), formerly veno-occlusive disease (VOD), in pediatric cancer patients often presents as a complication of hematopoietic stem cell transplantation, and less commonly secondary to nontransplant-associated chemotherapy. Therapy with defibrotide is well-described as standard care for transplant-associated SOS/VOD, but the treatment of nontransplant-associated SOS/VOD is less clear. We report a 3-year-old with relapsed Wilms tumor and recurrent SOS/VOD, with successful use of defibrotide during chemotherapy. A review of pediatric cancer patients with nontransplant-associated SOS/VOD treated with defibrotide revealed 83 patients, and 66 were in remission. This review supports early treatment with defibrotide in patients with nontransplant-associated SOS/VOD.
Caring for an Unconscious Transgender Patient at the End of Life
Authors: Lippe Megan , Eyer Joshua C. , Rosa William E. , McKinney Robert , Patterson Brianna , Matteo Rebecca A. , Townsend Haley , Halli-Tierney Anne
Published: April 2021

Individuals who identify as transgender (trans) or other gender-diverse identities are highly marginalized populations within the United States health care system. Transgender individuals experience a broad range of health disparities leading to devastating health outcomes. Experiences with discrimination and biased care often result in a lack of trust in providers and reduced care seeking, yet providers frequently rely on communication with trans patients to build competence. Consequently, when a trans patient has restricted communication, whether due to biological or psychological reasons, their care can be further disrupted. The nursing code of ethics compels the provision of competent care to all patients, regardless of demographics or gender identity, including individuals with serious illness and injury. This article describes an approach to the provision of affirmative, trans-inclusive care in a palliative nursing context that integrates cultural humility and self-reflection into an established patient care framework. The approach is then applied to identify ethical dilemmas present in the case of a trans patient who arrived at a hospital in an unconscious state following serious injury. Nurses' use of the ethical approach when caring for seriously ill trans patients would represent important progress toward fostering a health care system that provides affirmative, trans-inclusive care.
Immunohistochemical Expression Pattern of Mismatch Repair Genes in the Short-term Streptozotocin-induced Diabetic Rat Kidneys
Authors: Dragun Matea , Filipović Natalija , Racetin Anita , Kostić Sandra , Vukojević Katarina
Published: April 2021

We studied the expression of mismatch repair genes (MMRs)—mutS protein homolog 2 (MSH2), PMS2, MutL homolog 1 (MLH1), and yH2AFX in diabetic rat kidneys. Streptozotocin-induced diabetes mellitus type 1 rat model (DM1) was used. Renal samples were collected 2 weeks and 2 months after DM1 induction and immunohistochemical expression of MMR genes in the renal cortex was analyzed. Diabetic animals showed lower MSH2 and higher yH2AFX kidney expression both 2 weeks and 2 months after DM1 induction. MLH1 expression significantly increased 2 weeks after DM1 induction (P<0.0001). The most substantial differences were observed in the period 2 weeks after induction, with lower MSH2 and higher MLH1 expression in the proximal convoluted tubules and distal convoluted tubules (DCT) of diabetic animals (P<0.001). yH2AFX expression significantly increased in the DCT of diabetic animals at both time points (P<0.001; P<0.01). PMS2 expression changed only in the glomeruli, where it significantly decreased 2 months after DM1 induction (P<0.05). We concluded that the most substantial changes in renal expression of MMRs are happening already 2 weeks after diabetes induction, predominantly in the proximal convoluted tubules and DCT. Moreover, DCT could have a critical role in the pathophysiology of diabetic nephropathy (DN) and might be a future therapeutic target in this condition. The obtained results point to the MMRs as a potential factor in the development and progression of DN, as well as the possible link between DN and renal carcinogenesis.
Incidence of Bradycardia and the Use of Atropine in Pediatric Rapid Sequence Intubation in the Emergency Department
Authors: Kovacich Nikolas J. , Nelson Amelia C. , McCormick Taylor , Kaucher Kevin A.
Published: April 2021

Objective

Bradycardia during rapid sequence intubation (RSI) is an uncommon but serious adverse effect encountered in pediatric intubations. Atropine has historically been used in the pediatric population as RSI premedication to prevent bradycardia, especially when using succinylcholine as an induction agent. The objective of this analysis was to identify the incidence of bradycardia with or without atropine use.

Methods

This single-center, retrospective, observational case series reviewed pediatric patients up to 18 years old requiring intubation from January 1, 2015, to December 31, 2018. Bradycardia was determined by analyzing heart rates associated with time during and up to 5 minutes after intubation.

Results

A total of 62 patients were included. Three (4.8%) patients experienced a bradycardic event during intubation. A total of 15 (24.2%) patients received atropine for pretreatment of RSI. Incidence of bradycardia was similar between those who received atropine and those who did not. An increasing trend in atropine use was shown throughout the assessment period, yet only 18 (29%) patients met criteria for atropine pretreatment based on the 2015 Pediatric Advanced Life Support guideline recommendations for RSI.

Conclusion

Bradycardia incidence was low in pediatric patients undergoing RSI in our emergency department. Use of atropine or succinylcholine did not affect the incidence of bradycardia during pediatric intubation over this study period. Our results show a low incidence of bradycardia and support the 2015 Pediatric Advanced Life Support Guideline recommendation of limiting the use of atropine premedication in pediatric intubations.
Comparison of Different Clinical Decision Support Tools in Aiding Dental and Medical Professionals in Managing Primary Dentition Traumatic Injuries
Authors: Huh Amy Jee Hye , Chen Jung-Wei , Bakland Leif , Goodacre Charles
Published: April 2021

Background

Many patients are taken to the emergency room for dental trauma treatment, but studies reveal that medical professionals do not feel confident in diagnosing and treating children with traumatic dental injuries. The purpose of this study was to determine if a clinical decision support tool (CDST) would improve dental trauma knowledge of primary teeth in medical students and pediatric dentists. Another purpose was assessing effectiveness of print and mobile app CDSTs.

Methods

Medical students (n = 100) and pediatric dentists (n = 49) were given a pretest to assess baseline dental trauma knowledge. All subjects were randomly assigned to 1 of 3 groups for the posttest: no CDST, print CDST, and mobile app CDST. Test scores and total time spent on each test were recorded and analyzed.

Results

Compared with medical students, pediatric dentists scored significantly higher in both pretest (8.57 ± 0.96 vs 4.20 ± 1.58; P < 0.001) and posttest (8.37 ± 1.09 vs 4.96 ± 1.99; P < 0.001). There was no significant difference in time spent to complete the 2 tests between both groups. Medical students and pediatric dentists who utilized the mobile app CDST had scored highest (P = 0.028) but took the longest time (P < 0.001) on the posttest.

Conclusions

Both print and mobile app CDSTs improved diagnosing and managing traumatic dental injuries in primary dentition significantly compared with those without aid. Medical students with CDSTs showed significant improvement in managing primary dental trauma; therefore, it is recommended for better, more accurate diagnosis and treatment in patients.
Diagnosis and Management of Pediatric Venous Thromboembolism
Authors: Doshi Bhavya S. , Ellison Angela M.
Published: April 2021

The incidence of venous thromboembolism (VTE) is increasing in pediatric patients. Prompt recognition and evaluation of VTE in young patients could prevent significant morbidity or mortality. In contrast to VTE in adults, current treatment guidelines are largely based on expert opinion as limited randomized controlled trial data exist about the appropriate management in pediatric patients with traditional anticoagulants. However, recently approved direct-acting oral anticoagulants in adults are also being investigated in pediatric VTE and these data could inform future evidence-based treatment principles. Thus, healthcare providers must be well informed about the management of pediatric VTE and the data from these trials to date. This continuing medical education article will provide a summary of management of pediatric VTE with particular emphasis on emerging direct-acting oral anticoagulants.
Low-Resource Emergency Department Visits for Children With Complex Chronic Conditions
Authors: Pulcini Christian D. , Coller Ryan J. , Macy Michelle L. , Alpern Elizabeth , Harris Debbi , Rodean Jonathan , Hall Matt , Chung Paul J. , Berry Jay G.
Published: April 2021

Objective

Reducing emergency department (ED) use in children with complex chronic conditions (CCC) is a national health system priority. Emergency department visits with minimal clinical intervention may be the most avoidable. We assessed characteristics associated with experiencing such a low-resource ED visit among children with a CCC.

Methods

A retrospective study of 271,806 ED visits between 2014 and 2017 among patients with a CCC in the Pediatric Health Information System database was performed. The main outcome was a low-resource ED visit, where no medications, laboratory, procedures, or diagnostic tests were administered and the patient was not admitted to the hospital. χ2 Tests and generalized linear models were used to assess bivariable and multivariable relationships of patients' demographic, clinical, and health service characteristics with the likelihood of a low- versus higher-resource ED visit.

Results

Sixteen percent (n = 44,111) of ED visits among children with CCCs were low-resource. In multivariable analysis, the highest odds of experiencing a low- versus higher-resource ED visit occurred in patients aged 0 year (vs 16+ years; odds ratio [OR], 3.9 [95% confidence interval {CI}, 3.7–4.1]), living <5 (vs 20+) miles from the ED (OR, 1.7 [95% CI, 1.7–1.8]), and who presented to the ED in the day and evening versus overnight (1.5 [95% CI, 1.4–1.5]).

Conclusions

Infant age, living close to the ED, and day/evening-time visits were associated with the greatest likelihood of experiencing a low-resource ED visit in children with CCCs. Further investigation is needed to assess key drivers for ED use in these children and identify opportunities for diversion of ED care to outpatient and community settings.
Racial and Language Disparities in Pediatric Emergency Department Triage
Authors: Metzger Peter , Allum Leyla , Sullivan Erin , Onchiri Frankline , Jones Maya
Published: April 2021

Objective

The aim of this study was to assess the impact race and language have on emergency department (ED) triage scores while accounting for illness severity. We hypothesized that non-White and non–English-speaking patients were assigned lower-acuity triage scores compared with White and English-speaking patients, respectively.

Methods

We used a chart review–based retrospective cohort study design, examining patients aged 0 to 17 years at our pediatric ED from July 2015 through June 2016. Illness severity was measured using a truncated Modified Pediatric Early Warning Score calculated from patient vital signs. We used univariate and multivariate multinomial logistic regression to assess the association between race and language with Emergency Severity Index scores.

Results

Our final data set consisted of 10,815 visits from 8928 patients. Non-Hispanic (NH) White patients accounted for 34.6% of patients. In the adjusted analyses, non-White patients had significantly reduced odds of receiving a score of 2 (emergency) (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.33–0.49) or 3 (urgent) (OR, 0.5; 95% CI, 0.45–0.56) and significantly higher odds of receiving a score of 5 (minor) (OR, 1.34; 95% CI, 1.07–1.69) versus a score of 4 (nonurgent). We did not find a consistent disparity in Emergency Severity Index scores when comparing English- and non–English-speaking patients.

Conclusions

We confirm that non-White patients receive lower triage scores than White patients. A more robust tool is required to account for illness severity and will be critical to understanding whether the relationship we describe reflects bias within the triage system or differences in ED utilization by racial groups.
Update in Disaster Rehabilitation
Authors: Khan Fary , Amatya Bhasker
Published: April 2021

Disasters (both natural and man-made) are escalating worldwide, resulting in a significant increase in survivors with complex and long-term disabling injuries. Physical and rehabilitation medicine is integral in disaster management and should be included in all phases of the disaster management continuum, which comprise mitigation/prevention, preparation, response, and recovery phases. This Joel A. DeLisa Lecture was presented on February 11, 2021, at the Association of Academic Physiatrists Annual Scientific Meeting–“Physiatry 21.” The lecture highlights the synergistic position of the International Society of Physical and Rehabilitation Medicine and the Disaster Rehabilitation Committee, to provide crucial leadership and governance role in liaison and coordination with the World Health Organization (and other stakeholders), to provide rehabilitation input during future disasters.
Preliminary evidence for conserved transcriptional response to adversity in adults with temporomandibular disorder
Authors: King Christopher D. , Boggero Ian A. , Schulert Grant S. , Pickerill Hannah M. , Cole Steve
Published: April 2021

Introduction:

Temporomandibular disorder (TMD) is one of the most common orofacial pain conditions. Alteration in immune functioning is one promising biological mechanism underlying pain in TMD. However, there is a gap in the understanding of molecular bases contributing to altered immune functioning in these patients.

Objectives:

In the current study, we investigated whether individuals with TMD would exhibit differential activity of 3 specific transcription factors involved in inflammatory (nuclear factor-kappa B, NF-kB), antiviral (interferon-regulatory factors, IRF), and sympathetic (cAMP response element-binding protein, CREB) processes using a promoter-based bioinformatics analysis, which is characterized as the “Conserved Transcriptional Response to Adversity.”

Methods:

Adults with TMD (n = 19) and without (n = 17) underwent a standardized clinical examination for TMD. A blood sample was collected for genome-wide transcriptional RNA profiling. Bioinformatic analyses tested for differential prevalence of proinflammatory and antiviral transcription factor activity in core promoter sequences from all genes showing >1.2-fold differential expression in TMD vs controls.

Results:

Promoter-based bioinformatic analyses of genome-wide transcriptome profiles confirmed upregulation of genes bearing response elements for proinflammatory transcription factor (NF-kB, P = 0.002) and downregulation of genes with response elements for IRF (P = 0.037) in patients with TMD relative to controls. Results also indicated upregulated activity of CREB in patients with TMD (P = 0.08), consistent with increased activity of the sympathetic nervous system.

Conclusion:

These results provide initial support that the regulation of immune pathways is altered in individuals with TMD. A shift of transcriptional resources to a proinflammatory state may be driven by psychosocial stress and contributes to symptoms associated with TMD.
Potential for increased prevalence of neuropathic pain after the COVID-19 pandemic
Authors: Attal Nadine , Martinez Valéria , Bouhassira Didier
Published: April 2021

Although coronavirus disease 2019 (COVID-19) most commonly manifests with acute respiratory symptoms, one very common symptom of COVID-19 is pain. As COVID-19 often causes peripheral or central neurological complications, it is anticipated that a number of the chronic pain complications of COVID-19 will be neuropathic. This review first examines the most common viral infections responsible for neurological complications including neuropathic pain. These encompass herpes zoster, HIV, poliovirus, enteroviruses, and several tropical viruses. Neurological complications of COVID-19 including in particular Guillain–Barré syndrome, myelitis, and stroke are reviewed with regards to their potential risk of chronic neuropathic pain. Prospective longitudinal cohorts of patients should be implemented to evaluate the exact risk of neuropathic pain after COVID-19.
Implications of the national Stop the Bleed campaign: The swinging pendulum of prehospital tourniquet application in civilian limb trauma
Authors: Mikdad Sarah , Mokhtari Ava K. , Luckhurst Casey M. , Breen Kerry A. , Liu Betty , Kaafarani Haytham M.A. , Velmahos George , Mendoza April E. , Bloemers Frank W. , Saillant Noelle
Published: April 2021

BACKGROUND

Prehospital tourniquet (PHT) utilization has increased in response to mass casualty events. We aimed to describe the incidence, therapeutic effectiveness, and morbidity associated with tourniquet placement in all patients treated with PHT application.

METHODS

A retrospective observational cohort study was performed to evaluate all adults with a PHT who presented at two Level I trauma centers between January 2015 and December 2019. Medically trained abstractors determined if the PHT was clinically indicated (placed for limb amputation, vascular hard signs, injury requiring hemostasis procedure, or significant documented blood loss). Prehospital tourniquets were further designated as appropriately or inappropriately applied (based on PHT anatomic placement location, occurrence of a venous tourniquet, or ischemic time defined as >2 hours). Statistical analyses were performed to generate primary and secondary results.

RESULTS

A total of 147 patients met study inclusion criteria, of which 70% met the criteria for trauma registry inclusion. Total incidence of PHT utilization increased from 2015 to 2019, with increasing proportions of PHTs placed by nonemergency medical service personnel. Improvised PHTs were frequently used. Prehospital tourniquets were clinically indicated in 51% of patients. Overall, 39 (27%) patients had a PHT that was inappropriately placed, five of which resulted in significant morbidity.

CONCLUSION

In summary, prehospital tourniquet application has become widely adopted in the civilian setting, frequently performed by civilian and nonemergency medical service personnel. Of PHTs placed, nearly half had no clear indication for placement and over a quarter of PHTs were misapplied with notable associated morbidity. Results suggest that the topics of clinical indication and appropriate application of tourniquets may be important areas for continued focus in future tourniquet educational programs, as well as future quality assessment efforts.

LEVEL OF EVIDENCE

Epidemiological, level III; Therapeutic, level IV.
An Unusual Cause of Acute Pancreatitis in a Liver Transplant Recipient
Authors: Nizamuddin Imran , Kourkoumpetis Themistoklis , Wood Cecil G. , Levitsky Josh
Published: April 2021

Posttransplant lymphoproliferative disorder (PTLD) in liver transplant recipients is relatively uncommon, with an estimated incidence of 1%–3%. Retrospective reviews of liver transplant recipients have mainly reported posttransplant lymphoproliferative disorder affecting the liver, gastrointestinal tract, or lymph nodes. In this case report, we describe a 45-y-old female with a history of deceased donor liver transplantation for autoimmune hepatitis who had recurrent hospital admissions for acute pancreatitis. Ultimately, imaging revealed numerous complex pancreatic and peripancreatic masses, appearing to originate from pancreatic lymphoid tissue. Tissue biopsy later confirmed monomorphic Epstein-Barr virus-negative large B-cell lymphoma. Overall, PTLD involving the pancreas after liver transplantation is incredibly rare. The patient’s cumulative immunosuppression drug dose and time posttransplant were suspected to be her main risk factors, given that she had been exposed to several years of treatment with tacrolimus, azathioprine, mycophenolate mofetil, and prednisone. She was treated with rituximab monotherapy and later escalated to chemoimmunotherapy due to lack of response. PTLD involving the pancreas is an unusual cause of pancreatitis and should be considered in cases of recurrent pancreatitis in transplant recipients.
A De Novo Missense Variant of SCN2A: Implications and Limitations for Understanding Clinical Phenotype and Treatment Recommendations
Authors: Deutsch Stephen I. , Burket Jessica A.
Published: April 2021

Autism spectrum disorder can be associated with a variety of genetic findings. We report a heterozygous de novo missense variant of SCN2A, the gene coding a voltage-gated sodium ion channel enriched in the axon initial segment and nodes of Ranvier of “immature” neocortical pyramidal neurons. With further understanding of the neurodevelopmental and functional effects of this missense variant on neuronal excitability and neocortical circuitry, there may be targeted pharmacotherapeutic interventions, potentially with “disease-modifying effects.”
Adjunctive music improves the tolerability of intravenous ketamine for bipolar depression
Authors: Greenway Kyle T , Garel Nicolas , Goyette Nathalie , Turecki Gustavo , Richard-Devantoy Stephane
Published: April 2021

Intravenous ketamine is an effective treatment of bipolar depression. One of its most important side-effects is a transient altered state of consciousness commonly referred to as dissociation. These states can be anxiety-provoking, distressing and even treatment-limiting, warranting research into mitigation strategies. In this article, we present two cases that demonstrate the potential of adjunctive music to diminish the distress associated with ketamine-induced dissociation – though not necessarily its degree – in bipolar 1 disorder. Both patients suffering from severe depression underwent their first ketamine infusion without music and opted for music with subsequent infusions. They reported that music significantly improved the tolerance of their dissociative symptoms, thereby reducing distress and facilitating subsequent treatments. Both patients achieved remission from their highly treatment-resistant depressive episodes following six ketamine infusions. This is the first report of music’s benefits on ketamine for bipolar 1 depression, though there is precedence in the scientific literature on ‘psychedelics’ where the use of music in combination with medication-induced altered states has been studied. The principles regarding music selection that have resulted from this paradigm may be applicable to the use of ketamine in unipolar and bipolar depression. The optimal use of music with ketamine warrants further research.
Leonard George Goodwin. 11 July 1915—25 November 2008
Authors: Peaker Malcolm , Ogilvie Dame Bridget M.
Published: April 2021

For 24 years Leonard George Goodwin was responsible for developing chemotherapeutic agents against parasites at what became the Wellcome Laboratories of Tropical Medicine. Having degrees in pharmacy, physiology and, eventually, clinical medicine, he was active from the start of World War II in the drive to protect Allied forces in the field from tropical diseases. It was in the 1940s, 1950s and into the 1960s that Goodwin had most immediate and lasting impact, through the establishment of five major drugs: sodium stibogluconate, for treatment of leishmaniasis; pyrimethamine, for malaria; piperazine, to combat ascariasis; bephenium, for ankylostomiasis; and phenanthridine derivates, to treat trypanosomiasis. Such agents also became important in veterinary medicine. In 1963 he became director of the new Nuffield Institute of Comparative Medicine and then director of science at the Zoological Society of London. Although Goodwin never worked in higher education, he nonetheless influenced many careers through his involvement with scientific societies.
Caproicibacterium amylolyticum gen. nov., sp. nov., a novel member of the family Oscillospiraceae isolated from pit clay used for making Chinese strong aroma-type liquor
Authors: Gu Yang , Zhu Xiaojun , Lin Feng , Shen Caihong , Li Yong , Ao Ling , Fan Wenlai , Ren Cong , Xu Yan
Published: April 2021

An anaerobic, Gram-stain-positive, rod-shaped, motile and spore-forming bacterium, designated strain LBM18003T, was isolated from pit clay used for making Chinese strong aroma-type liquor. Growth occurred at 20–40 °C (optimum, 30–37 °C), pH 4.5–9.5 (optimum, pH 6.5–7.0) and in the presence of 0.0–1.0 % (w/v) sodium chloride (optimum, 0 %). The predominant fatty acids were C16:0, C14:0, C14:0 DMA and C16:0 3-OH, and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, two unidentified phospholipids and nine unidentified glycolipids. Phylogenetic analysis revealed that strain LBM18003T is a novel member of the family

Oscillospiraceae

. The 16S rRNA gene sequence similarities of strain LBM18003T to its two most closely related species were less than 94.5 % for distinguishing genera, i.e. closely related to

Caproiciproducens galactitolivorans

JCM 30532T (94.1 %) and

Caproicibacter fermentans

DSM 107079T (93.2 %). The genome size of strain LBM18003T was 2 996 201 bp and its DNA G+C content was 48.48 mol%. Strain LBM18003T exhibited 67.8 and 68.1% pairwise-determined whole-genome average nucleotide identity values to

Caproiciproducens galactitolivorans

JCM 30532T and

Caproicibacter fermentans

DSM 107079T, respectively; and showed 62.2 and 61.0 % the average amino acid identity values to

Caproiciproducens galactitolivorans

JCM 30532T and

Caproicibacter fermentans

DSM 107079T, respectively; and demonstrated 46.1 and 41.5 % conserved genes to

Caproiciproducens galactitolivorans

JCM 30532T and

Caproicibacter fermentans

DSM 107079T, respectively. The comparisons of 16S rRNA gene and genome sequences confirmed that strain LBM18003T represented a novel genus of the family

Oscillospiraceae

. Based on morphological, physiological, biochemical, chemotaxonomic, genotypic and phylogenetic results, strain LBM18003T represents a novel species of a novel genus of the family

Oscillospiraceae

, for which the name Caproicibacterium amylolyticum gen. nov., sp. nov. is proposed. The type strain is LBM18003T (=GDMCC 1.1626T=JCM 33783T).
Re-emergence of COVID-19 in Beijing was triggered by frozen virus: evidence from molecular clock
Authors: Zhang Yunjun , Zhang Yong , Liang Mifang , Zhang Yi , Li Yang , Ma Xuejun , Zhou Xiaohua
Published: April 2021

The COVID-19 outbreak in Xinfadi (XFD) Wholesale market in Beijing, China in June, 2020 caused 368 reported cases within 39 days. Genetic evidences indicated that imported SARS-CoV-2 (belong to the lineage B1.1.29) initiated this outbreak. However, the transmission route of the virus is still unknown. We obtained from public database three SARS-CoV-2 genomes isolated in XFD (XFD genomes) and adopted the leaf-dating method to calculate their expected collection dates using temporal calibrating information from other 241 genomes collected in mainland of China. All three XFD genomes were calculated to have earlier collection dates than the recorded (Bayes factor >1), and hence exhibited a lack of genetic divergence. We additionally combined the XFD genomes with other 225 genomes subsampled from those of the lineage B1.1.29, among which five sequences were also included for control analysis. Two of three XFD genomes were calculated to have earlier collection dates than the recorded (Bayes factor >1), while no control genomes provided such evidence. According to present understanding of SARS-CoV-2, a lack of genetic divergence is most likely due to being frozen. Considering the fact that the XFD outbreak started from a booth of frozen food, we judged that the XFD outbreak was caused by contaminated frozen food. Our results provided molecular evidence for the source of COVID-19 outbreak in Beijing XFD, which highlights new targets for SARS-CoV-2 surveillance for the public health.
Platelet Activation by Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Patient Serum is Blocked by COX, P2Y12 and Kinase Inhibitors
Authors: Smith Christopher W. , Kardeby Caroline , Di Ying , Lowe Gillian C. , Lester William A. , Watson Steve P. , Nicolson Phillip L.R.
Published: April 2021

Background

The novel coronavirus SARS-CoV-2 has caused a global pandemic. Vaccines are an important part of the response. Although rare, unusual thrombotic events and thrombocytopenia in recipients 4–16 days after vaccination with the AstraZeneca AZD1222 have been reported. This syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) clinically resembles heparin induced thrombocytopenia (HIT), which is caused by platelet activating antibodies against platelet factor 4 (PF4). Here, we investigate the effect of serum from patients with VITT on platelet activation, and assess the ability of clinically available therapeutics to prevent platelet activation.

Methods

Aggregation responses of healthy donor washed platelets were assessed in response to serum from patients with VITT pre- and post-intravenous immunoglobulin (IVIg) treatment and in the presence of anti-FcγRIIA blocking IV.3 F(ab), anti-platelet drugs and kinase inhibitors.

Findings

Four patients (21 - 48 years old) presented with thrombosis (three patients: cerebral venous sinus thrombosis, one patient: ischemic stroke) and thrombocytopenia 10-14 days after AZD1222 vaccination. All patients tested positive for anti-PF4 antibody despite no prior heparin exposure. Serum from patients with VITT, but not healthy donor controls, induced platelet aggregation, which was abrogated following IVIg treatment. Aggregation to patient sera was blocked by IV.3 F(ab) which targets FcγRIIA, and inhibitors of Src, Syk and Btk kinases downstream of the receptor. Anti-platelet therapies indomethacin and ticagrelor also blocked aggregation.

Interpretation

In conclusion, serum from patients with VITT activates platelets via the FcγRIIA, which can be blocked in vitro by anti-platelet therapies suggesting possible new therapeutic interventions for this rare syndrome.

Funding

This work was supported by an Accelerator Grant (AA/18/2/34218) from the British Heart Foundation (BHF).

Key points

Serum from patients with VITT activates platelets via the FcγRIIA.

Platelet activation by serum from patients with VITT can be blocked by COX, P2Y12, Src, Syk and Btk inhibition.