Barriers and facilitators to engaging with a digital self-management programme for painful distal upper limb musculoskeletal disorders: A qualitative exploratory study.

INTRODUCTION: People living with a painful distal upper limb musculoskeletal disorder (DUL-MSD) often experience pain, difficulty in doing everyday tasks and a reduced quality of life. Currently, there are challenges in the treatment of DUL-MSDs, highlighting the need to develop innovative approaches to rehabilitation. A potential solution is to develop and implement a digital self-management rehabilitation programme focussing on optimising recovery, improving function and reducing pain. Before developing this programme, we aimed to identify the barriers and facilitators to using a digital health intervention (DHI) for self-management of DUL-MSDs. OBJECTIVE: This study aimed to investigate the potential barriers and facilitators to using a DHI with people living with DUL-MSDs and healthcare professionals (HCPs). METHODS: A qualitative exploratory study was carried out with purposely selected participants consisting of 15 participants with DUL-MSDs and 13 HCPs. Three focus groups (FGs) and four semistructured interviews with DUL-MSD participants and semistructured interviews with 13 HCPs were conducted. FGs and interviews were digitally recorded, transcribed and analysed using reflexive thematic analysis. RESULTS: To address challenges in the care and management of DUL-MSDs, both HCPs and people living with a DUL-MSD welcomed the development of a DHI. This study identified several barriers and facilitators that would influence engagement with a digital intervention. Findings suggest that in developing a DHI, attention needs to be paid to digital design features, usability, tailoring, personalisation and consideration of how well usual care could be replicated digitally without direct HCP involvement. CONCLUSION: The identified digital design features of importance to participants will inform the design of a digital self-management rehabilitation programme for people living with DUL-MSDs. Addressing the barriers and facilitators to engagement with a DHI is essential in ensuring its relevance and acceptability to those who will use it. PATIENT OR PUBLIC CONTRIBUTION: Patient and Public Involvement and Engagement (PPIE) was integral throughout the study. PPIE members contributed to the development and planning of this study, checked and confirmed the relevance of the findings and are involved in the dissemination plans.

An unusual etiology of obstructive shock in the emergency department.

Obstructive shock describes any disease process that causes physical obstruction to blood flow into or out of the heart which results in impaired systemic oxygen or nutrient delivery. Common etiologies include cardiac tamponade, tension pneumothorax, and pulmonary embolus. However, several other causes exist and should prompt consideration in the correct clinical circumstances. In this report, we describe a 72-year-old female patient with history of hepatic cysts presenting with respiratory distress, mottled extremities, and abnormal vital signs. Contrast enhanced computed tomography scans showed a massive hepatic cyst which was compressing her vena cava and heart, causing hemodynamic instability. The patient was admitted to the ICU and the hepatic cyst was drained percutaneously, but ultimately, she succumbed to her illness post-operatively. This report highlights the importance of keeping a broad differential when considering etiologies of undifferentiated shock as well as the need for additional research regarding management of rare causes of obstructive shock.

Blood component utilization in COVID-19 patients in New York City: Transfusions do not follow the curve.

BACKGROUND: Blood suppliers and transfusion services have worked diligently to maintain an adequate blood supply during the COVID-19 pandemic. Our experience has shown that some COVID-19 inpatients require transfusion support; understanding this need is critical to blood product inventory management. STUDY DESIGN AND METHODS: Hospital-wide and COVID-19 specific inpatient blood product utilization data were collected retrospectively for our network's two tertiary academic medical centers over a 9-week period (March 1, 2020-May 2, 2020), when most inpatients had COVID-19. Utilization data were merged with a COVID-19 patient database to investigate clinical demographic characteristics of transfused COVID-19 inpatients relative to non-transfused ones. RESULTS: Overall, 11 041 COVID-19 patients were admitted and 364 received blood product transfusions for an overall transfusion rate of 3.3%. COVID-19 patients received 1746 blood components in total, the majority of which were red blood cells. COVID-19 patients' weekly transfusion rate increased as the pandemic progressed, possibly reflecting their increased severity of illness. Transfusion was significantly associated with several indicators of severe disease, including mortality, intubation, thrombosis, longer hospital admission, lower hemoglobin and platelet nadirs, and longer prothrombin and activated partial thromboplastin times. As the pandemic progressed, institutional adherence to transfusion guidelines improved for RBC transfusions compared to prior year trends but did not improve for platelets or plasma. CONCLUSION: There is a need to closely monitor the blood product inventory and demand throughout the COVID-19 pandemic as patients' transfusion needs may increase over time. Daily or weekly trending of patients' clinical status and laboratory values may assist blood banks in inventory management.

Separate Effect of Perioperative Recombinant Human Factor VIIa Administration and Packed Red Blood Cell Transfusions on Midterm Survival in Lung Transplantation Recipients.

OBJECTIVE: The purpose of this study was to determine the relationship between blood product transfusion, with or without recombinant human activated factor VIIa, and survival after lung transplantation. DESIGN: Retrospective analysis of a single center with follow-up out to 6 years post-transplantation. SETTING: Single-center academic lung transplantation program. PARTICIPANTS: The study comprised 265 adult patients who underwent single or bilateral sequential lung transplantation from March 2011 to June 2017. INTERVENTIONS: Overall survival using Kaplan-Meier curves was compared among the following 3 cohorts: those not transfused with blood products, those transfused with blood products, and those given blood products and recombinant human activated factor VIIa. Cox proportional hazards regression was used to estimate hazard ratios (HRs), confidence intervals (CIs), and p values. MEASUREMENTS AND MAIN RESULTS: Seventy-eight patients received no packed red blood cell transfusions, 149 received packed red blood cell transfusions, and 38 received both packed red blood cell transfusions and recombinant human activated factor VII. Packed red blood cell transfusion was associated with an increased risk of mortality that did not reach statistical significance (HR 2.168, CI 0.978-4.805; p = 0.057). Additional packed red blood cells beyond 15 U were associated with worsened survival (HR 1.363, CI 1.137-1.633; p = 0.001), but recombinant human activated factor VIIa did not increase the risk of mortality. CONCLUSION: Blood product transfusion during and after lung transplantation is associated with decreased survival, especially with large-volume transfusions. Survival is not worse with recombinant human activated factor VIIa administration, but additional studies are needed to determine whether recombinant human activated factor VIIa administration reduces the need for blood product transfusions.

Death from Transfusion-Transmitted Anaplasmosis, New York, USA, 2017.

We report a death from transfusion-transmitted anaplasmosis in a 78-year-old man. The patient died of septic shock 2 weeks after a perioperative transfusion with erythrocytes harboring Anaplasma phagocytophilum. The patient's blood specimens were positive for A. phagocytophilum DNA beginning 7 days after transfusion; serologic testing remained negative until death.

Standardized Direct Observation Assessment Tool: Using a Training Video.

BACKGROUND: We developed a DVD training tool to educate physicians evaluating emergency residents on accurate Standardized Direct Observation Assessment Tool (SDOT) application. OBJECTIVE: Our goal was to assess whether this training video improved attendings' and senior residents' SDOT use. METHODS: Participants voluntarily completed SDOT evaluations based on a scripted "test" video. A DVD with "positive" and "negative" scenarios of proper SDOT use was viewed. It included education on appropriate recording of 26 behaviors. The test scenario was viewed again and follow-up SDOTs submitted. Performances by attendings and residents on the pre- and post-test SDOTs were compared. RESULTS: Twenty-six attendings and 26 senior residents participated. Prior SDOT experience was noted for 8 attendings and 11 residents. For 20 anchors, participants recorded observed behaviors with statistically significant difference on one each of the pretest (no. 20; p = 0.034) and post-test (no. 14; p = 0.041) SDOTs. On global competency assessments, pretest medical knowledge (p = 0.016) differed significantly between groups. The training intervention changed one anchor (no. 5; p = 0.035) and one global assessment (systems-based practice; p = 0.031) more negatively for residents. Recording SDOTs with exact agreement occurred 48.73% for attendings pretest and 54.41% post-test; resident scores were 45.86% and 49.55%, respectively. DVD exposure slightly raised attending scores (p = 0.289) and significantly lowered resident scores (p = 0.046). CONCLUSIONS: Exposure to an independently developed SDOT training video tended to raise attending scores, though without significance, while at the same time lowered senior resident scores statistically significantly. Emergency attendings' and senior residents' SDOT scoring rarely differed with significance; about half of anchor behaviors were recorded with exact agreement. This suggests senior residents, with appropriate education, may participate in SDOT assessment.

Correlation Between United States Medical Licensing Examination and Comprehensive Osteopathic Medical Licensing Examination Scores for Applicants to a Dually Approved Emergency Medicine Residency.

BACKGROUND: It is important for emergency medicine (EM) residency programs to be able to correlate the United States (US) Medical Licensing Examination (USMLE) and Comprehensive Osteopathic Medical Licensing Examination (COMLEX) scores of applicants. OBJECTIVE: We sought to determine the correlation between USMLE and COMLEX scores for EM residency applicants. METHODS: Retrospectively, from 2006 through 2013, USMLE and COMLEX examination scores for applicants to our 4-year, 56-member, dually approved EM residency were analyzed. Using the COMLEX score as the outcome variable and USMLE score as the predictor, multiple linear regression models, stratified by test step, were created. RESULTS: There were 556 students representing 25 discrete medical schools included. Pair 1 consisted of applicants submitting COMLEX Level-1 and USMLE Step-1 scores (n = 486). Pair 2 were those with COMLEX Level-2 and USMLE Step-2 scores (n = 356). For Pair 1, mean, standard deviation, and median scores on the COMLEX were 551, 69, and 548, respectively; for the USMLE, scores were 216, 16, and 217, respectively. Results for Pair 2 on COMLEX were 566, 80, and 562, respectively; USMLE results were 228, 18, and 229, respectively. A strong correlation was observed for Pair 1 (r = 0.78; p < 0.001). A 1-point increase in USMLE Step-1 is associated with a 3.55-point increase in the COMLEX Level-1 score (ß = 3.55; 95% confidence interval [CI] 3.30-3.80; p < 0.001). A similar strong correlation was observed for Pair 2 (r = 0.72; p < 0.001), where a 1-point increase in USMLE Step-2 is associated with a 3.29-point increase in the COMLEX Level-2 score (ß = 3.29; 95% CI 2.96-3.62; p < 0.001). CONCLUSIONS: A strong positive correlation between Steps 1 and 2 of the USMLE and COMLEX was found.

Acute Cerebellar Ataxia: An Unusual Pediatric Case.

BACKGROUND: Acute cerebellar ataxia is a clinical syndrome with sudden onset of uncoordinated gait and normal mental status in young children. Although it has a benign clinical course, it often requires an exhaustive diagnostic work-up in order to rule out potentially life-threatening etiologies that present similarly. The wide differential encompasses causes from infections, brain masses, drugs, toxins, trauma, paraneoplastic syndromes, as well as hereditary or congenital disorders. CASE REPORT: We report on a 4-year-old boy with recent hand-foot-mouth disease who presented with acute cerebellar ataxia. In addition to his marked truncal ataxia and wide-based, staggering gait, he had slowness of speech, which is not commonly reported with this condition in the literature. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians have a unique role in being first to evaluate pediatric ataxia and can make a significant impact on identifying potentially fatal mimickers of acute cerebellar ataxia. This article will attempt to outline major diagnostic considerations in order to aid emergency physicians through their clinical approach.

Re-engineering protein interfaces yields copper-inducible ferritin cage assembly.

The ability to chemically control protein-protein interactions would allow the interrogation of dynamic cellular processes and lead to a better understanding and exploitation of self-assembling protein architectures. Here we introduce a new engineering strategy--reverse metal-templated interface redesign (rMeTIR)--that transforms a natural protein-protein interface into one that only engages in selective response to a metal ion. We have applied rMeTIR to render the self-assembly of the cage-like protein ferritin controllable by divalent copper binding, which has allowed the study of the structure and stability of the isolated ferritin monomer, the demonstration of the primary role of conserved hydrogen-bonding interactions in providing geometric specificity for cage assembly and the uniform chemical modification of the cage interior under physiological conditions. Notably, copper acts as a structural template for ferritin assembly in a manner that is highly reminiscent of RNA sequences that template virus capsid formation.

Recurrent (stump) appendicitis: a case series.

Stump appendicitis is a rare but serious postoperative complication of an appendectomy. In the emergency department, diagnosticians are likely to rule out appendicitis when a surgical history of an appendectomy is reported. We describe 2 patients in this case series who presented to the emergency department with right lower quadrant abdominal pain and a history of previous appendectomy. Both patients were identified with a remnant appendiceal stump and stump appendicitis. Upon admission to a surgical service, a nonoperative approach in management allowed each patient to stabilize and be discharged after treatment with antibiotics. The purpose of this article is to raise awareness about the diagnosis of stump appendicitis, as well as to discuss the treatments for it.

Gender differences in perceptions and self-reported driving behaviors among teenagers.

BACKGROUND: The Centers for Disease Control reports that motor vehicle crashes (MVCs) are the leading cause of injury and death among U.S. teenagers, and disproportionately affect males. Among preventable causes of MVCs involving teenage drivers, distracted driving continues to be a serious public health problem. OBJECTIVES: To describe gender differences in teenage drivers' self-perceptions of safe driving behaviors, and self-reported risk behaviors and distractions while driving. METHODS: We prospectively surveyed teenage drivers from four high schools in Pennsylvania and New Jersey. Gender comparisons were made between self-reported perceptions and self-reported driving behaviors. Descriptive statistics and chi-squared testing were used in data analyses; significance was set at p < 0.05. RESULTS: Seven hundred fifty-six high school teenage drivers completed surveys. Males (52%) and females (48%) were equally distributed; 32% of males reported that they were extremely safe drivers, whereas only 18% of females reported that they were extremely safe drivers (p < 0.001). Significantly more females (91%) compared to males (77%) reported always wearing their seatbelts (p < 0.001). Female drivers were more likely than male drivers to self-report that they always make their passengers wear a seat belt (76% vs. 63%, p < 0.001). A higher proportion of males reported using their cell phones while driving, compared to females (68% vs. 56%, p = 0.004), and 42% of males reported texting while driving, compared to 34% of females (p = 0.037). CONCLUSION: Teenage male drivers perceive themselves to be safe drivers, but report engaging in more distracted driving and risky behaviors compared to females. These results suggest that there is an opportunity for gender-specific educational and injury prevention programs for teen drivers.

The "ICE" study: feasibility of inexpensive commercial coolers on mobile EMS units.

INTRODUCTION: Prehospital postresuscitation induced hypothermia (IH) has been shown to reduce neurological complications in comatose cardiac-arrest survivors. Retrofitting ambulances to include equipment appropriate to initiate hypothermia, such as refrigeration units for cooled saline, is expensive. The objective of this nonhuman subject research study was to determine if inexpensive, commercially available coolers could, in conjunction with five reusable ice packs, keep two 1 L bags of precooled 0.9% normal saline solution (NSS) at or below 4°C for an average shift of eight to 12 hours in a real-world environment, on board in-service Emergency Medical Service (EMS) units, over varying weather conditions in all seasons. METHODS: The coolers were chosen based on availability and affordability from two nationally available brands: The Igloo MaxxCold (Igloo Products Corp., Katy, Texas USA) and Coleman (The Coleman Company, Wichita, Kansas USA). Both are 8.5 liter (nine-quart) coolers that were chosen because they adequately held two 1 L bags of saline solution, along with the reusable ice packs designated in the study design, and were small enough for ease of placement on ambulances. Initial testing of the coolers was conducted in a controlled environment. Thereafter, each EMS unit was responsible to cool the saline to less than 4°C prior to shift. Data were collected by emergency medical technicians, paramedics, and resident physicians working in seven different ambulance squads. Data analysis was performed using repeated measurements recorded over a 12-hour period from 19 individual coolers and were summarized by individual time points using descriptive statistics. RESULTS: Initial testing determined that the coolers maintained temperatures of 4°C for 12 hours in a controlled environment. On the ambulances, results based on the repeated measurements over time revealed that the saline solution samples as defined in the protocol, remained consistently below 4°C for 12 hours. Utilizing the lower bound of the 2-sided 95% exact binomial confidence intervals, there was less than a five percent chance that saline samples could not be maintained below 4°C for 12 hours, even during the summer months. CONCLUSIONS: Simple, commercially available coolers can maintain two 1 L bags of 0.9% NSS at 4°C for 12 hours in ambulances in varying environmental conditions. This suggests that EMS agencies could inexpensively initiate prehospital IH in appropriate cases.

Quality of life support in advanced cancer-web and technological interventions: systematic review and narrative synthesis.

BACKGROUND: As treatments continue to progress, patients with advanced cancer are living longer. However, ongoing physical side-effects and psychosocial concerns can compromise quality of life (QoL). Patients and physicians increasingly look to the internet and other technologies to address diverse supportive needs encountered across this evolving cancer trajectory. OBJECTIVES: 1. To examine the features and delivery of web and technological interventions supporting patients with advanced cancer. 2. To explore their efficacy relating to QoL and psychosocial well-being. METHODS: Relevant studies were identified through electronic database searches (MEDLINE, PsychINFO, Embase, CINAHL, CENTRAL, Web of Science and ProQuest) and handsearching. Findings were collated and explored through narrative synthesis. RESULTS: Of 5274 identified records, 37 articles were included. Interventions were evaluated within studies targeting advanced cancer (13) or encompassing all stages (24). Five subtypes emerged: Interactive Health Communication Applications (n=12), virtual programmes of support (n=11), symptom monitoring tools (n=8), communication conduits (n=3) and information websites (n=3). Modes of delivery ranged from self-management to clinically integrated. Support largely targeted psychosocial well-being, alongside symptom management and healthy living. Most studies (78%) evidenced varying degrees of efficacy through QoL and psychosocial measures. Intervention complexity made it challenging to distinguish the most effective components. Incomplete reporting limited risk of bias assessment. CONCLUSION: While complex and varied in their content, features and delivery, most interventions led to improvements in QoL or psychosocial well-being across the cancer trajectory. Ongoing development and evaluation of such innovations should specifically target patients requiring longer-term support for later-stage cancer. PROSPERO REGISTRATION NUMBER: CRD42018089153.

Remodelling of human atrial K+ currents but not ion channel expression by chronic ß-blockade.

Chronic ß-adrenoceptor antagonist (ß-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K(+) currents. The aim of this study was to investigate the effects of chronic ß-blockade on transient outward, sustained and inward rectifier K(+) currents (I(TO), I(KSUS) and I(K1)) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic ß-blockade was associated with a 41% reduction in I(TO) density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p < 0.05; without affecting its voltage-, time- or rate dependence. I(K1) was reduced by 34% at -120 mV (p < 0.05). Neither I(KSUS), nor its increase by acute ß-stimulation with isoprenaline, was affected by chronic ß-blockade. Mathematical modelling suggested that the combination of I(TO)- and I(K1)-decrease could result in a 28% increase in APD(90). Chronic ß-blockade did not alter mRNA or protein expression of the I(TO) pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvß1, Kvß2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in I(K1). A reduction in atrial I(TO) and I(K1) associated with chronic ß-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits.

A Severe Case of Odontogenic Infection and Necrotizing Fasciitis of the Anterior Chest Wall and Neck.

Necrotizing fasciitis is a life-threatening infection that can be rapidly fatal. Early identification and emergent surgical management are essential to minimize morbidity and mortality. This case report describes a 25-year-old male who presented to the emergency department with a three-day history of worsening left lower dental infection and new-onset neck pain and swelling. He received broad-spectrum antibiotics and intravenous fluid resuscitation and underwent computed tomography of the neck and chest. Following intensive care unit admission, he underwent tooth extraction where intraoperative evaluation revealed subcutaneous crepitus. Immediate debridement was performed, revealing copious foul-smelling purulent discharge and necrotic tissue extending over the anterior chest wall and neck. During his hospital course, he underwent multiple debridements to manage the expanding infection. The final tissue defect was substantial, with deep dissection to muscle extending over the entire anterior surface of the rib cage to just inferior to the clavicles. This significant tissue defect was managed with skin grafts, and he was discharged home in stable condition. The patient is doing well almost a year after discharge. The key to our patient's survival was the early identification and debridement of the affected tissue. Our study reinforces the tenants of wound care and aggressive management required to bolster patient odds of survival in the setting of necrotizing fasciitis and underscores the importance of maintaining vigilance in patients presenting with dental infections. This study is unique in that our patient was young, with a past medical history significant for polydrug use, and the area of debridement was substantial.

A phase I trial of high-dose clofarabine, etoposide, and cyclophosphamide and autologous peripheral blood stem cell transplantation in patients with primary refractory and relapsed and refractory non-Hodgkin lymphoma.

Clofarabine has significant single-agent activity in patients with indolent and aggressive non-Hodgkin lymphoma and synergizes with DNA-damaging drugs. Treatment, however, may be associated with severe and prolonged myelosuppression. We conducted a phase I trial to determine the maximum tolerated dose (MTD) of clofarabine in combination with high-dose etoposide and cyclophosphamide followed by autologous peripheral blood stem cell transplantation in patients with refractory non-Hodgkin lymphoma (NHL). Patients received clofarabine at 30-70 mg/m(2)/day on days -6 to -2 in successive cohorts, in combination with etoposide 60 mg/kg (day -8), and cyclophosphamide 100 mg/kg (day -6), followed by filgrastim-mobilized PBSC on day 0. Sixteen patients of median age 57 (range: 32-67) years with diffuse large B cell (n = 8), follicular (n = 5), or mantle cell (n = 3) lymphoma that was either primary refractory (n = 2) or relapsed and refractory (n = 14) were treated at 5 clofarabine dose levels: 30 (n = 3), 40 (n = 3), 50 (n = 3), 60 (n = 3), and 70 mg/m(2)/day (n = 4) in combination with etoposide and cyclophosphamide. All patients had grade 4 neutropenia and thrombocytopenia. Grade 3-4 nonhematologic toxicity was evenly distributed across all 5 dose levels, and included diarrhea (n = 3), mucositis (n = 1), nausea (n = 1), reversible elevation of alanine aminotranferease/aspartate aminotransferase (AST/ALT) (n = 1) or bilirubin (n = 1), and hemorrhagic cystitis (n = 1); all resolved by day +30 following transplantation. The MTD was not reached. No treatment-related deaths occurred. At day +30, 13 patients achieved a complete remission (CR) or unconfirmed CR (CR(U)), and 2 patients achieved a partial response, for an overall response rate of 94%. After a median follow-up of 691 days, the 1-year progression-free survival (PFS) and overall survival (OS) were 63% (95% confidence interval [CI]: 43%-91%) and 68% (95% CI: 49%-96%), respectively. We recommend clofarabine 70 mg/m(2)/day × 5 days as a phase II dose in combination with high-dose etoposide and cyclophosphamide for further testing as a preparative regimen in NHL patients undergoing autologous PBSC transplantation.

A ruptured ectopic pregnancy in a patient with an intrauterine device: A case report.

Intrauterine devices (IUDs) are used worldwide. The 2 types that are used are the levonorgestrel IUD and a copper containing IUD. This is a case study of a 30-year-old female with a levonorgestrel IUD who was diagnosed with a ruptured ectopic pregnancy in the emergency department (ED). Point-of-care urine pregnancy test and point-of-care ultrasound (POCUS) were vital in making this diagnosis and should be utilized in patients assigned female at birth who present with abdominal pain.

Targeting sphingosine-1-phosphate signalling for cardioprotection.

Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid generated by the sphingosine kinase (SK1 or SK2)-catalysed phosphorylation of sphingosine. Plasma S1P is carried in high-density lipoprotein (HDL) or bound to albumin and is reported to arise from activated platelets and erythrocytes. In addition, extracellular SK1 released from vascular endothelial cells may also contribute to plasma S1P levels. S1P exerts its effects through a family of five high affinity S1P-specific G protein-coupled receptors (GPCRs), S1P(1-5). Various S1P receptors are present in the cardiovascular system, including cardiac tissue. Additionally, intracellular S1P may have a second messenger action. Since S1P is recognised as a survival factor in many tissues, there has been much interest in S1P as a cardioprotective agent. Recent evidence indicates that S1P can pre-condition and post-condition the heart and that the cardioprotective effect of HDL may be because of its S1P content. In addition, evidence is emerging that the cardioprotective effects of cannabinoids and S1P may be linked.