Practical Guide to Budgeting and Funding a Clinical Trial in Surgery.

This Guide to Statistics and Methods outlines the considerations when determining a budget for a clinical trial in preparation for submitting applications to various funding agencies.

Proteomics of Coagulopathy Following Injury Reveals Limitations of Using Laboratory Assessment to Define Trauma-Induced Coagulopathy to Predict Massive Transfusion.

Objective: Trauma-induced coagulopathy (TIC) is provoked by multiple mechanisms and is perceived to be one driver of massive transfusions (MT). Single laboratory values using prothrombin time (INR) or thrombelastography (TEG) are used to clinically define this complex process. We used a proteomics approach to test whether current definitions of TIC (INR, TEG, or clinical judgement) are sufficient to capture the majority of protein changes associated with MT. Methods: Eight level-I trauma centers contributed blood samples from patients available early after injury. TIC was defined as INR >1.5 (INR-TIC), TEG maximum amplitude <50mm (TEG-TIC), or clinical judgement (Clin-TIC) by the trauma surgeon. MT was defined as > 10 units of red blood cells in 24 hours or > 4 units RBC/hour during the first 4 hr. SomaLogic proteomic analysis of 1,305 proteins was performed. Pathways associated with proteins dysregulated in patients with each TIC definition and MT were identified. Results: Patients (n=211) had a mean injury severity score of 24, with a MT and mortality rate of 22% and 12%, respectively. We identified 578 SOMAscan analytes dysregulated among MT patients, of which INR-TIC, TEG-TIC, and Clin-TIC patients showed dysregulation only in 25%, 3%, and 4% of these, respectively. TIC definitions jointly failed to show changes in 73% of the protein levels associated with MT, and failed to identify 26% of patients that received a massive transfusion. INR-TIC and TEG-TIC patients showed dysregulation of proteins significantly associated with complement activity. Proteins dysregulated in Clin-TIC or massive transfusion patients were not significantly associated with any pathway. Conclusion: These data indicate there are unexplored opportunities to identify patients at risk for massive bleeding. Only a small subset of proteins that are dysregulated in patients receiving MT are statistically significantly dysregulated among patients whose TIC is defined based solely on laboratory measurements or clinical assessment.

Evaluating the Cost-effectiveness of Prehospital Plasma Transfusion in Unstable Trauma Patients: A Secondary Analysis of the PAMPer Trial.

Importance: Prehospital plasma transfusion is lifesaving for trauma patients in hemorrhagic shock but is not commonly used owing to cost and feasibility concerns. Objective: To evaluate the cost-effectiveness of prehospital thawed plasma transfusion in trauma patients with hemorrhagic shock during air medical transport. Design, Setting, and Participants: A decision tree and Markov model were created to compare standard care and prehospital thawed plasma transfusion using published and unpublished patient-level data from the Prehospital Plasma in Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock (PAMPer) trial conducted from May 2014 to October 2017, health care and trauma-specific databases, and the published literature. Prehospital transfusion, short-term inpatient care, and lifetime health care costs and quality of life outcomes were included. One-way, 2-way, and Monte Carlo probabilistic sensitivity analyses were performed across clinically plausible ranges. Data were analyzed in December 2019. Main Outcomes and Measures: Relative costs and health-related quality of life were evaluated by an incremental cost-effectiveness ratio at a standard willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY). Results: The trial included 501 patients in the modified intention-to-treat cohort. Median (interquartile range) age for patients in the thawed plasma and standard care cohorts were 44 (31-59) and 46 (28-60) years, respectively. Overall, 364 patients (72.7%) were male. Thawed plasma transfusion was cost-effective with an incremental cost-effectiveness ratio of $50 467.44 per QALY compared with standard care. The preference for thawed plasma was robust across all 1- and 2-way sensitivity analyses. When considering only patients injured by a blunt mechanism, the incremental cost-effectiveness ratio decreased to $37 735.19 per QALY. Thawed plasma was preferred in 8140 of 10 000 iterations (81.4%) on probabilistic sensitivity analysis. A detailed analysis of incremental costs between strategies revealed most were attributable to the in-hospital and postdischarge lifetime care of critically ill patients surviving severe trauma. Conclusions and Relevance: In this study, prehospital thawed plasma transfusion during air medical transport for trauma patients in hemorrhagic shock was lifesaving and cost-effective compared with standard care and should become commonplace.

Climbing the grants ladder: Funding opportunities for surgeons.

Surgeon-scientists provide critical perspectives to academic medicine, both as lead scientists and as collaborators. Successfully applying for and obtaining funding is critical to sustain a research program; however, significant challenges exist. It is imperative to be aware of and consider all funding sources available to surgeons during the evolution of one's career. Additionally, a deep understanding of intramural and extramural nonfinancial resources, such as mentorship relationships, grant writing, and career development courses, and research infrastructure are required. In this article, we present a set of recommendations and guidelines for surgeon-scientists to leverage funding resources with active planning longitudinally during their careers to sustain their research programs and provide their unique perspectives on surgical disease to the scientific community.

Implementation of a prehospital air medical thawed plasma program: Is it even feasible?

BACKGROUND: The Prehospital Air Medical Plasma (PAMPer) trial demonstrated a 30-day survival benefit among hypotensive trauma patients treated with prehospital plasma during air medical transport. We characterized resources, costs and feasibility of air medical prehospital plasma program implementation. METHODS: We performed a secondary analysis using data derived from the recent PAMPer trial. Intervention patients received thawed plasma (5-day shelf life). Unused plasma units were recycled back to blood bank affiliates, when possible. Distribution method and capability of recycling varied across sites. We determined the status of plasma units deployed, utilized, wasted, and returned. We inventoried thawed plasma use and annualized costs for distribution and recovery. RESULTS: The PAMPer trial screened 7,275 patients and 5,103 plasma units were deployed across 22 air medical bases during a 42-month period. Only 368 (7.2%) units of this total thawed plasma pool were provided to plasma randomized PAMPer patients. Of the total plasma pool, 3,716 (72.8%) units of plasma were returned to the blood bank with the potential for transfusion prior to expiration and 1,019 (20.0%) thawed plasma units were deemed wasted for this analysis. The estimated average annual cost of implementation of a thawed plasma program per air medical base at an average courier distance would be between US $24,343 and US $30,077, depending on the ability to recycle plasma and distance of courier delivery required. CONCLUSION: A prehospital plasma program utilizing thawed plasma is resource intensive. Plasma waste can be minimized depending on trauma center and blood bank specific logistics. Implementation of a thawed plasma program can occur with financial cost. Products with a longer shelf life, such as liquid plasma or freeze-dried plasma, may provide a more cost-effective prehospital product relative to thawed plasma. LEVEL OF EVIDENCE: Therapeutic, level III.

Surgical rescue: The next pillar of acute care surgery.

BACKGROUND: The evolving field of acute care surgery (ACS) traditionally includes trauma, emergency general surgery, and critical care. However, the critical role of ACS in the rescue of patients with a surgical complication has not been explored. We here describe the role of "surgical rescue" in the practice of ACS. METHODS: A prospective, electronic medical record-based ACS registry spanning January 2013 to May 2014 at a large urban academic medical center was screened by ICD-9 codes for acute surgical complications of an operative or interventional procedure. Long-term outcomes were derived from the Social Security Death Index. RESULTS: Of 2,410 ACS patients, 320 (13%) required "surgical rescue": most commonly, from wound complications (32%), uncontrolled sepsis (19%), and acute obstruction (15%). The majority of complications (85%) were related to an operation; 15% were related to interventional procedures. The most common rescue interventions required were bowel resection (23%), wound debridement (18%), and source control of infection (17%); 63% of patients required operative intervention, and 22% required surgical critical care. Thirty-six percent of complications occurred in ACS primary patients ("local"), whereas 38% were referred from another surgical service ("institutional") and 26% referred from another institution ("regional"). Hospital length of stay was longer, and in-hospital and 1-year mortalities were higher in rescue patients compared with those without a complication. Outcomes were equivalent between "local" and "institutional" patients, but hospital length of stay and discharge to home were significantly worse in "institutional" referrals. CONCLUSION: We here describe the distinct role of the acute care surgeon in the surgical management of complications; this is an additional pillar of ACS. In this vital role, the acute care surgeon provides crucial support to other providers as well as direct patient care in the "surgical rescue" of surgical and procedural complications. LEVEL OF EVIDENCE: Epidemiological study, level III; therapeutic/care management study, level IV.

Clostridium difficile infection: clinical challenges and management strategies.

Clostridium difficile has become the leading cause of nosocomial diarrhea in adults. A substantial increase has occurred in morbidity and mortality associated with disease caused by C difficile and in the identification of new hypervirulent strains, warranting a high clinical index of suspicion for infections due to this organism. Prevention of infection requires a multidisciplinary approach, including early recognition of disease, effective contact isolation precautions, adherence to disinfectant policies, and judicious use of antibiotics. Current treatment approaches are based on the severity of illness. As hypervirulent strains evolve, unsuccessful treatments are more common. Complicated colitis caused by C difficile may benefit from surgical intervention. Subtotal colectomy and end ileostomy have been the procedures of choice, but are associated with a high mortality rate because of late surgical consultation and use of surgery as a salvage therapy. A promising surgical alternative is creation of a diverting loop ileostomy with colonic lavage.