Optimizing Nutritional Needs of Burn Patients: An Evaluation of Nutritional Assessment Tools, Feeding Strategies, and Their Impact on Patient Outcomes.

BACKGROUND: Optimal nutritional support is essential to the recovery and improved outcomes of burn patients. This review aims to explore existing literature to evaluate nutrition assessment tools, feeding formulations' caloric predictive ability, timing of initiation of feeding, optimal nutritional composition, and caloric intake in burn patients. METHODS: Three databases were searched to glean studies investigating nutrition in acute severe adult burn patient populations in four areas: outcomes based on feeding type and timing, the caloric predictability of nutritional assessment tools, outcomes associated with the composition of feeding formulas, and considerations related to caloric intake. Outcomes of interest included the effects of nutritional assessments using feeding type, nutritional administration timing, formula composition, and caloric intake on mortality rate, length of stay, and infection. RESULTS: A total of 19 studies were included. Nutritional assessment tools were determined to over- or underestimate resting energy expenditure (REE). Milner was the most accurate alternative to indirect calorimetry. Early enteral nutrition in burn patients within 24 hours of admission was preferred. 5 studies evaluated micronutrients and yielded variable results. Low-fat high-carbohydrate diets were the ideal macronutrient composition. Burn patients were shown to receive lower caloric intake than recommended. CONCLUSIONS: Findings showed that while nutritional assessment tools tend to inaccurately estimate REE in burn patients, the ideal alternative to indirect calorimetry is the Milner equation. Several new equations may be worthy alternatives but require further validation. Enteral feeding should be initiated within the first 24 hours of burn injury whenever possible and should contain a high-carbohydrate/low-fat composition.

A Technology-Assisted Web Application for Consumer Access to a Nonprescription Statin Medication.

BACKGROUND: Although statins reduce adverse cardiovascular outcomes, less than one-half of eligible patients receive treatment. A nonprescription statin has the potential to improve access to statins. OBJECTIVES: This study sought to assess concordance between clinician and consumer assessment of eligibility for nonprescription statin treatment using a technology assisted self-selection Web application (Web App) and evaluate effect on low-density lipoprotein cholesterol (LDL-C) levels. METHODS: This study was a prospective actual use 6-month study to evaluate use of a Web App to qualify participants without a medical background for a moderate-intensity statin based on current guidelines. Participants entered demographic information, cholesterol values, blood pressure, and concomitant medications into the Web App, resulting in 3 possible outcomes: "do not use," "ask a doctor," and "OK to use." RESULTS: The study included 1,196 participants, with a median age of 63 years (Q1-Q3: 57-68 years); 39.6% were women, 79.3% were White, 11.7% were Black, and 4.1% had limited literacy. Mean LDL-C was 139.6 ± 28.3 mg/dL and the median calculated 10-year risk of atherosclerotic cardiovascular disease was 10.1% (Q1-Q3: 7.3%-14.0%). Initial Web App self-selection resulted in an outcome concordant with clinician assessment in 90.7% (95% CI: 88.9%-92.3%) of participants, and 98.1% (95% CI: 97.1%-98.8%) had a concordant final use outcome during treatment. Mean percent change in LDL-C was -35.5% (95% CI: -36.6% to -34.3%). Serious adverse events occurred in 27 (2.3%) participants, none related to the study drug. CONCLUSIONS: In this actual use study, a technology-assisted Web App allowed >90% of consumers to correctly self-select for statin use and achieve clinically important LDL-C reductions. (Technology-Assisted Cholesterol Trial in Consumers [TACTiC]; NCT04964544).

Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial.

BACKGROUND: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases. METHODS: Urinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values. RESULTS: In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg. CONCLUSIONS: Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin.

Brachypodium distachyon Seedlings Display Accession-Specific Morphological and Transcriptomic Responses to the Microgravity Environment of the International Space Station.

Plants have been recognized as key components of bioregenerative life support systems for space exploration, and many experiments have been carried out to evaluate their adaptability to spaceflight. Unfortunately, few of these experiments have involved monocot plants, which constitute most of the crops used on Earth as sources of food, feed, and fiber. To better understand the ability of monocot plants to adapt to spaceflight, we germinated and grew Brachypodium distachyon seedlings of the Bd21, Bd21-3, and Gaz8 accessions in a customized growth unit on the International Space Station, along with 1-g ground controls. At the end of a 4-day growth period, seedling organ's growth and morphologies were quantified, and root and shoot transcriptomic profiles were investigated using RNA-seq. The roots of all three accessions grew more slowly and displayed longer root hairs under microgravity conditions relative to ground control. On the other hand, the shoots of Bd21-3 and Gaz-8 grew at similar rates between conditions, whereas those of Bd21 grew more slowly under microgravity. The three Brachypodium accessions displayed dramatically different transcriptomic responses to microgravity relative to ground controls, with the largest numbers of differentially expressed genes (DEGs) found in Gaz8 (4527), followed by Bd21 (1353) and Bd21-3 (570). Only 47 and six DEGs were shared between accessions for shoots and roots, respectively, including DEGs encoding wall-associated proteins and photosynthesis-related DEGs. Furthermore, DEGs associated with the "Oxidative Stress Response" GO group were up-regulated in the shoots and down-regulated in the roots of Bd21 and Gaz8, indicating that Brachypodium roots and shoots deploy distinct biological strategies to adapt to the microgravity environment. A comparative analysis of the Brachypodium oxidative-stress response DEGs with the Arabidopsis ROS wheel suggests a connection between retrograde signaling, light response, and decreased expression of photosynthesis-related genes in microgravity-exposed shoots. In Gaz8, DEGs were also found to preferentially associate with the "Plant Hormonal Signaling" and "MAP Kinase Signaling" KEGG pathways. Overall, these data indicate that Brachypodium distachyon seedlings exposed to the microgravity environment of ISS display accession- and organ-specific responses that involve oxidative stress response, wall remodeling, photosynthesis inhibition, expression regulation, ribosome biogenesis, and post-translational modifications. The general characteristics of these responses are similar to those displayed by microgravity-exposed Arabidopsis thaliana seedlings. However, organ- and accession-specific components of the response dramatically differ both within and between species. These results suggest a need to directly evaluate candidate-crop responses to microgravity to better understand their specific adaptability to this novel environment and develop cultivation strategies allowing them to strive during spaceflight.

Fatal Epileptic Seizures in Mice Having Compromised Glutathione and Ascorbic Acid Biosynthesis.

Reduced glutathione (GSH) and ascorbic acid (AA) are the two most abundant low-molecular-weight antioxidants in mammalian tissues. GclmKO knockout mice lack the gene encoding the modifier subunit of the rate-limiting enzyme in GSH biosynthesis; GclmKO mice exhibit 10-40% of normal tissue GSH levels and show no overt phenotype. GuloKO knockout mice, lacking a functional Gulo gene encoding L-gulono-γ-lactone oxidase, cannot synthesize AA and depend on dietary ascorbic acid for survival. To elucidate functional crosstalk between GSH and AA in vivo, we generated the GclmKO/GuloKO double-knockout (DKO) mouse. DKO mice exhibited spontaneous epileptic seizures, proceeding to death between postnatal day (PND)14 and PND23. Histologically, DKO mice displayed neuronal loss and glial proliferation in the neocortex and hippocampus. Epileptic seizures and brain pathology in young DKO mice could be prevented with AA supplementation in drinking water (1 g/L). Remarkably, in AA-rescued adult DKO mice, the removal of AA supplementation for 2-3 weeks resulted in similar, but more severe, neocortex and hippocampal pathology and seizures, with death occurring between 12 and 21 days later. These results provide direct evidence for an indispensable, yet underappreciated, role for the interplay between GSH and AA in normal brain function and neuronal health. We speculate that the functional crosstalk between GSH and AA plays an important role in regulating glutamatergic neurotransmission and in protecting against excitotoxicity-induced brain damage.

Relationship Between Preexisting Functional Mobility Impairments and Burn Treatment Outcomes.

Burn severity is determined by total body surface area affected, temperature of source, and duration of exposure. Patients with impaired mobility are less capable of avoiding hazards and escaping traumatic injuries. Additionally, patients with impaired mobility frequently suffer from other comorbid conditions and have specialized needs, which can complicate their acute treatment. This study was a retrospective electronic medical records review of all adult patients, aged 18 years and older with a preexisting mobility impairment, admitted as inpatients to a single burn center for treatment of burn-related injuries from January 1, 2009, to December 31, 2019. The 10-year review of 1520 adult burn admissions meeting the initial criteria of inpatient admission and burn injury revealed 174 patients with documentation supporting preexisting functional mobility impairment (11%). Surprisingly, patients' overall lengths of stays were consistent with all burn populations at 0.81 days per % TBSA, with the average length of stay being 6.7 days. The demographic data were consistent with national burn registry data as male, Caucasian, and older, with mean age of 61.1 years. Demographic data and details of hospital course focusing on treatment, complications, and outcomes were extracted and analyzed. There is a paucity of literature describing the needs of this unique burn population. Burn-injured patients with preexisting mobility impairments suffer from similar mechanisms of injury. By identifying attributes unique to this population, we hope to develop specialized prevention education and treatment protocols.

Cardiac events among patients with sarcoma treated with doxorubicin by method of infusion: A real-world database study.

BACKGROUND: Administration of doxorubicin by continuous intravenous (CIV) infusion, versus bolus (BOL) administration, has been proposed to mitigate the risk of cardiac events. This study used real-world data to explore the association between mode of doxorubicin administration and duration of treatment, time-to-treatment failure (TTF), and cardiac events. METHODS: Occurrence of cardiac events after initiation of BOL versus CIV doxorubicin for sarcoma in the International Business Machines MarketScan claims database were compared. Duration of doxorubicin treatment, TTF, and time-to-first-cardiac event (TCE) were evaluated using Kaplan-Meier method and unadjusted and adjusted Cox regression models. RESULTS: A total of 196 patients were included in the BOL group and 399 in the CIV group. In unadjusted analyses, there were significant differences between BOL versus CIV for duration of doxorubicin treatment (median 1.4 vs. 2.1 months, p = .002), TTF (median 8.8 vs. 5.6 months, p = .002), and TCE (medians not reached, p = .03). Adjusting for baseline covariates, only TTF remained significant (hazard ratio: 0.71, 95% confidence interval 0.59-0.86, p = .0004), favoring BOL. CONCLUSIONS: While the risk of cardiac complications was higher with BOL in unadjusted analysis, the risk was no longer present in the adjusted analysis. While we cannot draw causal inferences due to the retrospective, nonrandomized study design, these data suggest that replacing BOL with prolonged CIV administration has not been effective as a strategy to mitigate cardiac events, given community standards of oncologic practice.

Comparative Effects of Low-Dose Rosuvastatin, Placebo, and Dietary Supplements on Lipids and Inflammatory Biomarkers.

BACKGROUND: Supplements are commonly used by individuals with indications for lipid-lowering therapy, but evidence of their effectiveness to lower low-density lipoprotein cholesterol (LDL-C) is lacking, particularly when compared with statins. OBJECTIVES: The trial objective was to compare the efficacy of a low-dose statin with placebo and 6 common supplements in impacting lipid and inflammatory biomarkers. METHODS: This was a single-center, prospective, randomized, single-blind clinical trial among adults with no history of atherosclerotic cardiovascular disease (ASCVD), an LDL-C of 70 to 189 mg/dL, and an increased 10-year risk of ASCVD. Participants were randomized to rosuvastatin 5 mg daily, placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice. The primary endpoint was the percent change in LDL-C from baseline for rosuvastatin 5 mg daily compared with placebo and each supplement after 28 days. The primary endpoint was evaluated in a hierarchical fashion with rosuvastatin first compared with placebo, then each supplement in a prespecified order using analysis of covariance. RESULTS: A total of 190 participants completed the study. The percent LDL-C reduction with rosuvastatin was greater than all supplements and placebo (P < 0.001). The difference in LDL-C reduction with rosuvastatin compared with placebo was -35.2% (95% CI: -41.3% to -29.1%; P < 0.001). None of the dietary supplements demonstrated a significant decrease in LDL-C compared with placebo. Adverse event rates were similar across study groups. CONCLUSIONS: Among individuals with increased 10-year risk for ASCVD, rosuvastatin 5 mg daily lowered LDL-C significantly more than placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice. (Supplements, Placebo, or Rosuvastatin Study [SPORT]; NCT04846231).

Simulated galactic cosmic ray exposure activates dose-dependent DNA repair response and down regulates glucosinolate pathways in arabidopsis seedlings.

Outside the protection of Earth's magnetic field, organisms are constantly exposed to space radiation consisting of energetic protons and other heavier charged particles. With the goal of crewed Mars exploration, the production of fresh food during long duration space missions is critical for meeting astronauts' nutritional and psychological needs. However, the biological effects of space radiation on plants have not been sufficiently investigated and characterized. To that end, 10-day-old Arabidopsis seedlings were exposed to simulated Galactic Cosmic Rays (GCR) and assessed for transcriptomic changes. The simulated GCR irradiation was carried out in the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Lab (BNL). The exposures were conducted acutely for two dose points at 40 cGy or 80 cGy, with sequential delivery of proton, helium, oxygen, silicon, and iron ions. Control and irradiated seedlings were then harvested and preserved in RNAlater at 3 hrs post irradiation. Total RNA was isolated for transcriptomic analyses using RNAseq. The data revealed that the transcriptomic responses were dose-dependent, with significant upregulation of DNA repair pathways and downregulation of glucosinolate biosynthetic pathways. Glucosinolates are important for plant pathogen defense and for the taste of a plant, which are both relevant to growing plants for spaceflight. These findings fill in knowledge gaps of how plants respond to radiation in beyond-Earth environments.

Statin Use and Severe Acute Liver Injury Among Patients with Elevated Alanine Aminotransferase.

Introduction: While serious liver injury among statin users is extremely rare, baseline liver enzyme testing is still recommended prior to initiating therapy. The benefit of such screening should be reevaluated based on empirical evidence. This study compared the risk of severe acute liver injury (SALI) between statin initiators with an elevated ALT (>35U/L) matched to statin initiators with a normal ALT level (≤35U/L). Statin initiators with an elevated ALT were additionally compared against matched non-users. Methods: The study created cohorts from Optum and MarketScan claims data. Exposed and comparison cohorts were propensity score (PS) matched in each dataset and findings were pooled using meta-analysis. Proportional hazards regression was used to estimate hazard ratios (HRs), and a prespecified non-inferiority margin for SALI was set at a HR of 1.8. Results: 232,889 patients with elevated ALT were PS-matched to 232,889 with normal ALT level. The overall incidence rate of SALI was about 19/100,000 person-years among statin initiators. Statin initiators with elevated ALT had no meaningfully increased risk of SALI compared to those with normal ALT (HR=1.15; 95% CI 0.75 to 1.75). Comparing statin initiators with non-initiators with elevated ALT values equally yielded no increased risk (HR=0.76; 95% CI 0.52 to 1.11). Conclusion: In this large population-based study, SALI in statin users was rare. Importantly, the results showed no evidence that baseline ALT status is a reliable indicator for an increased risk of severe liver injury among statin initiators.

Feasibility of aspirin and/or vitamin D3 for men with prostate cancer on active surveillance with Prolaris® testing.

Objectives: To test the feasibility of a randomised controlled trial (RCT) of aspirin and/or vitamin D3 in active surveillance (AS) low/favourable intermediate risk prostate cancer (PCa) patients with Prolaris® testing. Patients and Methods: Newly-diagnosed low/favourable intermediate risk PCa patients (PSA ≤ 15 ng/ml, International Society of Urological Pathology (ISUP) Grade Group ≤2, maximum biopsy core length <10 mm, clinical stage ≤cT2c) were recruited into a multi-centre randomised, double-blind, placebo-controlled study (ISRCTN91422391, NCT03103152). Participants were randomised to oral low dose (100 mg), standard dose (300 mg) aspirin or placebo and/or vitamin D3 (4000 IU) versus placebo in a 3 × 2 factorial RCT design with biopsy tissue Prolaris® testing. The primary endpoint was trial acceptance/entry rates. Secondary endpoints included feasibility of Prolaris® testing, 12-month disease re-assessment (imaging/biochemical/histological), and 12-month treatment adherence/safety. Disease progression was defined as any of the following (i) 50% increase in baseline PSA, (ii) new Prostate Imaging-Reporting and Data System (PI-RADS) 4/5 lesion(s) on multi-parametric MRI where no previous lesion, (iii) 33% volume increase in lesion size, or radiological upstaging to ≥T3, (iv) ISUP Grade Group upgrade or (v) 50% increase in maximum cancer core length. Results: Of 130 eligible patients, 104 (80%) accepted recruitment from seven sites over 12 months, of which 94 patients represented the per protocol population receiving treatment. Prolaris® testing was performed on 76/94 (81%) diagnostic biopsies. Twelve-month disease progression rate was 43.3%. Assessable 12-month treatment adherence in non-progressing patients to aspirin and vitamin D across all treatment arms was 91%. Two drug-attributable serious adverse events in 1 patient allocated to aspirin were identified. The study was not designed to determine differences between treatment arms. Conclusion: Recruitment of AS PCa patients into a multi-centre multi-arm placebo-controlled RCT of minimally-toxic adjunctive oral drug treatments with molecular biomarker profiling is acceptable and safe. A larger phase III study is needed to determine optimal agents, intervention efficacy, and outcome-associated biomarkers.

Avoidance of injury to the posterior neurovascular bundle during total ankle arthroplasty - A simple technical tip.

Iatrogenic nerve injury to the tibial nerve is a serious but avoidable complication of total ankle replacements and may be under-reported as it may go unrecognised or thought to be due to tarsal tunnel syndrome. The tibial nerve is particularly vulnerable during the saw cuts at the posteromedial corner without appropriate protection. Prior to drilling the tibial and talar pins of the adjustment block for the Infinity ankle replacement we perform a 2 cm incision behind the medial malleolus. The tibialis posterior tendon sheath is identified and incised. A periosteal elevator is used to develop a plane between the back of the tibia and the tibialis posterior tendon and then exchanged for a mini Hohmann retractor protecting the neurovascular bundle. This allows us to drill the pins and saw cuts safely. The Hohmann retractor can be felt at the tip of the saw blade providing reassurance that the blade is not too deep. Our technique has not previously been reported in the literature. It acts as a simple reproducible way of avoiding injury to structures at the back of the ankle joint.

Tranexamic acid improves early postoperative mobilization in cancer patients undergoing endoprosthetic reconstruction.

BACKGROUND AND OBJECTIVES: Tranexamic acid (TXA) has been shown to decrease perioperative blood loss, transfusions, and cost in patients undergoing resection of aggressive bone tumors and endoprosthetic reconstruction. This study explored the effect of TXA administration on postoperative mobilization in these patients. METHODS: This study included 126 patients who underwent resection of an aggressive bone tumor and endoprosthetic reconstruction; 61 patients in the TXA cohort and 65 patients in the non-TXA cohort. Postoperative physical therapy (PT) and occupational therapy notes were reviewed; patient ambulation distance and duration of therapies were recorded. RESULTS: Patients in the TXA cohort ambulated further on all postoperative days, which was significant on postoperative Day 1 (POD1) (p = 0.002) and postoperative Day 2 (POD2) (p < 0.001). The TXA cohort ambulated 85% further per PT session 87.7 versus 47.4 ft (p < 0.001) and participated 14% longer, 36.1 versus 31.7 min (p < 0.001). Multivariate analysis identified a significant inverse association between postoperative hospitalization length and POD1, POD2, postoperative Day 3, and total ambulation (p < 0.001). Blood transfusion was independently associated with a 1.5 day increase in postoperative hospitalization (95% confidence interval: 0.64-2.5; p < 0.001). CONCLUSIONS: TXA administration was associated with increased postoperative ambulation and endurance. Increased postoperative ambulation was associated with decreased length of stay and increased likelihood to discharge home.

Response of Arabidopsis thaliana and Mizuna Mustard Seeds to Simulated Space Radiation Exposures.

One of the major concerns for long-term exploration missions beyond the Earth's magnetosphere is consequences from exposures to solar particle event (SPE) protons and galactic cosmic rays (GCR). For long-term crewed Lunar and Mars explorations, the production of fresh food in space will provide both nutritional supplements and psychological benefits to the astronauts. However, the effects of space radiation on plants and plant propagules have not been sufficiently investigated and characterized. In this study, we evaluated the effect of two different compositions of charged particles-simulated GCR, and simulated SPE protons on dry and hydrated seeds of the model plant Arabidopsis thaliana and the crop plant Mizuna mustard [Brassica rapa var. japonica]. Exposures to charged particles, simulated GCRs (up to 80 cGy) or SPEs (up to 200 cGy), were performed either acutely or at a low dose rate using the NASA Space Radiation Laboratory (NSRL) facility at Brookhaven National Lab (BNL). Control and irradiated seeds were planted in a solid phytogel and grown in a controlled environment. Five to seven days after planting, morphological parameters were measured to evaluate radiation-induced damage in the seedlings. After exposure to single types of charged particles, as well as to simulated GCR, the hydrated Arabidopsis seeds showed dose- and quality-dependent responses, with heavier ions causing more severe defects. Seeds exposed to simulated GCR (dry seeds) and SPE (hydrated seeds) had significant, although much less damage than seeds exposed to heavier and higher linear energy transfer (LET) particles. In general, the extent of damage depends on the seed type.

NASA's Ground-Based Microgravity Simulation Facility.

Since opportunities to conduct experiments in space are scarce, various microgravity simulators and analogs have been widely used in space biology ground studies. Even though microgravity simulators do not produce all of the biological effects observed in the true microgravity environment, they provide alternative test platforms that are effective, affordable, and readily available to facilitate microgravity research. The Microgravity Simulation Support Facility (MSSF) at the National Aeronautics and Space Administration (NASA) John F. Kennedy Space Center (KSC) has been established for conducting short duration experiments, typically less than 1 month, utilizing a variety of microgravity simulation devices for research at different gravity levels. The simulators include, but are not limited to, 2D Clinostats, 3D Clinostats, Random Positioning Machines, and Rotating Wall Vessels. In this chapter, we will discuss current MSSF capabilities, development concepts, and the physical characteristics of these microgravity simulators.

Tranexamic Acid in Patients With Cancer Undergoing Endoprosthetic Reconstruction: A Cost Analysis.

INTRODUCTION: Tranexamic acid (TXA) decreases blood loss, perioperative transfusion rates, and cost in total hip and total knee arthroplasty. In a previous study, topical TXA decreased both perioperative blood loss and transfusions in patients undergoing resection of aggressive bone tumors and endoprosthetic reconstruction. The purpose of this study was to explore the cost effectiveness of TXA in patients undergoing resection of an aggressive bone tumor and endoprosthetic reconstruction, assessing transfusion cost, TXA administration cost, postoperative hospitalization cost, posthospital disposition, and 30-day readmissions. METHODS: This study included 126 patients who underwent resection of an aggressive bone tumor and endoprosthetic resection at a single academic medical center; 61 patients in the TXA cohort and 65 patients in the non-TXA cohort. The cost of 1 unit of packed red blood cells, not including administration or complications, was estimated at our institution. The cost of hospitalization was estimated for lodging and basic care. The cost of TXA was $55 per patient. Patients were followed up for 30 days to identify hospital readmissions. RESULTS: Patients in the TXA cohort experienced a TXA and blood transfusion cost reduction of $155.88 per patient (P = 0.007). Proximal femur replacement patients experienced a $282.05 transfusion cost reduction (P = 0.008), whereas distal femur replacement patients only experienced a transfusion cost reduction of $32.64 (P = 0.43). An average hospital admission cost reduction of $5,072.23 per patient (P < 0.001) was associated with TXA use. Proximal femur replacement patients who received TXA experienced a hospital cost reduction of $5,728.38 (P < 0.001), whereas distal femur replacement patients experienced a reduction of $3,724.90 (P = 0.01). No differences between the cohorts were identified in discharge to home (P = 0.37) or readmissions (P = 0.77). DISCUSSION: TXA administration is cost effective in patients undergoing resection of an aggressive bone tumor and endoprosthetic reconstruction through reducing both perioperative transfusion rates and postoperative hospitalization. LEVEL OF EVIDENCE: III-Retrospective Cohort Study.

Technology-Assisted Self-Selection of Candidates for Nonprescription Statin Therapy.

BACKGROUND: Although statins reduce cardiovascular morbidity and mortality, only about one-half of eligible patients receive treatment. Safe and appropriate consumer access to statins could have a significant positive public health impact. OBJECTIVES: This study compares the concordance between a participant and clinician assessment of eligibility for statin therapy using a technology-assisted approach. METHODS: A total of 500 participants, 83 with limited literacy, completed an at-home Web-based application to assess appropriateness for treatment with rosuvastatin 5 mg. The Web application is designed to assess eligibility for a moderate-intensity statin based on current guidelines and deny access to individuals with contraindications to rosuvastatin. Subsequently, participants visited a research site where clinicians, blinded to the information the participant entered, performed an independent Web application assessment. The Web application is programmed for 1 of 3 rosuvastatin treatment outcomes: "OK to use," "not right for you," or "ask a doctor." The primary endpoint was the percent of participants whose self-selected eligibility for nonprescription rosuvastatin was concordant with clinician assessment. RESULTS: For the primary endpoint, participant selection for statin therapy was concordant with clinician selection in 481 (96.2%) of 500 participants (95% confidence interval: 94.1%-97.7%), of whom 23 (4.6%) were deemed appropriate and 458 (91.6%) were deemed inappropriate for treatment. Discordance was due to incorrect self-selection ("OK to use") in 3 cases, incorrect rejection ("not right for you") in 14 cases and an incorrect "ask a doctor" outcome in 2 cases. CONCLUSIONS: The use of a technology-assisted approach to consumer self-selection for statin therapy resulted in participant self-selection that showed substantial agreement with clinician selection.

Reconstruction with Total Scapular Reverse Total Shoulder Endoprosthesis after Radical Tumor Excision.

Malignant musculoskeletal tumors about the shoulder girdle region involving the scapula are fairly rare, but when diagnosed, challenging and complex surgical treatment may be warranted with the primary goal of improving patient survival. These tumors are typically extensive and infiltrative at the time of presentation, requiring radical resection to achieve margins and obtain local tumor control. Historically, forequarter amputation or flail extremity were the mainstays of treatment in these cases. Presently, with recent advances in diagnostics, imaging, adjuvant therapies, and surgical treatment, many patients presenting with malignant tumors involving the scapula are candidates for limb salvage surgery. Reconstruction with endoprosthesis seems to have gained acceptance as the preferred surgical treatment for such lesions, as this intervention has resulted in improved postoperative function and cosmesis, with an acceptable complication rate. We present our experience with recent advancement in these surgical efforts in the form of shoulder girdle reconstruction with total scapular reverse total shoulder prosthesis after radical tumor excision.

Measuring The Impact Of Air Pollution On Health Care Costs.

Air pollution contributes to the development of numerous adverse human health outcomes. The Environmental Protection Agency's Environmental Benefits Mapping and Analysis Program-Community Edition (BenMAP-CE) tool is widely used in estimating the health care costs of air pollution and in the development of federal and state regulations and policy. Its default features consider only the costs of hospital and emergency department admissions. A more complete accounting of the chain of costs would include ambulatory and other care. In this article we use employer health insurance claims data to infer additional costs that accompany hospitalizations but are not included in BenMAP-CE. Including additional categories increases BenMAP-CE health care cost estimates by approximately 40 percent for respiratory and cardiovascular patients. That is, for each dollar of health care costs captured by BenMAP-CE, a more complete accounting would include an additional 40 cents. These results suggest that because such air pollution costs are underestimated, the health care benefits associated with reducing air pollution may be much larger than previously estimated.

Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial.

BACKGROUND: The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. METHODS: We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7-10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60-68). Median follow-up was 4·9 years (IQR 3·0-6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81-1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58-1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3-4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020). INTERPRETATION: These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. FUNDING: Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.