Outcomes of a research project to identify the enablers and barriers to effective preceptorship for newly qualified nurses

Poster presentationFunded by Chesterfield Royal Hospital NHS Trus

Optic Nerve Head Gene Transcription Sequelae to a Single Elevated IOP Exposure Provides Insights Into Known Responses to Chronically Elevated IOP

Purpose: To clarify the optic nerve head (ONH) gene expression responses associated with a single, axon-damaging exposure to elevated IOP in relation to the composite cellular events previously identified in models of chronically elevated IOP. Methods: Anesthetized rats were exposed unilaterally to an 8-hour pulse-train controlled elevation of IOP (PT-CEI) at 60 mm Hg, while others received normotensive CEI at 20 mm Hg. ONH RNA was harvested at 0 hours and 1, 2, 3, 7, and 10 days after either CEI and from naïve animals. RNA sequencing was performed to analyze ONH gene expression. DAVID Bioinformatics tools were used to identify significant functional annotation clusters. Gene function was compared between PT-CEI and two models of chronic ocular hypertension from the literature. Results: The number of significantly changed genes peaked immediately (n = 1354) after PT-CEI (0 hours). This was followed by a lull (point) at 1 and 2 days after PT-CEI. Gene activity increased again at 3 days (136 genes) and persisted at 7 (78 genes) and 10 (339 genes) days. Significant gene functional categories included an immediate upregulation of Defense Response at 0 hours, followed by upregulation in Cell Cycle, a reduction in Axonal-related genes at 3 to 10 days, and upregulation of Immune Response–related genes at 10 days following PT-CEI. The most commonly upregulated gene expression across our PT-CEI study and two chronic models of ocular hypertension were cell cycle related. Conclusions: The PT-CEI model places in sequence ONH gene expression responses previously reported in models with chronically elevated IOP and may provide insights into their role in optic nerve damage

Life-Cycle impacts of Inland Northwest and Northeast/North central forest resources

Determining the life-cycle inventory (LCI) and impact of forest harvest, regeneration, and growth is necessary in conducting a life-cycle assessment of wood products. This publication provides quantitative assessments of the economic and environmental impacts of forest management activities covering portions of the Inland Northwest (INW), including Montana, Idaho, and eastern Washington, and of the Northeastern and North Central (NE/NC) forests from Minnesota to Maine and south as far as Missouri, West Virginia, and Pennsylvania. The management scenarios provide the inputs needed to develop an LCI on all the inputs and outputs for wood products as impacted by forest treatments and the harvesting of logs in the region. Productive timberlands were grouped according to forest type, productivity, management intensity, and ownership into three broad forest types in the west: cold, dry, and moist; and four in the east: spruce/fir, northern hardwoods, oak/hickory, and aspen/birch. Spruce/fir represented the feedstock to softwood lumber and a composite of northern hardwoods and oak/hickory the feedstock to hardwood lumber. Simulations used the US Forest Service Forest Vegetation Simulator to estimate standing and harvested biomass and log volumes passed on as resources to the manufacturing segments for lumber, plywood, or oriented strandboard. The combinations of ownership, management intensity, and forest type were stratified and averaged to produce a single estimate of yield and the corresponding harvesting impacts. Both historic harvest rates and increased management intensity scenarios were simulated for each region. In the INW, the shift to the higher intensity scenario increased the average production of merchantable volume at harvest to 249 - 399 m3/ha when averaged across the forested land in each ownership class. For the NE/NC region, the production of merchantable volume averaged 263 m3/ha for softwood and 328 m3/ha for hardwood forests with an insignificant volume response from shifting land into more intensive management. Average growth varied widely for INW forest categories from a low on federal land for the base case of 0.7 - 6.7 m3/haha·yr for moist state and private land under the intensive management alternative. Current condition estimates of softwood log and bark carbon exported for mill processing in the INW and NE/NC regions were 751 and 988 kg/ha·yr, respectively

Deep and abyssal ocean warming from 35 years of repeat hydrography

Global and regional ocean warming deeper than 2000 m is investigated using 35 years of sustained repeat hydrographic survey data starting in 1981. The global long-term temperature trend below 2000 m, representing the time period 1991–2010, is equivalent to a mean heat flux of 0.065 ± 0.040 W m?2 applied over the Earth's surface area. The strongest warming rates are found in the abyssal layer (4000–6000 m), which contributes to one third of the total heat uptake with the largest contribution from the Southern and Pacific Oceans. A similar regional pattern is found in the deep layer (2000–4000 m), which explains the remaining two thirds of the total heat uptake yet with larger uncertainties. The global average warming rate did not change within uncertainties pre-2000 versus post-2000, whereas ocean average warming rates decreased in the Pacific and Indian Oceans and increased in the Atlantic and Southern Oceans

The range and suitability of outcome measures used in the assessment of palliative treatment for inoperable malignant bowel obstruction: A systematic review

Background: Malignant bowel obstruction, a complication of certain advanced cancers, causes severe symptoms which profoundly affect quality of life. Clinical management remains complex, and outcome assessment is inconsistent.Aim: To identify outcomes evaluating palliative treatment for inoperable malignant bowel obstruction, as part of a four-phase study developing a core outcome set. Design: The review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); PROSPERO (ID: CRD42019150648). Eligible studies included at least one subgroup with obstruction below the ligament of Treitz undergoing palliative treatment for inoperable malignant bowel obstruction. Study quality was not assessed because the review does not evaluate efficacy. Data sources: Medline, Embase, the Cochrane Database, CINAHL, PSYCinfo Caresearch, Open Grey and BASE were searched for trials and observational studies in October 2021. Results: A total of 4769 studies were screened, 290 full texts retrieved and 80 (13,898 participants) included in a narrative synthesis; 343 outcomes were extracted verbatim and pooled into 90 unique terms across six domains: physiological, nutrition, life impact, resource use, mortality and survival. Prevalent outcomes included adverse events (78% of studies), survival (54%), symptom control (39%) and mortality (31%). Key individual symptoms assessed were vomiting (41% of studies), nausea (34%) and pain (33%); 19% of studies assessed quality of life. Conclusions: Assessment focuses on survival, complications and overall symptom control. There is a need for definitions of treatment ‘success’ that are meaningful to patients, a more consistent approach to symptom assessment, and greater consideration of how to measure wellbeing in this population

Development of a Core Outcome Set for the research and assessment of inoperable malignant bowel obstruction

BackgroundMalignant bowel obstruction is experienced by 15% of people with advanced cancer, preventing them from eating and drinking and causing pain, nausea and vomiting. Surgery is not always appropriate. Management options include tube or stent drainage of intestinal contents and symptom control using medication. Published literature describing palliative interventions uses a broad range of outcome measures, few of which are patient-relevant. This hinders evidence synthesis, and fails to consider the perspectives of people undergoing treatment.AimsTo develop a Core Outcome Set for the assessment of inoperable malignant bowel obstruction with clinician, patient and caregiver involvement, using COMET methodology (Core Outcome Measures in Effectiveness Trials).MethodsA systematic review of clinical trials and observational studies, a rapid review of the qualitative literature and in-depth patient and clinician interviews were conducted to identify a comprehensive list of outcomes. Outcomes were compared and consolidated by the study Steering Group and Patient and Public Involvement contributors, and presented to an international clinical Expert Panel for review. Outcomes from the finalised list were rated for importance in a three-round international Delphi process: results of two survey rounds were circulated to respondents, and two separate consensus meetings were conducted with clinicians and with patients and caregivers via virtual conferencing, using live polling to reach agreement on a Core Outcome Set.Results130 unique outcomes were identified. Following the independent Expert Panel review, 82 outcomes were taken into round 1 of the Delphi survey; 24 outcomes reached criteria for critical importance across all stakeholder groups and none reached criteria for dropping. All outcomes rated critically important were taken forward for re-rating in round 2 and all other outcomes dropped. In round 2, all outcomes were voted critically important by at least one stakeholder group. Round 2 outcomes were presented again at online consensus meetings, categorised as high ranking (n = 9), middle ranking (n = 7) or low ranking (n = 8). Stakeholders reached agreement on 16 core outcomes across four key domains: Symptom control, Life impact, Treatment outcomes, and Communication and patient preferences.ConclusionUse of this Core Outcome Set can help to address current challenges in making sense of the evidence around treatment for inoperable malignant bowel obstruction to date, and underpin a more robust future approach. Clearer communication and an honest understanding between all stakeholders will help to provide a basis for responsible decision-making in this distressing situation in clinical practice

Application of pharmacogenomics and bioinformatics to exemplify the utility of human <i>ex vivo</i> organoculture models in the field of precision medicine

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response

O-3 Opioids, benzodiazepines, anti-cholinergic load and clinical outcomes in patients with advanced cancer

Background Medications used to manage symptoms in patients with cancer have associated, but poorly understood, harms. The aim of this study was to explore the temporal relationship between oral morphine equivalent daily dose (MEDD), oral diazepam equivalent daily dose (DEDD) and the daily anti-cholinergic load (ACL) with cognitive and gastrointestinal symptoms, performance status, quality of life and survival in patients receiving palliative care. Methods Secondary longitudinal analysis of cancer decedents (n=235) from a palliative care trial with multiple outcome measures. At each time-point MEDD, DEDD and ACL were calculated. Multilevel modelling was used to investigate independent associations between MEDD, DEDD and ACL, and cognitive and gastrointestinal symptoms, quality of life, performance status and survival. Results Cognitive and gastrointestinal symptoms, performance status, and quality of life worsened over time. In the adjusted multilevel analysis significance remained for worsening performance status (MEDD, p=0.001; DEDD, p<0.001; ACL p=0.035) and shorter time to death (MEDD, p<0.001; ACL, p<0.01). Conclusion Commonly used palliative medications were associated with deteriorating performance status and shorter time to death. This analysis highlights the importance of adjusting for other variables, including other medication when exploring medication-related harms. An understanding of the risk-benefit balance of medications is needed to maximise net benefit for patients. Future work to delineate interactions between classes of drugs and drug-related harms and to evaluate early assessment and management of side-effects is needed in order to maximise net benefit