Effect of a hospital command centre on patient safety: An interrupted time series study

Background Command centres have been piloted in some hospitals across the developed world in the last few years. Their impact on patient safety, however, has not been systematically studied. Hence, we aimed to investigate this. Methods This is a retrospective population-based cohort study. Participants were patients who visited Bradford Royal Infirmary Hospital and Calderdale & Huddersfield hospitals between 1 January 2018 and 31 August 2021. A five-phase, interrupted time series, linear regression analysis was used. Results After introduction of a Command Centre, while mortality and readmissions marginally improved, there was no statistically significant impact on postoperative sepsis. In the intervention hospital, when compared with the preintervention period, mortality decreased by 1.4% (95% CI 0.8% to 1.9%), 1.5% (95% CI 0.9% to 2.1%), 1.3% (95% CI 0.7% to 1.8%) and 2.5% (95% CI 1.7% to 3.4%) during successive phases of the command centre programme, including roll-in and activation of the technology and preparatory quality improvement work. However, in the control site, compared with the baseline, the weekly mortality also decreased by 2.0% (95% CI 0.9 to 3.1), 2.3% (95% CI 1.1 to 3.5), 1.3% (95% CI 0.2 to 2.4), 3.1% (95% CI 1.4 to 4.8) for the respective intervention phases. No impact on any of the indicators was observed when only the software technology part of the Command Centre was considered. Conclusion Implementation of a hospital Command Centre may have a marginal positive impact on patient safety when implemented as part of a broader hospital-wide improvement programme including colocation of operations and clinical leads in a central location. However, improvement in patient safety indicators was also observed for a comparable period in the control site. Further evaluative research into the impact of hospital command centres on a broader range of patient safety and other outcomes is warranted

Natural products as starting points for future anti-malarial therapies: going back to our roots?

Abstract Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal medicinal products already used by the community. This first step forms a solid basis of observations, before moving to in vivo pharmacological characterization and ultimately identifying the active ingredient. A large part of the population uses herbal medicinal products despite limited numbers of well-controlled clinical studies. Increased awareness by the regulators and public health bodies of the need for safety information on herbal medicinal products also lends support to obtaining more clinical data on such products. Conclusions The relative paucity of new herbal medicinal product scaffolds active against malaria results discovered in recent years suggest it is time to re-evaluate the ‘smash and grab’ approach of randomly testing purified natural products and replace it with a patient-data led approach. This will require a change of perspective form many in the field. It will require an investment in standardisation in several areas, including: the ethnopharmacology and design and reporting of clinical observation studies, systems for characterizing anti-malarial activity of patient plasma samples ex vivo followed by chemical and pharmacological characterisation of extracts from promising sources. Such work falls outside of the core mandate of the product development partnerships, such as MMV, and so will require additional support. This call is timely, given the strong interest from researchers in disease endemic countries to support the research arm of a malaria eradication agenda. Para-national institutions such as the African Network for Drugs and Diagnostics Innovation (ANDi) will play a major role in facilitating the development of their natural products patrimony and possibly clinical best practice to bring forward new therapeutics. As in the past, with quinine, lapinone and artemisinin, once the activity of herbal medicinal products in humans is characterised, it can be used to identify new molecular scaffolds which will form the basis of the next generation of anti-malarial therapies.</p

Demographic and Genetic Patterns of Variation among Populations of Arabidopsis thaliana from Contrasting Native Environments

Background: Understanding the relationship between environment and genetics requires the integration of knowledge on the demographic behavior of natural populations. However, the demographic performance and genetic composition of Arabidopsis thaliana populations in the species' native environments remain largely uncharacterized. This information, in combination with the advances on the study of gene function, will improve our understanding on the genetic mechanisms underlying adaptive evolution in A. thaliana. Methodology/Principal Findings: We report the extent of environmental, demographic, and genetic variation among 10 A. thaliana populations from Mediterranean (coastal) and Pyrenean (montane) native environments in northeast Spain. Geographic, climatic, landscape, and soil data were compared. Demographic traits, including the dynamics of the soil seed bank and the attributes of aboveground individuals followed over a complete season, were also analyzed. Genetic data based on genome-wide SNP markers were used to describe genetic diversity, differentiation, and structure. Coastal and montane populations significantly differed in terms of environmental, demographic, and genetic characteristics. Montane populations, at higher altitude and farther from the sea, are exposed to colder winters and prolonged spring moisture compared to coastal populations. Montane populations showed stronger secondary seed dormancy, higher seedling/juvenile mortality in winter, and initiated flowering later than coastal populations. Montane and coastal regions were genetically differentiated, montane populations bearing lower genetic diversity than coastal ones. No significant isolation-by-distance pattern and no shared multilocus genotypes among populations were detected. Conclusions/Significance: Between-region variation in climatic patterns can account for differences in demographic traits, such as secondary seed dormancy, plant mortality, and recruitment, between coastal and montane A. thaliana populations. In addition, differences in plant mortality can partly account for differences in the genetic composition of coastal and montane populations. This study shows how the interplay between variation in environmental, demographic, and genetic parameters may operate in natural A. thaliana populations. © 2009 Montesinos et al

Molecular fingerprinting of radiation resistant tumors: Can we apprehend and rehabilitate the suspects?

Radiation therapy continues to be one of the more popular treatment options for localized prostate cancer. One major obstacle to radiation therapy is that there is a limit to the amount of radiation that can be safely delivered to the target organ. Emerging evidence suggests that therapeutic agents targeting specific molecules might be combined with radiation therapy for more effective treatment of tumors. Recent studies suggest that modulation of these molecules by a variety of mechanisms (e.g., gene therapy, antisense oligonucleotides, small interfering RNA) may enhance the efficacy of radiation therapy by modifying the activity of key cell proliferation and survival pathways such as those controlled by Bcl-2, p53, Akt/PTEN and cyclooxygenase-2. In this article, we summarize the findings of recent investigations of radiosensitizing agents in the treatment of prostate cancer

Strategies to enhance routine physical activity in care home residents: the REACH research programme including a cluster feasibility RCT

This is the final version. Available from NIHR via the DOI in this record. Background: Care home residents are mainly inactive, leading to increased dependency and low mood. Although exercise classes may increase activity, a more sustainable model is to engage staff and residents in increasing routine activity. Objectives: The objectives were to develop and preliminarily test strategies to enhance the routine physical activity of care home residents to improve their physical, psychological and social well-being through five overlapping workstreams. Design: This trial had a mixed-methods research design to develop and test the feasibility of undertaking an evaluative study consisting of gaining an understanding of the opportunities for and barriers to enhancing physical activity in care homes (workstream 1); testing physical activity assessment instruments (workstream 2); developing an intervention through a process of intervention mapping (workstream 3); refining the provisional intervention in the care home setting and clarifying outcome measurement (workstream 4); and undertaking a cluster randomised feasibility trial of the intervention [introduced via three facilitated workshops at baseline (with physiotherapist input), 2 weeks (with artist input) and 2 months], with embedded process and health economic evaluations (workstream 5). Setting: The trial was set in 12 residential care homes differing in size, location, ownership and provision in Yorkshire, UK. Participants: The participants were elderly residents, carers, managers and staff of care homes. Intervention: The intervention was MoveMore, designed for the whole home, to encourage and support the movement of residents in their daily routines. Main outcome measures: The main outcome measures related to the feasibility and acceptability of implementing a full-scale trial in terms of recruitment and retention of care homes and residents, intervention delivery, completion and reporting of baseline data and outcomes (including hours of accelerometer wear, hours of sedentary behaviour and hours and type of physical activity), and safety and cost data (workstream 5). Results: Workstream 1 – through a detailed understanding of life in a care home, a needs assessment was produced, and barriers to and facilitators of activity were identified. Key factors included ethos of care; organisation, management and delivery of care; use of space; and the residents’ daily routines. Workstream 2 – 22 (73.3%) out of 30 residents who wore a hip accelerometer had valid data (≥ 8 hours on ≥ 4 days of the week). Workstream 3 – practical mechanisms for increasing physical activity were developed, informed by an advisory group of stakeholders and outputs from workstreams 1 and 2, framed by the process of intervention mapping. Workstream 4 – action groups were convened in four care homes to refine the intervention, leading to further development of implementation strategies. The intervention, MoveMore, is a whole-home intervention involving engagement with a stakeholder group to implement a cyclical process of change to encourage and support the movement of residents in their daily routines. Workstream 5 – 12 care homes and 153 residents were recruited to the cluster randomised feasibility trial. Recruitment in the care homes varied (40–89%). Five care homes were randomised to the intervention and seven were randomised to usual care. Predetermined progression criteria were recruitment of care homes and residents (green); intervention delivery (amber); and data collection and follow-up – 52% of residents provided usable accelerometer data at 9 months (red), &gt; 75% of residents had reported outcomes at 9 months (green, but self-reported resident outcomes were red), 26% loss of residents to follow-up at 9 months [just missing green criterion (no greater than 25%)] and safety concerns (green). Limitations: Observations of residents’ movements were not conducted in private spaces. Working with care home residents to identify appropriate outcome measures was challenging. Take-up of the intervention was suboptimal in some sites. It was not possible to make a reliably informed decision on the most appropriate physical activity end point(s) for future use in a definitive trial. Conclusions: A whole-home intervention was developed that was owned and delivered by staff and was informed by residents and staff. The feasibility of conducting a cluster randomised controlled trial was successfully tested: the target numbers of care homes and residents were recruited, demonstrating that it is possible to recruit care home residents to a cluster randomised trial, although this process was time-consuming and resource heavy. A large data set was collected, which provided a comprehensive picture of the environment, residents and staff in care homes. Extensive quantitative and qualitative work comprehensively explored a neglected area of health and social care research. Completion of ethnographic work in a range of settings enabled the production of an in-depth picture of life in care homes that will be helpful for other researchers considering organisational change in this setting. Future work: The content and delivery of the intervention requires optimisation and the outcome measurement requires further refinement prior to undertaking a full trial evaluation. Consideration could be given to a recommended, simplified, core outcome set, which would facilitate data collection in this population.National Institute for Health Researc

Quality-of-life assessment in dementia: the use of DEMQOL and DEMQOL-Proxy total scores

Purpose There is a need to determine whether health-related quality-of-life (HRQL) assessments in dementia capture what is important, to form a coherent basis for guiding research and clinical and policy decisions. This study investigated structural validity of HRQL assessments made using the DEMQOL system, with particular interest in studying domains that might be central to HRQL, and the external validity of these HRQL measurements. Methods HRQL of people with dementia was evaluated by 868 self-reports (DEMQOL) and 909 proxy reports (DEMQOL-Proxy) at a community memory service. Exploratory and confirmatory factor analyses (EFA and CFA) were conducted using bifactor models to investigate domains that might be central to general HRQL. Reliability of the general and specific factors measured by the bifactor models was examined using omega (?) and omega hierarchical (? h) coefficients. Multiple-indicators multiple-causes models were used to explore the external validity of these HRQL measurements in terms of their associations with other clinical assessments. Results Bifactor models showed adequate goodness of fit, supporting HRQL in dementia as a general construct that underlies a diverse range of health indicators. At the same time, additional factors were necessary to explain residual covariation of items within specific health domains identified from the literature. Based on these models, DEMQOL and DEMQOL-Proxy overall total scores showed excellent reliability (? h > 0.8). After accounting for common variance due to a general factor, subscale scores were less reliable (? h < 0.7) for informing on individual differences in specific HRQL domains. Depression was more strongly associated with general HRQL based on DEMQOL than on DEMQOL-Proxy (?0.55 vs ?0.22). Cognitive impairment had no reliable association with general HRQL based on DEMQOL or DEMQOL-Proxy. Conclusions The tenability of a bifactor model of HRQL in dementia suggests that it is possible to retain theoretical focus on the assessment of a general phenomenon, while exploring variation in specific HRQL domains for insights on what may lie at the ‘heart’ of HRQL for people with dementia. These data suggest that DEMQOL and DEMQOL-Proxy total scores are likely to be accurate measures of individual differences in HRQL, but that subscale scores should not be used. No specific domain was solely responsible for general HRQL at dementia diagnosis. Better HRQL was moderately associated with less depressive symptoms, but this was less apparent based on informant reports. HRQL was not associated with severity of cognitive impairment

Cognitive Reserve and the Prevention of Dementia: the Role of Physical and Cognitive Activities

Purpose of Review: The article discusses the two most significant modifiable risk factors for dementia, namely, physical inactivity and lack of stimulating cognitive activity, and their effects on developing cognitive reserve. Recent Findings: Both of these leisure-time activities were associated with significant reductions in the risk of dementia in longitudinal studies. In addition, physical activity, particularly aerobic exercise, is associated with less age-related gray and white matter loss and with less neurotoxic factors. On the other hand, cognitive training studies suggest that training for executive functions (e.g., working memory) improves prefrontal network efficiency, which provides support to brain functioning in the face of cognitive decline. Summary: While physical activity preserves neuronal structural integrity and brain volume (hardware), cognitive activity strengthens the functioning and plasticity of neural circuits (software), thus supporting cognitive reserve in different ways. Future research should examine whether lifestyle interventions incorporating these two domains can reduce incident dementia

Revised Lithostratigraphy of the Sonsela Member (Chinle Formation, Upper Triassic) in the Southern Part of Petrified Forest National Park, Arizona

BACKGROUND: Recent revisions to the Sonsela Member of the Chinle Formation in Petrified Forest National Park have presented a three-part lithostratigraphic model based on unconventional correlations of sandstone beds. As a vertebrate faunal transition is recorded within this stratigraphic interval, these correlations, and the purported existence of a depositional hiatus (the Tr-4 unconformity) at about the same level, must be carefully re-examined. METHODOLOGY/PRINCIPAL FINDINGS: Our investigations demonstrate the neglected necessity of walking out contacts and mapping when constructing lithostratigraphic models, and providing UTM coordinates and labeled photographs for all measured sections. We correct correlation errors within the Sonsela Member, demonstrate that there are multiple Flattops One sandstones, all of which are higher than the traditional Sonsela sandstone bed, that the Sonsela sandstone bed and Rainbow Forest Bed are equivalent, that the Rainbow Forest Bed is higher than the sandstones at the base of Blue Mesa and Agate Mesa, that strata formerly assigned to the Jim Camp Wash beds occur at two stratigraphic levels, and that there are multiple persistent silcrete horizons within the Sonsela Member. CONCLUSIONS/SIGNIFICANCE: We present a revised five-part model for the Sonsela Member. The units from lowest to highest are: the Camp Butte beds, Lot's Wife beds, Jasper Forest bed (the Sonsela sandstone)/Rainbow Forest Bed, Jim Camp Wash beds, and Martha's Butte beds (including the Flattops One sandstones). Although there are numerous degradational/aggradational cycles within the Chinle Formation, a single unconformable horizon within or at the base of the Sonsela Member that can be traced across the entire western United States (the "Tr-4 unconformity") probably does not exist. The shift from relatively humid and poorly-drained to arid and well-drained climatic conditions began during deposition of the Sonsela Member (low in the Jim Camp Wash beds), well after the Carnian-Norian transition