Effectiveness of oral versus intravenous tranexamic acid in primary total hip and knee arthroplasty: a randomised, non-inferiority trial.

BACKGROUND: Tranexamic acid (TXA) reduces rates of blood transfusion for total hip arthroplasty (THA) and total knee arthroplasty (TKA). Although the use of oral TXA rather than intravenous (i.v.) TXA might improve safety and reduce cost, it is not clear whether oral administration is as effective. METHODS: This noninferiority trial randomly assigned consecutive patients undergoing primary THA or TKA under neuraxial anaesthesia to either one preoperative dose of oral TXA or one preoperative dose of i.v. TXA. The primary outcome was calculated blood loss on postoperative day 1. Secondary outcomes were transfusions and complications within 30 days of surgery. RESULTS: Four hundred participants were randomised (200 THA and 200 TKA). The final analysis included 196 THA patients (98 oral, 98 i.v.) and 191 TKA patients (93 oral, 98 i.v.). Oral TXA was non-inferior to i.v. TXA in terms of calculated blood loss for both THA (effect size=-18.2 ml; 95% confidence interval [CI], -113 to 76.3; P<0.001) and TKA (effect size=-79.7 ml; 95% CI, -178.9 to 19.6; P<0.001). One patient in the i.v. TXA group received a postoperative transfusion. Complication rates were similar between the two groups (5/191 [2.6%] oral vs 5/196 [2.6%] i.v.; P=1.00). CONCLUSIONS: Oral TXA can be administered in the preoperative setting before THA or TKA and performs similarly to i.v. TXA with respect to blood loss and transfusion rates. Switching from i.v. to oral TXA in this setting has the potential to improve patient safety and decrease costs.

Minimizing Opioid Use After Total Hip Arthroplasty: Comparing Periarticular Injection Versus Patient-Controlled Epidural Analgesia Versus a Combination Protocol.

BACKGROUND: Effective management of postoperative pain after total hip arthroplasty (THA) may be challenging. We sought to develop an opioid-sparing pain management pathway by comparing the relative effectiveness of 3 different protocols: (1) Local anesthetic administered patient-controlled epidural analgesia (PCEA) without intrathecal opioids; (2) Periarticular injection (PAI); and (3) PCEA + PAI. METHODS: In this double-blinded randomized controlled trial, 180 patients undergoing THA were randomized to receive either (1) PCEA with 0.06% bupivacaine, (2) PAI, or (3) a PAI + PCEA with 0.06% bupivacaine. All patients received the same postoperative multimodal analgesic regimen. The primary outcome was opioid consumption, measured in oral morphine equivalents, at 24, 48, and 72 hours after anesthesia stop time. Secondary measures included pain at rest and with movement, opioid side effects, patient satisfaction, and quality of recovery, as assessed via standardized self-reporting scales and surveys. RESULTS: Opioid consumption was significantly higher in the PAI group in the first 24 hours postoperatively compared to the PAI + PCEA group (30 versus 15, P = .012). No differences were detected among groups for length of stay, pain scores, patient satisfaction, or duration of surgery. More patients in the PAI + PCEA group were opiate-free in the first 24 hours compared to PAI (23.7 versus 8.5%, P = .043). CONCLUSION: Use of PAI + PCEA regimen was opioid-sparing in the first 24 hours after surgery, favoring this group when opioid reduction is desired. Increased drowsiness was noted in the subsequent 24 to 48 hours once the epidural catheter was removed and opioid consumption also increased.

The Utilization of Regional Anesthesia Among Pediatric Patients: A Retrospective Study.

BACKGROUND: The use of regional anesthesia (RA) in pediatric patients remains understudied, although evidence suggests benefits over general anesthesia. QUESTIONS/PURPOSES: We sought to identify factors associated with RA use in patients under the age of 21 years undergoing ambulatory orthopedic surgery. METHODS: Patients under the age of 21 who underwent anterior cruciate ligament (ACL) repair or reconstruction, knee arthroscopy (KA), or shoulder arthroscopy (SA) were identified from the NY Statewide Planning and Research Cooperative System (SPARCS) database (2005-2015). Frequencies of RA use (defined by femoral nerve block, spinal, epidural, caudal, or brachial plexus anesthesia) were calculated. Multivariable regression analysis identified patient- and healthcare system-related factors associated with the use of RA. Odds ratios (OR) and 95% confidence intervals (CI) were reported. RESULTS: We identified 87,273 patients who underwent the procedures of interest (ACL n = 28,226; SA n = 18,155; KA n = 40,892). In our primary analysis, 14.4% (n = 1404) had RA as their primary anesthetic; this percentage increased for patients who had ACL or KA. When adjusting for covariates, Hispanic ethnicity (OR 0.78; CI 0.65-0.94) and Medicaid insurance (OR 0.75; CI 0.65-0.87) were associated with decreased odds for the provision of RA. Further, we identified increasing age (OR 1.10; CI 1.08-1.11), ACL versus SA (OR 1.91; CI 1.74-2.10), and sports injuries (OR 1.20; CI 1.10-1.31) as factors associated with increased odds of RA use. CONCLUSION: In this analysis, RA was used in a minority of patients under the age of 21 undergoing ambulatory orthopedic surgery. Older age was associated with increased use while Hispanic ethnicity and lower socioeconomic status were associated with lower use.

Lack of July effect in the utilization of neuraxial and peripheral nerve block in US teaching hospitals: a retrospective analysis.

BACKGROUND: Given the steep learning curve for neuraxial and peripheral nerve blocks, utilization of general anesthesia may increase as new house staff begin their residency programs. We sought to determine whether "July effect" affects the utilization of neuraxial anesthesia, peripheral nerve blocks, and opioid prescribing for lower extremity total joint arthroplasties (TJA) in July compared with June in teaching and non-teaching hospitals. METHODS: Neuraxial anesthesia, peripheral nerve block use, and opioid prescribing trends were assessed using the Premier database (2006-2016). Analyses were conducted separately for teaching and non-teaching hospitals. Differences in proportions were evaluated via χ2 test, while differences in opioid prescribing were analyzed via Wilcoxon rank-sum tests. RESULTS: A total of 1 723 256 TJA procedures were identified. The overall proportion of neuraxial anesthesia use in teaching hospitals was 14.4% in both June and July (p=0.940). No significant changes in neuraxial use were seen in non-teaching hospitals (24.5% vs 24.9%; p=0.052). Peripheral nerve block utilization rates did not differ in both teaching (15.4% vs 15.3%; p=0.714) and non-teaching hospitals (10.7% vs 10.5%; p=0.323). Overall median opioid prescribing at teaching hospitals changed modestly from 262.5 oral morphine equivalents (OME) in June to 260 in July (p=0.026) while median opioid prescribing remained at a constant value of 255 OME at non-teaching hospitals (p=0.893). CONCLUSION: Utilization of neuraxial and regional anesthesia techniques was not affected during the initial transition period of new house staff in US teaching institutions. It is feasible that enough resources are available in the system to accommodate periods of turnover and maintain levels of regional anesthetic care including additional attending anesthesiologist oversight.

Effects of a multimodal analgesic pathway with transversus abdominis plane block for lumbar spine fusion: a prospective feasibility trial.

PURPOSE: Lumbar spine fusion with anterior (ALIF) or lateral (LLIF) approach is a moderately painful procedure associated with significant length of hospital stay (LoS) and opioid requirements. We developed an opioid-sparing analgesic pathway of care for ALIF and LLIF, featuring transversus abdominis plane (TAP) block. In this study, we assessed the feasibility of performing the TAP block as an analgesic adjunct for ALIF or LLIF. METHODS: This is a prospective feasibility study of 32 patients. All patients received pre-incisional TAP block, regularly scheduled non-opioid analgesics (gabapentin, acetaminophen, ketorolac), and oral tramadol, as needed. The primary feasibility outcomes were rates of recruitment, adherence and adverse events associated with the TAP block. Secondary outcomes included assessment of TAP block efficacy and duration, numeric rating scale (NRS) pain scores, LoS and opioid consumption. RESULTS: Thirty-three patients were approached for the study, and all were enrolled. One patient did not have surgery. All patients received the intervention. There were no block-related adverse events. PACU NRS scores were significantly lower (1.9 ± 3.0) than at postoperative day 1 (POD1; 3.3 ± 2.5). The TAP block was effective in 31/32 patients, with 1 failed block. Median LoS was 26.8 h (IQR 22.8-49.5 h). Median opioid consumption was 57.5 oral morphine equivalents (IQR 30-74.38). One patient required opioid iv patient-controlled analgesia. CONCLUSIONS: Applying TAP block to spine surgery is a novel pain management strategy. This study demonstrates high patient acceptance and the general safety of the technique. Although lacking a control arm, these results also provide preliminary data supporting efficacy. These slides can be retrieved under Electronic Supplementary Material.

Genetically transforming human osteoblasts to sarcoma: development of an osteosarcoma model.

Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Although histologically defined by the presence of malignant osteoid, the tumor possesses lineage multipotency suggesting it could be derived from a cell anywhere on the differentiation pathway between a mesenchymal stem cell (MSC) and a mature osteoblast. To determine if preosteoblasts (pOB) could be the cell of origin differentiated MSCs were transformed with defined genetic elements. MSCs and pOB differentiated from the same MSCs were serially transformed with the oncogenes hTERT, SV40 large T antigen and H-Ras. Assays were performed to determine their tumorigenic properties, differentiation capacity and histologic appearance. When subcutaneously implanted in immunocompromised mice, cell lines derived from transformed MSC and pOB formed tumors in 4 weeks. In contrast to the transformed MSC, the pOB tumors demonstrated a histological appearance characteristic of osteosarcoma. The cell lines derived from the transformed pOB only had osteogenic and chondrogenic differentiation potential, but not adipogenic ones. However, the transformed MSC cells and standard osteosarcoma cell lines maintained their tri-lineage differentiation capacity. The inability of the transformed pOB cell line to undergo adipogenic differentiation, may suggest that osteosarcoma is derived from a cell intermediate in differentiation between an MSC and a pOB, with partial commitment to the osteoblastic lineage.

Pediatric and neonatal extracorporeal membrane oxygenation: does center volume impact mortality?*.

OBJECTIVE: Extracorporeal membrane oxygenation, an accepted rescue therapy for refractory cardiopulmonary failure, requires a complex multidisciplinary approach and advanced technology. Little is known about the relationship between a center's case volume and patient mortality. The purpose of this study was to analyze the relationship between hospital extracorporeal membrane oxygenation annual volume and in-hospital mortality and assess if a minimum hospital volume could be recommended. DESIGN: Retrospective cohort study. SETTING: A retrospective cohort admitted to children's hospitals in the Pediatric Health Information System database from 2004 to 2011 supported with extracorporeal membrane oxygenation was identified. Indications were assigned based on patient age (neonatal vs pediatric), diagnosis, and procedure codes. Average hospital annual volume was defined as 0-19, 20-49, or greater than or equal to 50 cases per year. Maximum likelihood estimates were used to assess minimum annual case volume. PATIENTS: A total of 7,322 pediatric patients aged 0-18 were supported with extracorporeal membrane oxygenation and had an indication assigned. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Average hospital extracorporeal membrane oxygenation volume ranged from 1 to 58 cases per year. Overall mortality was 43% but differed significantly by indication. After adjustment for case-mix, complexity of cardiac surgery, and year of treatment, patients treated at medium-volume centers (odds ratio, 0.86; 95% CI, 0.75-0.98) and high-volume centers (odds ratio, 0.75; 95% CI, 0.63-0.89) had significantly lower odds of death compared with those treated at low-volume centers. The minimum annual case load most significantly associated with lower mortality was 22 (95% CI, 22-28). CONCLUSIONS: Pediatric centers with low extracorporeal membrane oxygenation average annual case volume had significantly higher mortality and a minimum volume of 22 cases per year was associated with improved mortality. We suggest that this threshold should be evaluated by additional study.

Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥60 years of age.

BACKGROUND: Incidence and severity of herpes zoster (HZ) and postherpetic neuralgia increase with age, associated with age-related decrease in immunity to varicella-zoster virus (VZV). One dose of zoster vaccine (ZV) has demonstrated substantial protection against HZ; this study examined impact of a second dose of ZV. METHODS: Randomized, double-blind, multicenter study with 210 subjects ≥60 years old compared immunity and safety profiles after one and two doses of ZV, separated by 6 weeks, vs. placebo. Immunogenicity was evaluated using VZV interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay and VZV glycoprotein enzyme-linked immunosorbent antibody (gpELISA) assay. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card. RESULTS: No serious vaccine-related AEs occurred. VZV IFN-γ ELISPOT geometric mean count (GMC) of spot-forming cells per 10(6) peripheral blood mononuclear cells increased in the ZV group from 16.9 prevaccination to 49.5 and 32.8 at 2 and 6 weeks postdose 1, respectively. Two weeks, 6 weeks and 6 months postdose 2, GMC was 44.3, 42.9, and 36.5, respectively. GMC in the placebo group did not change during the study. The peak ELISPOT response occurred ∼2 weeks after each ZV dose. The gpELISA geometric mean titers (GMTs) in the ZV group were higher than in the placebo group at 6 weeks after each dose. Correlation between the IFN-γ ELISPOT and gpELISA assays was poor. CONCLUSIONS: ZV was generally well-tolerated and immunogenic in adults ≥60 years old. A second dose of ZV was generally safe, but did not boost VZV-specific immunity beyond levels achieved postdose 1.

The self-incompatibility locus (S) and quantitative trait loci for self-pollination and seed dormancy in sunflower.

Wild populations of common sunflower (Helianthus annuus L.) are self-incompatible and have deep seed dormancy, whereas modern cultivars, inbreds, and hybrids are self-compatible and partially-to-strongly self-pollinated, and have shallow seed dormancy. Self-pollination (SP) and seed dormancy are genetically complex traits, the number of self-compatibility (S) loci has been disputed, and none of the putative S loci have been genetically mapped in sunflower. We genetically mapped quantitative trait loci (QTL) for self-incompatibility (SI), SP, and seed dormancy in a backcross population produced from a cross between an elite, self-pollinated, nondormant inbred line (NMS373) and a wild, self-incompatible, dormant population (ANN1811). A population consisting of 212 BC(1) progeny was subsequently produced by backcrossing a single hybrid individual to NMS373. BC(1) progeny produced 0-838 seeds per primary capitula when naturally selfed and 0-518 seeds per secondary capitula when manually selfed and segregated for a single S locus. The S locus mapped to linkage group 17 and was tightly linked to a cluster of previously identified QTL for several domestication and postdomestication traits. Two synergistically interacting QTL were identified for SP among self-compatible (ss) BC(1) progeny (R(2)=34.6%). NMS373 homozygotes produced 271.5 more seeds per secondary capitulum than heterozygotes. Germination percentages of seeds after-ripened for 4 weeks ranged from 0% to 100% among self-compatible BC(1)S(1) families. Three QTL for seed dormancy were identified (R(2)=38.3%). QTL effects were in the predicted direction (wild alleles decreased self-pollination and seed germination). The present analysis differentiated between loci governing SI and SP and identified DNA markers for bypassing SI and seed dormancy in elite x wild crosses through marker-assisted selection.