The ribosome-inactivating proteins MAP30 and Momordin inhibit SARS-CoV-2.

The continuing emergence of SARS-CoV-2 variants has highlighted the need to identify additional points for viral inhibition. Ribosome inactivating proteins (RIPs), such as MAP30 and Momordin which are derived from bitter melon (Momordica charantia), have been found to inhibit a broad range of viruses. MAP30 has been shown to potently inhibit HIV-1 with minimal cytotoxicity. Here we show that MAP30 and Momordin potently inhibit SARS-CoV-2 replication in A549 human lung cells (IC50 ~ 0.2 µM) with little concomitant cytotoxicity (CC50 ~ 2 µM). Both viral inhibition and cytotoxicity remain unaltered by appending a C-terminal Tat cell-penetration peptide to either protein. Mutation of tyrosine 70, a key residue in the active site of MAP30, to alanine completely abrogates both viral inhibition and cytotoxicity, indicating the involvement of its RNA N-glycosylase activity. Mutation of lysine 171 and lysine 215, residues corresponding to those in Ricin which when mutated prevented ribosome binding and inactivation, to alanine in MAP30 decreased cytotoxicity (CC50 ~ 10 µM) but also the viral inhibition (IC50 ~ 1 µM). Unlike with HIV-1, neither Dexamethasone nor Indomethacin exhibited synergy with MAP30 in the inhibition of SARS-CoV-2. From a structural comparison of the two proteins, one can explain their similar activities despite differences in both their active-sites and ribosome-binding regions. We also note points on the viral genome for potential inhibition by these proteins.

Successful kinetic impact into an asteroid for planetary defence.

Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation1,2. Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid1-3. A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation1. NASA's Double Asteroid Redirection Test (DART) mission is a full-scale test of kinetic impact technology. The mission's target asteroid was Dimorphos, the secondary member of the S-type binary near-Earth asteroid (65803) Didymos. This binary asteroid system was chosen to enable ground-based telescopes to quantify the asteroid deflection caused by the impact of the DART spacecraft4. Although past missions have utilized impactors to investigate the properties of small bodies5,6, those earlier missions were not intended to deflect their targets and did not achieve measurable deflections. Here we report the DART spacecraft's autonomous kinetic impact into Dimorphos and reconstruct the impact event, including the timeline leading to impact, the location and nature of the DART impact site, and the size and shape of Dimorphos. The successful impact of the DART spacecraft with Dimorphos and the resulting change in the orbit of Dimorphos7 demonstrates that kinetic impactor technology is a viable technique to potentially defend Earth if necessary.

Unique tRNA Fragment Upregulation with SARS-CoV-2 but Not with SARS-CoV Infection.

Unlike other coronaviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly infected the global population, with some suffering long-term effects. Thanks to extensive data on SARS-CoV-2 made available through global, multi-level collaborative research, investigators are getting closer to understanding the mechanisms of SARS-CoV-2 infection. Here, using publicly available total and small RNAseq data of Calu3 cell lines, we conducted a comparative analysis of the changes in tRNA fragments (tRFs; regulatory small noncoding RNAs) in the context of severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 infections. We found extensive upregulation of multiple tRFs in SARS-CoV-2 infection that was not present in SARS-CoV or other virus infections our group has studied. By comparing the total RNA changes in matching samples, we identified significant downregulation of TRDMT1 (tRNA methyltransferase), only in SARS-CoV-2 infection, a potential upstream event. We further found enriched neural functions among downregulated genes with SARS-CoV-2 infection. Interestingly, theoretically predicted targets of the upregulated tRFs without considering mRNA expression data are also enriched in neural functions such as axon guidance. Based on a combination of expression data and theoretical calculations, we propose potential targets for tRFs. For example, among the mRNAs downregulated with SARS-CoV-2 infection (but not with SARS-CoV infection), SEMA3C is a theoretically calculated target of multiple upregulated tRFs and a ligand of NRP1, a SARS-CoV-2 receptor. Our analysis suggests that tRFs contribute to distinct neurological features seen in SARS-CoV-2.

A comprehensive update on CIDO: the community-based coronavirus infectious disease ontology.

BACKGROUND: The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the development of the community-based Coronavirus Infectious Disease Ontology (CIDO) in early 2020. RESULTS: As an Open Biomedical Ontology (OBO) library ontology, CIDO is open source and interoperable with other existing OBO ontologies. CIDO is aligned with the Basic Formal Ontology and Viral Infectious Disease Ontology. CIDO has imported terms from over 30 OBO ontologies. For example, CIDO imports all SARS-CoV-2 protein terms from the Protein Ontology, COVID-19-related phenotype terms from the Human Phenotype Ontology, and over 100 COVID-19 terms for vaccines (both authorized and in clinical trial) from the Vaccine Ontology. CIDO systematically represents variants of SARS-CoV-2 viruses and over 300 amino acid substitutions therein, along with over 300 diagnostic kits and methods. CIDO also describes hundreds of host-coronavirus protein-protein interactions (PPIs) and the drugs that target proteins in these PPIs. CIDO has been used to model COVID-19 related phenomena in areas such as epidemiology. The scope of CIDO was evaluated by visual analysis supported by a summarization network method. CIDO has been used in various applications such as term standardization, inference, natural language processing (NLP) and clinical data integration. We have applied the amino acid variant knowledge present in CIDO to analyze differences between SARS-CoV-2 Delta and Omicron variants. CIDO's integrative host-coronavirus PPIs and drug-target knowledge has also been used to support drug repurposing for COVID-19 treatment. CONCLUSION: CIDO represents entities and relations in the domain of coronavirus diseases with a special focus on COVID-19. It supports shared knowledge representation, data and metadata standardization and integration, and has been used in a range of applications.

Profiling COVID-19 Vaccine Adverse Events by Statistical and Ontological Analysis of VAERS Case Reports.

Since the beginning of the COVID-19 pandemic, vaccines have been developed to mitigate the spread of SARS-CoV-2, the virus that causes COVID-19. These vaccines have been effective in reducing the rate and severity of COVID-19 infection but also have been associated with various adverse events (AEs). In this study, data from the Vaccine Adverse Event Reporting System (VAERS) was queried and analyzed via the Cov19VaxKB vaccine safety statistical analysis tool to identify statistically significant (i.e., enriched) AEs for the three currently FDA-authorized or approved COVID-19 vaccines. An ontology-based classification and literature review were conducted for these enriched AEs. Using VAERS data as of 31 December 2021, 96 AEs were found to be statistically significantly associated with the Pfizer-BioNTech, Moderna, and/or Janssen COVID-19 vaccines. The Janssen COVID-19 vaccine had a higher crude reporting rate of AEs compared to the Moderna and Pfizer COVID-19 vaccines. Females appeared to have a higher case report frequency for top adverse events compared to males. Using the Ontology of Adverse Event (OAE), these 96 adverse events were classified to different categories such as behavioral and neurological AEs, cardiovascular AEs, female reproductive system AEs, and immune system AEs. Further statistical comparison between different ages, doses, and sexes was also performed for three notable AEs: myocarditis, GBS, and thrombosis. The Pfizer vaccine was found to have a closer association with myocarditis than the other two COVID-19 vaccines in VAERS, while the Janssen vaccine was more likely to be associated with thrombosis and GBS AEs. To support standard AE representation and study, we have also modeled and classified the newly identified thrombosis with thrombocytopenia syndrome (TTS) AE and its subclasses in the OAE by incorporating the Brighton Collaboration definition. Notably, severe COVID-19 vaccine AEs (including myocarditis, GBS, and TTS) rarely occur in comparison to the large number of COVID-19 vaccinations administered in the United States, affirming the overall safety of these COVID-19 vaccines.

Monkeypox in a Traveler Returning from Nigeria - Dallas, Texas, July 2021.

Monkeypox is a rare, sometimes life-threatening zoonotic infection that occurs in west and central Africa. It is caused by Monkeypox virus, an orthopoxvirus similar to Variola virus (the causative agent of smallpox) and Vaccinia virus (the live virus component of orthopoxvirus vaccines) and can spread to humans. After 39 years without detection of human disease in Nigeria, an outbreak involving 118 confirmed cases was identified during 2017-2018 (1); sporadic cases continue to occur. During September 2018-May 2021, six unrelated persons traveling from Nigeria received diagnoses of monkeypox in non-African countries: four in the United Kingdom and one each in Israel and Singapore. In July 2021, a man who traveled from Lagos, Nigeria, to Dallas, Texas, became the seventh traveler to a non-African country with diagnosed monkeypox. Among 194 monitored contacts, 144 (74%) were flight contacts. The patient received tecovirimat, an antiviral for treatment of orthopoxvirus infections, and his home required large-scale decontamination. Whole genome sequencing showed that the virus was consistent with a strain of Monkeypox virus known to circulate in Nigeria, but the specific source of the patient's infection was not identified. No epidemiologically linked cases were reported in Nigeria; no contact received postexposure prophylaxis (PEP) with the orthopoxvirus vaccine ACAM2000.

Changes of Small Non-coding RNAs by Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

The ongoing pandemic of coronavirus disease 2019 (COVID-19), which results from the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a significant global public health threat, with molecular mechanisms underlying its pathogenesis largely unknown. In the context of viral infections, small non-coding RNAs (sncRNAs) are known to play important roles in regulating the host responses, viral replication, and host-virus interaction. Compared with other subfamilies of sncRNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), tRNA-derived RNA fragments (tRFs) are relatively new and emerge as a significant regulator of host-virus interactions. Using T4 PNK-RNA-seq, a modified next-generation sequencing (NGS), we found that sncRNA profiles in human nasopharyngeal swabs (NPS) samples are significantly impacted by SARS-CoV-2. Among impacted sncRNAs, tRFs are the most significantly affected and most of them are derived from the 5'-end of tRNAs (tRF5). Such a change was also observed in SARS-CoV-2-infected airway epithelial cells. In addition to host-derived ncRNAs, we also identified several small virus-derived ncRNAs (svRNAs), among which a svRNA derived from CoV2 genomic site 346 to 382 (sv-CoV2-346) has the highest expression. The induction of both tRFs and sv-CoV2-346 has not been reported previously, as the lack of the 3'-OH ends of these sncRNAs prevents them to be detected by routine NGS. In summary, our studies demonstrated the involvement of tRFs in COVID-19 and revealed new CoV2 svRNAs.

Development and Pilot Test of a Culturally Relevant Toolkit to Enhance Advance Care Planning With Chinese American Patients.

BACKGROUND: First-generation Chinese American patients have low engagement in advance care planning (ACP). Among the causes may be clinician uncertainty about traditional cultural values. AIM: Based on a survey identifying barriers to ACP among older ethnic Chinese American patients, we created a toolkit to support clinicians in culturally relevant ACP practices and conducted a pilot test to evaluate usability, acceptability, and preliminary outcomes. DESIGN/SETTING/PARTICIPANTS: The toolkit includes culturally relevant information and an ACP guideline with a prompt list of questions. Six clinicians (three physicians, two nurse practitioners, and one physician assistant) in two New York City-based practices piloted the toolkit through discussions with 66 patients. RESULTS: Patients' age averaged 70.2 years (SD=12.4); 56.1% were women. Almost two-thirds had not finished high school and 53.0% spoke only Cantonese. More than three-quarters (78.8%) did not understand the purpose of ACP before the discussion. During the discussion, 58 patients (87.9%) completed a new proxy naming a health care agent, 21 (31.8%) requested a nonhospital DNR order, and two (3%) completed a living will. Topics discussed included treatment preferences (discussed with 80.3% of patients); health care values (77.3%); treatment decisions (72.7%); goals of care (68.2%), and hospice (1.5%). Five of the six clinicians expressed satisfaction ("very" or "somewhat") with the toolkit, four were "very" comfortable using it, and three stated that it helped them "a lot" with effective discussions. CONCLUSIONS: An ACP toolkit may facilitate culturally relevant ACP discussions by increasing clinician competency and patient engagement. Further studies of this approach are needed.

Endothelial Nitric Oxide Synthase Knockdown in Human Stem Cells Impacts Mitochondrial Biogenesis and Adipogenesis: Live-Cell Real-Time Fluorescence Imaging.

We carried out live-cell real-time fluorescence imaging to follow the effects of genetic (siRNA) knockdown (KD) of endothelial nitric oxide synthase (eNOS) on mitochondrial biogenesis and adipogenesis in human mesenchymal stem cells (hMSCs). We report here that eNOS KD in hMSCs blocks mitochondrial biogenesis and adipogenesis. The transfer of mitochondria from normal hMSCs to eNOS-deficient hMSCs restores adipogenesis. Furthermore, cell-free mitochondria purified from normal hMSCs also restores adipogenesis in eNOS-deficient cells. Thus, eNOS and NO signaling are essential for mitochondrial biogenesis, and mitochondrial activity is indispensable for adipogenesis in hMSC differentiation. We mapped the path and identified the mechanisms of mitochondrial transfer. We captured real-time images of differentiated mature adipocytes in mitosis and replication. These results reveal that human stem cell-differentiated fat cells are capable of replication. This new finding offers novel insights into our understanding of fat cell expansion and the development of obesity. Real-time imaging in live cells allows synchronized investigation of mitochondrial biogenesis and adipogenesis in stem cell differentiation without reducing living cells to nonliving samples for functional analysis. Live-cell real-time imaging can thus be a faithful and immediate tool for molecular diagnostic medicine. Furthermore, our results suggest that mitochondrial remodeling can be a useful approach in treating adiposity, diabetes, and abnormalities in energy metabolism and vascular signaling.

Cov19VaxKB: A Web-based Integrative COVID-19 Vaccine Knowledge Base.

The development of SARS-CoV-2 vaccines during the COVID-19 pandemic has prompted the emergence of COVID-19 vaccine data. Timely access to COVID-19 vaccine information is crucial to researchers and public. To support more comprehensive annotation, integration, and analysis of COVID-19 vaccine information, we have developed Cov19VaxKB, a knowledge-focused COVID-19 vaccine database (http://www.violinet.org/cov19vaxkb/). Cov19VaxKB features comprehensive lists of COVID-19 vaccines, vaccine formulations, clinical trials, publications, news articles, and vaccine adverse event case reports. A web-based query interface enables comparison of product information and host responses among various vaccines. The knowledge base also includes a vaccine design tool for predicting vaccine targets and a statistical analysis tool that identifies enriched adverse events for FDA-authorized COVID-19 vaccines based on VAERS case report data. To support data exchange, Cov19VaxKB is synchronized with Vaccine Ontology and the Vaccine Investigation and Online Information Network (VIOLIN) database. The data integration and analytical features of Cov19VaxKB can facilitate vaccine research and development while also serving as a useful reference for the public.

Changes of small non-coding RNAs by severe acute respiratory syndrome coronavirus 2 infection.

The ongoing pandemic of coronavirus disease 2019 (COVID-19), which results from the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a significant global public health threat, with molecular mechanisms underlying its pathogenesis largely unknown. Small non-coding RNAs (sncRNAs) are known to play important roles in almost all biological processes. In the context of viral infections, sncRNAs have been shown to regulate the host responses, viral replication, and host-virus interaction. Compared with other subfamilies of sncRNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), tRNA-derived RNA fragments (tRFs) are relatively new and emerge as a significant regulator of host-virus interactions. Using T4 PNK-RNA-seq, a modified next-generation sequencing (NGS), we recently found that nasopharyngeal swabs (NPS) samples from SARS-CoV-2 positive and negative subjects show a significant difference in sncRNA profiles. There are about 166 SARS-CoV-2-impacted sncRNAs. Among them, tRFs are the most significantly affected and almost all impacted tRFs are derived from the 5'-end of tRNAs (tRF5). Using a modified qRT-PCR, which was recently developed to specifically quantify tRF5s by isolating the tRF signals from its corresponding parent tRNA signals, we validated that tRF5s derived from tRNA GluCTC (tRF5-GluCTC), LysCTT (tRF5-LysCTT), ValCAC (tRF5-ValCAC), CysGCA (tRF5-CysGCA) and GlnCTG (tRF5-GlnCTG) are enhanced in NPS samples of SARS-CoV2 patients and SARS-CoV2-infected airway epithelial cells. In addition to host-derived ncRNAs, we also identified several sncRNAs derived from the virus (svRNAs), among which a svRNA derived from CoV2 genomic site 346 to 382 (sv-CoV2-346) has the highest expression. The induction of both tRFs and sv-CoV2-346 has not been reported previously, as the lack of the 3'-OH ends of these sncRNAs prevents them to be detected by routine NGS. In summary, our studies demonstrated the involvement of tRFs in COVID-19 and revealed new CoV2 svRNAs.

Tibial tray rotation and posterior slope increase risk for outliers in coronal alignment.

AIMS: The extensive variation in axial rotation of tibial components can lead to coronal plane malalignment. We analyzed the change in coronal alignment induced by tray malrotation. METHODS: We constructed a computer model of knee arthroplasty and used a virtual cutting guide to cut the tibia at 90° to the coronal plane. The virtual guide was rotated axially (15° medial to 15° lateral) and with posterior slopes (0° to 7°). To assess the effect of axial malrotation, we measured the coronal plane alignment of a tibial tray that was axially rotated (25° internal to 15° external), as viewed on a standard anteroposterior (AP) radiograph. RESULTS: Axial rotation of the cutting guide induced a varus-valgus malalignment up to 1.8° (for 15° of axial rotation combined with 7° of posterior slope). Axial malrotation of tibial tray induced a substantially higher risk of coronal plane malalignment ranging from 1.9° valgus with 15° external rotation, to over 3° varus with 25° of internal rotation. Coronal alignment of the tibial cut changed by 0.07° per degree of axial rotation and 0.22° per degree of posterior slope (linear regression, R2 > 0.99). CONCLUSION: While the effect of axial malalignment has been studied, the impact on coronal alignment is not known. Our results indicate that the direction of the cutting guide and malalignment in axial rotation alter coronal plane alignment and can increase the incidence of outliers. Cite this article: Bone Joint J 2020;102-B(6 Supple A):43-48.

Attitudes and Beliefs Toward Advance Care Planning Among Underserved Chinese-American Immigrants.

CONTEXT: Many in the rapidly growing Chinese-American population are non-English-speaking and medically underserved, and few engage in advance care planning (ACP). Evaluating culturally-determined factors that may inhibit ACP can inform programs designed to increase ACP engagement. OBJECTIVES: To describe attitudes and beliefs concerning ACP in older, non-English-speaking Chinese Americans in a medically-underserved urban region. METHODS: Patients were consecutively recruited from a primary care practice in New York City to participate in a cross-sectional survey. Attitudes and beliefs were measured using an ACP Survey Tool and the validated Traditional Chinese Death Beliefs measure. Exploratory analyses evaluated associations between these two measures and between each measure and sociodemographics, primary dialect, acculturation (using the Suinn-Lew Asian Self Identity Acculturation Scale), and health status (using the Short Form-8 Health Survey). RESULTS: Patients (n = 179) were 68.2 years on average; 55.9% were women, and 81.0% were non-English speaking (42.8% Cantonese, 15.2% Mandarin, 19.3% Toisanese, and 19.3% Fuzhounese). Most had low acculturation (mean 1.7/5.0) and highly-rated physical and mental health (mean 70.1/100 and 81.5/100, respectively). Few patients (15.1%) had an advance directive and 56.8% were unfamiliar with any type; 74.4% were willing to complete one in the future. Thirty-two percent "agreed" that "talking about death in the presence of a dying person would accelerate death". The analyses revealed no significant associations. CONCLUSION: These Chinese-American older adults had low acculturation and very limited knowledge of, or engagement in, ACP. Factors that may predict culturally-determined attitudes and beliefs about ACP were not identified. Further research can inform efforts to improve ACP engagement in this population.

Self-Reported Metal Allergy and Early Outcomes After Total Knee Arthroplasty.

The impact of self-reported metal allergy (SRMA) in total knee arthroplasty (TKA) remains controversial. In the absence of objective tests, SRMA is often used as a screening tool for implant selection. The objective of this study was to determine the effect of SRMA on early outcomes after TKA. Between 2010 and 2014, 168 patients with SRMA underwent TKA; 150 (89%) received nickel-free implants, and 18 (11%) received cobalt-chrome implants that contained nickel. Mean age was 67 years, and 95% were female. A cohort of 858 TKA patients (mean age, 68 years) without SRMA matched by sex served as the control group. Outcomes included Knee Society Score (function [KSS-F] and knee [KSS-K]), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, knee flexion, further surgery, and complications. No differences were seen in KSS-F and KSS-K between patients with and without SRMA. The mean WOMAC pain scores were 89.1 for patients with SRMA and 85.2 for patients without SRMA (P=.030). Stiffness and physical function scores were similar. Knee flexion was similar. No differences were found between nickel-free and cobalt-chrome SRMA groups. Patients with SRMA and those without demonstrated similar early functional outcomes. Patients with SRMA who received standard cobalt-chrome implants had no significant difference in functional outcomes compared with patients with nickel-free implants. Better identifiers of patients at risk for adverse events due to implant material are needed. [Orthopedics. 2019; 42(6):330-334.].

RAVAN: CubeSat Demonstration for Multi-Point Earth Radiation Budget Measurements.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) 3U CubeSat mission is a pathfinder to demonstrate technologies for the measurement of Earth's radiation budget, the quantification of which is critical for predicting the future course of climate change. A specific motivation is the need for lower-cost technology alternatives that could be used for multi-point constellation measurements of Earth outgoing radiation. RAVAN launched 11 November 2016, into a nearly 600-km, Sun-synchronous orbit, and collected data for over 20 months. RAVAN successfully demonstrates two key technologies. The first is the use of vertically aligned carbon nanotubes (VACNTs) as absorbers in broadband radiometers for measuring Earth's outgoing radiation and the total solar irradiance. VACNT forests are arguably the blackest material known and have an extremely flat spectral response over a wide wavelength range, from the ultraviolet to the far infrared. As radiometer absorbers, they have greater sensitivity for a given time constant and are more compact than traditional cavity absorbers. The second technology demonstrated is a pair of gallium phase-change black body cells that are used as a stable reference to monitor the degradation of RAVAN's radiometer sensors on orbit. Four radiometers (two VACNT, two cavity), the pair of gallium black bodies, and associated electronics are accommodated in the payload of an agile 3U CubeSat bus that allows for routine solar and deep-space attitude maneuvers, which are essential for calibrating the Earth irradiance measurements. The radiometers show excellent long-term stability over the course of the mission and a high correlation between the VACNT and cavity radiometer technologies. Short-term variability-at greater than the tenths-of-a-Watt/m2 needed for climate accuracy-is a challenge that remains, consistent with insufficient thermal knowledge and control on a 3U CubeSat. There are also VACNT-cavity biases of 3% and 6% in the Total and SW channels, respectively, which would have to be overcome in a future mission. Although one of the black bodies failed after four months, the other provided a repeatable standard for the duration of the project. We present representative measurements from the mission and demonstrate how the radiometer time series can be used to reconstruct outgoing radiation spatial information. Improvements to the technology and approach that would lead to better performance and greater accuracy in future missions are discussed.

Oral Opioids Are Overprescribed in the Opiate-Naive Patient Undergoing Total Joint Arthroplasty.

INTRODUCTION: The opioid epidemic in the United States continues to escalate and contribute to potentially preventable deaths. Because many opioid addictions begin with prescription medication, focus on limiting exposure and decreasing availability are essential. This study identifies the average number of opioid pills consumed following primary total knee and hip arthroplasty (TKA and THA) at our institution in opiate-naive patients to provide an estimate of medication required. We hypothesized that the average number of pills consumed for both TKA and THA was significantly less than the amount prescribed at discharge. METHODS: We prospectively evaluated 99 consecutive patients undergoing primary TKA (51) and THA (48). Patient characteristics and opioid prescription information were pulled from review of medical records. Patients brought remaining pain medications to their first follow-up visit (30 days). We calculated the number of pills consumed. Pill consumption was converted into opioid morphine equivalents. Current pain level and the need for pain medication refill were assessed. RESULTS: Median number of pills prescribed over 30 days was 90 for both TKA and THA. Median number of pain pills consumed was 67 in TKA patients and 37 in THA patients (P < 0.001). Higher oral morphine equivalent consumption was seen in TKA patients compared with THA patients. Mean pain scores of TKA and THA patients were 3.2 and 1.8, respectively (P = 0.002). Also, TKA patients were 5 times more likely to require a refill (P = 0.006) compared with THA patients. DISCUSSION: Pain medication was significantly overprescribed by more than 34% in TKA and 140% in THA. Prescribing practices of narcotic pain medications following total joint arthroplasty result in significantly excess amount of opioids available for potential abuse.

Standardized Opioid Prescription Protocol Reduces Opioid Consumption After Total Joint Arthroplasty.

Previous studies demonstrate routine overprescription of pain medications after total joint arthroplasty (TJA). A standardized reduced opioid prescription protocol for TJA was initiated at our institution, which we hypothesized would lead to a reduction in opioid consumption compared with patients who had surgery before initiation of the new protocol. METHODS: We evaluated 97 consecutive opioid-naive patients undergoing primary total knee arthroplasty (TKA) and total hip arthroplasty (THA) using a standardized opioid prescription protocol (standardized group). A control subject group consisted of 99 patients undergoing TKA and THA just before the adaptation of the standardized prescribing protocol (historic group). Postoperatively, patients brought their remaining pain medication to their 1-month follow-up visit. The number of pills consumed was counted and converted into oral morphine equivalents (OME). Current pain level and the need for pain medication refill was assessed. RESULTS: Among TKA patients, mean opioid consumption in the standardized group (48.5 pills; 432 OME) was markedly less than the historic group (76.2 pills; 903 OME) (both P < 0.01). Refills were required in 50% of the standardized group and 29% of the historic group (P = 0.038). Average pain scores for the standardized and historic groups were 2.3 and 3.2, respectively (P = 0.057). Among THA patients, mean opioid consumption in the standardized group (19.1 pills; 200 OME) was markedly less than the historic group (41.3 pills; 504 OME) (both P < 0.01). Refills were required in 16% of the standardized group and 8% of the historic group (P = 0.263). Average pain scores for the standardized and historic groups were 1.7 and 1.8, respectively (P = 0.608). DISCUSSION: Initiation of a standardized opioid prescribing protocol after TJA for opioid-naive patients led to a reduction in opioid consumption, but resulted in an increased need for refills.

Complete Talar Extrusion Treated With an Antibiotic Cement Spacer and Staged Femoral Head Allograft.

Complete talar extrusion is rare and usually associated with a high-energy mechanism of injury causing complete dissociation of the talus from the surrounding bony and soft-tissue structures with enough force to expel the talus out of the body. Treatment can be complicated by infection, osteonecrosis, posttraumatic osteoarthritis, and leg length discrepancy, which may require multiple subsequent surgeries for improved outcome and quality of life. Reimplantation of the native talus affords maintenance of joint height and favorable outcomes have been reported. Failed reimplantations have been successfully managed with arthrodesis with or without a bone allograft. We report a case of talar extrusion initially treated with a talus-shaped impregnated antibiotic spacer, followed by femoral head allograft and tibiocalcaneal fusion. This treatment resulted in radiographic evidence of bony fusion at 12 weeks without subsequent infection and good clinical outcome at 2-year follow-up.

Efficacy of Intravenous Acetaminophen for Postoperative Analgesia in Primary Total Knee Arthroplasty.

BACKGROUND: The use of intravenous acetaminophen has seen recent enthusiasm as one component of a multimodal approach to pain management. However, there is a lack of literature examining the efficacy of intravenous acetaminophen for pain control in total joint arthroplasty. The purpose of this study was to evaluate the efficacy of intravenous acetaminophen following primary total knee arthroplasty. METHODS: This is a retrospective review of 38 patients undergoing primary total knee arthroplasty by a single surgeon at one institution. Twenty-five patients received 1 gram of intravenous acetaminophen every 6 hours for 24 hours postoperatively. Thirteen patients received no additional intervention. Exclusion criteria were bilateral or concomitant procedures, allergy to medications included in the standard postoperative protocol, neuropathy or sensory disturbances, history of opioid dependence or abuse, deviations from protocol, revision procedures, and incomplete data. Primary outcomes were change in patient-reported visual analog scale (VAS) pain score, overall opioid consumption measured in morphine milligram equivalents, and hospital length of stay. RESULTS: We found no difference in length of stay, at 3.3 days in the control group and 2.9 days in the intervention group. There was a significant difference in VAS score between 16 and 24 hours. There was a statistically significant decrease in overall opioid consumption in the intravenous acetaminophen group 37.6 vs 18.6 morphine milligram equivalents. CONCLUSION: Intravenous acetaminophen is effective in significantly reducing opioid requirements in the first 24 hours following primary total knee arthroplasty. Additionally, there is a clinically significant decrease in VAS pain scores in patients receiving this intervention.

Effects of a Tobacco-Free Work Site Policy on Employee Tobacco Attitudes and Behaviors, Travis County, Texas, 2010-2012.

BACKGROUND: The adoption of tobacco-free policies in behavioral health settings is an important step in reducing staff tobacco use as well as the high rates of tobacco use among people with mental illness and behavioral disorders. Studies have demonstrated the importance of staff support when implementing tobacco-free workplace policies, but there is limited research examining tobacco use prevalence among staff and staff attitude before and after policy adoption. COMMUNITY CONTEXT: Integral Care, a local authority for behavioral health and developmental disabilities in Austin, Texas, and Austin Public Health embarked on a comprehensive planning process before implementing a 100% tobacco-free campus policy. The objectives were 1) assess staff tobacco use and attitudes toward a tobacco-free policy, 2) communicate policy to staff, 3) provide staff education and training, and 4) provide cessation resources. METHODS: Integral Care and Austin Public Health conducted a web-based employee survey 6 months before and 6 and 12 months after implementation of the policy to measure tobacco use prevalence and attitudes among employees. OUTCOME: Employees had significant improvements in tobacco use prevalence and attitudes toward the tobacco-free policy from pre-implementation to post-implementation. Tobacco use prevalence among staff decreased from 27.6% to 13.8%, and support for the policy increased from 60.6% to 80.3% at 12 months post-implementation. INTERPRETATION: Adoption of 100% tobacco-free campus policies in behavioral health settings can result in significant reductions in staff tobacco use. Leadership should provide staff with education, training, and cessation support before adoption of tobacco-free work site policies to ensure success.