Effect of an evidence based quality improvement framework on patient safety

Objectives To investigate the impact of the introduction of The Productive Ward Program™ on two patient safety indicators; patient falls and medication errors. Design Retrospective quantitative study. Setting The study was conducted at a major metropolitan acute care hospital in Sydney, Australia. Subjects This study was conducted in a medical, surgical and two aged care wards, with a combined total of 120 inpatient beds over a 32 month time period. Main Outcome Measures The number of patient falls and medication errors for each of the participating wards. Results The implementation of The Productive Ward Program™, did not have an overall significant statistical reduction in the number of falls and medication incidents. Aged Care 1, had a reduction of 13 falls between intervention and post intervention phase, these results were not statistically significant (OR 1.17; 95% CI 0.86, 1.59). For Aged Care 1 ward there was a statistically significant reduction in medication errors from 66 errors pre intervention to 27 medication errors post intervention (OR 2.73;95% CI 1.71, 4.38). Conclusion The results of this small study indicate that the implementation of The Productive Ward Program™, did not have an overall significant statistical reduction in the number of falls and medication errors. This paper highlights the need for future research on the impact of the Productive Ward Program on patient safety

A non-randomised controlled pilot study of clinical pharmacist collaborative intervention for community dwelling patients with COPD

UK, home-based patients with COPD receive specialist care from respiratory physicians, nurses, and general practitioners (GPs), but increasing complexity of therapeutic options and a GP/Nurse workforce crisis suggests merit in testing the role of home visits by a clinical pharmacist. We conducted a non-randomised intervention study with a contemporaneous comparator group, in Glasgow (Scotland). A clinical pharmacist (working closely with a consultant respiratory physician) visited patients with COPD living at home, assessing respiratory and other co-morbid conditions, and medicines then, with patient approval, agreed treatment modifications with a consultant physician. Comparator group-patients were drawn from another hospital out-patient clinic. Main outcomes were exacerbations during 4-months of follow-up and respiratory hospitalisations (number and duration) after 1 year. In the intervention group, 86 patients received a median of three home visits; 87 received usual care (UC). At baseline, patients in the intervention group were similar to those in UC in terms of respiratory hospitalisations although slightly younger, more likely to receive specific maintenance antibiotics/Prednisolone and to have had exacerbations. Sixty-two (72.1%) of the intervention group received dose changes; 45 (52.3%) had medicines stopped/started and 21 (24.4%) received an expedited review at the specialist respiratory consultant clinic; 46 (53.5%) were referred to other healthcare services. Over one-third were referred for bone scans and 11% received additional investigations. At follow-up, 54 (63.5%) of intervention group participants had an exacerbation compared with 75 (86.2%) in the UC group (p = 0.001); fewer had respiratory hospitalisations (39 (45.3%) vs. 66 (76.7%); p < 0.001). Hospitalisations were shorter in the intervention group. Pharmacist-consultant care for community dwelling patients with COPD, changed clinical management and improved outcomes. A randomised controlled trial would establish causality

Land systems as surrogates for biodiversity in conservation planning

Environmental surrogates (land classes) for the distribution of biodiversity are increasingly being used for conservation planning. However; data that demonstrate coincident patterns in land classes and biodiversity are limited. We ask the overall question, "Are land systems effective surrogates for the spatial configuration of biodiversity for conservation planning?" and we address three specific questions: (1) Do different land systems represent different biological assemblages.? (2) Do biological assemblages on the same land system remain similar with increasing geographic separation? and (3) Do biological assemblages on the same land system remain similar with increasing land system isolation? Vascular plants, invertebrates, and microbiota were surveyed from 24 sites in four land systems in and northwest New South Wales, Australia. Within each land system, sites were located to give a hierarchy of inter-site distances, and land systems were classified as either "low isolation" (large and continuous) or "high isolation" (small patches interspersed among other land systems). Each type of land system supported components of biodiversity either not found, or found infrequently, on other land systems, suggesting that land systems function as surrogates for biodiversity, and that conservation-area networks representing land-system diversity will also represent biological diversity. However, the majority of taxa were found on more than one land-system type, suggesting that a large proportion of the plant, arthropod, and microbial biodiversity may be characterized by widespread species with low fidelity to particular land systems. Significant relationships between geographic distance among sites and differences among assemblages were revealed for all taxa except the microbiota. Therefore, as sites on the same land system were located farther apart, the assemblages at those sites became more different. This finding strongly suggests that conservation planning based on land-system diversity should also sample the geographic range occupied by each land system. Land-system isolation was not revealed to be a significant Source of variation in assemblage composition. Our research finds support for environmental surrogates for biodiversity in conservation planning, specifically the use of land systems and similarly derived land classifications. However, the need for explicit modeling of geographic distance in conservation planning is clearly indicated

Integrating quantitative and qualitative data and findings when undertaking randomised controlled trials

It is common to undertake qualitative research alongside randomised controlled trials (RCTs) when evaluating complex interventions. Researchers tend to analyse these datasets one by one and then consider their findings separately within the discussion section of the final report, rarely integrating quantitative and qualitative data or findings, and missing opportunities to combine data in order to add rigour, enabling thorough and more complete analysis, provide credibility to results, and generate further important insights about the intervention under evaluation. This paper reports on a 2 day expert meeting funded by the United Kingdom Medical Research Council Hubs for Trials Methodology Research with the aims to identify current strengths and weaknesses in the integration of quantitative and qualitative methods in clinical trials, establish the next steps required to provide the trials community with guidance on the integration of mixed methods in RCTs and set-up a network of individuals, groups and organisations willing to collaborate on related methodological activity. We summarise integration techniques and go beyond previous publications by highlighting the potential value of integration using three examples that are specific to RCTs. We suggest that applying mixed methods integration techniques to data or findings from studies involving both RCTs and qualitative research can yield insights that might be useful for understanding variation in outcomes, the mechanism by which interventions have an impact, and identifying ways of tailoring therapy to patient preference and type. Given a general lack of examples and knowledge of these techniques, researchers and funders will need future guidance on how to undertake and appraise them

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Multisystem Inflammatory Syndrome in Children — Initial Therapy and Outcomes

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Background: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. Methods: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. Results: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. Conclusions: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.)

Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Importance Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Exposures Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19–related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown

Protection with Recombinant \u3ci\u3eClostridium botulinum\u3c/i\u3e C1 And D Binding Domain Subunit (Hc) Vaccines Against C and D Neurotoxins

Recombinant botulinum Hc (rBoNT Hc) vaccines for serotypes C1 and D were produced in the yeast Pichia pastoris and used to determine protection against four distinct BoNT C and D toxin subtypes. Mice were vaccinated with rBoNT/C1 Hc, rBoNT/D Hc, or with a combination of both vaccines and challenged with BoNT C1, D, C/D, or D/C toxin. Mice receiving monovalent vaccinations were partially or completely protected against homologous toxin and not protected against heterologous toxin. Bivalent vaccine candidates completely survived challenges from all toxins except D/C toxin. These results indicate the recombinant C1 and D Hc vaccines are not only effective in a monovalent formula but offer complete protection against both parental and C/D mosaic toxin and partial protection against D/C mosaic toxin when delivered as a bivalent vaccine