The purpose of this study was to evaluate the effects of different quantities of prescribed opioid tablets on patient opioid utilization, postoperative pain and function, and satisfaction after ...anterior cruciate ligament reconstruction (ACLR).
This was a prospective, randomized trial enrolling patients undergoing primary ACLR. Patients were assigned to 1 of 3 prescription groups: 15, 25, or 35 tablets containing 5-mg oxycodone. Patients completed visual analog scale (VAS) pain and medication logs, opioid medication satisfaction surveys, and International Knee Documentation Committee (IKDC) questionnaires postoperatively.
Among the 180 patients included in the analysis, there was no significant difference in VAS pain scores (p > 0.05), IKDC scores (p > 0.05), morphine milligram equivalents (MMEs) (p = 0.510) consumed, or patient satisfaction with regard to pain control (p = 0.376) between treatment groups. Seventy-two percent of opioids were consumed in the first 3 days postoperatively, and 83% of patients in the 15-tablet cohort felt that they received the "right amount" of or even "too many" opioids.
The prescription of 15 opioid tablets resulted in equivalent pain control, patient satisfaction, and short-term functional outcomes as prescriptions of 25 or 35 opioid tablets after ACLR. Lower prescription quantities of opioid medication may provide equivalent postoperative pain and help to minimize the number of unused opioid doses at risk for possible diversion after ACLR.
Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.
Abstract
Background
Multidrug-resistant organisms (MDROs) spread between hospitals, nursing homes (NHs), and long-term acute care facilities (LTACs) via patient transfers. The Shared Healthcare ...Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County is a regional public health collaborative involving decolonization at 38 healthcare facilities selected based on their high degree of patient sharing. We report baseline MDRO prevalence in 21 NHs/LTACs.
Methods
A random sample of 50 adults for 21 NHs/LTACs (18 NHs, 3 LTACs) were screened for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum β-lactamase–producing organisms (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE) using nares, skin (axilla/groin), and peri-rectal swabs. Facility and resident characteristics associated with MDRO carriage were assessed using multivariable models clustering by person and facility.
Results
Prevalence of MDROs was 65% in NHs and 80% in LTACs. The most common MDROs in NHs were MRSA (42%) and ESBL (34%); in LTACs they were VRE (55%) and ESBL (38%). CRE prevalence was higher in facilities that manage ventilated LTAC patients and NH residents (8% vs <1%, P < .001). MDRO status was known for 18% of NH residents and 49% of LTAC patients. MDRO-colonized adults commonly harbored additional MDROs (54% MDRO+ NH residents and 62% MDRO+ LTACs patients). History of MRSA (odds ratio OR = 1.7; confidence interval CI: 1.2, 2.4; P = .004), VRE (OR = 2.1; CI: 1.2, 3.8; P = .01), ESBL (OR = 1.6; CI: 1.1, 2.3; P = .03), and diabetes (OR = 1.3; CI: 1.0, 1.7; P = .03) were associated with any MDRO carriage.
Conclusions
The majority of NH residents and LTAC patients harbor MDROs. MDRO status is frequently unknown to the facility. The high MDRO prevalence highlights the need for prevention efforts in NHs/LTACs as part of regional efforts to control MDRO spread.
Multidrug-resistant organism (MDRO) colonization prevalence was 67% in nursing homes and long-term acute care facilities in a large-scale, randomized point-prevalence study. These data raise questions about allocation of infection control and antimicrobial stewardship resources. The Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County collaborative will measure regional impacts of a coordinated infection prevention initiative on MDRO carriage and infection.
The ability to perform motor actions depends, in part, on the brain’s initial state. We hypothesized that initial state dependence is a more general principle and applies to cognitive control. To ...test this idea, we examined human single units recorded from the dorsolateral prefrontal (dlPFC) cortex and dorsal anterior cingulate cortex (dACC) during a task that interleaves motor and perceptual conflict trials, the multisource interference task (MSIT). In both brain regions, variability in pre-trial firing rates predicted subsequent reaction time (RT) on conflict trials. In dlPFC, ensemble firing rate patterns suggested the existence of domain-specific initial states, while in dACC, firing patterns were more consistent with a domain-general initial state. The deployment of shared and independent factors that we observe for conflict resolution may allow for flexible and fast responses mediated by cognitive initial states. These results also support hypotheses that place dACC hierarchically earlier than dlPFC in proactive control.
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•dlPFC and dACC human neuron “initial state” firing patterns predicted response times•A domain-general initial state collapsed across conflict responses in dACC•In dlPFC, the initial state comprised domain-specific components•The dlPFC domain-specific components were oriented orthogonally
Biological sciences; Neuroscience; Systems neuroscience; Cognitive neuroscience
Environmental contamination is suspected to play an important role in Candida auris transmission. Understanding speed and risks of contamination after room disinfection could inform environmental ...cleaning recommendations.
We conducted a prospective multicenter study of environmental contamination associated with C. auris colonization at 6 ventilator-capable skilled nursing facilities and 1 acute care hospital in Illinois and California. Known C. auris carriers were sampled at 5 body sites followed by sampling of nearby room surfaces before disinfection and at 0, 4, 8, and 12 hours after disinfection. Samples were cultured for C. auris and bacterial multidrug-resistant organisms (MDROs). Odds of surface contamination after disinfection were analyzed using multilevel generalized estimating equations.
Among 41 known C. auris carriers, colonization was detected most frequently on palms/fingertips (76%) and nares (71%). C. auris contamination was detected on 32.2% (66/205) of room surfaces before disinfection and 20.5% (39/190) of room surfaces by 4 hours after disinfection. A higher number of C. auris-colonized body sites was associated with higher odds of environmental contamination at every time point following disinfection, adjusting for facility of residence. In the rooms of 38 (93%) C. auris carriers co-colonized with a bacterial MDRO, 2%-24% of surfaces were additionally contaminated with the same MDRO by 4 hours after disinfection.
C. auris can contaminate the healthcare environment rapidly after disinfection, highlighting the challenges associated with environmental disinfection. Future research should investigate long-acting disinfectants, antimicrobial surfaces, and more effective patient skin antisepsis to reduce the environmental reservoir of C. auris and bacterial MDROs in healthcare settings.
Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin (HTT) gene. Consequently, the mutant ...protein is ubiquitously expressed and drives pathogenesis of HD through a toxic gain-of-function mechanism. Animal models of HD have demonstrated that reducing huntingtin (HTT) protein levels alleviates motor and neuropathological abnormalities. Investigational drugs aim to reduce HTT levels by repressing HTT transcription, stability or translation. These drugs require invasive procedures to reach the central nervous system (CNS) and do not achieve broad CNS distribution. Here, we describe the identification of orally bioavailable small molecules with broad distribution throughout the CNS, which lower HTT expression consistently throughout the CNS and periphery through selective modulation of pre-messenger RNA splicing. These compounds act by promoting the inclusion of a pseudoexon containing a premature termination codon (stop-codon psiExon), leading to HTT mRNA degradation and reduction of HTT levels.
As the need for novel antibiotic classes to combat bacterial drug resistance increases, the paucity of leads resulting from target-based antibacterial screening of pharmaceutical compound libraries ...is of major concern. One explanation for this lack of success is that antibacterial screening efforts have not leveraged the eukaryotic bias resulting from more extensive chemistry efforts targeting eukaryotic gene families such as G protein-coupled receptors and protein kinases. Consistent with a focus on antibacterial target space resembling these eukaryotic targets, we used whole-cell screening to identify a series of antibacterial pyridopyrimidines derived from a protein kinase inhibitor pharmacophore. In bacteria, the pyridopyrimidines target the ATP-binding site of biotin carboxylase (BC), which catalyzes the first enzymatic step of fatty acid biosynthesis. These inhibitors are effective in vitro and in vivo against fastidious Gram-negative pathogens including Haemophilus influenzae. Although the BC active site has architectural similarity to those of eukaryotic protein kinases, inhibitor binding to the BC ATP-binding site is distinct from the protein kinase-binding mode, such that the inhibitors are selective for bacterial BC. In summary, we have discovered a promising class of potent antibacterials with a previously undescribed mechanism of action. In consideration of the eukaryotic bias of pharmaceutical libraries, our findings also suggest that pursuit of a novel inhibitor leads for antibacterial targets with active-site structural similarity to known human targets will likely be more fruitful than the traditional focus on unique bacterial target space, particularly when structure-based and computational methodologies are applied to ensure bacterial selectivity.
Copaxone is an efficacious and safe therapy that has demonstrated clinical benefit for over two decades in patients with relapsing forms of multiple sclerosis (MS). On an individual level, patients ...show variability in their response to Copaxone, with some achieving significantly higher response levels. The involvement of genes (e.g., HLA-DRB1*1501) with high inter-individual variability in Copaxone's mechanism of action (MoA) suggests the potential contribution of genetics to treatment response. This study aimed to identify genetic variants associated with Copaxone response in patient cohorts from late-phase clinical trials.
Single nucleotide polymorphisms (SNPs) associated with high and low levels of response to Copaxone were identified using genome-wide SNP data in a discovery cohort of 580 patients from two phase III clinical trials of Copaxone. Multivariable Bayesian modeling on the resulting SNPs in an expanded discovery cohort with 1171 patients identified a multi-SNP signature of Copaxone response. This signature was examined in 941 Copaxone-treated MS patients from seven independent late-phase trials of Copaxone and assessed for specificity to Copaxone in 310 Avonex-treated and 311 placebo-treated patients, also from late-phase trials.
A four-SNP signature consisting of rs80191572 (in UVRAG), rs28724893 (in HLA-DQB2), rs1789084 (in MBP), and rs139890339 (in ZAK(CDCA7)) was identified as significantly associated with Copaxone response. Copaxone-treated signature-positive patients had a greater reduction in annualized relapse rate (ARR) compared to signature-negative patients in both discovery and independent cohorts, an effect not observed in Avonex-treated patients. Additionally, signature-positive placebo-treated cohorts did not show a reduction in ARR, demonstrating the predictive as opposed to prognostic nature of the signature. A 10% subset of patients, delineated by the signature, showed marked improvements across multiple clinical parameters, including ARR, MRI measures, and higher proportion with no evidence of disease activity (NEDA).
This study is the largest pharmacogenetic study in MS reported to date. Gene regions underlying the four-SNP signature have been linked with pathways associated with either Copaxone's MoA or the pathophysiology of MS. The pronounced association of the four-SNP signature with clinical improvements in a ~10% subset of the MS patient population demonstrates the complex interplay of immune mechanisms and the individualized nature of response to Copaxone.
Police shooting decisions have come under increasing scrutiny, and public understanding of those decisions is correspondingly important. Recent research demonstrated that profanity on the part of an ...officer in an OIS may strongly influence public assessment of police performance, even when that profanity was completely unrelated to police performance in the OIS per se; this demonstrated the importance of contextual factors, not directly related to the tactical reality of the OIS, to public judgment of the given incident. The present research extended these results into additional contextual areas. Using paragraphs describing an officer-involved shooting (OIS), which varied in the presence or absence of a violent history on the part of the officer and/or suspect, judgments of police performance in OISs were evaluated with reference to a measure of respondents’ verbal skills. It was shown that the language in which guilt and performance were discussed mediated respondent judgment of officer performance with reference to violent or nonviolent history. No such effect was observed for suspect history. General verbal skills as indicated by vocabulary also influenced judgment of the given OIS, but this influence was also mediated by the language in which guilt or innocence was expressed. Results highlight the importance of language use and abilities in the judgment of conduct, guilt, and innocence in officer involved shootings.
Project Extension for Community Healthcare Outcomes (ECHO) utilizes telemedicine to connect a multidisciplinary team of experts with a -network of primary care physicians to enable rapid ...dissemination of evidence-based -guidelines and practices at scale. In this study, the Project ECHO model disseminated the Arizona Pain and Addiction Curriculum to providers in rural Arizona with the goal to educate providers on medication-assisted treatment (MAT).
Participants engaged in biweekly, virtual teleECHO sessions, and post-session surveys were used to collect data on provider satisfaction, self-efficacy, knowledge, barriers to change, and changes in practice behavior.
Between February 2020 and November 2020, the MAT-ECHO program hosted 20 teleECHO sessions (N = 20) with 255 unique participating providers and delivered 877 learning hours. Analysis of a 6-month post-ECHO survey (N = 13) demonstrated that teleECHO sessions had broad geographic outreach. Participants had an average of 12 years of experience, 38 percent held NP/PA professional degrees, and 54 percent practiced in opioid treatment program settings. Assessment of job satisfaction and well-being revealed overall improved satisfaction among the small cohort of nonwaivered respondents (N = 8), except for meeting patient's needs. MAT-waivered respondents reported no post-session changes.
Data from this study demonstrated that teleECHO sessions were well attended, consisted of a diverse cohort with various degrees, and had broad geographic outreach; hence, the utilization of the teleECHO model has the potential to reach rural providers and subsequently increase the availability and -efficacy of MAT in rural America.
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