EMS Care of Adult Hospice Patients- a Position Statement and Resource Document of NAEMSP and AAHPM.

Emergency medical services (EMS) systems are designed to provide care in the field and while transporting patients to a hospital; however, patients enrolled in hospice may not want invasive therapies nor benefit from hospitalization. For many reasons, encounters with hospice patients can be challenging for EMS systems, EMS clinicians, hospice clinicians, hospice patients, and their families.

EMS clinicians should receive hospice-focused education that fosters a basic understanding of hospice, palliative therapies, and advance care planning documents (e.g., Physician Orders for Life Sustaining Treatment). This education should emphasize the ongoing development of end-of-life communication skills.EMS medical directors and local hospice organizations should collaborate to develop hospice patient-centered EMS protocols that address symptom management and delineate appropriate and goal concordant clinical interventions, and that are within the agency-level scope of practice for local EMS clinicians. Partnerships between EMS and hospice organizations can facilitate access to hospice teams who can provide clear guidance on whether to treat-in-place with follow-up care or to transport hospice patients to the hospital.EMS medical directors and local hospice organizations should collaborate to perform needs assessments of hospice patient EMS utilization.EMS medical directors should consider including a focus on EMS care of hospice patients as part of their overall quality management program(s). Ideally these efforts should be collaborative with local hospice agencies in order to facilitate meaningful process improvement strategies that include both EMS and hospice stakeholders.Reimbursement programs should reasonably compensate EMS agencies for scene treatment in place, as well as transport to alternative destinations such as in-patient hospice facilities.

Colitis-induced IL11 promotes colon carcinogenesis.

Colitis increases the risk of colorectal cancer; however, the mechanism of the association between colitis and cancer remains largely unknown. To identify colitis-associated cancer promoting factors, we investigated gene expression changes caused by dextran sulfate sodium (DSS)-induced colitis in mice. By analyzing gene expression profiles, we found that IL11 was upregulated in DSS-induced colitis tissue and 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP)/DSS-induced colon tumours in mice as well as in human colorectal cancer. By characterizing the activation/phosphorylation of STAT3 (pSTAT3), we found that pSTAT3 was induced transiently in colitis, but maintained at higher levels from hyper-proliferative dysplastic lesions to tumours. Using the IL11 receptor (IL11Rα1) knockout mice, we found that pSTAT3 in the newly regenerated crypt epithelial cells in colitis is abolished in IL11Rα1+/- and -/- mice, suggesting that colitis-induced IL11 activates STAT3 in colon crypt epithelial cells. Moreover, colitis-promoted colon carcinogenesis was significantly reduced in IL11Rα1+/- and -/- mice. To determine the roles of the IL11 in colitis, we found that the inhibition of IL11 signalling by recombinant IL11 antagonist mutein during colitis was sufficient to attenuate colitis-promoted carcinogenesis. Together, our results demonstrated that colitis-induced IL11 plays critical roles in creating cancer promoting microenvironment to facilitate the development of colon cancer from dormant premalignant cells.

United States Best Practice Guidelines for Primary Palliative Care in the Emergency Department.

The growing palliative care needs of emergency department (ED) patients in the United States have motivated the development of ED primary palliative care principles. An expert panel convened to develop best practice guidelines for ED primary palliative care to help guide frontline ED clinicians based on available evidence and consensus opinion of the panel. Results include recommendations for screening and assessment of palliative care needs, ED management of palliative care needs, goals of care conversations, ED palliative care and hospice consults, and transitions of care.

GEAMP, a novel gastroesophageal junction carcinoma cell line derived from a malignant pleural effusion.

Gastroesophageal junction (GEJ) cancer remains a clinically significant disease in Western countries due to its increasing incidence, which mirrors that of esophageal cancer, and poor prognosis. To develop novel and effective approaches for prevention, early detection, and treatment of patients with GEJ cancer, a better understanding of the mechanisms driving pathogenesis and malignant progression of this disease is required. These efforts have been limited by the small number of available cell lines and appropriate preclinical animal models for in vitro and in vivo studies. We have established and characterized a novel GEJ cancer cell line, GEAMP, derived from the malignant pleural effusion of a previously treated GEJ cancer patient. Comprehensive genetic analyses confirmed a clonal relationship between GEAMP cells and the primary tumor. Targeted next-generation sequencing identified 56 nonsynonymous alterations in 51 genes including TP53 and APC, which are commonly altered in GEJ cancer. In addition, multiple copy-number alterations were found including EGFR and K-RAS gene amplifications and loss of CDKN2A and CDKN2B. Histological examination of subcutaneous flank xenografts in nude and NOD-SCID mice showed a carcinoma with mixed squamous and glandular differentiation, suggesting GEAMP cells contain a subpopulation with multipotent potential. Finally, pharmacologic inhibition of the EGFR signaling pathway led to downregulation of key downstream kinases and inhibition of cell proliferation in vitro. Thus, GEAMP represents a valuable addition to the limited number of bona fide GEJ cancer cell lines.

Increasing Safe Outpatient Management of Emergency Department Patients With Pulmonary Embolism: A Controlled Pragmatic Trial.

Background: Many low-risk patients with acute pulmonary embolism (PE) in the emergency department (ED) are eligible for outpatient care but are hospitalized nonetheless. One impediment to home discharge is the difficulty of identifying which patients can safely forgo hospitalization. Objective: To evaluate the effect of an integrated electronic clinical decision support system (CDSS) to facilitate risk stratification and decision making at the site of care for patients with acute PE. Design: Controlled pragmatic trial. (ClinicalTrials.gov: NCT03601676). Setting: All 21 community EDs of an integrated health care delivery system (Kaiser Permanente Northern California). Patients: Adult ED patients with acute PE. Intervention: Ten intervention sites selected by convenience received a multidimensional technology and education intervention at month 9 of a 16-month study period (January 2014 to April 2015); the remaining 11 sites served as concurrent controls. Measurements: The primary outcome was discharge to home from either the ED or a short-term (<24-hour) outpatient observation unit based in the ED. Adverse outcomes included return visits for PE-related symptoms within 5 days and recurrent venous thromboembolism, major hemorrhage, and all-cause mortality within 30 days. A difference-in-differences approach was used to compare pre-post changes at intervention versus control sites, with adjustment for demographic and clinical characteristics. Results: Among 881 eligible patients diagnosed with PE at intervention sites and 822 at control sites, adjusted home discharge increased at intervention sites (17.4% pre- to 28.0% postintervention) without a concurrent increase at control sites (15.1% pre- and 14.5% postintervention). The difference-in-differences comparison was 11.3 percentage points (95% CI, 3.0 to 19.5 percentage points; P = 0.007). No increases were seen in 5-day return visits related to PE or in 30-day major adverse outcomes associated with CDSS implementation. Limitation: Lack of random allocation. Conclusion: Implementation and structured promotion of a CDSS to aid physicians in site-of-care decision making for ED patients with acute PE safely increased outpatient management. Primary Funding Source: Garfield Memorial National Research Fund and The Permanente Medical Group Delivery Science and Physician Researcher Programs.

Sex differences in concussion: a review of brain anatomy, function, and biomechanical response to impact.

OBJECTIVE: Provide a potential explanation for sex differences associated with concussions. RESEARCH DESIGN: Review of current literature from complementary disciplines to synthesize a theory to explains sex differences in individuals with concussion. METHODS: Systematic review focusing on sex-related differences in individuals with concussion. Articles published in peer-reviewed journals after 2000 were reviewed and discussed among the authors to determine common themes across the different disciplines represented in the literature review. RESULTS: There are differences in brain structure between sexes. The male corpus callosum has larger fibers and cross-sectional area compared to females. Females tend to utilize both hemispheres of the brain for most tasks, while males are more lateralized. Computation models of concussive impacts indicate that the greater strains occur at the corpus callosum. The corpus callosum is the conduit for interhemispheric connections within the brain; therefore, it stands to reason that increased strain in this area may affect interhemispheric communications resulting in a difference in perceived symptoms between males and females. CONCLUSIONS: Strain injury of the corpus callosum may affect females to a greater extent since their ability to process information may become more disrupted than males.

Aspirin prevents NF-κB activation and CDX2 expression stimulated by acid and bile salts in oesophageal squamous cells of patients with Barrett's oesophagus.

OBJECTIVE: In previous studies using oesophageal squamous cells from patients with Barrett's oesophagus (normal oesophageal squamous (NES)-B cells) and from patients without Barrett's oesophagus (NES-G cells), we showed that acid and bile salts induced caudal-related homeobox transcription factor 2 (CDX2) expression only in NES-B cells. CDX2, a transcription factor required to form intestinal epithelium, is a target of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling, which can be inhibited by aspirin. We explored mechanisms underlying differences between NES-B and NES-G cells in CDX2 expression and effects of aspirin on that CDX2 expression. DESIGN: We exposed NES-B and NES-G cells to acid and bile salts, with and without aspirin, and evaluated effects on IκB-NF-κB-PKAc complex activation, p65 NF-κB subunit function, and CDX2 expression. RESULTS: In both NES-B and NES-G cells, acid and bile salts activated nicotinamide adenine dinucleotide phosphate oxidase to generate H2O2, which activated the IκB-NF-κB-PKAc complex. NES-B cells exhibited higher levels of phosphorylated IκB and p65 and greater NF-κB transcriptional activity than NES-G cells, indicating greater IκB-NF-κB-PKAc complex activation by acid and bile salts in NES-B cells, and p65 siRNA prevented their increased expression of CDX2. Aspirin blocked IκB phosphorylation, p65 nuclear translocation, CDX2 promoter activation and CDX2 expression induced by acid and bile salts in NES-B cells. CONCLUSIONS: Differences between NES-B and NES-G cells in NF-κB activation by acid and bile salts can account for their differences in CDX2 expression, and their CDX2 expression can be blocked by aspirin. These findings might explain why some patients with GORD develop Barrett's oesophagus while others do not, and why aspirin might protect against development of Barrett's oesophagus.

The Dynamic and Transient Immune Microenvironment in Locally Advanced Esophageal Adenocarcinoma Post Chemoradiation.

OBJECTIVE: The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials. SUMMARY BACKGROUND DATA: Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients. METHODS: To determine the effects of chemoradiation on resected esophageal adenocarcinomas, we examined the immune microenvironment pre- and post-chemoradiation using immunohistochemistry, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and functional analysis of tumor-infiltrating lymphocytes. Additionally, to assess the duration and dependency of radiation-induced PD-L1 upregulation, a surgical rat reflux model of esophageal adenocarcinoma is used. First, tumor-bearing animals were dosed with single-fraction 13Gy or 16Gy radiation to determine safety, dose correlation, and PD-L1 upregulation using qRT-PCR post-radiation. Next, longitudinal PD-L1 expression levels within individual animals were determined using serial endoscopic biopsies at baseline, 1, 5, and 9 weeks post 16Gy radiation. RESULTS: The majority of cancers displayed enhanced interferon γ and activated CD8+ T lymphocytes at the tumor stroma interface. These tumors also demonstrated enhanced upregulation of PD-L1 and multiple other immune checkpoints including TIM3, GITR, IDO1, LAG3, OX40, and KIR. The animal model results indicated PD-L1 upregulation is dose-dependent and transiently elevated post radiation exposure. CONCLUSIONS: Collectively, these findings provide insights into the evolving immune landscape after chemoradiation and have significant implications for neoadjuvant trial designs that will combine radiotherapy with immune checkpoint inhibitors.

Serum Albumin at Diagnosis is an Independent Predictor of Early Mortality in Veteran Patients with Esophageal Cancer.

AIMS: To identify independent factors that could predict mortality within 6 months in a cohort of patients with esophageal cancer. METHODS: Esophageal cancer patients were grouped into early (≤6 months, n = 41) and late (>6 months, n = 81) mortality groups. 52 variables were analyzed by univariable analysis (UA). A multivariable (MVA) regression model was created to identify predictors of early mortality. RESULTS: When comparing early and late mortality groups, there was no difference in age, BMI, race, histology, or anatomic location between the two groups. UA demonstrated that the early mortality group had a lower mean albumin level (3.3 ± 0.1 g/dl vs. 3.8 ± 0.1 g/dl; P < 0.001), poorer ECOG performance status (1.9 ± 0.2 vs. 1.1 ± 0.1, P = 0.02), higher WBC count (9.6 ± 0.7 K/µL vs. 8.2 ± 0.3 K/µL, P = 0.04), and were less likely to receive surgery (2.4% vs. 22.2%; P = 0.003), neoadjuvant treatment (4.9% vs. 28.4%; P = 0.009) and definitive chemoradiation (7.3% vs. 27.2%; P = 0.01). MVA revealed that only low albumin at diagnosis was an independent predictor of survival (P = 0.016). CONCLUSION: Albumin level at diagnosis is an independent predictor of early mortality and might be used with other variables to provide prognostic information for patients and to guide treatment.

No Easy Way Out: A Case of Physician-Assisted Dying in the Emergency Department.

Currently, 1 out of 6 Americans lives within a jurisdiction in which physician-assisted dying is legally authorized. In most cases, patients ingest lethal physician-assisted dying medications at home without involvement of emergency medical services (EMS) or the emergency department (ED). However, occasionally the dying process is interrupted as a result of incomplete ingestion or vomiting of medications, confusion about timing of dying trajectory, familial emotional distress, and other variables. A case is presented here of a patient who arrived by ambulance to an urban ED after ingesting physician-assisted dying medication. Stepwise analysis of communication and actions between providers (paramedics, emergency physician, and admitting physician), risk management, and family are described chronologically. This case highlights the significant distress experienced by each party, as well as key challenges and learning points. Guidance is provided to emergency providers about expectations and communication. In states with limited physician-assisted dying experience, many EMS agencies, EDs, and hospitals require comprehensive protocols to handle the complex ethical and psychosocial issues surrounding physician-assisted dying in the ED.

Outpatient Management of Emergency Department Patients With Acute Pulmonary Embolism: Variation, Patient Characteristics, and Outcomes.

STUDY OBJECTIVE: Outpatient management of emergency department (ED) patients with acute pulmonary embolism is uncommon. We seek to evaluate the facility-level variation of outpatient pulmonary embolism management and to describe patient characteristics and outcomes associated with home discharge. METHODS: The Management of Acute Pulmonary Embolism (MAPLE) study is a retrospective cohort study of patients with acute pulmonary embolism undertaken in 21 community EDs from January 2013 to April 2015. We gathered demographic and clinical variables from comprehensive electronic health records and structured manual chart review. We used multivariable logistic regression to assess the association between patient characteristics and home discharge. We report ED length of stay, consultations, 5-day pulmonary embolism-related return visits and 30-day major hemorrhage, recurrent venous thromboembolism, and all-cause mortality. RESULTS: Of 2,387 patients, 179 were discharged home (7.5%). Home discharge varied significantly between EDs, from 0% to 14.3% (median 7.0%; interquartile range 4.2% to 10.9%). Median length of stay for home discharge patients (excluding those who arrived with a new pulmonary embolism diagnosis) was 6.0 hours (interquartile range 4.6 to 7.2 hours) and 81% received consultations. On adjusted analysis, ambulance arrival, abnormal vital signs, syncope or presyncope, deep venous thrombosis, elevated cardiac biomarker levels, and more proximal emboli were inversely associated with home discharge. Thirteen patients (7.2%) who were discharged home had a 5-day pulmonary embolism-related return visit. Thirty-day major hemorrhage and recurrent venous thromboembolism were uncommon and similar between patients hospitalized and those discharged home. All-cause 30-day mortality was lower in the home discharge group (1.1% versus 4.4%). CONCLUSION: Home discharge of ED patients with acute pulmonary embolism was uncommon and varied significantly between facilities. Patients selected for outpatient management had a low incidence of adverse outcomes.

Cellular Origins of Barrett's Esophagus: the Search Continues.

PURPOSE OF REVIEW: The cellular origins of Barrett's esophagus remain elusive. In this review, we discuss the potential cellular mechanisms behind squamous to columnar metaplasia as well as the limitations of these proposed mechanisms. RECENT FINDINGS: Several theories have been proposed, including the reprogramming of native squamous cells, repopulation from submucosal glands, contributions from circulating bone marrow-derived cells, and direct extension of gastric cells. Most recent data support an innate progenitor cell unique to the squamocolumnar junction that can expand into metaplastic glands. Active investigation to clarify each of these potential cells of origin is being pursued, but ultimately each could contribute to the pathogenesis of Barrett's esophagus depending on the clinical context. Nonetheless, identifying cells of origin is critical to understand the molecular mechanisms behind Barrett's esophagus and developing strategies to better treat (and possibly prevent) this increasingly significant premalignant disease.

Origins of Metaplasia in Barrett's Esophagus: Is this an Esophageal Stem or Progenitor Cell Disease?

The incidence of esophageal adenocarcinoma has been increasing in Western countries over the past several decades. Though Barrett's esophagus, in which the normal esophageal squamous epithelium is replaced with metaplastic intestinalized columnar cells due to chronic damage from gastroesophageal reflux, is accepted as the requisite precursor lesion for esophageal adenocarcinoma, the Barrett's esophagus cell of origin and the molecular mechanism underlying esophageal epithelial metaplasia remain controversial. Much effort has been dedicated towards identifying the Barrett's esophagus cell of origin since this could lead to more effective prevention and treatment strategies for both Barrett's esophagus and esophageal adenocarcinoma. Previously, it was hypothesized that terminally differentiated esophageal squamous cells might undergo direct conversion into specialized intestinal columnar cells via the process of transdifferentiation. However, there is increasing evidence that stem and/or progenitor cells are molecularly reprogrammed through the process of transcommitment to differentiate into the columnar cell lineages that characterize Barrett's esophagus. Given that Barrett's esophagus originates at the gastroesophageal junction, the boundary between the distal esophagus and gastric cardia, potential sources of these stem and/or progenitor cells include columnar cells from the squamocolumnar junction or neighboring gastric cardia, native esophageal squamous cells, native esophageal cuboidal or columnar cells from submucosal glands or ducts, or circulating bone marrow-derived cells. In this review, we focus on native esophageal specific stem and/or progenitor cells and detail molecular mediators of transcommitment based on recent insights gained from novel mouse models and clinical observations from patients.

High-Temperature and High-Energy-Density Dipolar Glass Polymers Based on Sulfonylated Poly(2,6-dimethyl-1,4-phenylene oxide).

A new class of high-temperature dipolar polymers based on sulfonylated poly(2,6-dimethyl-1,4-phenylene oxide) (SO2 -PPO) was synthesized by post-polymer functionalization. Owing to the efficient rotation of highly polar methylsulfonyl side groups below the glass transition temperature (Tg ≈220 °C), the dipolar polarization of these SO2 -PPOs was enhanced, and thus the dielectric constant was high. Consequently, the discharge energy density reached up to 22 J cm-3 . Owing to its high Tg , the SO2 -PPO25 sample also exhibited a low dielectric loss. For example, the dissipation factor (tan δ) was 0.003, and the discharge efficiency at 800 MV m-1 was 92 %. Therefore, these dipolar glass polymers are promising for high-temperature, high-energy-density, and low-loss electrical energy storage applications.

Hypoxia-inducible factor-2α plays a role in mediating oesophagitis in GORD.

OBJECTIVE: In an earlier study wherein we induced acute reflux by interrupting proton pump inhibitor (PPI) therapy in patients with reflux oesophagitis (RO) healed by PPIs, we refuted the traditional concept that RO develops as an acid burn. The present study explored our alternative hypothesis that RO results from reflux-stimulated production of pro-inflammatory molecules mediated by hypoxia-inducible factors (HIFs). DESIGN: Using oesophageal biopsies taken from patients in our earlier study at baseline and at 1 and 2 weeks off PPIs, we immunostained for HIF-1α, HIF-2α and phospho-p65, and measured pro-inflammatory molecule mRNAs. We exposed human oesophageal squamous cell lines to acidic bile salts, and evaluated effects on HIF activation, p65 function, pro-inflammatory molecule production and immune cell migration. RESULTS: In patient biopsies, increased immunostaining for HIF-2α and phospho-p65, and increased pro-inflammatory molecule mRNA levels were seen when RO redeveloped 1 or 2 weeks after stopping PPIs. In oesophageal cells, exposure to acidic bile salts increased intracellular reactive oxygen species, which decreased prolyl hydroxylase function and stabilised HIF-2α, causing a p65-dependent increase in pro-inflammatory molecules; conditioned media from these cells increased T cell migration rates. HIF-2α inhibition by small hairpin RNA or selective small molecule antagonist blocked the increases in pro-inflammatory molecule expression and T cell migration induced by acidic bile salts. CONCLUSIONS: In patients developing RO, increases in oesophageal HIF-2α correlate with increased pro-inflammatory molecule expression. In oesophageal epithelial cells, acidic bile salts stabilise HIF-2α, which mediates expression of pro-inflammatory molecules. HIF-2α appears to have a role in RO pathogenesis. TRIAL REGISTRATION NUMBER: NCT01733810; Results.

Laparoscopic ischemic conditioning of the stomach increases neovascularization of the gastric conduit in patients undergoing esophagectomy for cancer.

BACKGROUND AND OBJECTIVES: Gastric ischemic preconditioning has been proposed to improve blood flow and reduce the incidence of anastomotic complications following esophagectomy with gastric pull-up. This study aimed to evaluate the effect of prolonged ischemic preconditioning on the degree of neovascularization in the distal gastric conduit at the time of esophagectomy. METHODS: A retrospective review of a prospectively maintained database identified 30 patients who underwent esophagectomy. The patients were divided into three groups: control (no preconditioning, n = 9), partial (short gastric vessel ligation only, n = 8), and complete ischemic preconditioning (left and short gastric vessel ligation, n = 13). Microvessel counts were assessed, using immunohistologic analysis to determine the degree of neovascularization at the distal gastric margin. RESULTS: The groups did not differ in age, gender, BMI, pathologic stage, or cancer subtype. Ischemic preconditioning durations were 163 ± 156 days for partial ischemic preconditioning, compared to 95 ± 50 days for complete ischemic preconditioning (P = 0.2). Immunohistologic analysis demonstrated an increase in microvessel counts of 29% following partial ischemic preconditioning (P = 0.3) and 67% after complete ischemic preconditioning (P < 0.0001), compared to controls. CONCLUSIONS: Our study indicates that prolonged ischemic preconditioning is safe and does not interfere with subsequent esophagectomy. Complete ischemic preconditioning increased neovascularization in the distal gastric conduit.

"Futile Care"-An Emergency Medicine Approach: Ethical and Legal Considerations.

Futility often serves as a proposed reason for withholding or withdrawing medical treatment, even in the face of patient and family requests. Although there is substantial literature describing the meaning and use of futility, little of it is specific to emergency medicine. Furthermore, the literature does not provide a widely accepted definition of futility, and thus is difficult if not impossible to apply. Some argue that even a clear concept of futility would be inappropriate to use. This article will review the origins of and meanings suggested for futility, specific challenges such cases create in the emergency department (ED), and the relevant legal background. It will then propose an approach to cases of perceived futility that is applicable in the ED and does not rely on unilateral decisions to withhold treatment, but rather on avoiding and resolving the conflicts that lead to physicians' believing that patients are asking them to provide "futile" care.

Nutritional Supplements for the Treatment and Prevention of Sports-Related Concussion-Evidence Still Lacking.

Concussions are common neurologic events that affect many athletes. Very little has been studied on the treatment of concussions with supplements and medications. The U.S. Food and Drug Administration (FDA) reminds us that no supplement has been proven to treat concussions. Many animal studies show that supplements have potential for improving the effects of a brain injury but none have been shown to be of consistent benefit in human studies. Animal studies on severe traumatic brain injury (TBI) may not therefore be applicable transfer to sports-related concussions (SRC).Of the many supplements reviewed in this article, omega-3 fatty acids (Ω-3 FA) have potential for SRC treatment but in the one human trial those taking higher dosages preinjury had more concussions. In animal studies, postinjury administration was as effective as pretreatment. N-acetyl-cysteine has demonstrated a positive short-term effect on blast injuries in soldiers if administered within 24 h, but there are no studies in SRC. Caffeine, conversely, may be detrimental if taken after SRC. Lower serum levels of vitamins D, C, or E preinjury have worse outcomes in animal studies. Preinjury correction of deficiencies may be of benefit. Current human trials for nicotinamide ribose, melatonin, and branched chain amino acids (BCAA) may soon provide more evidence for the use of these supplements to reduce the impact of SRC in athletes.