Transfer of care – a randomised control trial investigating the effect of sending the details of patients’ discharge medication to their community pharmacist on discharge from hospital

Objective: There is substantial evidence demonstrating that transferring patients between care providers is a high-risk area for medicines management. This study aimed to investigate the effect of sending patients’ hospital discharge letters to their nominated community pharmacists on the number of discrepancies between the patient’s general practitioner (GP) records and the discharge letter and between the patient’s self-described medication regime and the discharge letter. Methods: In a randomised, controlled trial, 33 participants in two groups, control and intervention, had their discharge letter sent to either their GP only or their GP and nominated community pharmacy after hospital discharge. At least 3 weeks after hospital discharge, the participant’s current GP’s medication record and their self-described medication regime was obtained. Discrepancies between their GP medication record and their discharge letter and between the participant’s self-described medication regime and their discharge letter were counted. The number of discrepancies (relative to the number of drugs pre- scribed) in the intervention group was compared with the control group for each of the above two categories, using the chi-squared test to determine the statistical significance of any differences between the two groups. Results: The intervention group had statistically fewer discrepancies than the control group for both data sets: GP records compared with the discharge letters (P < 0.0005); participants’ self-described medication regimes compared with the discharge letters (P < 0.00005). Conclusions: Sending a copy of patients’ discharge letters to their community pharmacists could be beneficial in reducing post-discharge prescribing discrepancies and improving patient understanding of the changes made to their medicines

Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease

AbstractUnlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD

How can frontline expertise and new models of care best contribute to safely reducing avoidable acute admissions? A mixed-methods study of four acute hospitals

BackgroundHospital emergency admissions have risen annually, exacerbating pressures on emergency departments (EDs) and acute medical units. These pressures have an adverse impact on patient experience and potentially lead to suboptimal clinical decision-making. In response, a variety of innovations have been developed, but whether or not these reduce inappropriate admissions or improve patient and clinician experience is largely unknown.AimsTo investigate the interplay of service factors influencing decision-making about emergency admissions, and to understand how the medical assessment process is experienced by patients, carers and practitioners.MethodsThe project used a multiple case study design for a mixed-methods analysis of decision-making about admissions in four acute hospitals. The primary research comprised two parts: value stream mapping to measure time spent by practitioners on key activities in 108 patient pathways, including an embedded study of cost; and an ethnographic study incorporating data from 65 patients, 30 carers and 282 practitioners of different specialties and levels. Additional data were collected through a clinical panel, learning sets, stakeholder workshops, reading groups and review of site data and documentation. We used a realist synthesis approach to integrate findings from all sources.FindingsPatients’ experiences of emergency care were positive and they often did not raise concerns, whereas carers were more vocal. Staff’s focus on patient flow sometimes limited time for basic care, optimal communication and shared decision-making. Practitioners admitted or discharged few patients during the first hour, but decision-making increased rapidly towards the 4-hour target. Overall, patients’ journey times were similar, although waiting before being seen, for tests or after admission decisions, varied considerably. The meaning of what constituted an ‘admission’ varied across sites and sometimes within a site. Medical and social complexity, targets and ‘bed pressure’, patient safety and risk, each influenced admission/discharge decision-making. Each site responded to these pressures with different initiatives designed to expedite appropriate decision-making. New ways of using hospital ‘space’ were identified. Clinical decision units and observation wards allow potentially dischargeable patients with medical and/or social complexity to be ‘off the clock’, allowing time for tests, observation or safe discharge. New teams supported admission avoidance: an acute general practitioner service filtered patients prior to arrival; discharge teams linked with community services; specialist teams for the elderly facilitated outpatient treatment. Senior doctors had a range of roles: evaluating complex patients, advising and training juniors, and overseeing ED activity.ConclusionsThis research shows how hospitals under pressure manage complexity, safety and risk in emergency care by developing ‘ground-up’ initiatives that facilitate timely, appropriate and safe decision-making, and alternative care pathways for lower-risk, ambulatory patients. New teams and ‘off the clock’ spaces contribute to safely reducing avoidable admissions; frontline expertise brings value not only by placing senior experienced practitioners at the front door of EDs, but also by using seniors in advisory roles. Although the principal limitation of this research is its observational design, so that causation cannot be inferred, its strength is hypothesis generation. Further research should test whether or not the service and care innovations identified here can improve patient experience of acute care and safely reduce avoidable admissions.FundingThe National Institute for Health Research (NIHR) Health Services and Delivery Research programme (project number 10/1010/06). This research was supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula

Next generation sequencing of chromosomal rearrangements in patients with split-hand/split-foot malformation provides evidence for DYNC1I1 exonic enhancers of DLX5/6 expression in humans

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this recordSplit-hand/foot malformation type 1 is an autosomal dominant condition with reduced penetrance and variable expression. We report three individuals from two families with split-hand/split-foot malformation (SHFM) in whom next generation sequencing was performed to investigate the cause of their phenotype.Wellcome Trus

Stability testing of the Pfizer-BioNTech BNT162b2 COVID-19 vaccine: a translational study in UK vaccination centres

Objective - The roll-out of the Pfizer-BioNTech BNT162b2 COVID-19 vaccine has brought many logistical challenges, such as the absence of comprehensive stability data leading to strict handling instructions during dilution and administration. Accidental mishandling therefore presents challenging clinical dilemmas, which often led vaccine providers to err on the side of caution and discard mishandled vials rather than risk administering ineffective vaccine. This study aims to answer key questions about the vaccine’s stability to allow for a more informed decision-making process should a non-conformity occur. Methods - Residual vaccine in freshly used, but appropriately stored vials collected from vaccination centres in Brighton, UK, were tested after exposure to various handling conditions and analysed by dynamic light scattering to determine the size of the lipid-mRNA nanoparticles, and gel electrophoresis to visualise the mRNA integrity and separation from the lipid formulation. Results - Knocking or dropping vaccine samples from small heights resulted in lowest levels of instability, indicating low risk of compromising clinical efficacy. However, repeated drawing and injecting through 23 G needles at high speed and, more significantly, shaking and vortexing led to progressive increase in the size and polydispersity index of the lipid-mRNA nanoparticles, coupled with or caused by up to ~50% release of mRNA from the lipid formulation. This is thought to impact the vaccine’s efficacy due to lack of free mRNA protection and cellular internalisation. Conclusions - These results reiterate the importance of adhering to the manufacturer’s instructions on handling, especially with regard to shaking and exposing the vaccine to excessive vibration

Quantifying prediction of pathogenicity for within-codon concordance (PM5) using 7541 functional classifications of BRCA1 and MSH2 missense variants.

PURPOSE: Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical classifications, there is little evidence for variation in practice. METHODS: We used as a truthset 7541 dichotomous functional classifications of BRCA1 and MSH2, spanning 311 codons of BRCA1 and 918 codons of MSH2, generated from large-scale functional assays that have been shown to correlate excellently with clinical classifications. We assessed PM5 at 5 stringencies with incorporation of 8 in silico tools. For each analysis, we quantified a positive likelihood ratio (pLR, true positive rate/false positive rate), the predictive value of PM5-lookup in ClinVar compared with the functional truthset. RESULTS: pLR was 16.3 (10.6-24.9) for variants for which there was exactly 1 additional colocated deleterious variant on ClinVar, and the variant under examination was equally or more damaging when analyzed using BLOSUM62. pLR was 71.5 (37.8-135.3) for variants for which there were 2 or more colocated deleterious ClinVar variants, and the variant under examination was equally or more damaging than at least 1 colocated variant when analyzed using BLOSUM62. CONCLUSION: These analyses support the graded use of PM5, with potential to use it at higher evidence weighting where more stringent criteria are met

A Specific CNOT1 Mutation Results in a Novel Syndrome of Pancreatic Agenesis and Holoprosencephaly through Impaired Pancreatic and Neurological Development.

We report a recurrent CNOT1 de novo missense mutation, GenBank: NM_016284.4; c.1603C>T (p.Arg535Cys), resulting in a syndrome of pancreatic agenesis and abnormal forebrain development in three individuals and a similar phenotype in mice. CNOT1 is a transcriptional repressor that has been suggested as being critical for maintaining embryonic stem cells in a pluripotent state. These findings suggest that CNOT1 plays a critical role in pancreatic and neurological development and describe a novel genetic syndrome of pancreatic agenesis and holoprosencephaly.IB is funded by Wellcome (WT206194). ATH and SE are the recipients of a Wellcome Trust Senior Investigator award and ATH is employed as a core member of staff within the NIHR funded Exeter Clinical Research Facility and is an NIHR senior investigator. EDF was a Naomi Berrie Fellow in Diabetes Research during the study. SEF has a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number: 105636/Z/14/Z). CCW holds a Wellcome Trust Intermediate Clinical Fellowship (Grant Number: 105914/Z/14/Z). HH is funded by the Research Foundation-Flanders (FWO), the VUB Research Council and Stichting Diabetes Onderzoek Nederland

Red-flag sepsis and SOFA identifies different patient population at risk of sepsis-related deaths on the general ward

Controversy exists regarding the best diagnostic and screening tool for sepsis outside the intensive care unit (ICU). Sequential organ failure assessment (SOFA) score has been shown to be superior to systemic inflammatory response syndrome (SIRS) criteria, however, the performance of “Red Flag sepsis criteria” has not been tested formally. The aim of the study was to investigate the ability of Red Flag sepsis criteria to identify the patients at high risk of sepsis-related death in comparison to SOFA based sepsis criteria. We also investigated the comparison of Red Flag sepsis to quick SOFA (qSOFA), SIRS, and national early warning score (NEWS) scores and factors influencing patient mortality. Patients were recruited into a 24-hour point-prevalence study on the general wards and emergency departments across all Welsh acute hospitals. Inclusion criteria were: clinical suspicion of infection and NEWS 3 or above in-line with established escalation criteria in Wales. Data on Red Flag sepsis and SOFA criteria was collected together with qSOFA and SIRS scores and 90-day mortality. 459 patients were recruited over a 24-hour period. 246 were positive for Red Flag sepsis, mortality 33.7% (83/246); 241 for SOFA based sepsis criteria, mortality 39.4% (95/241); 54 for qSOFA, mortality 57.4% (31/54), and 268 for SIRS, mortality 33.6% (90/268). 55 patients were not picked up by any criteria. We found that older age was associated with death with OR (95% CI) of 1.03 (1.02–1.04); higher frailty score 1.24 (1.11–1.40); DNA-CPR order 1.74 (1.14–2.65); ceiling of care 1.55 (1.02–2.33); and SOFA score of 2 and above 1.69 (1.16–2.47). The different clinical tools captured different subsets of the at-risk population, with similar sensitivity. SOFA score 2 or above was independently associated with increased risk of death at 90 days. The sequalae of infection-related organ dysfunction cannot be reliably captured based on routine clinical and physiological parameters alone

Not all waits are equal: An investigation of emergency care patient pathway.

Abstract Background: Increasing pressure in the United Kingdom (UK) urgent care system has led to Emergency Departments (EDs) failing to meet the national requirement that 95% of patients are admitted, discharged or transferred within 4-h of arrival. Despite the target being the same for all acute hospitals, individual Trusts organise their services in different ways. The impact of this variation on patient journey time and waiting is unknown. Our study aimed to apply the Lean technique of Value Stream Mapping (VSM) to investigate care processes and delays in patient journeys at four contrasting hospitals. Methods: VSM timing data were collected for patients accessing acute care at four hospitals in South West England. Data were categorised according to waits and activities, which were compared across sites to identify variations in practice from the patient viewpoint. We included Public and Patient Involvement (PPI) to fully interpret our findings; observations and initial findings were considered in a PPI workshop. Results: One hundred eight patients were recruited, comprising 25,432 min of patient time containing 4098 episodes of care or waiting. The median patient journey was 223 min (3 h, 43 min); just within the 4-h target. Although total patient journey times were similar between sites, the stage where the greatest proportion of waiting occurred varied. Reasons for waiting were dominated by waits for beds, investigations or results to be available. From our sample we observed that EDs without a discharge/clinical decision area exhibited a greater proportion of waiting time following an admission or discharge decision. PPI interpretation indicated that patients who experience waits at the beginning of their journey feel more anxious because they are ‘not in the system yet’. Conclusions: The novel application of VSM analysis across different hospitals, coupled with PPI interpretation, provides important insight into the impact of care provision on patient experience. Measures that could reduce patient waiting include automatic notification of test results, and the option of discharge/clinical decision areas for patients awaiting results or departure. To enhance patient experience, good communication with patients and relatives about reasons for waits is essential. Keywords: Health service research, Acute care, Emergency admissions, Patient care, Value stream mapping, Emergency department, Patient public involvemen