Antibiotic prescribing in UK care homes 2016-2017: retrospective cohort study of linked data.

BACKGROUND: Older people living in care homes are particularly susceptible to infections and antibiotics are therefore used frequently for this population. However, there is limited information on antibiotic prescribing in this setting. This study aimed to investigate the frequency, patterns and risk factors for antibiotic prescribing in a large chain of UK care homes. METHODS: Retrospective cohort study of administrative data from a large chain of UK care homes (resident and care home-level) linked to individual-level pharmacy data. Residents aged 65 years or older between 1 January 2016 and 31 December 2017 were included. Antibiotics were classified by type and as new or repeated prescriptions. Rates of antibiotic prescribing were calculated and modelled using multilevel negative binomial regression. RESULTS: 13,487 residents of 135 homes were included. The median age was 85; 63% residents were female. 28,689 antibiotic prescriptions were dispensed, the majority were penicillins (11,327, 39%), sulfonamides and trimethoprim (5818, 20%), or other antibacterials (4665, 16%). 8433 (30%) were repeat prescriptions. The crude rate of antibiotic prescriptions was 2.68 per resident year (95% confidence interval (CI) 2.64-2.71). Increased antibiotic prescribing was associated with residents requiring more medical assistance (adjusted incidence rate ratio for nursing opposed to residential care 1.21, 95% CI 1.13-1.30). Prescribing rates varied widely by care home but there were no significant associations with the care home-level characteristics available in routine data. CONCLUSIONS: Rates of antibiotic prescribing in care homes are high and there is substantial variation between homes. Further research is needed to understand the drivers of this variation to enable development of effective stewardship approaches that target the influences of prescribing

Assessing Specific Cognitive Deficits Associated with Dementia in Older Adults with Down Syndrome: Use and Validity of the Arizona Cognitive Test Battery (ACTB)

BACKGROUND: Down syndrome is associated with specific cognitive deficits. Alongside this, older adults with Down syndrome are a high risk group for dementia. The Arizona Cognitive Test Battery (ACTB), a cognitive assessment battery specifically developed for use with individuals with Down syndrome, has been proposed for use as outcome measures for clinical trials in this population. It has not been validated in older adults with Down syndrome. This study aims to assess the use and validity of the ACTB in older adults with Down syndrome. METHODS: Participants with Down syndrome aged 45 and over were assessed using the ACTB, standard tabletop tests and informant ratings. RESULTS: Assessment outcomes of 49 participants were analysed. Of these, 19 (39%) had a diagnosis of dementia or possible dementia. Most participants were able to attempt most of the tasks, although some tasks had high floor effects (including CANTAB Intra-Extra Dimensional shift stages completed and Modified Dots Task). Of the ACTB tasks, statistically significant differences were observed between the dementia and no dementia groups on CANTAB Simple Reaction Time median latency, NEPSY Visuomotor Precision-Car and Motorbike and CANTAB Paired Associates Learning stages completed. No significant differences were observed for CANTAB Intra-Extra Dimensional Shift, Modified Dots Task, Finger Sequencing, NEPSY Visuomotor precision-Train and Car and CANTAB Paired Associates Learning first trial memory score. Several of the tasks in the ACTB can be used in older adults with Down syndrome and have mild to moderate concurrent validity when compared to tabletop tests and informant ratings, although this varies on a test by test basis. CONCLUSIONS: Overall, scores for a number of tests in the ACTB were similar when comparing dementia and no dementia groups of older adults with Down syndrome, suggesting that it would not be an appropriate outcome measure of cognitive function for clinical trials of dementia treatments without further modification and validation

A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population

The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia

BACKGROUND: A systems approach to understanding the etiology of schizophrenia requires a theory which is able to integrate genetic as well as neurodevelopmental factors. PRESENTATION OF THE HYPOTHESIS: Based on a co-localization of loci approach and a large amount of circumstantial evidence, we here propose that a functional deficiency of glial growth factors and of growth factors produced by glial cells are among the distal causes in the genotype-to-phenotype chain leading to the development of schizophrenia. These factors include neuregulin, insulin-like growth factor I, insulin, epidermal growth factor, neurotrophic growth factors, erbB receptors, phosphatidylinositol-3 kinase, growth arrest specific genes, neuritin, tumor necrosis factor alpha, glutamate, NMDA and cholinergic receptors. A genetically and epigenetically determined low baseline of glial growth factor signaling and synaptic strength is expected to increase the vulnerability for additional reductions (e.g., by viruses such as HHV-6 and JC virus infecting glial cells). This should lead to a weakening of the positive feedback loop between the presynaptic neuron and its targets, and below a certain threshold to synaptic destabilization and schizophrenia. TESTING THE HYPOTHESIS: Supported by informed conjectures and empirical facts, the hypothesis makes an attractive case for a large number of further investigations. IMPLICATIONS OF THE HYPOTHESIS: The hypothesis suggests glial cells as the locus of the genes-environment interactions in schizophrenia, with glial asthenia as an important factor for the genetic liability to the disorder, and an increase of prolactin and/or insulin as possible working mechanisms of traditional and atypical neuroleptic treatments

For local governments, adopting more inclusionary practices is about preparation and action.

Why do some cities make intentional efforts to become more inclusive of their diverse populations while others do not? Using the food metaphor of a “roux”, Jonathan M. Fisk, Geoffrey A. Silvera, John C. Morris, Xi Chen, Xiaofeng Chen, Mac-Jane Crayton and Jan Hume write that without careful consideration by local governments, diverse constituencies may not be able to participate in the communities in which they live. They find that local governments – especially those with a professional city or county manager – are more willing to offer inclusion initiatives such as cultural competency training for their employees when more of their residents are foreign born

The art and science of chart review

BACKGROUND: Explicit chart review was an integral part of an ongoing national cooperative project, Using Achievable Benchmarks of Care to Improve Quality of Care for Outpatients with Depression, conducted by a large managed care organization (MCO) and an academic medical center. Many investigators overlook the complexities involved in obtaining high-quality data. Given a scarcity of advice in the quality improvement (QI) literature on how to conduct chart review, the process of chart review was examined and specific techniques for improving data quality were proposed. METHODS: The abstraction tool was developed and tested in a prepilot phase; perhaps the greatest problem detected was abstractor assumption and interpretation. The need for a clear distinction between symptoms of depression or anxiety and physician diagnosis of major depression or anxiety disorder also became apparent. In designing the variables for the chart review module, four key aspects were considered: classification, format, definition, and presentation. For example, issues in format include use of free-text versus numeric variables, categoric variables, and medication variables (which can be especially challenging for abstraction projects). Quantitative measures of reliability and validity were used to improve and maintain the quality of chart review data. Measuring reliability and validity offers assistance with development of the chart review tool, continuous maintenance of data quality throughout the production phase of chart review, and final documentation of data quality. For projects that require ongoing abstraction of large numbers of clinical records, data quality may be monitored with control charts and the principles of statistical process control. RESULTS: The chart review module, which contained 140 variables, was built using MedQuest software, a suite of tools designed for customized data collection. The overall interrater reliability increased from 80% in the prepilot phase to greater than 96% in the final phase (which included three abstractors and 465 unique charts). The mean time per chart was calculated for each abstractor, and the maximum value was 13.7 +/- 13 minutes. CONCLUSIONS: In general, chart review is more difficult than it appears on the surface. It is also project specific, making a cookbook approach difficult. Many factors, such as imprecisely worded research questions, vague specification of variables, poorly designed abstraction tools, inappropriate interpretation by abstractors, and poor or missing recording of data in the chart, may compromise data quality

Interventions to improve appropriate antibiotic prescribing in long-term care facilities: a systematic review

BACKGROUND: Overuse of antibiotics has contributed to antimicrobial resistance; a growing public health threat. In long-term care facilities, levels of inappropriate prescribing are as high as 75%. Numerous interventions targeting long-term care facilities' antimicrobial stewardship have been reported with varying, and largely unexplained, effects. Therefore, this review aimed to apply behavioural science frameworks to specify the component behaviour change techniques of stewardship interventions in long-term care facilities and identify those components associated with improved outcomes. METHOD: A systematic review (CRD42018103803) was conducted through electronic database searches. Two behavioural science frameworks, the Behaviour Change Wheel and Behaviour Change Technique Taxonomy were used to classify intervention descriptions into intervention types and component behaviour change techniques used. Study design and outcome heterogeneity prevented meta-analysis and meta-regression. Interventions were categorised as 'very promising' (all outcomes statistically significant), 'quite promising' (some outcomes statistically significant), or 'not promising' (no outcomes statistically significant). 'Promise ratios' (PR) were calculated for identified intervention types and behaviour change techniques by dividing the number of (very or quite) promising interventions featuring the intervention type or behaviour change technique by the number of interventions featuring the intervention type or behaviour change technique that were not promising. Promising intervention types and behaviour change techniques were defined as those with a PR ≥ 2. RESULTS: Twenty studies (of19 interventions) were included. Seven interventions (37%) were 'very promising', eight 'quite promising' (42%) and four 'not promising' (21%). Most promising intervention types were 'persuasion' (n = 12; promise ratio (PR) = 5.0), 'enablement' (n = 16; PR = 4.33) and 'education' (n = 19; PR = 3.75). Most promising behaviour change techniques were 'feedback on behaviour' (n = 9; PR = 8.0) and 'restructuring the social environment' (e.g. staff role changes; n = 8; PR = 7.0). CONCLUSION: Systematic identification of the active ingredients of antimicrobial stewardship in long-term care facilities was facilitated through the application of behavioural science frameworks. Incorporating environmental restructuring and performance feedback may be promising intervention strategies for antimicrobial stewardship interventions within long-term care facilities

Effect of cyclo-oxygenase inhibitor use during checkpoint blockade immunotherapy in patients with metastatic melanoma and non-small cell lung cancer

Background Immune checkpoint inhibitors (ICIs) improve survival outcomes in metastatic melanoma and non-small cell lung cancer (NSCLC). Preclinical evidence suggests that overexpression of cyclo-oxygenase-2 (COX2) in tumors facilitates immune evasion through prostaglandin E2 production and that COX inhibition synergizes with ICIs to promote antitumor T-cell activation. This study investigates whether concurrent COX inhibitor (COXi) use during ICI treatment compared with ICI alone is associated with improved time-to-progression (TTP), objective response rate (ORR) and overall survival (OS) in patients with metastatic melanoma and NSCLC.Methods We retrospectively reviewed 90 metastatic melanoma and 37 metastatic NSCLC patients, treated with ICI between 2011 and 2019. Differences in TTP and OS by ICI+COXi versus ICI alone were compared using Kaplan-Meier and Cox regression. Interaction between ICI+COXi versus ICI alone and pretreatment neutrophil–lymphocyte ratio (NLR) was examined. Independent radiology review per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was performed.Results For patients with melanoma, median TTP was significantly prolonged in ICI+COXi versus ICI alone (245 vs 100.5 days, p=0.002). On multivariate analysis, ICI+COXi associated with increased TTP (HR 0.36, 95% CI 0.2 to 0.66, p=0.001), adjusted for age, pretreatment NLR, and gender. For NSCLC patients, ICI+COXi also associated with increased TTP compared with ICI alone on multivariate analysis (HR 0.45; 95% CI 0.21 to 0.97; p=0.042) adjusted for age. ORR at 6 months was significantly higher in patients who received ICI+COXi compared with ICI alone in both melanoma (58.6% vs 19.2%, p=0.0005) and NSCLC (73.7% vs 33.3%, p=0.036) cohorts. In the melanoma cohort, high pretreatment NLR (>5) associated with decreased TTP (HR 3.21, 95% CI 1.64 to 6.3; p=0.0007); however, ICI+COXi significantly associated with increased TTP in high NLR (>5) patients (HR 0.08, 95% CI 0.03 to 0.25), but not in low NLR (≤5) patients (HR 0.65, 95% CI 0.32 to 1.32). Similar outcomes were found in an adjusted melanoma cohort after RECIST review.Conclusions Our study suggests that COXi use concurrently with ICI significantly associated with longer TTP and improved ORR at 6 months in patients with metastatic melanoma and NSCLC compared with ICI alone. Furthermore, COXi use appears to reverse the negative prognostic effect of a high NLR by prolonging TTP in patients with melanoma