How, in what contexts, and why do quality dashboards lead to improvements in care quality in acute hospitals? Protocol for a realist feasibility evaluation

Introduction: National audits are used to monitor care quality and safety and are anticipated to reduce unexplained variations in quality by stimulating quality improvement (QI). However, variation within and between providers in the extent of engagement with national audits means that the potential for national audit data to inform QI is not being realised. This study will undertake a feasibility evaluation of QualDash, a quality dashboard designed to support clinical teams and managers to explore data from two national audits, the Myocardial Ischaemia National Audit Project (MINAP) and the Paediatric Intensive Care Audit Network (PICANet). Methods and analysis: Realist evaluation, which involves building, testing and refining theories of how an intervention works, provides an overall framework for this feasibility study. Realist hypotheses that describe how, in what contexts, and why QualDash is expected to provide benefit will be tested across five hospitals. A controlled interrupted time series analysis, using key MINAP and PICANet measures, will provide preliminary evidence of the impact of QualDash, while ethnographic observations and interviews over 12 months will provide initial insight into contexts and mechanisms that lead to those impacts. Feasibility outcomes include the extent to which MINAP and PICANet data are used, data completeness in the audits, and the extent to which participants perceive QualDash to be useful and express the intention to continue using it after the study period. Ethics and dissemination: The study has been approved by the University of Leeds School of Healthcare Research Ethics Committee. Study results will provide an initial understanding of how, in what contexts, and why quality dashboards lead to improvements in care quality. These will be disseminated to academic audiences, study participants, hospital IT departments and national audits. If the results show a trial is feasible, we will disseminate the QualDash software through a stepped wedge cluster randomised trial

Historical changes in the stomatal limitation of photosynthesis: empirical support for an optimality principle

The ratio of leaf‐internal (ci) to ambient (ca) partial pressure of CO2, defined here as χ, is an index of adjustments in both leaf stomatal conductance and photosynthetic rate to environmental conditions. Measurements and proxies of this ratio can be used to constrain vegetation models uncertainties for predicting terrestrial carbon uptake and water use. We test a theory based on the least‐cost optimality hypothesis for modelling historical changes in χ over the 1951‐2014 period, across different tree species and environmental conditions, as reconstructed from stable carbon isotopic measurements across a global network of 103 absolutely‐dated tree‐ring chronologies. The theory predicts optimal χ as a function of air temperature, vapour pressure deficit, ca and atmospheric pressure. The theoretical model predicts 39% of the variance in χ values across sites and years, but underestimates the inter‐site variability in the reconstructed χ trends, resulting in only 8% of the variance in χ trends across years explained by the model. Overall, our results support theoretical predictions that variations in χ are tightly regulated by the four environmental drivers. They also suggest that explicitly accounting for the effects of plant‐available soil water and other site‐specific characteristics might improve the predictions

Biomarkers and outcome after tamoxifen treatment in node-positive breast cancers from elderly women

The predictive role of tumour proliferative rate and expression of p53, bcl-2 and bax proteins, alone and in association with tumour size, nodal involvement and oestrogen receptors (ER), was analysed on 145 elderly patients (≥70 years of age) with histologically assessed node-positive breast cancers treated with radical or conservative surgery plus radiotherapy followed by adjuvant tamoxifen for at least 1 year. The 7-year probability of relapse was significantly higher for patients with tumours rapidly proliferating (hazard ratio (HR) = 2.0, P = 0.01), overexpressing p53 (HR = 4.4, P = 0.0001), weakly or not exhibiting bcl-2 (HR = 1.9, P = 0.02), without ERs (HR = 3.4, P = 0.0001) or with ≥ 4 positive lymph nodes (HR = 2.3, P = 0.003) than for patients with tumours expressing the opposite patho-biological profile. Conversely, tumour size and bax expression failed to influence relapse-free survival. Adjustment for the duration of tamoxifen treatment did not change these findings. Oestrogen receptors, cell proliferation, p53 accumulation and bcl-2 expression were also predictive for overall survival. Within ER-positive tumours, cell proliferation, p53 accumulation, bcl-2 expression and lymph node involvement provided significant and independent information for relapse and, in association, identified subgroups of patients with relapse probabilities of 20% (low-risk group, exhibiting only one unfavourable factor) to 90% (high-risk group, exhibiting three unfavourable factors). Such data could represent the initial framework for a biologically tailored therapy even for elderly patients and highlight the importance of a patho-biological characterization of their breast cancers. © 2000 Cancer Research Campaig

Characteristics and Outcomes of People With Gout Hospitalized Due to COVID-19: Data From the COVID-19 Global Rheumatology Alliance Physician-Reported Registry

Objective: To describe people with gout who were diagnosed with coronavirus disease 2019 (COVID-19) and hospitalized and to characterize their outcomes. Methods: Data on patients with gout hospitalized for COVID-19 between March 12, 2020, and October 25, 2021, were extracted from the COVID-19 Global Rheumatology Alliance registry. Descriptive statistics were used to describe the demographics, comorbidities, medication exposures, and COVID-19 outcomes including oxygenation or ventilation support and death. Results: One hundred sixty-three patients with gout who developed COVID-19 and were hospitalized were included. The mean age was 63 years, and 85% were male. The majority of the group lived in the Western Pacific Region (35%) and North America (18%). Nearly half (46%) had two or more comorbidities, with hypertension (56%), cardiovascular disease (28%), diabetes mellitus (26%), chronic kidney disease (25%), and obesity (23%) being the most common. Glucocorticoids and colchicine were used pre-COVID-19 in 11% and 12% of the cohort, respectively. Over two thirds (68%) of the cohort required supplemental oxygen or ventilatory support during hospitalization. COVID-19-related death was reported in 16% of the overall cohort, with 73% of deaths documented in people with two or more comorbidities. Conclusion: This cohort of people with gout and COVID-19 who were hospitalized had high frequencies of ventilatory support and death. This suggests that patients with gout who were hospitalized for COVID-19 may be at risk of poor outcomes, perhaps related to known risk factors for poor outcomes, such as age and presence of comorbidity

Short and long term treatment of asthma with intravenous nutrients

BACKGROUND: Asthma is an increasing problem in this country and others. Although medications for the treatment of asthma abound and are improving, there are inherent risks and side effects with all of them. Intravenous magnesium has been employed in the treatment of acute asthma, but its use has not become universal, nor has it been studied for the treatment of chronic asthma. It is known to be a safe drug with minimal side effects. In this study, the author investigates the use of magnesium and other nutrients in the treatment of both acute and chronic asthma. METHODS: In this non-blinded outcome study, following informed consent, forty-three (43) randomly selected volunteer patients with both acute and chronic asthma were treated with IV infusions described herein. All patients were observed with spirometry 10 minutes post-infusion; two sub-groups of patients were also observed after multiple infusions over a short period of time (less than one month) and a longer period of time (average 5.8 months). Pulmonary function was analyzed by spirometric testing with pre- and post-infusion spirometric measurements with the pre/post group. For longer term (Trend) patients, baseline spirometry measurements were compared to spirometry measurements after patients had received multiple infusions over a period of time. Eight (8) patients were measured for both pre/post and Trend data. RESULTS: The 38 pre-infusion/post-infusion patients with acute and chronic asthma demonstrated an overall average improvement (percentage improvement in percent predicted) of 45%. The 13 patients measured for improvement over time (Trend data, average duration 5.82 months), demonstrated an overall average improvement (percentage improvement in percent predicted) of 57%. Of the 13 patients in the multiple infusion group, 9 patients who received longer-term therapy (average duration of 12.58 months) for chronic asthma demonstrated an overall average improvement of 95% (percentage improvement in percent predicted). CONCLUSION: The use of intravenous treatment with multiple nutrients, including magnesium, for acute and chronic asthma may be of considerable benefit. Pulmonary function improved progressively the longer patients received treatment

Learning time-varying categories

Many kinds of objects and events in our world have a strongly time-dependent quality. However, most theories about concepts and categories either are insensitive to variation over time or treat it as a nuisance factor that produces irrational order effects during learning. In this article, we present two category learning experiments in which we explored peoples’ ability to learn categories whose structure is strongly time-dependent. We suggest that order effects in categorization may in part reflect a sensitivity to changing environments, and that understanding dynamically changing concepts is an important part of developing a full account of human categorization.Daniel J. Navarro, Amy Perfors, Wai Keen Von

Redox-Induced Src Kinase and Caveolin-1 Signaling in TGF-β1-Initiated SMAD2/3 Activation and PAI-1 Expression

Plasminogen activator inhibitor-1 (PAI-1), a major regulator of the plasmin-based pericellular proteolytic cascade, is significantly increased in human arterial plaques contributing to vessel fibrosis, arteriosclerosis and thrombosis, particularly in the context of elevated tissue TGF-β1. Identification of molecular events underlying to PAI-1 induction in response to TGF-β1 may yield novel targets for the therapy of cardiovascular disease.Reactive oxygen species are generated within 5 minutes after addition of TGF-β1 to quiescent vascular smooth muscle cells (VSMCs) resulting in pp60(c-src) activation and PAI-1 expression. TGF-β1-stimulated Src kinase signaling sustained the duration (but not the initiation) of SMAD3 phosphorylation in VSMC by reducing the levels of PPM1A, a recently identified C-terminal SMAD2/3 phosphatase, thereby maintaining SMAD2/3 in an active state with retention of PAI-1 transcription. The markedly increased PPM1A levels in triple Src kinase (c-Src, Yes, Fyn)-null fibroblasts are consistent with reductions in both SMAD3 phosphorylation and PAI-1 expression in response to TGF-β1 compared to wild-type cells. Activation of the Rho-ROCK pathway was mediated by Src kinases and required for PAI-1 induction in TGF-β1-stimulated VSMCs. Inhibition of Rho-ROCK signaling blocked the TGF-β1-mediated decrease in nuclear PPM1A content and effectively attenuated PAI-1 expression. TGF-β1-induced PAI-1 expression was undetectable in caveolin-1-null cells, correlating with the reduced Rho-GTP loading and SMAD2/3 phosphorylation evident in TGF-β1-treated caveolin-1-deficient cells relative to their wild-type counterparts. Src kinases, moreover, were critical upstream effectors of caveolin-1(Y14) phosphoryation and initiation of downstream signaling.TGF-β1-initiated Src-dependent caveolin-1(Y14) phosphorylation is a critical event in Rho-ROCK-mediated suppression of nuclear PPM1A levels maintaining, thereby, SMAD2/3-dependent transcription of the PAI-1 gene