Nurse-Led Medicines' Monitoring for Patients with Dementia in Care Homes: A Pragmatic Cohort Stepped Wedge Cluster Randomised Trial

People with dementia are susceptible to adverse drug reactions (ADRs). However, they are not always closely monitored for potential problems relating to their medicines: structured nurse-led ADR Profiles have the potential to address this care gap. We aimed to assess the number and nature of clinical problems identified and addressed and changes in prescribing following introduction of nurse-led medicines' monitoring.Pragmatic cohort stepped-wedge cluster Randomised Controlled Trial (RCT) of structured nurse-led medicines' monitoring versus usual care.Five UK private sector care homes.41 service users, taking at least one antipsychotic, antidepressant or anti-epileptic medicine.Nurses completed the West Wales ADR (WWADR) Profile for Mental Health Medicines with each participant according to trial step.Problems addressed and changes in medicines prescribed.Information was collected from participants' notes before randomisation and after each of five monthly trial steps. The impact of the Profile on problems found, actions taken and reduction in mental health medicines was explored in multivariate analyses, accounting for data collection step and site.Five of 10 sites and 43 of 49 service users approached participated. Profile administration increased the number of problems addressed from a mean of 6.02 [SD 2.92] to 9.86 [4.48], effect size 3.84, 95% CI 2.57-4.11, P <0.001. For example, pain was more likely to be treated (adjusted Odds Ratio [aOR] 3.84, 1.78-8.30), and more patients attended dentists and opticians (aOR 52.76 [11.80-235.90] and 5.12 [1.45-18.03] respectively). Profile use was associated with reduction in mental health medicines (aOR 4.45, 1.15-17.22).The WWADR Profile for Mental Health Medicines can improve the quality and safety of care, and warrants further investigation as a strategy to mitigate the known adverse effects of prescribed medicines.ISRCTN 48133332

Calpain Inhibition Restores Autophagy and Prevents Mitochondrial Fragmentation in a Human iPSC Model of Diabetic Endotheliopathy

The relationship between diabetes and endothelial dysfunction remains unclear, particularly the association with pathological activation of calpain, an intracellular cysteine protease. Here, we used human induced pluripotent stem cells-derived endothelial cells (iPSC-ECs) to investigate the effects of diabetes on vascular health. Our results indicate that iPSC-ECs exposed to hyperglycemia had impaired autophagy, increased mitochondria fragmentation, and was associated with increased calpain activity. In addition, hyperglycemic iPSC-ECs had increased susceptibility to cell death when subjected to a secondary insult-simulated ischemia-reperfusion injury (sIRI). Importantly, calpain inhibition restored autophagy and reduced mitochondrial fragmentation, concurrent with maintenance of ATP production, normalized reactive oxygen species levels and reduced susceptibility to sIRI. Using a human iPSC model of diabetic endotheliopathy, we demonstrated that restoration of autophagy and prevention of mitochondrial fragmentation via calpain inhibition improves vascular integrity. Our human iPSC-EC model thus represents a valuable platform to explore biological mechanisms and new treatments for diabetes-induced endothelial dysfunction.Singapore Ministry of Health's National Medical Research Council Open Fund-Young Individual Research Grant [NMRC/OFYIRG/0021/2016]; Khoo Postdoctoral Fellowship Award [Duke-NUS-KPFA/2016/0010]; Hitachi Scholarship Research Support Grant from the Hitachi Global Foundation, Japan [RS-13, H-1]; American Heart Association Scientist Development Grant [16SDG27560003]; Stanford Diabetes Research Center under NIH [P30DK116074]; Frontier Research Grant 2017 from the Frontier Science Research Cluster (FSRC), Universiti Malaya, Malaysia [FG021-17AFR]; NIH [R01HL126516, R00HL130416]; Samsung Biomedical Research Institute [OTC 1180261]; National Research Foundation of Korea [NRF-2016R1A2B4008235]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Treatment effects may remain the same even when trial participants differed from the target population

Objective RCTs have been criticised for lacking external validity. We assessed whether a trial in people with type I diabetes mellitus (T1DM) mirrored the wider population, and applied sample-weighting methods to assess the impact of differences on our trial's findings. Study design and setting The REPOSE trial was nested within a large UK cohort capturing demographic, clinical and quality of life (QoL) data for people with T1DM undergoing structured diabetes-specific education. We firstly assessed whether our RCT participants were comparable to this cohort using propensity score modelling. Following this we re-weighted the trial population to better match the wider cohort and re-estimated the treatment effect. Results Trial participants differed from the cohort in regards to sex, weight, HbA1c and also QoL and satisfaction with current treatment. Nevertheless, the treatment effects derived from alternative model weightings were similar to that of the original RCT. Conclusions Our RCT participants differed in composition to the wider population but the original findings were unaffected by sampling adjustments. We encourage investigators take steps to address criticisms of generalisability, but doing so is problematic: external data, even if available, may contain limited information and analyses can be susceptible to model misspecification

Muddying the Picture? Forecasting Particulate Sources and Dispersal Patterns in Managed Catchments

Satellite imagery and climate change projections improve our ability to map and forecast sediment sources and transport pathways at high resolution, which is vital for catchment management. Detailed assessment of temporal and spatial changes in erosion risk are key to forecasting pollutant dispersal, which affects water treatment costs and ecology. Outputs from scenario modeling of the River Derwent catchment, Yorkshire, indicate clear spatial and temporal trends in erosion risk. These trends are not picked up by using traditional methods, which rely on static land use maps. Using satellite-derived maps show that lower resolution traditional land-use maps relatively underestimate erosion risk in terms of location of source areas and seasonal variation in erosion risk. Seasonal variation in agricultural practices can be assessed by incorporating bare land variation into models, which show that erosion risk is relatively overestimated if all agricultural land is assumed to have the same character. Producing seasonal land use maps also allows the assessment of temporal variation in rainfall, which in combination with climate change projections allows for adaptable management plans. The bias in gradient in modeling, which assumes that high gradients result in greater sediment erosion risk, show that traditional models underestimate the contribution of erosion risk in lowland areas. This is compounded by the absence of artificial drainages in topographic rasters, which increases connectivity in lowland areas. By producing end member scenarios, model outputs help to inform where catchment management should be targeted, and whether seasonal interventions should be implemented. This information is vital to communicate with landowners when they implement catchment management practices, such as sediment traps and earth bunds. Adaption of erosion risk modeling practices is urgently needed in order to quantify the impact of artificial interference in which human activity disrupts ‘natural’ sediment source-to sink configurations, such as integrating new pathways and stores due to land use change and management. Furthermore, integrating higher resolution catchment modeling and improved seasonal forecasts of pollutant flux to oceans will permit more effective interventions. This paper highlights single output erosion risk maps are not effective to inform catchment management

Medication Monitoring for People with Dementia in Care Homes: the Feasibility and Clinical Impact of Nurse-led monitoring

Objectives. People with dementia are susceptible to adverse effects of medicines. However, they are not always closely monitored. We explored (1) feasibility and (2) clinical impact of nurse-led medication monitoring. Design. Feasibility “before-and-after” intervention study. Setting. Three care homes in Wales. Participants. Eleven service users diagnosed with dementia, taking at least one antipsychotic, antidepressant, or antiepileptic medicine. Intervention. West Wales Adverse Drug Reaction (ADR) Profile for Mental Health Medicines. Outcome Measures. (1) Feasibility: recruitment, retention, and implementation. (2) Clinical impact: previously undocumented problems identified and ameliorated, as recorded in participants’ records before and after introduction of the profile, and one month later. Results. Nurses recruited and retained 11 of 29 eligible service users. The profile took 20–25 minutes to implement, caused no harm, and supplemented usual care. Initially, the profile identified previously undocumented problems for all participants (mean 12.7 (SD 4.7)). One month later, some problems had been ameliorated (mean 4.9 (3.6)). Clinical gains included new prescriptions to manage pain (2 participants), psoriasis (1), Parkinsonian symptoms (1), rash (1), dose reduction of benzodiazepines (1), new care plans for oral hygiene, skin problems, and constipation. Conclusions. Participants benefited from structured nurse-led medication monitoring. Clinical trials of our ADR Profile are feasible and necessary