The prediction of radiationâ induced liver dysfunction using a local dose and regional venous perfusion model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134805/1/mp1081.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

Background: Hospital 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. Aims: To 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. Methods: The 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. Findings: Patients’ 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. Conclusions: This 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. Funding: The 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

CloneQC: lightweight sequence verification for synthetic biology

Synthetic biology projects aim to produce physical DNA that matches a designed target sequence. Chemically synthesized oligomers are generally used as the starting point for building larger and larger sequences. Due to the error rate of chemical synthesis, these oligomers can have many differences from the target sequence. As oligomers are joined together to make larger and larger synthetic intermediates, it becomes essential to perform quality control to eliminate intermediates with errors and retain only those DNA molecules that are error free with respect to the target. This step is often performed by transforming bacteria with synthetic DNA and sequencing colonies until a clone with a perfect sequence is identified. Here we present CloneQC, a lightweight software pipeline available as a free web server and as source code that performs quality control on sequenced clones. Input to the server is a list of desired sequences and forward and reverse reads for each clone. The server generates summary statistics (error rates and success rates target-by-target) and a detailed report of perfect clones. This software will be useful to laboratories conducting in-house DNA synthesis and is available at http://cloneqc.thruhere.net/ and as Berkeley Software Distribution (BSD) licensed source

A multi‐institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99090/1/cncr28117.pd

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

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

Background Hospital 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. Aims To 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. Methods The 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. Findings Patients’ 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. Conclusions This 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

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Complete Genome Sequence of the Aerobic CO-Oxidizing Thermophile Thermomicrobium roseum

In order to enrich the phylogenetic diversity represented in the available sequenced bacterial genomes and as part of an “Assembling the Tree of Life” project, we determined the genome sequence of Thermomicrobium roseum DSM 5159. T. roseum DSM 5159 is a red-pigmented, rod-shaped, Gram-negative extreme thermophile isolated from a hot spring that possesses both an atypical cell wall composition and an unusual cell membrane that is composed entirely of long-chain 1,2-diols. Its genome is composed of two circular DNA elements, one of 2,006,217 bp (referred to as the chromosome) and one of 919,596 bp (referred to as the megaplasmid). Strikingly, though few standard housekeeping genes are found on the megaplasmid, it does encode a complete system for chemotaxis including both chemosensory components and an entire flagellar apparatus. This is the first known example of a complete flagellar system being encoded on a plasmid and suggests a straightforward means for lateral transfer of flagellum-based motility. Phylogenomic analyses support the recent rRNA-based analyses that led to T. roseum being removed from the phylum Thermomicrobia and assigned to the phylum Chloroflexi. Because T. roseum is a deep-branching member of this phylum, analysis of its genome provides insights into the evolution of the Chloroflexi. In addition, even though this species is not photosynthetic, analysis of the genome provides some insight into the origins of photosynthesis in the Chloroflexi. Metabolic pathway reconstructions and experimental studies revealed new aspects of the biology of this species. For example, we present evidence that T. roseum oxidizes CO aerobically, making it the first thermophile known to do so. In addition, we propose that glycosylation of its carotenoids plays a crucial role in the adaptation of the cell membrane to this bacterium's thermophilic lifestyle. Analyses of published metagenomic sequences from two hot springs similar to the one from which this strain was isolated, show that close relatives of T. roseum DSM 5159 are present but have some key differences from the strain sequenced

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine