Impact of a Virtual Game, 'Name That Band,' on Older People's and PharmD Students' Feelings of Social Isolation During COVID-19.

Background Prior to the COVID-19 pandemic, PharmD students at the University of Arizona (UArizona) had a long-standing relationship with the older people at St. Luke's Home, a local Eden Alternative assisted-living community. Hosting community engagement programs for assisted-living residents was challenging with COVID-19 precautions and older individuals suffering from social isolation and loneliness. Objective To determine the impact of playing a virtual game, 'Name That Band,' on older people's and PharmD students' feelings of social isolation during the COVID-19 pandemic. Methods Questionnaires were administered before and after a virtual game to residents at St. Luke's Home and PharmD students at UArizona. Participants were asked about their mood before COVID-19 and pre-and postgame, as well as their social interactions and feelings of loneliness using the Modified UCLA Three-Item Loneliness Scale, which assesses a composite score of lack of companionship, feelings of being left out, and isolation. Results Fifteen older people and 11 students participated in the game (N = 26). All participants completed the pregame survey and 25 completed the postgame survey. The older people reported fewer feelings of isolation and loneliness (measured by a reduction in UCLA Loneliness Scale score) postgame compared with pregame. The students reported a higher total UCLA Loneliness Scale score during the pandemic than prepandemic, but there was no difference in their scores postgame compared with pregame. More older people and students reported feeling 'happy' after playing the virtual game together compared with before the pandemic and before playing. The aspect of the activity that helped older people and students feel more socially engaged was playing a game. Conclusion A social intervention using a virtual game may be a tool that can be used to decrease feelings of isolation and increase engagement for older people residing in an assisted-living community.

Off-Label Reduced Dose Apixaban in Older Adults With Atrial Fibrillation and Associated Outcomes.

BACKGROUND: Apixaban is commonly used to prevent stroke in older adults with nonvalvular atrial fibrillation (AF). Although its package insert has specific dose reduction criteria, providers may dose reduce outside of these parameters based on clinical scenarios. OBJECTIVE: The primary objective was to determine the incidence of apixaban off-label reduced dosing, while secondarily determining the safety and efficacy outcomes associated with such dosing. METHODS: A retrospective analysis of patients aged 65 and older with orders for apixaban for AF was institutional review board (IRB)-approved and conducted across 3 academic medical centers. Patients receiving off-label reduced-dose apixaban (ie, "underdosed") were matched to a cohort of patients dosed according to the package insert at the standard dosing (5 mg twice daily) using stratified random sampling. Secondary outcomes included 1-year incidence of major bleeding, clinically relevant non-major bleeding (CRNMB), stroke or transient ischemic attack (TIA), and mortality. The Fisher exact tests were used to compare between-group differences. RESULTS: Of the 1172 patients meeting initial inclusion criteria, 201 (17%) were dosed off-label, with 175 (15%) "underdosed." The 147 "underdosed" patients with documented follow-up were matched with 139 patients receiving standard Food and Drug Administration (FDA)-labeled dosing. There were no significant differences in incidence of stroke (2.7% vs 2.2%), major bleeding (0% vs 0.7%), and CRNMB (2.7% vs 1.4%) in the off-label reduced dosing versus standard dosing groups. All-cause mortality was higher in the off-label reduced-dose group (16 [10.9%] vs 2 [1.4%], P < 0.05). CONCLUSION AND RELEVANCE: Older adults with nonvalvular AF are commonly prescribed lower-than-recommended doses of apixaban. However, no significant association was found between empiric off-label reduced dosing and stroke or bleeding outcomes.

Use of Melatonin and/on Ramelteon for the Treatment of Insomnia in Older Adults: A Systematic Review and Meta-Analysis.

To investigate the efficacy of melatonin and/or ramelteon reporting sleep outcomes for older adults with chronic insomnia, a systematic review and a meta-analysis of PubMed, EMBASE, Cochrane library, International Pharmaceutical Abstracts, PsycINFO, science citation index, center for reviews and dissemination, CINAHL, grey literature and relevant sleep journal searches were conducted from 1 January 1990 to 20 June 2021. Randomized controlled trials and other comparative studies with melatonin and/or ramelteon use among older patients with chronic insomnia were included. Funnel plot and Egger's test was used to determine publication bias. A forest plot was constructed to obtain a pooled standardized mean difference using either a fixed or random effects model for each of the two broad categories of sleep outcomes: objective and subjective. Of 5247 studies identified, 17 studies met the inclusion criteria for MA. Study sample size ranged from 10 to 829 with the mean age ≥55 years. There were significant improvements in total sleep time (objective), sleep latency and sleep quality (objective and subjective) for melatonin and/or ramelteon users compared with placebo. Sleep efficiency was not significantly different. The effects of these agents are modest but with limited safe treatment options for insomnia in older adults, these could be the drugs of choice.

Beyond the Basics of Athletic Hip Evaluation.

ABSTRACT: There is a growing trend in the world of orthopedics and sports medicine revolving around the nonarthritic hip. The incidence of hip arthroscopy has exponentially grown in the past decade and despite the importance of the recognition of these hip pathologies as contributors to pain and dysfunction, there is an ever-increasing rate of "failed" procedures emerging in the literature. The etiology of femoroacetabular impingement (FAI) syndrome and associated pathologies of the hip are now better understood. With this understanding there appears a tendency to point a finger at the hip joint without consideration for the involvement of the surrounding joints or extraarticular structures. Because of the nature of the morphological condition of FAI and the high incidence of a gradual progression of pain and impairments over time, as opposed to an acute injury, there is a need for a more robust assessment of the hip. The purpose of this commentary is to discuss the importance of a combined traditional orthopedic exam, imaging, and movement assessment in diagnosis and treatment recommendations in those with nonarthritic hip pain. It is our belief that this combined model can assist in identifying movement dysfunction that may lead to poor surgical outcomes and developing improved nonoperative or preoperative care pathways. LEVEL OF EVIDENCE: Level V.

Epstein-Barr Virus BGLF2 commandeers RISC to interfere with cellular miRNA function.

The Epstein-Barr virus (EBV) BGLF2 protein is a tegument protein with multiple effects on the cellular environment, including induction of SUMOylation of cellular proteins. Using affinity-purification coupled to mass-spectrometry, we identified the miRNA-Induced Silencing Complex (RISC), essential for miRNA function, as a top interactor of BGLF2. We confirmed BGLF2 interaction with the Ago2 and TNRC6 components of RISC in multiple cell lines and their co-localization in cytoplasmic bodies that also contain the stress granule marker G3BP1. In addition, BGLF2 expression led to the loss of processing bodies in multiple cell types, suggesting disruption of RISC function in mRNA regulation. Consistent with this observation, BGLF2 disrupted Ago2 association with multiple miRNAs. Using let-7 miRNAs as a model, we tested the hypothesis that BGLF2 interfered with the function of RISC in miRNA-mediated mRNA silencing. Using multiple reporter constructs with 3'UTRs containing let-7a regulated sites, we showed that BGLF2 inhibited let-7a miRNA activity dependent on these 3'UTRs, including those from SUMO transcripts which are known to be regulated by let-7 miRNAs. In keeping with these results, we showed that BGLF2 increased the cellular level of unconjugated SUMO proteins without affecting the level of SUMO transcripts. Such an increase in free SUMO is known to drive SUMOylation and would account for the effect of BGLF2 in inducing SUMOylation. We further showed that BGLF2 expression inhibited the loading of let-7 miRNAs into Ago2 proteins, and conversely, that lytic infection with EBV lacking BGLF2 resulted in increased interaction of let-7a and SUMO transcripts with Ago2, relative to WT EBV infection. Therefore, we have identified a novel role for BGLF2 as a miRNA regulator and shown that one outcome of this activity is the dysregulation of SUMO transcripts that leads to increased levels of free SUMO proteins and SUMOylation.

N-Acetylcysteine for Cardiac Protection During Coronary Artery Reperfusion: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Coronary artery reperfusion is essential for the management of symptoms in the patients with myocardial ischemia. However, the benefit of reperfusion often comes at an expense of paradoxical injury, which contributes to the adverse events, and sometimes heart failure. Reperfusion is known to increase the production of reactive oxygen species (ROS). We address whether N-acetylcysteine (NAC) reduces the ROS and alleviates reperfusion injury by improving the clinical outcomes. A literature search for the randomized controlled trials (RCTs) was carried out in the five biomedical databases for testing the effects of NAC in patients undergoing coronary artery reperfusion by percutaneous coronary intervention, thrombolysis, or coronary artery bypass graft. Of 787 publications reviewed, 28 RCTs were identified, with a summary of 2,174 patients. A meta-analysis using the random effects model indicated that NAC administration during or prior to the reperfusion procedures resulted in a trend toward a reduction in the level of serum cardiac troponin (cTn) [95% CI, standardized mean difference (SMD) -0.80 (-1.75; 0.15), p = 0.088, n = 262 for control, 277 for NAC group], and in the incidence of postoperative atrial fibrillation [95% CI, relative risk (RR) 0.57 (0.30; 1.06), p = 0.071, n = 484 for control, 490 for NAC group]. The left ventricular ejection fraction or the measures of length of stay in intensive care unit (ICU) or in hospital displayed a positive trend that was not statistically significant. Among the nine trials that measured ROS, seven showed a correlation between the reduction of lipid peroxidation and improved clinical outcomes. These lines of evidence support the potential benefit of NAC as an adjuvant therapy for cardiac protection against reperfusion injury.

Corticosteroid Tapering Regimens in Rheumatic Disease: A Systematic Review.

BACKGROUND/OBJECTIVE: Corticosteroids have long been used to effectively treat rheumatic disorders, but adverse effects associated with extended-duration regimens generate disagreement among clinicians regarding optimal tapering strategies. The objective of this systematic review was to assess clinical outcomes of differing tapering regimens after corticosteroid monotherapy in adults with rheumatic disorders. METHODS: A systematic review of Medline/PubMed, Embase, Cochrane, International Pharmaceutical Abstracts, Web of Science, Scopus, Global Index Medicus, American College of Rheumatology, gray literature, and reference lists up to June 27, 2018, was conducted by 2 authors. Randomized controlled trials, case-control studies, and prospective observational studies comparing at least 2 tapering strategies of medium- to high-dose (>7.5 mg but ≤100 mg oral prednisone equivalent daily), extended-duration (≥10 days) corticosteroids were included if they reported at least 1 efficacy and 1 adverse effect parameter. RESULTS: Two studies met criteria for the review, which included 62 patients. One study examined a prednisolone versus a modified release prednisone taper for giant cell arteritis and suggested 80% (n = 4) and 85.7% (n = 6) remission rates, respectively, at 26 weeks. The other study examined a methylprednisolone versus a prednisone taper for polymyalgia rheumatica and reported 100% and 89% remission rates, respectively, at 26 weeks. Adverse effects reported between the 2 studies included sleep, hyperglycemia, infection, and fractures. However, the studies were not powered to detect differences in these outcomes. CONCLUSIONS: There is no high-level evidence to guide tapering until discontinuation after extended courses of medium- to high-dose treatment regimens, as current guidelines rely heavily on expert opinion and small case series with a trial-and-error approach. This review supports the need for additional research to shift tapering recommendations to a more evidence-based practice.

Rivaroxaban Versus Warfarin for Stroke Prevention and Venous Thromboembolism Treatment in Extreme Obesity and High Body Weight.

Background: Limited clinical data exist describing the use of direct-acting oral anticoagulants (DOACs) in patients with body mass index (BMI) >40 kg/m2 or body weight >120 kg. Thus, DOAC therapy in this population remains controversial. Objectives: To investigate rivaroxaban as a safe and effective alternative to warfarin for venous thromboembolism (VTE) treatment and prevention of stroke in patients with atrial fibrillation identified as extremely obese or of high body weight. Methods: A retrospective chart review was performed at 2 academic medical centers in patients ≥18 years old and BMI >40 kg/m2 or weight >120 kg, newly initiated on warfarin or rivaroxaban for atrial fibrillation or VTE treatment. The primary end point was incidence of clinical failure, defined as VTE recurrence, stroke incidence, and mortality, within 12 months of initiation. Secondary end points included length of stay (LOS) and bleeding complications. Results: A total of 176 patients were included, with 84 and 92 patients in the rivaroxaban and warfarin arms, respectively. Clinical failure was lower in the rivaroxaban group but did not reach statistical significance when compared with warfarin (5% vs 13%; P = 0.06). LOS was significantly shorter in the rivaroxaban arm (2 days [1-3] vs 4 days [2-7], P < 0.0001). Percentage of bleeding complications was higher in the rivaroxaban arm but not statistically significant (8% vs 2%, P = 0.06). Conclusion and Relevance: Although not statistically significant, rivaroxaban trended toward a lower incidence of clinical failure while demonstrating a significantly shorter LOS when compared with warfarin for VTE treatment or atrial fibrillation in morbidly obese or high-body-weight patients.

Melatonin for the prevention of postoperative delirium in older adults: a systematic review and meta-analysis.

BACKGROUND: Older surgical patients are at high risk of developing postoperative delirium. Non-pharmacological strategies are recommended for delirium prevention, but no pharmacological agents have compelling evidence to decrease the incidence of delirium. The purpose of this study was to assess whether perioperative melatonin decreases the incidence of delirium in older adults undergoing surgical procedures. METHODS: A systematic search using PubMed/Medline, Embase, PsycINFO, CINAHL, and references of identified articles published in English between January 1990 and October 2017 was performed. Two independent reviewers screened titles and abstracts, and then extracted data following a full-text review of included articles with consensus generation and bias assessment. Studies reporting outcomes for melatonin or ramelteon use to prevent delirium in postoperative hospitalized patients (mean age ≥ 50 years) were eligible for inclusion. Data were pooled using a fixed-effects model to generate a forest plot and obtain a summary odds ratio for the outcome of interest (delirium incidence). Cochran's Q and I2 values were used to investigate heterogeneity. RESULTS: Of 335 records screened, 6 studies were selected for the qualitative analysis and 6 were included in the meta-analysis (n = 1155). The mean age of patients in included studies ranged from 59 to 84 years. Patients in intervention groups typically received melatonin or ramelteon at daily doses of two to eight milligrams around cardiothoracic, orthopedic, or hepatic surgeries for one to nine days, starting on the evening before or the day of surgery. The incidence of delirium ranged from 0 to 30% in the intervention groups versus 4-33% in the comparator groups, and was significantly reduced in the melatonin group, with a summary effect of the meta-analysis yielding an odds ratio of 0.63 (95% CI 0.46 to 0.87; 0.006; I2 = 72.1%). A one study removed analysis reduced overall odds ratio to 0.310 (95% CI 0.19 to 0.50), while reducing heterogeneity (Cochran's Q = 0.798, I2 = 0.000). CONCLUSION: Perioperative melatonin reduced the incidence of delirium in older adults in the included studies. While optimal dosing remains an unanswered question, the potential benefit of melatonin and melatonin receptor agonists may make them a reasonable option to use for delirium prevention in older adults undergoing surgical procedures.

Pharmacist-Led Drug Therapy Problem Management in an Interprofessional Geriatric Care Continuum: A Subset of the PIVOTS Group.

BACKGROUND: Drug therapy problems, which are adverse events involving medications that can ultimately interfere with a patient's therapeutic goals, occur frequently in older adults. If not identified, resolved, and prevented through clinical decision-making, drug therapy problems may negatively affect patient health outcomes. OBJECTIVE: To quantify the impact of pharmacist interventions on the care of older adults by identifying the most common drug therapy problems, the medications most often involved in these problems, and the actions taken by pharmacists to resolve these problems. METHODS: This retrospective chart review included individuals seen by a geriatric pharmacist in one geriatric practice, where 4 pharmacists provide continuous, comprehensive medication management across 2 outpatient geriatric clinics, skilled-nursing facilities, and assisted-living facilities. The individuals were seen between August 2014 and November 2015. For all patient care encounters during this time frame, pharmacists used the Assurance System to document each drug therapy problem, the medications involved, the patient's care setting (ie, outpatient clinic, assisted-living facility, skilled-nursing facility), the actions taken to resolve any drug therapy problems, and the estimated 90-day impact on the patient and the healthcare system. RESULTS: A total of 3100 drug therapy problems were identified during 3309 patient-pharmacist encounters for 452 patients (mean age, 81.4 years), 48.7% of whom were seen in the skilled-nursing facility. The most common drug therapy problem was dose too low, followed by dose too high, and warfarin was the most common drug associated with drug therapy problems. Pharmacists provided 4921 interventions, often more than 1 intervention per drug therapy problem, for 275 different medications. Laboratory monitoring and dose change were the most common interventions, with an estimated annual financial savings between $268,690 and $270,591. CONCLUSION: Older patients are a vulnerable patient population who often receive unsafe medication regimens, which can result in adverse drug reactions and other critical problems. When integrated into interprofessional geriatric care teams, pharmacists' interventions provide an invaluable qualitative and monetary resource to the medication-based management of patients with well-recognized, high-risk geriatric syndromes as they transition to and through various levels of care.

THE RELATIONSHIP BETWEEN SEGMENTAL ROLLING ABILITY AND LUMBAR MULTIFIDUS ACTIVATION TIME.

BACKGROUND: Segmental rolling has been utilized as an assessment and intervention tool to identify and affect dysfunction of the upper quarter, core, and lower quarter. One theory to explain dysfunctional segmental rolling is a lack of segmental spinal control / stabilization. Faulty muscle firing sequencing has been related to poor spinal stability, however to date, no assessment tool exists to evaluate a patient's motor coordination of local and global musculature. PURPOSE: The purpose of this study was to assess the temporal sequence of lumbar multifidus activation associated with anterior deltoid activation, and to determine if faulty sequencing was associated with the inability to segmentally roll in subjects without mobility restrictions. The authors hypothesized that in individuals who could not roll, a multifidus muscle onset latency relative to a prime mover activation would be present. In addition, a subset of the individuals with an inability to roll were utilized for a pilot study examining the ability to address the firing pattern with corrective exercise. METHODS: Twenty healthy subjects (13 females, 7 males), ages 19-25, participated in the study. Each subject underwent an upper and lower quarter screen and assessment of thoracic spine mobility. Subjects were excluded from the study if they had previous spine surgery, or were currently experiencing back pain. In addition, subjects who had any disease, disorders, or pathology that would hinder participation in segmental rolling or who had spinal movement contraindications were excluded. Since shoulder flexion is performed during the study, participants who had shoulder pathology or contraindications to upper extremity movement were excluded as well. Subjects with less than 50 degrees of trunk rotation were excluded from the study due to a possible physical mobility limitation that would prevent proficient segmental rolling. Included subjects were assessed on their ability to segmentally roll. Subjects who could complete the rolling task were placed in cohort A ("can roll"), and subjects who could not roll were placed in cohort B ("can't roll").Electromyographic (EMG) activity of the multifidus was recorded adjacent to the lamina of the L4 vertebrae using intramuscular fine-wire electrodes. EMG activity of the anterior deltoid was also recorded with a surface electrode during a single arm movement into shoulder flexion. While in a standing position, subjects were instructed to move their right upper arm into flexion as quickly as possible. Subjects flexed their shoulder to 90 degrees for three trials while muscle activity was recorded. Data were high-pass filtered at 30 Hz to remove baseline artifact, and the onset EMG times was selected as the point at which EMG increased two SD above baseline levels. Onset of the multifidus muscle was reported relative to that of the prime mover (anterior deltoid). Muscle onset latency was defined as the time difference between the onset of contraction of the multifidus and the anterior deltoid. RESULTS: Nine subjects were placed in cohort A, 11 subjects were placed in cohort B. The mean firing time of the lumbar multifidus for the cohort A was 16.67msec before the anterior deltoid, and the mean firing time of the lumbar multifidus for cohort B was 57.36msec after the anterior deltoid. There was a statistically significant difference (p<0.00) in the firing time between cohorts A and B. CONCLUSIONS: In subjects who could segmentally roll, the multifidus muscle activation always preceded that of the prime mover muscle activation. In subjects who could not segmentally roll, the results of this study confirm that there is a multifidus muscle onset latency relative to the activation of the anterior deltoid. The inability to segmentally roll may be related to faulty sequencing of lumbar multifidus firing.

Hepatic expression of serum amyloid A1 is induced by traumatic brain injury and modulated by telmisartan.

Traumatic brain injury affects the whole body in addition to the direct impact on the brain. The systemic response to trauma is associated with the hepatic acute-phase response. To further characterize this response, we performed controlled cortical impact injury on male mice and determined the expression of serum amyloid A1 (SAA1), an apolipoprotein, induced at the early stages of the acute-phase response in liver and plasma. After cortical impact injury, induction of SAA1 was detectable in plasma at 6 hours post-injury and in liver at 1 day post-injury, followed by gradual diminution over time. In the liver, cortical impact injury increased neutrophil and macrophage infiltration, apoptosis, and expression of mRNA encoding the chemokines CXCL1 and CXCL10. An increase in angiotensin II AT1 receptor mRNA at 3 days post-injury was also observed. Administration of the AT1 receptor antagonist telmisartan 1 hour post-injury significantly decreased liver SAA1 levels and CXCL10 mRNA expression, but did not affect CXCL1 expression or the number of apoptotic cells or infiltrating leukocytes. To our knowledge, this is the first study to demonstrate that SAA1 is induced in the liver after traumatic brain injury and that telmisartan prevents this response. Elucidating the molecular pathogenesis of the liver after brain injury will assist in understanding the efficacy of therapeutic approaches to brain injury.

LPS antagonism of TGF-ß signaling results in prolonged survival and activation of rat primary microglia.

Accumulating evidence indicates that activated microglia contribute to the neuropathology involved in many neurodegenerative diseases and after traumatic injury to the CNS. The cytokine transforming growth factor-beta 1 (TGF-ß1), a potent deactivator of microglia, should have the potential to reduce microglial-mediated neurodegeneration. It is therefore perplexing that high levels of TGF-ß1 are found in conditions where microglia are chronically activated. We hypothesized that TGF-ß1 signaling is suppressed in activated microglia. We therefore activated primary rat microglia with lipopolysaccharide (LPS) and determined the expression of proteins important to TGF-ß1 signaling. We found that LPS treatment decreased the expression of the TGF-ß receptors, TßR1 and TßR2, and reduced protein levels of Smad2, a key mediator of TGF-ß signaling. LPS treatment also antagonized the ability of TGF-ß to suppress expression of pro-inflammatory cytokines and to induce microglial cell death. LPS treatment similarly inhibited the ability of the TGF-ß related cytokine, Activin-A, to down-regulate expression of pro-inflammatory cytokines and to induce microglial cell death. Together, these data suggest that microglial activators may oppose the actions of TGF-ß1, ensuring continued microglial activation and survival that eventually may contribute to the neurodegeneration prevalent in chronic neuroinflammatory conditions.