Robust Improvement Research Articles

Robust improvement in prevalence of symptoms of depression or anxiety in persons with osteoarthritis after total knee arthroplasty–The best knee cohort study

Purpose: In individuals with knee osteoarthritis (OA), chronic pain and disability give rise to a high prevalence of symptoms of depression and anxiety, which have a marked impact on overall wellbeing and quality of life. However, few studies have assessed the influence of treatment of knee OA on improvement in these symptoms. Further, while it is recommended to screen for mood disorder prior to total knee arthroplasty (TKA) in individuals with OA, it currently remains unclear which individuals are likely to have resolution of their mood symptoms after TKA; understanding this could allow more targeted intervention in those likely to have persistent symptoms.

Facial emotion training as an intervention in autism spectrum disorder: A meta‐analysis of randomized controlled trials

AbstractA large number of computer‐based training programs have been developed as an intervention to help individuals with autism spectrum disorders (ASD) improve their facial emotion recognition ability, as well as social skills. However, it is unclear to what extent these facial emotion training programs can produce beneficial, long‐lasting, and generalizable results. Using standard meta‐analytic techniques, we investigated the effects of facial emotion training including generalization and maintenance restricted to randomized control trial studies comprising a total of 595 individuals with ASD. Our findings revealed that the intervention resulted in a robust improvement in emotion recognition for individuals receiving training compared with controls. However, while there was also some evidence for generalization of training effects, the small number of studies which conducted follow‐ups and assessed social skills reported that improvements were not maintained and there was no evidence for general improvement in social skills. Overall, the analysis revealed a medium effect size in training improvement indicating that facial emotion training may be an effective method for enhancing emotion recognition skills in ASD although more studies are required to assess maintenance of effects and possible general improvements in social skills.Lay summaryFacial emotion training as an intervention may be a potential way to help improve emotion recognition in autism spectrum disorder (ASD), however robust empirical support for its efficacy has not been sufficiently established. Here, we conducted a meta‐analysis of previous studies to summarize the effects of facial emotion training on ASD. Our results show that the training produces a robust improvement in subsequent emotion recognition, while maintenance and generalization effects still need further investigation. To date, no experimentally verified improvements in social skills have been reported.

Defining the Areas of Cooperation between Russia and China Within the SCO: Organizational and Economic Aspects

Purpose. The article discusses the interaction of Russia and China within the framework of the Shanghai Cooperation Organization, and the formation and development of legal relations in the context of goals, objectives and functions defined by the SCO Declaration. The article characterizes the regulatory aspects of the priority directions and the prospects of Sino-Russian cooperation, in particular in the sphere of security and stability in the Central Asia.Design/methodology/approach. The SCO constituent instruments and statistical information on the Sino-Russian relations were analyzed.Findings. Russia and China’s common objectives in their joint activities were defined. The differences were indicated in the approaches to the further development of the SCO in the near future. The legal instruments regulating multilateral cooperation of the SCO member states, including Russia and China as major actors, require further dynamic improvement. The Sino-Russian relations transformed the SCO into a multi-sectoral eclectic structure. Although these two countries have significantly different interests in the SCO, contradictions can be resolved through bilateral agreements.Originality. The study points to the problem that international treaties that formalize the cooperation of the SCO member states, including Russia and China despite their leading role, need robust improvement, and the international treaty framework should evolve multilaterally.

Strictly regulated agonist-dependent activation of AMPA-R is the key characteristic of TAK-653 for robust synaptic responses and cognitive improvement

Agonistic profiles of AMPA receptor (AMPA-R) potentiators may be associated with seizure risk and bell-shaped dose-response effects. Here, we report the pharmacological characteristics of a novel AMPA-R potentiator, TAK-653, which exhibits minimal agonistic properties. TAK-653 bound to the ligand binding domain of recombinant AMPA-R in a glutamate-dependent manner. TAK-653 strictly potentiated a glutamate-induced Ca2+ influx in hGluA1i-expressing CHO cells through structural interference at Ser743 in GluA1. In primary neurons, TAK-653 augmented AMPA-induced Ca2+ influx and AMPA-elicited currents via physiological AMPA-R with little agonistic effects. Interestingly, TAK-653 enhanced electrically evoked AMPA-R-mediated EPSPs more potently than AMPA (agonist) or LY451646 (AMPA-R potentiator with a prominent agonistic effect) in brain slices. Moreover, TAK-653 improved cognition for both working memory and recognition memory, while LY451646 did so only for recognition memory, and AMPA did not improve either. These data suggest that the facilitation of phasic AMPA-R activation by physiologically-released glutamate is the key to enhancing synaptic and cognitive functions, and nonselective activation of resting AMPA-Rs may negatively affect this process. Importantly, TAK-653 had a wide safety margin against convulsion; TAK-653 showed a 419-fold (plasma Cmax) and 1017-fold (AUC plasma) margin in rats. These findings provide insight into a therapeutically important aspect of AMPA-R potentiation.

Family history of obesity and the influence on physical activity and dietary adherence after bariatric surgery.

The causes of obesity are multifactorial, with genetic, environmental, behavioural and societal contributions. These factors also affect adherence to diet and exercise after bariatric surgery. The objective of this study was to evaluate changes in perceived obesity-related stigma, exercise and dietary adherence perioperatively as well as what demographic factors most influence the magnitude of these changes. Validated questionnaires regarding perception of stigma and adherence to diet and exercise regimens were administered to 104 bariatric surgery patients preoperatively and postoperatively at three, six and 12 months. Scoring was compared for improvement, and concomitant factors were analysed for effect on magnitude of improvement. Our study found overall improvement in perception of stigma as well as adherence to diet and exercise regimens. Those with a family history of obesity had less robust improvement compared to those without a family history of obesity. Those who were Caucasian also did not have as robust of an improvement in their scores. Patient perception of obesity-related stigma and adherence to diet and exercise regimens improve after bariatric surgery. However, a patient with a family history of obesity and/or a Caucasian ethnicity may have a less robust improvement in these facets.

Improving the robustness of DI and PVI further using fast guided filter on radiographic images

To further improve the robustness of the weld defect index (DI) and peak-valley index (PVI), which are key indices for detecting weld defects in radiographic testing (RT) images accurately and reliably, a robust improvement method is proposed, in which a fast guided filter (Fast-GF) is introduced and its effect on the DI and PVI is analysed. In this paper, the principle of the proposed robust improvement method, the related theory of Fast-GF, the definition and the calculational method of the DI and PVI are systematically analysed. Taking some practical RT images from industrial welding as an example, smoothing experiments with different filters and comparative computational experiments for the DI and PVI both with and without Fast-GF are carried out. The experimental results show that the robustness of the DI and PVI is further improved by the proposed robust improvement method, which is a desirable outcome. More specifically, the values of the DI and PVI are computed accurately and reliably regardless of some non-uniform distribution of grey levels, noise, irregular surfaces and artefacts in the RT images.

Neutrophil-specific deletion of Syk results in recruitment-independent stabilization of the barrier and a long-term improvement in cognitive function after traumatic injury to the developing brain

While traumatic brain injury (TBI) is the leading cause of death and disability in children, we have yet to identify those pathogenic events that determine the extent of recovery. Neutrophils are best known as “first responders” to sites of infection and trauma where they become fully activated, killing pathogens via proteases that are released during degranulation. However, this activational state may generate substantial toxicity in the young brain after TBI that is partially due to developmentally regulated inadequate antioxidant reserves. Neutrophil degranulation is triggered via a downstream signaling pathway that is dependent on spleen tyrosine kinase (Syk). To test the hypothesis that the activational state of neutrophils is a determinant of early pathogenesis and long-term recovery, we compared young, brain-injured conditional knockouts of Syk (sykf/fMRP8-cre+) to congenic littermates (sykf/f). Based upon flow cytometry, there was an extended recruitment of distinct leukocyte subsets, including Ly6G+/Ly6C− and Ly6G+/Ly6Cint, over the first several weeks post-injury which was similar between genotypes. Subsequent assessment of the acutely injured brain revealed a reduction in blood-brain barrier disruption to both high and low molecular weight dextrans and reactive oxygen species in sykf/fMRP8-cre+ mice compared to congenic littermates, and this was associated with greater preservation of claudin 5 and neuronal integrity, as determined by Western blot analyses. At adulthood, motor learning was less affected in brain-injured sykf/fMRP8-cre+ mice as compared to sykf/f mice. Performance in the Morris Water Maze revealed a robust improvement in hippocampal-dependent acquisition and short and long-term spatial memory retention in sykf/fMRP8-cre+ mice. Subsequent analyses of swim path lengths during hidden platform training and probe trials showed greater thigmotaxis in brain-injured sykf/f mice than sham sykf/f mice and injured sykf/fMRP8-cre+ mice. Our results establish the first mechanistic link between the activation state of neutrophils and long-term functional recovery after traumatic injury to the developing brain. These results also highlight Syk kinase as a novel therapeutic target that could be further developed for the brain-injured child.

How to sustainably build capacity in quality improvement within a healthcare organisation: a deep-dive, focused qualitative analysis

BackgroundA key characteristic of healthcare systems that deliver high quality and cost performance in a sustainable way is a systematic approach to capacity and capability building for quality improvement. The aim of this research was to explore the factors that lead to successful implementation of a program of quality improvement projects and a capacity and capability building program that facilitates or support these.MethodsBetween July 2018 and February 2020, the Southern Adelaide Local Health Network (SALHN), a network of health services in Adelaide, South Australia, conducted three capability-oriented capacity building programs that incorporated 82 longstanding individual quality improvement projects. Qualitative analysis of data collected from interviews of 19 project participants and four SALHN Improvement Faculty members and ethnographic observations of seven project team meetings were conducted.ResultsWe found four interacting components that lead to successful implementation of quality improvement projects and the overall program that facilitates or support these: an agreed and robust quality improvement methodology, a skilled faculty to assist improvement teams, active involvement of leadership and management, and a deep understanding that teams matter. A strong safety culture is not necessarily a pre-requisite for quality improvement gains to be made; indeed, undertaking quality improvement activities can contribute to an improved safety culture. For most project participants in the program, the time commitment for projects was significant and, at times, maintaining momentum was a challenge.ConclusionsHealthcare systems that wish to deliver high quality and cost performance in a sustainable way should consider embedding the four identified components into their quality improvement capacity and capability building strategy.

Lean Six Sigma Methodology and the Future of Quality Improvement Education in Anesthesiology.

Lean Six Sigma Methodology and the Future of Quality Improvement Education in Anesthesiology.

706-P: Robust Glycemic Outcomes after MiniMed Advanced Hybrid Closed-Loop (AHCL) System Use in the Pivotal Trial Regardless of Previous Therapy

Background: The Medtronic MiniMed™ AHCL system that autocorrects to 120mg/dL every five minutes and has an automated basal target of 100mg/dL or 120mg/dL has demonstrated improved A1C and time in range1,2 or improved time in closed-loop control,3 compared to open-loop run-in or control. Glycemic outcomes of study participants who used a different baseline therapy (HCL, SAP or CSII) during the MiniMed™ AHCL pivotal trial were analyzed. Methods: Across 16 sites, participants (N=157, 14-75 years) with T1D underwent a baseline run-in period (~2 weeks) of HCL, SAP or CSII followed by a 90-day study phase with AHCL automated basal and auto-correction. An exploratory analysis compared the mean sensor glucose and percentage of time spent across glucose ranges during the baseline run-in and AHCL-study phase for each cohort. Results: Glycemic outcomes for the overall group and each cohort are shown in the table. Significant changes were observed from run-in to study period for the overall group. The glycemic outcomes that were achieved were similar regardless of the baseline therapy. Conclusion: These MiniMed™ AHCL pivotal trial data demonstrate that the system achieves robust glycemic improvement regardless of baseline therapy. Disclosure J. Shin: Employee; Self; Medtronic. X. Chen: None. M. Liu: None. S. Huang: None. T. L. Cordero: Employee; Self; Medtronic. A. S. Rhinehart: Employee; Self; Medtronic, Stock/Shareholder; Self; AstraZeneca, Lexicon Pharmaceuticals, Inc., Medtronic. R. Vigersky: Employee; Self; Medtronic. Funding Medtronic

Simultaneous Pharmacologic Inhibition of Yes-Associated Protein 1 and Glutaminase 1 via Inhaled Poly(Lactic-co-Glycolic) Acid-Encapsulated Microparticles Improves Pulmonary Hypertension.

BackgroundPulmonary hypertension (PH) is a deadly disease characterized by vascular stiffness and altered cellular metabolism. Current treatments focus on vasodilation and not other root causes of pathogenesis. Previously, it was demonstrated that glutamine metabolism, as catalyzed by GLS1 (glutaminase 1) activity, is mechanoactivated by matrix stiffening and the transcriptional coactivators YAP1 (yes‐associated protein 1) and transcriptional coactivator with PDZ‐binding motif (TAZ), resulting in pulmonary vascular proliferation and PH. Pharmacologic inhibition of YAP1 (by verteporfin) or glutaminase (by CB‐839) improved PH in vivo. However, systemic delivery of these agents, particularly YAP1 inhibitors, may have adverse chronic effects. Furthermore, simultaneous use of pharmacologic blockers may offer additive or synergistic benefits. Therefore, a strategy that delivers these drugs in combination to local lung tissue, thus avoiding systemic toxicity and driving more robust improvement, was investigated.Methods and ResultsWe used poly(lactic‐co‐glycolic) acid polymer‐based microparticles for delivery of verteporfin and CB‐839 simultaneously to the lungs of rats suffering from monocrotaline‐induced PH. Microparticles released these drugs in a sustained fashion and delivered their payload in the lungs for 7 days. When given orotracheally to the rats weekly for 3 weeks, microparticles carrying this drug combination improved hemodynamic (right ventricular systolic pressure and right ventricle/left ventricle+septum mass ratio), histologic (vascular remodeling), and molecular markers (vascular proliferation and stiffening) of PH. Importantly, only the combination of drug delivery, but neither verteporfin nor CB‐839 alone, displayed significant improvement across all indexes of PH.ConclusionsSimultaneous, lung‐specific, and controlled release of drugs targeting YAP1 and GLS1 improved PH in rats, addressing unmet needs for the treatment of this deadly disease.

Numerical Analysis of a Highly Sensitive Surface Plasmon Resonance Sensor for SARS-CoV-2 Detection.

In this paper, we propose a surface plasmon resonance (SPR) structure based on Kretschmann configuration incorporating layers of silicon and BaTiO3 on top of Ag for real-time detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using thiol-tethered DNA as a ligand. Extensive numerical analysis based on transfer matrix theory as well as finite-difference time-domain (FDTD) technique has been performed to characterize the sensor response considering sensitivity, full width at half maxima, and minimum reflection. About 7.6 times enhanced sensitivity has been obtained using the proposed architecture for SARS-CoV-2 detection, compared to the basic Kretschmann configuration. Notably, the structure provides consistent enhancement over other competitive SPR structures for both angular and wavelength interrogations with a figure-of-merit of 692.28. Additionally, we repeated simulations for various ligate–ligand pairs to assess the range of applicability and robust performance improvement has been observed. As a result, the proposed sensor design provides a suitable configuration for highly sensitive, rapid, noninvasive biosensing which can be useful if adopted in experimental sensing protocols.

Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial

Despite advances in the treatment of Hodgkin lymphoma with the introduction of PET-adapted regimens, practical challenges prevent more widespread use of these approaches. The ECHELON-1 study assessed the safety and efficacy of front-line A+AVD (brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine) versus ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in patients with stage III or IV classical Hodgkin lymphoma. The primary analysis showed improved modified progression-free survival with A+AVD. We present an updated analysis of ECHELON-1 at 5 years, an important landmark for this patient population. ECHELON-1 was an international, open-label, randomised, phase 3 trial done at 218 clinical sites, including hospitals, cancer centres, and community clinics, in 21 countries. Previously untreated patients (≥18 years with an Eastern Cooperative Oncology Group performance status of ≤2) with stage III or IV classical Hodgkin lymphoma were randomly assigned (1:1) to receive A+AVD (brentuximab vedotin, 1·2 mg/kg of bodyweight, doxorubicin 25 mg/m2 of body surface area, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2) or ABVD (doxorubicin 25 mg/m2, bleomycin 10 U/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2) intravenously on days 1 and 15 of each 28-day cycle for up to six cycles. Stratification factors included region (Americas vs Europe vs Asia) and International Prognostic Score risk group (low, intermediate, or high risk). The primary endpoint was modified progression-free survival; this 5-year update includes analysis of progression-free survival as per investigator assessment in the intention-to-treat population, which was an exploratory endpoint, although the 5-year analysis was not prespecified in the protocol. This trial is registered with ClinicalTrials.gov (NCT01712490) and EudraCT (2011-005450-60), and is ongoing. Between Nov 19, 2012, and Jan 13, 2016, 1334 patients were randomly assigned to receive A+AVD (n=664) or ABVD (n=670). At a median follow-up of 60·9 months (IQR 52·2-67·3), 5-year progression-free survival was 82·2% (95% CI 79·0-85·0) with A+AVD and 75·3% (71·7-78·5) with ABVD (hazard ratio [HR] 0·68 [95% CI 0·53-0·87]; p=0·0017). Among PET-2-negative patients, 5-year progression-free survival was higher with A+AVD than with ABVD (84·9% [95% CI 81·7-87·6] vs 78·9% [75·2-82·1]; HR 0·66 [95% CI 0·50-0·88]; p=0·0035). 5-year progression-free survival for PET-2-positive patients was 60·6% (95% CI 45·0-73·1) with A+AVD versus 45·9% (32·7-58·2) with ABVD (HR 0·70 [95% CI 0·39-1·26]; p=0·23). Peripheral neuropathy continued to improve or resolve over time with both A+AVD (375 [85%] of 443 patients) and ABVD (245 [86%] of 286 patients); more patients had ongoing peripheral neuropathy in the A+AVD group (127 [19%] of 662) than in the ABVD group (59 [9%] of 659). Fewer secondary malignancies were reported with A+AVD (19 [3%] of 662) than with ABVD (29 [4%] of 659). More livebirths were reported in the A+AVD group (n=75) than in the ABVD group (n=50). With 5 years of follow-up, A+AVD showed robust and durable improvement in progression-free survival versus ABVD, regardless of PET-2 status, and a consistent safety profile. On the basis of these findings, A+AVD should be preferred over ABVD for patients with previously untreated stage III or IV classical Hodgkin lymphoma. Millennium Pharmaceuticals (a wholly owned subsidiary of Takeda Pharmaceutical Company), and Seagen.

The Effects of 4 Weeks of Chiropractic Spinal Adjustments on Motor Function in People with Stroke: A Randomized Controlled Trial.

Chiropractic spinal adjustments have been shown to result in short-term increases in muscle strength in chronic stroke patients, however, the effect of longer-term chiropractic spinal adjustments on people with chronic stroke is unknown. This exploratory study assessed whether 4 weeks of chiropractic spinal adjustments, combined with physical therapy (chiro + PT), had a greater impact than sham chiropractic with physical therapy (sham + PT) did on motor function (Fugl Meyer Assessment, FMA) in 63 subacute or chronic stroke patients. Secondary outcomes included health-related quality of life and other measures of functional mobility and disability. Outcomes were assessed at baseline, 4 weeks (post-intervention), and 8 weeks (follow-up). Data were analyzed using linear mixed-effects models or generalized linear mixed models. A post-hoc responder analysis was performed to investigate the clinical significance of findings. At 4 weeks, there was a larger effect of chiro + PT, compared with sham + PT, on the FMA (difference = 6.1, p = 0.04). The responder analysis suggested the improvements in motor function seen following chiropractic spinal adjustments may have been clinically significant. There was also a robust improvement in both groups in most measures from baseline to the 4- and 8-week assessments, but between-group differences were no longer significant at the 8-week assessment. Four weeks of chiro + PT resulted in statistically significant improvements in motor function, compared with sham + PT, in people with subacute or chronic stroke. These improvements appear to be clinically important. Further trials, involving larger group sizes and longer follow-up and intervention periods, are required to corroborate these findings and further investigate the impacts of chiropractic spinal adjustments on motor function in post-stroke survivors. ClinicalTrials.gov Identifier NCT03849794.

Randomized, Placebo-Controlled Trial of the Angiotensin Receptor Antagonist Losartan for Posttraumatic Stress Disorder

BackgroundEvidence-based pharmacological treatments for posttraumatic stress disorder (PTSD) are few and of limited efficacy. Previous work suggests that angiotensin type 1 receptor inhibition facilitates fear inhibition and extinction, important for recovery from PTSD. This study tests the efficacy of the angiotensin type 1 receptor antagonist losartan, an antihypertensive drug, repurposed for the treatment of PTSD. MethodsA randomized controlled trial was conducted for 10 weeks in 149 men and women meeting DSM-5 PTSD criteria. Losartan (vs. placebo) was flexibly titrated from 25 to 100 mg/day by week 6 and held at highest tolerated dose until week 10. Primary outcome was the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) change score at 10 weeks from baseline. A key secondary outcome was change in CAPS-5 associated with a single nucleotide polymorphism of the ACE gene. Additional secondary outcomes included changes in the PTSD Checklist for DSM-5 and the Patient Health Questionnaire-9, and proportion of responders with a Clinical Global Impressions–Improvement scale of “much improved” or “very much improved.” ResultsBoth groups had robust improvement in PTSD symptoms, but there was no significant difference on the primary end point, CAPS-5 measured as week 10 change from baseline, between losartan and placebo (mean change difference, 0.9, 95% confidence interval, −3.2 to 5.0). There was no significant difference in the proportion of Clinical Global Impressions–Improvement scale responders for losartan (58.6%) versus placebo (57.9%), no significant differences in changes in PTSD Checklist for DSM-5 or Patient Health Questionnaire-9, and no association between ACE genotype and CAPS-5 improvement on losartan. ConclusionsAt these doses and durations, there was no significant benefit of losartan compared with placebo for the treatment of PTSD. We discuss implications for failure to determine the benefit of a repurposed drug with strong a priori expectations of success based on preclinical and epidemiological data.

Implementing a Robust Process Improvement Program in the Neonatal Intensive Care Unit to Reduce Harm.

ABSTRACTIntroduction:Preventable harm continues to occur with critically ill neonates despite efforts by hospital neonatal intensive care units (NICUs) to improve processes and reduce harm. Attaining significant and sustainable improvements will require training including leadership support, mentoring, and patient family engagement to improve care processes. This paper describes the implementation of a robust process improvement (RPI) program in the NICU to reduce harm.Methods:Leaders, staff, and parents were trained in RPI concepts and tools. Multidisciplinary teams including parent members applied the training and received regular mentorship for their improvement initiatives.Results:Participants (N = 67) completed pretraining and post-training surveys. Training scores (0–10 scale) improved from an average of 4.45–7.60 (p < .001) for confidence in leading process improvement work, 2.36 to 7.49 (p < .001) for RPI knowledge, and 2.19 to 7.30 (p < .001) for confidence in using RPI tools; relative improvement of 71%, 217%, and 233% respectively. Participants applied their RPI training on improvement initiatives that resulted in improvements of central line blood stream infections, very low birth weight infant nutrition, and unplanned extubations.Conclusions:Implementing an RPI program in the NICU to reduce harm resulted in significant and sustainable improvements on their improvement initiatives.

Optimizing blood product utilization: A whole lot to gain and nothing to lose!

e18669 Background: Transfusion stewardship is a vital part of managing patients with hematologic malignancies (HM). Blood products are limited resources and blood product transfusion (txn) is costly and poses complications. Randomized trials in different clinical settings have shown that a conservative txn strategy is not inferior to more liberal txn strategy. As a result, the AABB and ASCO have recommended following a conservative txn strategy in patients with cancer (hemoglobin (hg) &lt;7-8g/dL and platelets (plt) &lt;10K in stable non-bleeding patients). Here we report our early outpatient institution’s experience implementing a contemporary txn approach in patients with HM. Methods: We formed a multi-disciplinary team to analyze blood product utilization. Overutilization was defined as orders for multi-units, packed red blood cells (pRBC) for hg &gt;8 or plt for plt &gt;10K in stable non-bleeding patients. Patients’ charts were audited during the baseline period to understand practice patterns. Data were collected using Qlik database. The baseline period (May 1, 2019-Feb 29, 2020) was compared to the intervention period (March 1 – December 31, 2020). A root cause analysis was performed. When possible 2-sided paired T-test was performed. If not possible, descriptive statistics were performed. Three interventions were developed and implemented sequentially: March 2020 – Blood bank began real-time review of blood products overutilization. May 2020 – Electronic Medical Record txn order set was revised to reflect recommended best practices. October 2020 –Txn guidelines revised for patients with HM. Results: During the study period, there were 3,227 pRBC and 2,817 plt transfused units in the outpatient setting. Monthly pRBC txn decreased from (mean(SD)) 168.5 (16.6) to 154.2(16.4) (p value: 0.14). Monthly plt txn decreased from 166.5 (26.5) to 115.2 (26.2) (p value: 0.001). Rates of multi-unit orders decreased significantly. Average monthly multi-unit orders decreased for pRBC (pre-48.6(5.9);post-24.3(7.6);p value 0.00007) and plts (pre-67.4(11.8);post-21.3(23.3);p value: 0.0002). Average hb at time of txn in the pre- and post-intervention period was 7.47 and 7.22. The percentage of txn in which the indication for txn was hb &lt;7, 7-8, &gt;8 changed from 34.6% to 56.3%, 52.6% to 32.8%, and 12.8% to 10.9% respectively. There was no significant increase in admissions for bleeding or increase in number of outpatient visits during the study period. Conclusions: Over 10-months, we significantly reduced outpatient blood product. Robust quality improvement methodology, engaging key stakeholders, and changing the culture of outpatient management were keys to success. To date, we have not seen any unintended consequences of these changes. These results are encouraging, as outpatient transfusion stewardship is thought to be harder given concerns about patients not being monitored as closely as in the inpatient setting.

Do small baby units improve extremely premature infant outcomes?

Increasing numbers of neonatal intensive care units have formed small baby units or small baby teams with the intention to optimize care of extremely premature infants. Considerable time, energy, and resources are required to develop and sustain complex quality improvement constructs, so legitimate questions about effectiveness, unintended consequences, and lost opportunity costs warrant scrutiny. The small baby unit literature is diminutive. Errors of chance, bias, and confounding secondary to insufficient definitions of process and outcome metrics, overlapping quality improvement projects, and limited cost analyses restrict firm conclusions. Well-established quality improvement methodologies such as evidence-based guidelines, standardized variability reduction using measurement-and-adjust techniques, family-integrated focus, and developmentally sensitive care, reliably improve outcomes for all-sized premature infants. There is not compelling published evidence that adding specialized small baby units or designated teams for extremely premature infants further enhances short- or long-term health if robust quality improvement fundamentals are already imbedded within local culture.

Pairing a high-resolution statistical potential with a nucleobase-centric sampling algorithm for improving RNA model refinement

Refining modelled structures to approach experimental accuracy is one of the most challenging problems in molecular biology. Despite many years’ efforts, the progress in protein or RNA structure refinement has been slow because the global minimum given by the energy scores is not at the experimentally determined “native” structure. Here, we propose a fully knowledge-based energy function that captures the full orientation dependence of base–base, base–oxygen and oxygen–oxygen interactions with the RNA backbone modelled by rotameric states and internal energies. A total of 4000 quantum-mechanical calculations were performed to reweight base–base statistical potentials for minimizing possible effects of indirect interactions. The resulting BRiQ knowledge-based potential, equipped with a nucleobase-centric sampling algorithm, provides a robust improvement in refining near-native RNA models generated by a wide variety of modelling techniques.

α7-Acetylcholine Receptor Signaling Reduces Neuroinflammation After Subarachnoid Hemorrhage in Mice.

Aneurysmal subarachnoid hemorrhage (aSAH) causes a robust inflammatory response which leads worse brain injury and poor outcomes. We investigated if stimulation of nicotinic acetylcholine α7 receptors (α7-AChR) (receptors shown to have anti-inflammatory effects) would reduce inflammation and improve outcomes. To investigate the level of peripheral inflammation after aSAH, inflammatory markers were measured in plasma samples collected in a cohort of aSAH patients. To study the effect of α7-AChR stimulation, SAH was induced in adult mice which were then treated with a α7-AChR agonist, galantamine, or vehicle. A battery of motor and cognitive tests were performed 24h after subarachnoid hemorrhage. Mice were euthanized and tissue collected for analysis of markers of inflammation or activation of α7-AChR-mediated transduction cascades. A separate cohort of mice was allowed to survive for 28days to assess long-term neurological deficits and histological outcome. Microglia cell culture subjected to hemoglobin toxicity was used to assess the effects of α7-AChR agonism. Analysis of eighty-two patient plasma samples confirmed enhanced systemic inflammation after aSAH. α7-AChR agonism reduced neuroinflammation at 24h after SAH in male and female mice, which was associated with improved outcomes. This coincided with JAK2/STAT3 and IRAK-M activity modulations and a robust improvement in neurological/cognitive status that was effectively reversed by interfering with various components of these signaling pathways. Pharmacologic inhibition partially reversed the α7-AChR agonist's benefits, supporting α7-AChR as a target of the agonist's therapeutic effect. The cell culture experiment showed that α7-AChR agonism is directly beneficial to microglia. Our results demonstrate that activation of α7-AChR represents an attractive target for treatment of SAH. Our findings suggest that α7-AChR agonists, and specifically galantamine, might provide therapeutic benefit to aSAH patients.