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The objective of this evidence-based project was to determine if a best practice alert (BPA) will decrease the number of oral antibiotic prescriptions for adults with acute bronchitis. The BPA is an electronic prompt that describes the guidelines for the treatment of acute bronchitis. The study sample included prescribing clinicians (N = 41) at 11 retail health clinics that are associated with 1 larger health care organization. A quantitative quasi-experimental pre-/post-study design was used. The chi-square test was used to compare antibiotic prescribing rates. Antibiotic prescribing rates decreased by 40%. The use of a targeted BPA significantly decreased antibiotic prescriptions for acute bronchitis.

Maar-diatreme volcanoes are the second-most common type on land, occurring in volcanic fields within all major tectonic environments. Their deposits typically contain an abundance of lithic fragments quarried from the substrate, and many contain large, deep-sourced lithic fragments that were erupted to the surface. Primary volcaniclastic deposits fill the diatreme structure formed during eruption. There is negligible inelastic deformation of diatreme-adjacent country rock, indicating that country rock is removed to create the diatreme structures, either by being shifting downward below observable levels, ejected upward to contribute to surficial deposits, or dissolved and hidden in magma erupted or intruded at depth. No previous study has systematically reviewed and analysed the reported lithic fragments of maar-diatreme systems. We present a comprehensive compilation from published work of lithic characteristics in maar ejecta rims and in diatreme deposits of both common and kimberlite maar-diatremes. For maar-diatremes and their tephra ring deposits, we find no correlations among lithic clast sizes, shapes, depositional sites, and excavation depths. This is difficult to reconcile with models involving systematic diatreme deepening coupled with tephra-ring growth, but consistent with those involving chaotic explosions and mixing. Larger amounts of data are needed to further examine how these types of volcanoes operate.

PURPOSE—: Left ventricular assist device (LVAD) support is associated with peripheral vascular abnormalities beyond those associated with heart failure (HF). These abnormalities are associated with persistent functional impairments that adversely impact quality of life (QoL). Methods for measuring peripheral vascular function in this population are needed. METHODS—: This pilot study investigated the use of contrast-enhanced ultrasound (CEUS) using standardized protocols to estimate changes in peripheral (quadriceps) muscle perfusion among patients with HF (INTERMACS profile 3) undergoing LVAD implantation (n = 7). Patients were then stratified by those who did (“responders”, n = 4) and did not (“nonresponders”, n = 3) report QoL improvement with LVAD support. RESULTS—: Serial measurements obtained preoperatively and 3 months following LVAD implantation showed no significant change (P > .23) in muscle perfusion by all CEUS-based measures at rest or with an exercise stimulus for the overall population. Responders exhibited improved muscle perfusion at rest (P = .043) and decreased time to peak contrast enhancement (P = .010) at 3 months compared with baseline, suggesting improved delivery of blood to the extremities post-LVAD. Nonresponders showed unchanged resting muscle perfusion (P > .99), time to peak contrast enhancement (P = .59), and response to exercise stimulus (P > .99) following LVAD therapy. CONCLUSION—: Our findings suggest that CEUS evaluation is a promising noninvasive, quantitative modality for real-time assessment of peripheral vasculature and muscle perfusion as an indication of treatment response in LVAD recipients and that this modality may capture perfusion measures important to QoL following LVAD implantation.

Objective Exercise prevents falls in the general older population, but evidence is inconclusive for older adults living with cognitive impairment. We performed an updated systematic review and meta-analysis to assess the potential effectiveness of interventions for reducing falls in older persons with cognitive impairment. Methods PubMed, EMBASE, CINAHL, Scopus, CENTRAL and PEDro were searched from inception to 10 November 2020. We included randomised controlled trials (RCTs) that evaluated the effects of physical training compared to a control condition (usual care, waitlist, education, placebo control) on reducing falls among community-dwelling older adults with cognitive impairment (i.e. any stage of Alzheimer’s disease and related dementias, mild cognitive impairment). Results We identified and meta-analysed nine studies, published between 2013 and 2020, that included 12 comparisons (N = 1,411; mean age = 78 years; 56% women). Overall, in comparison to control, interventions produced a statistically significant reduction of approximately 30% in the rate of falls (incidence rate ratio = 0.70; 95% CI, 0.52-0.95). There was significant between-trial heterogeneity (I2 = 74%), with most trials (n = 6 studies [eight comparisons]) showing no reductions on fall rates. Subgroup analyses showed no differences in the fall rates by trial-level characteristics. Exercise-based interventions had no impact on reducing the number of fallers (relative risk = 1.01; 95% CI, 0.90–1.14). Concerns about risk of bias in these RCTs were noted, and the quality of evidence was rated as low. Conclusions The positive statistical findings on reducing fall rate in this meta-analysis were driven by a few studies. Therefore, current evidence is insufficient to inform evidence-based recommendations or treatment decisions for clinical practice. PROSPERO Registration number: CRD42020202094.

Aims The purpose of the pilot study was to determine if an educational program on opioid safety and disposal during a preoperative joint replacement class would increase the frequency of disposal of unused opioids with a disposal pouch at the end of the episode of care in patients undergoing joint replacement. A secondary aim was to quantify the milligrams of morphine equivalents prescribed, used, disposed, and remaining in joint replacement patients. Design The study design is quasi-experimental. Methods A medication disposal pouch was provided to all study subjects preoperatively. A 2-minute opioid safety and disposal instruction and demonstration of the use of the disposal pouch was performed at a weekly preoperative joint replacement class which was optional for subjects to attend. A nine-question phone survey was then administered to subjects postoperatively. Results One hundred and four patients completed the study survey. Of the subjects who attended the class and had opioids remaining, 74% disposed of their opioids compared with 36% that did not attend the class (p = .005). Conclusions Provision of a disposal pouch in combination with a live educational program on opioid safety and disposal increased the rate of disposal of unused opioids in a postoperative population.

Diabetic retinopathy is a potentially blinding eye disease that threatens the vision of a ninth of diabetic patients. Progression of the disease has long been attributed to an initial dropout of pericytes that enwrap the retinal microvasculature. Revealed through retinal vascular digests, a subsequent increase in basement membrane bridges is observed. Using cell-specific markers, we demonstrate that pericytes rather than endothelial cells colocalize with these bridges. We show that the density of bridges transiently increases with elevation of Ang-2, PDGF-BB, and blood sugar, is rapidly reversed on a time scale of days, and often associated with a pericyte cell body located off-vessel. Cell-specific knockout of KLF4 in pericytes fully replicates this phenotype. In vivo imaging of limbal vessels demonstrates pericyte migration off-vessel, with rapid pericyte filopodial-like process formation between adjacent vessels. Accounting for off-vessel and on-vessel pericytes, we observe no pericyte loss relative to non-diabetic control retina. These findings reveal the possibility that pericyte perturbations in location and process formation may play a role in the development of pathological vascular remodeling in diabetic retinopathy.

Purpose To establish Myh11 as a marker of a subset of corneal endothelial cells (CECs), and to demonstrate the feasibility of restoring the corneal endothelium with Myh11-lineage (Myh11-Lin[+]) adipose-derived stromal cells (ASCs). Methods Intraperitoneal administration of tamoxifen and (Z)-4-hydroxytamoxifen eyedrops were used to trace the lineage of Myh11-expressing cells with the Myh11-Cre-ERT2-flox-tdTomato mouse model. Immunostaining and Western blot characterized marker expression and spatial distribution of Myh11-Lin(+) cells in the cornea, and administration of 5-ethynyl-2'-deoxyuridine labeled proliferating cells. ASCs were isolated from epididymal adipose Myh11+ mural cells and treated with cornea differentiation media to evaluate corneal endothelial differentiation potential. Differentiated ASCs were injected into the anterior chamber to test for incorporation into corneal endothelium following scratch injury. Results A subset of CECs express Myh11, a marker previously thought restricted to only mural cells. Myh11-Lin(+) CECs marked a stable subpopulation of cells in the cornea endothelium. Myh11-Lin(+) ASCs undergo CEC differentiation in vitro and incorporate into injured corneal endothelium. Conclusions Dystrophy and dysfunction of the corneal endothelium accounts for almost half of all corneal transplants, the maintenance of the cornea endothelium is poorly understood, and there are a lack of mouse models to study specific CEC populations. We establish a mouse model that can trace the cell fate of a subpopulation of CECs based on Myh11 expression. A subset of ASCs that share this Myh11 transcriptional lineage are capable of differentiating into CECs that can incorporate into injured corneal endothelium, revealing a potential cell source for creating engineered transplant material.

Diabetic retinopathy threatens the vision of a third of diabetic patients. Progression of the disease is attributed to the dropout of pericytes, a cell type that enwraps and stabilizes the microvasculature. In tandem with this presumptive pericyte dropout, there is enriched formation of structures assumed to be remnants of collapsed or regressed vessels, previously classified as acellular capillaries, string vessels, and basement membrane bridges. Instead of endothelial cells, we show that pericytes colocalize with basement membrane bridges, and both bridging structures are enriched by cell-specific knockout of KLF4 and reversibly enriched with elevation of Ang-2, PDGF-BB, and blood sugar. Our data suggests that pericyte counts from retinal digests have misclassified pericyte bridges as endothelial structures and have exaggerated the role of pericyte loss in DR progression. In vivo imaging of corneal limbal vessels demonstrates pericyte migration off-vessel, implicating pericyte movement in formation of pericyte bridges and pathogenesis of diabetic retinopathy.

Diabetic retinopathy is a potentially blinding eye disease that threatens the vision of one-ninth of patients with diabetes. Progression of the disease has long been attributed to an initial dropout of pericytes that enwrap the retinal microvasculature. Revealed through retinal vascular digests, a subsequent increase in basement membrane bridges was also observed. Using cell-specific markers, we demonstrate that pericytes rather than endothelial cells colocalize with these bridges. We show that the density of bridges transiently increases with elevation of Ang-2, PDGF-BB, and blood glucose; is rapidly reversed on a timescale of days; and is often associated with a pericyte cell body located off vessel. Cell-specific knockout of KLF4 in pericytes fully replicates this phenotype. In vivo imaging of limbal vessels demonstrates pericyte migration off vessel, with rapid pericyte filopodial-like process formation between adjacent vessels. Accounting for off-vessel and on-vessel pericytes, we observed no pericyte loss relative to nondiabetic control retina. These findings reveal the possibility that pericyte perturbations in location and process formation may play a role in the development of pathological vascular remodeling in diabetic retinopathy.

This follow-up analysis of a randomized clinical trial compares the effectiveness of tai ji quan, multimodal exercises, and stretching exercise interventions for older adults at high risk of falling., Key Points Question Is a therapeutically tailored tai ji quan intervention more effective than stretching exercise or a proven multimodal exercise intervention in decreasing injurious falls among community-dwelling older adults at high risk of falling? Findings In this follow-up analysis of a randomized clinical trial that included 670 older adults with a history of falls or impaired mobility, a therapeutic tai ji quan intervention, Tai Ji Quan: Moving for Better Balance, was significantly more effective for lowering the incidence of both moderate injurious falls compared with stretching exercise and serious injurious falls compared with stretching exercise and multimodal exercise. Meaning The therapeutically tailored tai ji quan training intervention proved to be more safe and effective than stretching or multimodal exercises in reducing the incidence of injurious falls in older adults at high risk of falling., Importance Exercise has been shown to reduce injurious falls in older adults. Evidence, however, is lacking regarding the types of intervention that are most effective in preventing injurious falls among older adults at high risk of falling. Objective To determine the longer-term effectiveness of therapeutic tai ji quan intervention vs multimodal exercise and stretching exercise in decreasing injurious falls among older adults at high risk of falling. Design, Setting, and Participants This trial involves a prespecified analysis with the data analyzed by intent-to-treat. Follow-up analysis of a single-blind randomized trial conducted in community settings of 7 urban and suburban cities in Oregon from February 20, 2015, to September 15, 2018, compared a therapeutic tai ji quan intervention with multimodal exercise and stretching exercise. Eligible participants were community-dwelling adults aged at least 70 years who were considered by a clinician to be at high risk of falling because they had fallen during the preceding year or who had impaired mobility with scores higher than 13.5 seconds on the Timed Up & Go test. Participants were randomized to 1 of the 3 interventions and were assessed monthly after randomization for 12 months, encompassing a 6-month active intervention phase and a 6-month after intervention follow-up phase. Interventions The 3 group-based interventions were therapeutic tai ji quan (Tai Ji Quan: Moving for Better Balance [TJQMBB]), multimodal exercise, and stretching exercise, each implemented twice weekly in 60-minute sessions for 24 weeks. Main Outcomes and Measures Primary outcomes were the incidence of moderate and serious injurious falls at 12 months, measured as incidence rate ratios (IRRs). Results Of the 1147 persons screened, 670 (mean [SD] age, 77.7 [5.6] years; 436 women [65.1%]) were randomly assigned to 1 of 3 intervention groups: 224 persons in TJQMBB, 223 in multimodal exercise, and 223 in stretching exercise. At 12 months, the unadjusted IRR for moderate injurious falls was lower in the TJQMBB (IRR, 0.51; 95% CI, 0.35-0.74; P

Falls in older adults are a global public health crisis, but mounting evidence from randomized controlled trials shows that falls can be reduced through exercise. Public health authorities and healthcare professionals endorse the use of evidence-based, exercise-focused fall interventions, but there are major obstacles to translating and disseminating research findings into healthcare practice, including lack of evidence of the transferability of efficacy trial results to clinical and community settings, insufficient local expertise to roll out community exercise programs, and inadequate infrastructure to integrate evidence-based programs into clinical and community practice. The practical solutions highlighted in this article can be used to address these evidence-to-practice challenges. Falls and their associated healthcare costs can be reduced by better integrating research on exercise intervention into clinical practice and community programs.

BackgroundData on the cost-effectiveness of proven fall prevention exercise interventions are limited. We aimed to establish the cost-effectiveness of Tai Ji Quan: Moving for Better Balance (TJQMBB) compared with a conventional exercise intervention for older adults at high risk of falling.MethodsWe conducted a trial-based cost-effectiveness analysis involving 670 older adults who had a history of falling or impaired mobility. Participants received one of three interventions—TJQMBB, multimodal exercise, or stretching exercise (control)—each of which was implemented twice weekly for 24 weeks. The primary cost-effectiveness measure was the incremental cost per additional fall prevented, comparing TJQMBB and multimodal exercise to Stretching and TJQMBB to multimodal exercise, with a secondary measure of incremental cost per additional quality-adjusted life-year (QALY) gained. The intervention was conducted between February 2015 and January 2018, and cost-effectiveness was estimated from a health care system perspective over a 6-month time horizon.ResultsThe total cost to deliver the TJQMBB intervention was $202,949 (an average of $906 per participant); for multimodal exercise, it was $223,849 ($1,004 per participant); and for Stretching, it was $210,468 ($903 per participant). Incremental cost-effectiveness ratios showed that the multimodal exercise was cost-effective ($850 per additional fall prevented; $27,614 per additional QALY gained) relative to Stretching; however, TJQMBB was the most economically dominant strategy (ie, having lower cost and being clinically more efficacious) compared with multimodal and stretching exercises with regard to cost per additional fall prevented and per additional QALY gained. TJQMBB had a 100% probability of being cost-effective, relative to Stretching, at a threshold of $500 per each additional fall prevented and $10,000 per additional QALY gained. Sensitivity analyses showed the robustness of the results when extreme cases, medical costs only, and missing data were considered.ConclusionsAmong community-dwelling older adults at high risk for falls, TJQMBB is a cost-effective means of reducing falls compared with conventional exercise approaches.Trial RegistrationClinicaltrials.gov (NCT02287740).

Introduction: Older patients with acute decompensated heart failure (ADHF) have impaired physical function (PF) and reduced quality of life (QOL). However, the relationship between impairments in PF and QOL are unknown but relevant to clinical practice and design of targeted intervention trials in this high-risk population. Methods: We assessed 202 consecutive patients hospitalized with ADHF in the multicenter Rehabilitation Therapy in Older Acute HF Patients (REHAB-HF) Trial. Standard measures of PF included the Short Physical Performance Battery (SPPB), a validated PF outcome measure in frail elderly, and 6-minute Walking Distance (6MWD). QOL was assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ). Pearson’s correlation statistics examined associations between PF and QOL. Stepwise regressions were performed to identify independent predictors of QOL including PF measures, demographics, and disease severity indicators (NYHA class, previous hospitalizations, duration of current hospitalization, and number of HF signs and symptoms). Results: Participants were 72±7.5 years, BMI 33.2±8.8 kg/m 2 , 54% women, 52% non-white, 52% with reduced ejection fraction, and 44% with previous hospitalizations within 6 months. Participants had marked deficits in PF (SPPB 6.0±2.5 units, 6MWD 185±99 meters) and low QOL (KCCQ Physical Limitation Score (PLS) 47.3±23.8). There were modest but highly significant correlations of QOL measures with SPPB, 6MWD, and number of HF symptoms and signs (Table). Using stepwise regressions, 6MWD and BMI were modest, significant independent predictors of QOL (partial r=0.18, p=0.012 and partial r=-0.27, p=0.0003, respectively), while SPPB, demographics, and HF severity indicators were not. Conclusion: In older, hospitalized ADHF patients, PF and QOL are both severely impaired, but are only modestly related. PF and QOL assess unique domains of impairment and provide complementary information for characterizing clinically meaningful patient-oriented outcomes in ADHF.

As the world’s population ages, the management of chronic diseases pressures the health-care systems to provide efficacious care while reducing mounting costs. The use of technological advancements to augment health-care services provides one such method to meet those demands. Telerehabilitation robotics is one of the newest additions to technologically mediated health care that combines established features of robot-assisted rehabilitation and telehealthcare to provide rehabilitation services at a distance. Several studies have documented clinically and statistically significant improvements in upper and lower extremity functioning, while several feasibility studies have documented improvements in high-fidelity kinematics. Telerehabilitation robotic delivery has also been shown to expand access to rehabilitation services. While telerehabilitation robotics is a promising adjunct to conventional care, numerous barriers that limit practice integration will need to be addressed to allow more widespread acceptance and use in rehabilitation.