Sleep Deprivation in the Intensive Care Unit: Lowering Elective Intervention Times

Sleep deprivation is a multifactorial phenomenon, occurring frequently in the intensive care unit (ICU) and linked to adverse patient healthcare outcomes. The key practice question of this project focused on determining if retiming of routine laboratory and imaging testing outside of the designated “quiet time” can improve sleep quality among adult patients in the ICU. The purpose was to evaluate the effectiveness of implementing an evidence-based intervention to improve sleep quality in the ICU setting. The theoretical framework was the plan-do-study-act model, which offered a process for implementing a practice change and reevaluation of the intervention’s sustainability within the organization. A thorough literature search of over 100 scholarly journal articles, book references, and expert scholarly reports was completed to gain an understanding of this phenomenon in the ICU setting. The Richards-Campbell Sleep Questionnaire (RCSQ) was the data collection tool used to measure improvement in sleep quality. There were 72 participants that are included in the project. The Wilcoxon rank sum and chi square tests were used for the statistical analysis. The findings did not show statistical significance in the improvement in the RCSQ scores after implementation of the intervention. The recommendations include sleep deprivation training for nursing staff and providers, routine use of the RCSQ for data collection, and repeating the study with an increased number of participants and redefined inclusion and exclusion criteria to be more representative of the ICU patient population. The implication for social change is that this project empowers nursing to embrace a leadership role in using evidence-based practice to change clinical guidelines and improve patient outcomes

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Does α-Amino-β-methylaminopropionic Acid (BMAA) Play a Role in Neurodegeneration?

The association of α-amino-β-methylaminopropionic acid (BMAA) with elevated incidence of amyotrophic lateral sclerosis/Parkinson’s disease complex (ALS/PDC) was first identified on the island of Guam. BMAA has been shown to be produced across the cyanobacterial order and its detection has been reported in a variety of aquatic and terrestrial environments worldwide, suggesting that it is ubiquitous. Various in vivo studies on rats, mice, chicks and monkeys have shown that it can cause neurodegenerative symptoms such as ataxia and convulsions. Zebrafish research has also shown disruption to neural development after BMAA exposure. In vitro studies on mice, rats and leeches have shown that BMAA acts predominantly on motor neurons. Observed increases in the generation of reactive oxygen species (ROS) and Ca2+ influx, coupled with disruption to mitochondrial activity and general neuronal death, indicate that the main mode of activity is via excitotoxic mechanisms. The current review pertaining to the neurotoxicity of BMAA clearly demonstrates its ability to adversely affect neural tissues, and implicates it as a potentially significant compound in the aetiology of neurodegenerative disease. When considering the potential adverse health effects upon exposure to this compound, further research to better understand the modes of toxicity of BMAA and the environmental exposure limits is essential

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Origins of Dinophysis blooms which impact Irish aquaculture

The main unresolved issue with Dinophysis blooms and their contamination of shellfish with DSP toxins has been the identification of their source. From cruises covering the shelf region south of Ireland over the past years, it was shown that extensive blooms of D. acuta develop in summer in the productive region close to the Celtic Sea Front, a tidal front extending from southeast Ireland across to Britain. Of particular note has been the development of D. acuta populations with cells ranging from 2,000 cells L-1 to 55,000 (2014) and 75,000 (2015) cells L-1 located in a layer at the top of the sub-surface chlorophyll fluorescence maximum.Despite the blooms being localized to stratified water adjacent to the tidal front, they extended over a very large area. Over the rest of the Celtic Sea Shelf, cell densities were less than 100 cells L-1 at this time. These blooms are transported westwards along the south coast of Ireland towards the economically important shellfish culture region of southwest Ireland where they subsequently do harm. The source of these Dinophysis blooms is thus in excess of 300 km from their point of impac

Shelf sea subsurface chlorophyll maximum thin layers have a distinct phytoplankton community structure

The Western English Channel is a seasonally stratified temperate coastal sea where a subsurface chlorophyll maximum (SCM) is typically detectable within the seasonal thermocline. The SCM often develops as a thin layer(&lt;5m) that may contain elevated concentrations of phytoplankton (subsurface chlorophyll maximum thin layer;SCMTL). During summer 2013 a study was conducted offshore of Falmouth, UK to assess spatial and short-termtemporal variability in SCM thickness in relation to water column structure and physical conditions and to evaluateany associated changes in phytoplankton community structure. SCMTL were observed in 18 of 52 verticalprofiles, typically characterised by higher chlorophyll concentrations than broader SCM. SCMTL were generallyassociated with a ‘stepped’ thermocline, likely representing the presence of one or more shallow mixed layersforming above/within the seasonal thermocline, and related to increased stratification and stability compared tobroader SCM. Pseudo-nitzschia was almost exclusively the dominant diatom taxon in SCM, yet statistically distinctdifferences in community structure existed between SCMTL and broader SCM. Within the phytoplankton,the distinction was largely due to a greater biomass of Proboscia alata and other rhizosolenid diatoms, and thedinoflagellate Ceratium lineatum in SCMTL, and a smaller population of the diatom Chaetoceros spp. There wasalso a distinction amongst heterotrophic dinoflagellates, with enhanced biomass of Gyrodinium spp. in SCMTLand a reduction in Diplopsalis lenticula. We propose that this observed difference resulted from promotion of phytoplanktonbetter adapted to environmental conditions more specific to SCMTL compared to broader SCM. Withmore intense and prolonged stratification projected for the NW European shelf, there may be increased prevalenceof SCMTL and the associated larger-sized specialised taxa, with implications for increased carbon export.This study adds to a growing body of evidence of the importance of SCMTL in coastal and shelf seas, and highlightsthe requirement for improved understanding of physical forcing, and the ecology and physiology of keytaxa, particularly as predicted changes in stratification could alter the role of SCM phytoplankton in a future influencedby climate chang

Total water column analysis shows the importance of a single species in subsurface chlorophyll maximum thin layers in stratified waters

Marine phytoplankton form the base of marine food webs and are the driving force of the marine carbon cycle, so understanding the dynamics of their blooms is critical. While near-surface marine productivity (&lt;10 m water depths) is extensively documented, that of the subsurface is less well characterised. Increasing evidence of the importance of subsurface chlorophyll maxima (SCM) and climatically driven increases in stratification of surface waters that promote SCM development call for improved sampling of the subsurface. To address this, we targeted the summer stratified waters of the Western English Channel, part of the NW European shelf seas, where SCM are commonly developed. In situ holography was applied to undertake the highest ever resolution, total water column, quantitative analysis of microplankton distribution, and demonstrated the importance of a SCM, collocated with the thermocline, dominated by a single species, the dinoflagellate Ceratium fusus. This species was dominant in the SCM over a wide area of the NW European shelf in the June/ July 2015 study period and comprised up to 85% of the SCM biomass. Analysis of similarity and multivariate non-metric multidimensional scaling showed the phytoplankton community of the SCM to be statistically distinct from those of the surface and deep waters. Holography also revealed a fine scale layering of taxa at different levels within the SCM, likely reflecting ecological differences. Some taxa followed the peak abundance of C. fusus, while others reached maximum abundances immediately below or above the C. fusus maximum, suggesting the possible operation of exclusion mechanisms. Additionally, the detection of abundant aggregates located only within and beneath the SCM demonstrates the potential importance of this deep production for the export of carbon to the sea floor. Some predictions of phytoplankton productivity propose a shift to smaller cells in the more stratified oceans of the future resulting in declining production and export. Results presented here, however, contribute to a growing body of evidence that suggests, on the contrary, that key species among the larger celled/ colonial, SCM-adapted diatoms and dinoflagellates may instead be selected in stratified conditions, driving increased production and export