Opioid and non-opioid analgesic regimens after fracture and risk of serious opioid-related events.

Background: Non-opioid analgesics are prescribed in combination with opioids among patients with long bone fracture to reduce opioid prescribing needs, yet evidence is limited on whether they reduce the risk of serious opioid-related events (SOREs). We compared the risk of SOREs among hospitalized patients with long bone fracture discharged with filled opioid prescriptions, with and without non-opioid analgesics. Design: We identified a retrospective cohort of analgesic-naïve adult patients with a long bone fracture hospitalization using the Merative MarketScan Commercial Database (2013-2020). The exposure was opioid and non-opioid analgesic (gabapentinoids, muscle relaxants, non-steroidal anti-inflammatory drugs, acetaminophen) prescriptions filled in the 3 days before through 42 days after discharge. The outcome was the development of new persistent opioid use or opioid use disorder during follow-up (day 43 through day 408 after discharge). We used Cox proportional hazards regression with inverse probability of treatment weighting with overlap trimming to compare outcomes among those that filled an opioid and a non-opioid analgesic to those that filled only an opioid analgesic. In secondary analyses, we used separate models to compare those that filled a prescription for each specific non-opioid analgesic type with opioids to those that filled only opioids. Results: Of 29 489 patients, most filled an opioid prescription alone (58.4%) or an opioid and non-opioid (22.0%). In the weighted proportional hazards regression model accounting for relevant covariates and total MME, filling both a non-opioid analgesic and an opioid analgesic was associated with 1.63 times increased risk of SOREs compared with filling an opioid analgesic only (95% CI 1.41 to 1.89). Filling a gabapentin prescription in combination with an opioid was associated with an increased risk of SOREs compared with those that filled an opioid only (adjusted HR: 1.84 (95% CI1.48 to 2.27)). Conclusions: Filling a non-opioid analgesic in combination with an opioid was associated with an increased risk of SOREs after long bone fracture. Level of evidence: Level III, prognostic/epidemiological. Study type: Retrospective cohort study.

Transretroperitoneal Pedicled Omental Flap for Coverage of Traumatic Sacral Defect: A Case Report.

The greater omentum is a reliable choice for salvage soft-tissue reconstruction. Benefits include consistent anatomy, long pedicle length, and a high concentration of lymphatic tissue that is resistant to infection. We report the case of a 46-year-old man with a complex traumatic sacral wound resulting in severe limitation of reconstructive options. A pedicled greater omentum flap was transposed through the retroperitoneum via the lumbosacral triangle, resulting in durable soft-tissue coverage.

The Spillover Effect of the Medicare Mandatory Bundled Payment Program on Joint Replacement Outcomes: Analysis of Patients with Commercial Insurance and Medicare Advantage.

BACKGROUND: To improve the value and efficiency of care among traditional Medicare enrollees, the Centers for Medicare & Medicaid Services has implemented alternative payment models designed to control health-care spending and improve quality. These models may affect care beyond traditional Medicare enrollees, "spilling over" into other populations. Established in April 2016, the Medicare mandatory bundled payment program, called the Comprehensive Care for Joint Replacement (CJR) model, holds hospitals accountable for spending and quality of care for traditional Medicare joint-replacement patients during care episodes that span from the index hospitalization to 90 days post-discharge. We assessed the extent to which the CJR model was associated with outcomes for patients enrolled in commercial insurance and Medicare Advantage plans. METHODS: With use of Health Care Cost Institute claims data from 2012 through 2017, we assessed the association of the CJR model with total expenditures, discharges to institutional post-acute care, and readmissions among commercial insurance and Medicare Advantage joint-replacement patients. The exposure variable was the implementation of the CJR model in 67 randomly selected metropolitan statistical areas compared with 103 similar areas without CJR implementation. We utilized difference-in-differences models to estimate the spillover effects of the CJR model by comparing outcomes between these areas before and after CJR implementation. RESULTS: The study included 174,893 joint-replacement episodes of care in commercial insurance enrollees and 202,070 episodes in Medicare Advantage enrollees. Among both commercial insurance and Medicare Advantage enrollees, CJR implementation was associated with no meaningful changes in total episode expenditures, discharges to institutional post-acute care, or readmissions. CONCLUSIONS: We found no evidence for spillover effects of the CJR model on commercial insurance and Medicare Advantage patients, suggesting that alternative payment models targeting traditional Medicare patients may have limited effects on the cost and quality of care for patients outside of the traditional Medicare system.

Kidney Histopathology and Prediction of Kidney Failure: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: The use of kidney histopathology for predicting kidney failure is not established. We hypothesized that the use of histopathologic features of kidney biopsy specimens would improve prediction of clinical outcomes made using demographic and clinical variables alone. STUDY DESIGN: Retrospective cohort study and development of a clinical prediction model. SETTING & PARTICIPANTS: All 2,720 individuals from the Biopsy Biobank Cohort of Indiana who underwent kidney biopsy between 2002 and 2015 and had at least 2 years of follow-up. NEW PREDICTORS & ESTABLISHED PREDICTORS: Demographic variables, comorbid conditions, baseline clinical characteristics, and histopathologic features. OUTCOMES: Time to kidney failure, defined as sustained estimated glomerular filtration rate ≤ 10mL/min/1.73m2. ANALYTICAL APPROACH: Multivariable Cox regression model with internal validation by bootstrapping. Models including clinical and demographic variables were fit with the addition of histopathologic features. To assess the impact of adding a histopathology variable, the amount of variance explained (r2) and the C index were calculated. The impact on prediction was assessed by calculating the net reclassification index for each histopathologic variable and for all combined. RESULTS: Median follow-up was 3.1 years. Within 5 years of biopsy, 411 (15.1%) patients developed kidney failure. Multivariable analyses including demographic and clinical variables revealed that severe glomerular obsolescence (adjusted HR, 2.03; 95% CI, 1.51-2.03), severe interstitial fibrosis and tubular atrophy (adjusted HR, 1.99; 95% CI, 1.52-2.59), and severe arteriolar hyalinosis (adjusted HR, 1.53; 95% CI, 1.14-2.05) were independently associated with the primary outcome. The addition of all histopathologic variables to the clinical model yielded a net reclassification index for kidney failure of 5.1% (P < 0.001) with a full model C statistic of 0.915. Analyses addressing the competing risk for death, optimism, or shrinkage did not significantly change the results. LIMITATIONS: Selection bias from the use of clinically indicated biopsies and exclusion of patients with less than 2 years of follow-up, as well as reliance on surrogate indicators of kidney failure onset. CONCLUSIONS: A model incorporating histopathologic features from kidney biopsy specimens improved prediction of kidney failure and may be valuable clinically. Future studies will be needed to understand whether even more detailed characterization of kidney tissue may further improve prognostication about the future trajectory of estimated glomerular filtration rate.

Surgical Management of Pelvic Organ Prolapse in Ethiopian Women: What Is the Preferred Approach?

OBJECTIVES: The aim of this study was to determine the most effective approach to surgical repair of pelvic organ prolapse for Ethiopian women and to characterize this population. METHODS: This is a prospective cohort study of women presenting for prolapse repair. Demographics and assessments of prolapse were obtained preoperatively. Information surrounding the surgical encounter was collected. The same anatomic and symptomatic measures were ascertained postoperatively. Information regarding surgical complications was collected. RESULTS: Two hundred thirty-three women with stage III or IV prolapse underwent surgical prolapse repair between March 2015 and November 2017. Seventy-eight of these women participated with a median length of follow-up of 255 days. All of the sacrocolpopexy patients (n = 21) and 56 of 57 vaginal repair patients had follow-up anatomic data. Anatomic failure as defined by Pelvic Organ Prolapse-Quantification (Ba, C, or Bp > 0) occurred in 0% (0/21) of sacrocolpopexy patients and 34% (19/56) of vaginal repair patients (P = 0.005). Symptomatic failure, as defined by self-reported recurrence of vaginal bulge, occurred in 0% (0/21) of sacrocolpopexy patients and 23% (13/56) of vaginal repair patients (P = 0.015). A global assessment of improvement (worse, same, or improved) revealed that 100% (21/21) of sacrocolpopexy patients reported improvement, whereas 91% (50/55) of vaginal repair patients reported improvement, 7% (4/55) reported being the same, and 2% (1/55) reported being worse. There were 2 intraoperative complications and 3 postoperative complications. There were no cases of mesh erosion. CONCLUSIONS: Although both vaginal and abdominal routes of prolapse surgery seem to be safe, an abdominal approach with mesh augmentation may be the preferred surgical repair in Ethiopian women.

Comparing cervical mucus changes in response to an oral progestin or oestrogen withdrawal in ovarian-suppressed women: a clinical pilot.

Purpose: Prior studies evaluating the effect of administered progestogens on peak cervical mucus have not controlled for the influence of endogenous hormones. To address this, we treated women with a gonadotropin-releasing hormone (GnRH) agonist to suppress the hypothalamus-pituitary-ovarian (HPO) axis and used transdermal oestradiol replacement to stimulate peak cervical mucus and then evaluated the effects of an oral progestin or oestradiol withdrawal. Materials and methods: We used a crossover design to examine cervical mucus changes in women receiving transdermal oestradiol replacement following intramuscular administration of leuprolide acetate. After increasing oestradiol patches to mid-cycle levels, subjects were assigned to either 0.35 mg oral norethindrone with continuation of the patches (NET) or oestradiol withdrawal by patch removal (E2WD). We collected serum and cervical mucus samples at 0, 2, 4, 6, 22 and 24 h following the intervention. Results: We analysed 12 cycles (6 NET, 6 E2WD) from three subjects. Baseline cervical mucus scores were favourable to sperm penetration [NET median 11, interquartile range (9-12), E2WD 13 (12-13)]. Two hours after removal of oestradiol patch or administration of norethindrone, cervical mucus scores declined [NET 8.5 (4-9), E2WD 10.5 (10-12)]. Low cervical mucus scores persisted at 24 h with NET [8.0 (7-8)] but not E2WD [10.5 (8-11)]. Conclusions: We observed a rapid decline in cervical mucus Insler scores following administration of a single dose of oral norethindrone, and scores remained lower and unfavourable through 24 h. Oestradiol withdrawal did not result in similar unfavourable changes.

The role of environmental factors and lifestyle on male reproductive health, the epigenome, and resulting offspring.

Many environmental and genetic variables affect male reproductive health. Some of these factors, however, interfere not only with fertility, but also the non-genomic materials within spermatozoa that can cause phenotypic changes in the offspring, and in some cases, multiple generations. This intergenerational and transgenerational inheritance is due to epigenetic modifications, which is a complex adjunct to traditional Mendelian genetics whose influence on a wide range of human diseases is an active area of research. As the epigenome is a gestalt of individual exposures to the world, ongoing research is evaluating the scope of environmental impacts on the epigenome, as well as its mechanisms for adjusting the phenotypic expression of the organism without changing the code itself. Of particular interest is how these traits are passable to subsequent generations. This article will cover the latest data concerning how the overall quality of nutrition and lifestyle of an individual has been demonstrated to have a significant effect on male reproductive health, and how the accumulation of these modifications are risk factors for the health of their offspring.

Ionic-Functionalized Polymers of Intrinsic Microporosity for Gas Separation Applications.

Ionic-functionalized microporous materials are attractive for energy-efficient gas adsorption and separation processes and have shown promising results in gas mixtures at pressure ranges and compositions that are relevant for industrial applications. In this work, we studied the influence of different counterions (Li+, Na+, K+, Rb+, and Mg2+) on the porosity, carbon dioxide (CO2) gas adsorption, and selectivity in ionic-functionalized PIM-1 (IonomIMs), a polymer belonging to the class of linear and amorphous microporous polymers known as polymers of intrinsic microporosity (PIMs). It was found that an increase in the concentration of ionic groups led to a decrease in the free volume, resulting in a less porous polymer framework, and Mg2+-functionalized IonomIMs exhibited a relatively larger porosity compared to other IonomIMs. The CO2 adsorption capacity was affected by the different counterions for IonomIM-1, and a higher loading capacity for pure CO2 was observed for Mg2+. Furthermore, the IonomIMs showed an enhanced CO2 selectivity in CO2/CH4 and CO2/N2 gas mixtures at conditions used in pressure swing adsorption and vacuum swing adsorption applications. It was also observed that the concentration of ionic groups plays a vital role in changing the CO2 gas adsorption and selectivity.

Assessment of three point-of-care platelet function assays in adult trauma patients.

BACKGROUND: Antiplatelet (AP) medication use is common among trauma patients and is associated with poor outcomes. Management options for platelet dysfunction in trauma patients are controversial, expensive, and potentially harmful. Although light transmission platelet aggregometry is considered the standard test to assess platelet function, it is cumbersome and not generally available. Currently, there are no widely accepted platelet function point-of-care tests for acute trauma. STUDY DESIGN: Prospective observational study from 2014 to 2015. Baseline Multiplate aggregometry aspirin area under the platelet aggregation curve (ASPI AUC), Thrombelastography Platelet Mapping percent inhibition of arachidonic acid (TEG-PM AA), and VerifyNow Aspirin Test (ARU) were compared for ability to detect any AP medication use (aspirin or clopidogrel), platelet dysfunction, and identify patients at risk for intracranial hemorrhage (ICH) progression by calculating the area under receiver operating characteristic curves (AUC), sensitivity, specificity, and positive and negative predictive values. Adenosine diphosphate assays were similarly evaluated. RESULTS: Sixty-four patients were enrolled, 25 were taking AP medications. AP patients were older (71.6 versus 35.0 y, P < 0.001) and received more platelet transfusions, but other baseline characteristics were similar. Median ASPI AUC (22.0 versus 53.5 P < 0.001) and VerifyNow ARU (503.5 versus 629.0, P < 0.001) were lower, whereas TEG-PM AA (51.8% versus 18.3%, P < 0.001) was higher in AP patients. Multiplate ASPI AUC, TEG-PM AA percent inhibition, and VerifyNow ARU could identify AP medication use (AUC: 0.90, 0.77, and 0.90, respectively). Adenosine diphosphate assays did not correlate with AP medication use in this population. TEG-PM AA percent inhibition and VerifyNow ARU correlated well with Multiplate ASPI AUC to identify platelet dysfunction (AUC: 0.78, 0.89, respectively). ICH occurred in 29 patients; 12 of which had progression of their injury. ASPI AUC (AUC: 0.50) and VerifyNow ARU (AUC: 0.59) did not correlate, and TEG-PM AA percent inhibition (AUC: 0.66) minimally correlated with progression. CONCLUSIONS: Multiplate, TEG-PM, and VerifyNow are useful point-of-care tests which identify AP medication use and platelet dysfunction in trauma patients. Initial TEG-PM AA percent inhibition may be associated with risk for ICH progression. However, additional large, prospective studies are needed.

Splenectomy is associated with higher infection and pneumonia rates among trauma laparotomy patients.

Splenectomy increases lifetime risk of thromboembolism (VTE) and is associated with long-term infectious complications, primarily, overwhelming post-splenectomy infection (OPSI). Our objective was to evaluate risk of VTE and infection at index hospitalization post-splenectomy. Retrospective review of all patients who received a laparotomy in the NTDB. Propensity score matching for splenectomy was performed, based on ISS, abdominal abbreviated injury score >3, GCS, sex and mechanism. Major complications, VTE, and infection rates were compared. Multiple logistic regression models were utilized to evaluate splenectomy-associated complications. 93,221 laparotomies were performed and 17% underwent splenectomy. Multiple logistic regression models did not demonstrate an association between splenectomy and major complications (OR 0.96, 95% CI 0.91-1.03, p = 0.25) or VTE (OR 1.05, 95% CI 0.96-1.14, p = 0.33). Splenectomy was independently associated with infection (OR 1.07, 95% CI 1.00-1.14, p = 0.045). Subgroup analysis of patients with infection demonstrated that splenectomy was most strongly associated with pneumonia (OR 1.41, 95% CI 1.26-1.57, p < 0.001). Splenectomy is not associated with higher overall complication or VTE rates during index hospitalization. However, splenectomy is associated with a higher rate of pneumonia.

Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?

OBJECTIVE: There is currently no consensus regarding how to address pelvic sentinel lymph nodes (PSLNs) in melanoma. Thus, our objectives were to identify the incidence and clinical impact of PSLNs. METHODS: Retrospective review of a prospectively collected multi-institutional melanoma database. RESULTS: Of 2476 cases of lower extremity and trunk melanomas, 227 (9%) drained to PSLNs (181 to both PSLNs and superficial (inguinal or femoral) sentinel lymph nodes (SSLN) and 46 to PSLNs alone). Seventeen (7.5%) of 227 PSLN cases were positive for nodal metastasis, 8 of which drained to PSLNs only while 9 drained to both PSLNs and SSLNs. Complication rates between PSLN and SSLN biopsy were similar (15% vs. 14% respectively). In 181 cases with drainage to both SSLNs and PSLNs, PSLN biopsy upstaged one patient (0.6%), and completion dissection based on a positive PSLN did not upstage any. CONCLUSIONS: PSLN biopsy is safe, however in the setting of negative SSLNs there is minimal clinical impact. We therefore recommend PSLN biopsy when the SSLNs are positive or when the tumor drains to PSLNs alone.

The Affordable Care Act and its association with length of stay and payer status for trauma patients at a level I trauma center.

BACKGROUND: We hypothesized that the ACA would shorten length of stay and increase numbers of insured patients without changing trauma patient outcomes. METHODS: A retrospective review of adult trauma patients admitted to a level I trauma center between 2012 and 2014 was performed. Demographics, length of stay, payer status, discharge disposition, and complications before and after the ACA implementation were analyzed. RESULTS: 4448 trauma patients were admitted during the study period. Patients treated after ACA implementation were older (53 vs 51, p = 0.05) with shorter ICU stays (1.7 vs 1.5 days, p = 0.04), but longer overall hospital stays (3.7 vs 4.1 days, p < 0.01). The proportion of self-pay patients decreased 11%-3% (p=<0.001). A higher proportion of patients were discharged to skilled nursing facilities (SNF, 17.1% vs 19.9%, p = 0.02). There was no change in rates of death, readmission, infection, pneumonia or decubiti. CONCLUSION: Among trauma patients, there was a decrease in self-pay status and increase in public insurance without change in private insurance after implementation of the ACA. More patients were discharged to SNF without changes in reported outcomes.

Damage control laparotomy utilization rates are highly variable among Level I trauma centers: Pragmatic, Randomized Optimal Platelet and Plasma Ratios findings.

BACKGROUND: Damage control laparotomy (DCL) is intended to limit deleterious effects from trauma-induced coagulopathy. DCL has been associated with mortality reduction, but may increase complications including sepsis, abscess, respiratory failure, hernia, and gastrointestinal fistula. We hypothesized that (1) DCL incidence would vary between institutions; (2) mortality rates would vary with DCL rates; (3) standard DCL criteria of pH, international normalized ratio, temperature and major intra-abdominal vascular injury would not adequately capture all patients. METHODS: Trauma patients at 12 Level 1 North American trauma centers were randomized based on transfusion ratios as described in the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. We analyzed outcomes after emergent laparotomy using a mixed-effects logistic model comparing DCL versus definitive surgical management with random effect for study site. Primary outcomes were 24-hour and 30-day mortality. RESULTS: Three hundred twenty-nine patients underwent emergent laparotomy: 213 (65%) DCL and 116 (35%) definitive surgical management. DCL rates varied between institutions (33-83%), (p = 0.002). Median Injury Severity Score (ISS) was higher in the DCL group, 29 (interquartile range, 13-34) versus 21 (interquartile range, 22-41) (p < 0.001). Twenty-four-hour mortality was 19% with DCL versus 4% (p < 0.001); 30-day mortality was 28% with DCL versus 19% (p < 0.001). In a mixed-effects model, ISS and major intra-abdominal vascular injury were correlates of DCL (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.02-1.07 and OR, 2.7; 95% CI, 1.4-5.2). DCL was not associated with 30-day mortality (OR, 2.33; 95% CI, 0.97-5.60). Correlates included ISS (OR, 1.06; 95% CI, 1.02-1.09), PRBCs in 24 hours (OR, 1.10; 95% CI, 1.03-1.18), and age (OR, 1.04; 95% CI, 1.01-1.06). No significant mortality difference was detected between institutions (p = 0.63). Sepsis and VAP occurred more frequently with DCL (p < 0.05). Eighty percent (135/213) of DCL patients met standard criteria. CONCLUSION: Although DCL utilization varied significantly between institutions, there was no significant mortality difference between centers. This finding suggests tempering DCL use may not decrease mortality, but could decrease related complications. LEVEL OF EVIDENCE: Therapeutic study, level III.

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios can Predict Treatment Response to Neoadjuvant Therapy in Esophageal Cancer.

INTRODUCTION: We hypothesized that serum neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios may predict pathologic complete response to neoadjuvant chemoradiotherapy in esophageal cancer patients. The ability to predict favorable treatment response to therapy may aid in determining optimal treatment regimens. MATERIALS AND METHODS: A retrospective review of a prospective esophageal disease registry was conducted. Neutrophil-to-lymphocyte ratio was defined as the pre-chemoradiotherapy serum neutrophil count divided by lymphocyte count. Platelet-to-lymphocyte ratio was similarly defined. Logistic regression was applied to analyze these ratios and their effect on pathologic complete response. A Cox proportional-hazards model was used to analyze survival. RESULTS: Sixty patients were included. Elevated neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were both negative predictors of pathologic complete response (odds ratio: 0.62; 95% confidence interval: 0.37-0.89, P = 0.037 and odds ratio: 0.91; 95% confidence interval: 0.82-0.98, P = 0.028, respectively). Only platelet-to-lymphocyte ratio was predictive of decreased overall survival (hazard ratio: 1.05, 95% confidence interval: 0.94-1.16, P = 0.40). CONCLUSION: Elevated neutrophil and platelet-to-lymphocyte ratios were significant predictors of a poor treatment response to neoadjuvant therapy. Only elevated platelet-to-lymphocyte ratio was predictive of worse overall survival. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios may offer a simple serum test to assess the likelihood of a pathologic complete response after neoadjuvant therapy in esophageal cancer.

Sponge Sampling with Fluorescent In Situ Hybridization as a Screening Tool for the Early Detection of Esophageal Cancer.

INTRODUCTION: Sponge cytology is a novel screening tool for esophageal cancer but has been unable to be validated for widespread use. Our aim was to apply fluorescent in situ hybridization to sponge cytology samples in order to evaluate the safety and efficacy of this modality in screening for esophageal cancer. MATERIALS AND METHODS: At a single, multidisciplinary, NCI-designated cancer center, patients completed sponge cytology sampling prior to upper endoscopy. Samples were analyzed by p53 fluorescent in situ hybridization, and results were compared to the endoscopic diagnosis. RESULTS: Fifty patients were enrolled (96 % Caucasian, 68 % male, median age of 67). All patients successfully swallowed the capsule. No complications (string breakage, bleeding, mucosal injury) occurred. Endoscopy revealed that 38 % had normal esophageal mucosa and 62 % had an esophageal mucosal abnormality. In total, six samples demonstrated p53 loss (94 % specificity for any abnormality). The sensitivity of the p53 fluorescent in situ hybridization probe was13.3 % for any abnormality, 10 % for intestinal metaplasia, and 0 % for dysplasia or esophageal cancer. DISCUSSION: Esophageal sponge cytology is a promising, safe, and tolerable method for collecting esophageal cell samples. However, our data suggest that p53 fluorescent in situ hybridization does not improve the sensitivity for detecting cancer in these samples.

Patterns of Care in Hospitalized Vascular Surgery Patients at End of Life.

Importance: There is limited literature reporting circumstances surrounding end-of-life care in vascular surgery patients. Objective: To identify factors driving end-of-life decisions in vascular surgery patients. Design, Setting, and Participants: In this cohort study, medical records were reviewed for all vascular surgery patients at a tertiary care university hospital who died during their hospitalization from 2005 to 2014. Main Outcomes and Measures: Patient, family, and hospitalization variables potentially important to influencing end-of-life decisions. Results: Of 111 patients included (67 [60%] male; median age, 75 [range, 24-94] years), 81 (73%) were emergent vs 30 (27%) elective admissions. Only 15 (14%) had an advance directive. Of the 81 (73%) patients placed on comfort care, 31 (38%) had care withheld or withdrawn despite available medical options, 15 (19%) had an advance directive, and 28 (25%) had a palliative care consultation. The median time from palliative care consultation to death was 10 hours (interquartile range, 3.36-66 hours). Comparing the 31 patients placed on comfort care despite available medical options with an admission diagnosis-matched cohort, we found that more than 5 days admitted to the intensive care unit (odds ratio [OR], 4.11; 95% CI, 1.59-10.68; P < .001), more than 5 days requiring ventilator support (OR, 9.45; 95% CI, 3.41-26.18; P < .001), new renal failure necessitating dialysis (OR, 14.48; 95% CI, 3.69-56.86; P < .001), and new respiratory failure necessitating tracheostomy (OR, 23.92; 95% CI, 2.80-204; P < .001) correlated with transition to comfort care. Conclusions and Relevance: Palliative care consultations may be underused at the end of life. A large percentage of patients were transitioned to comfort measures despite available treatment, yet few presented with advance directives. In high-risk patients, discussions regarding extended stays in the intensive care unit, prolonged ventilator management, and possible dialysis and tracheostomy should be communicated with patients and families at time of hospitalization and advance directives solicited.

Thrombelastography-Based Dosing of Enoxaparin for Thromboprophylaxis in Trauma and Surgical Patients: A Randomized Clinical Trial.

Importance: Prophylactic enoxaparin is used to prevent venous thromboembolism (VTE) in surgical and trauma patients. However, VTE remains an important source of morbidity and mortality, potentially exacerbated by antithrombin III or anti-Factor Xa deficiencies and missed enoxaparin doses. Recent data suggest that a difference in reaction time (time to initial fibrin formation) greater than 1 minute between heparinase and standard thrombelastogram (TEG) is associated with a decreased risk of VTE. Objective: To evaluate the effectiveness of TEG-adjusted prophylactic enoxaparin dosing among trauma and surgical patients. Design, Setting, and Participants: This randomized clinical trial, conducted from October 2012 to May 2015, compared standard dosing (30 mg twice daily) with TEG-adjusted enoxaparin dosing (35 mg twice daily) for 185 surgical and trauma patients screened for VTE at 3 level I trauma centers in the United States. Main Outcomes and Measures: The incidence of VTE, bleeding complications, anti-Factor Xa deficiency, and antithrombin III deficiency. Results: Of the 185 trial participants, 89 were randomized to the control group (median age, 44.0 years; 55.1% male) and 96 to the intervention group (median age, 48.5 years; 74.0% male). Patients in the intervention group received a higher median enoxaparin dose than control patients (35 mg vs 30 mg twice daily; P < .001). Anti-Factor Xa levels in intervention patients were not higher than levels in control patients until day 6 (0.4 U/mL vs 0.21 U/mL; P < .001). Only 22 patients (11.9%) achieved a difference in reaction time greater than 1 minute, which was similar between the control and intervention groups (10.4% vs 13.5%; P = .68). The time to enoxaparin initiation was similar between the control and intervention groups (median [range] days, 1.0 [0.0-2.0] vs 1.0 [1.0-2.0]; P = .39), and the number of patients who missed at least 1 dose was also similar (43 [48.3%] vs 54 [56.3%]; P = .30). Rates of VTE (6 [6.7%] vs 6 [6.3%]; P > .99) were similar, but the difference in bleeding complications (5 [5.6%] vs 13 [13.5%]; P = .08) was not statistically significant. Antithrombin III and anti-Factor Xa deficiencies and hypercoagulable TEG parameters, including elevated coagulation index (>3), maximum amplitude (>74 mm), and G value (>12.4 dynes/cm2), were prevalent in both groups. Identified risk factors for VTE included older age (61.0 years vs 46.0 years; P = .04), higher body mass index (calculated as weight in kilograms divided by height in meters squared; 30.6 vs 27.1; P = .03), increased Acute Physiology and Chronic Health Evaluation II score (8.5 vs 7.0; P = .03), and increased percentage of missed doses per patient (14.8% vs 2.5%; P = .05). Conclusions and Relevance: The incidence of VTE was low and similar between groups; however, few patients achieved a difference in reaction time greater than 1 minute. Antithrombin III deficiencies and hypercoagulable TEG parameters were prevalent among patients with VTE. Low VTE incidence may be due to an early time to enoxaparin initiation and an overall healthier and less severely injured study population than previously reported. Trial Registration: clinicaltrials.gov Identifier: NCT00990236.

HIV positivity and anal cancer outcomes: A single-center experience.

BACKGROUND: Anal cancer remains common among human immunodeficiency virus (HIV) patients. Chemoradiation has had mixed results. We evaluated outcome differences by HIV status. METHODS: We retrospectively analyzed 14 HIV+ and 72 HIV- anal cancer patients (2000 to 2013). Outcomes included chemoradiation tolerance, recurrence, and survival. RESULTS: HIV+ patients were more often male (100% vs 38%, P < .001) but diagnosed at similar stages (P = .49). They were less likely to receive traditional chemotherapy (36% vs 86%, P < .001). Recurrence (P = .55) and survival time (P = .48) were similar across groups. HIV+ patients had similar colostomy-free survival (P = .053). Receipt of 5-fluorouracil/mitomycin C (MMC) chemotherapy predicted recurrence-free and overall survival (Hazard ratios .278, .32). HIV status did not worsen recurrence (P = .71) or survival (P = .57). CONCLUSIONS: HIV+ patients received more non-MMC-based chemoradiation but had equivalent colostomy-free, recurrence, and overall survival. Use of 5-fluorouracil/MMC chemotherapy increased after 2008.