Military environmental exposures and risk of breast cancer in active-duty personnel and veterans: a scoping review.

Background: The effects of military environmental exposures (MEE) such as volatile organic compounds (VOCs), endocrine-disrupting chemicals (EDCs), tactile herbicides, airborne hazards and open burn pits (AHOBP), and depleted uranium on health are salient concerns for service members and Veterans. However, little work has been done to investigate the relationship between MEE and risk of breast cancer. Data sources and methods: We conducted a scoping review on MEE, military deployment/service, and risk of breast cancer among active-duty service members and Veterans. PRISMA was used. PubMed, Embase, and citations of included articles were searched, resulting in 4,364 articles to screen: 28 articles were included. Results: Most papers on military deployment and military service found a lower/equivalent risk of breast cancer when comparing rates to those without deployment or civilians. Exposure to VOCs due to military occupation or contaminated groundwater was associated with a slightly higher risk of breast cancer. Exposure to Agent Orange was not associated with an increased risk of breast cancer. Evidence regarding EDCs was limited. No paper directly measured exposure to AHOBP or depleted uranium, but deployments with known exposures to AHOBP or depleted uranium were associated with an equivalent/lower risk of breast cancer. Conclusions: Women are the fastest growing population within the military, and breast cancer poses a unique risk to women Veterans who were affected by MEE during their service. Unfortunately, the literature on MEE and breast cancer is mixed and limited, in part due to the Healthy Soldier Paradox and poor classification of exposure(s).

Economic evaluations of adult critical care pharmacy services: a scoping review.

OBJECTIVES: To summarise the extent and type of evidence available regarding economic evaluations of adult critical care pharmacy services in the context of UK practice. METHODS: A literature search was conducted in eight electronic databases and hand searching of full-text reference lists. Of 2409 journal articles initially identified, 38 were included in the final review. Independent literature review was undertaken by two investigators in a two-step process against the inclusion and exclusion criteria; title and abstract screening were followed by full-text screening. Included studies were taken from high-income economy countries that contained economic data evaluating any key aspect of adult critical care pharmacy services. Grey literature and studies that could not be translated into the English language were excluded. RESULTS: The majority were before-and-after studies (18, 47%) or other observational studies (17, 45%), and conducted in North America (25, 66%). None of the included studies were undertaken in the UK. Seven studies (18%) included cost-benefit analysis; all demonstrated positive cost-benefit values for clinical pharmacist activities. CONCLUSIONS: Further high-quality primary research focussing on the economic evaluation of UK adult critical care pharmacy services is needed, before undertaking a future systematic review. There is an indication of a cost-benefit value for critical care pharmacist activities. The lack of UK-based economic evaluations is a limitation to further development and standardisation of critical care pharmacy services nationally.

Understanding medication safety involving patient transfer from intensive care to hospital ward: a qualitative sociotechnical factor study.

OBJECTIVE: To understand the sociotechnical factors affecting medication safety when intensive care patients are transferred to a hospital ward. Consideration of these medication safety factors would provide a theoretical basis, on which future interventions can be developed and evaluated to improve patient care. DESIGN: Qualitative study using semistructured interviews of intensive care and hospital ward-based healthcare professionals. Transcripts were anonymised prior to thematic analysis using the London Protocol and Systems Engineering in Patient Safety V.3.0 model frameworks. SETTING: Four north of England National Health Service hospitals. All hospitals used electronic prescribing in intensive care and hospital ward settings. PARTICIPANTS: Intensive care and hospital ward healthcare professionals (intensive care medical staff, advanced practitioners, pharmacists and outreach team members; ward-based medical staff and clinical pharmacists). RESULTS: Twenty-two healthcare professionals were interviewed. We identified 13 factors within five broad themes, describing the interactions that most strongly influenced the performance of the intensive care to hospital ward system interface. The themes were: Complexity of process performance and interactions; Time pressures and considerations; Communication processes and challenges; Technology and systems and Beliefs about consequences for the patient and organisation. CONCLUSIONS: The complexity of the interactions on the system performance and time dependency was clear. We make several recommendations for policy change and further research based on improving: availability of hospital-wide integrated and functional electronic prescribing systems, patient flow systems, sufficient multiprofessional critical care staffing, knowledge and skills of staff, team performance, communication and collaboration and patient and family engagement.

Critical care pharmacist research activity, experience and interests: a 2021 United Kingdom survey.

BACKGROUND: Research and innovation are essential for effective healthcare service delivery, leading to improvements in patient health and wellbeing. National policy dictates that research delivery is embedded into daily practice of United Kingdom (UK) healthcare professionals, including pharmacists. There is a limited understanding of critical care pharmacist research activities, experiences and interests. It is, therefore, important to describe current practice including barriers and facilitators to enable increased engagement. OBJECTIVES: To describe UK critical care pharmacist research activity, experiences, interests and barriers to better engagement. METHOD: An electronic survey was developed, piloted and distributed (June to October 2021) to all critical care pharmacists via UK professional organisations. KEY FINDINGS: The survey was completed by 126 pharmacists, providing a 54% response rate. Few pharmacists reported research capability (postgraduate qualification with a research component, 31% (39/126)) and opportunity (dedicated research time, 28.6% (36/126)), only 12.7% (16/126) have both these influencers. Those that did, produced significantly more research outputs (median 4 (0,9) versus 0 (0,1), P = 0.023) and undertook grant funding applications (X2 (1, n = 126) = 25.8, P < 0.001), compared to those without. The most frequently reported barrier to research was the time (opportunity), (71.4%, 90/126). Few pharmacists reported having a research mentor (13.3%, 16/120). Most pharmacists reported an interest in collaborating on research projects across a broad range of areas. CONCLUSIONS: Critical care pharmacists are motivated to participate in the evaluation continuum including research, although most report capability and opportunity barriers to delivery. We suggest policy recommendations to address limitations and increase pharmacist research involvement.

The role of the brainstem in sleep disturbances and chronic pain of Gulf War and Iraq/Afghanistan veterans.

Introduction: Gulf War Illness is a type of chronic multisymptom illness, that affects about 30% of veterans deployed to the 1990-91 Persian Gulf War. Veterans deployed to Iraq/Afghanistan after 2000 are reported to have a similar prevalence of chronic multisymptom illness. More than 30 years after the Persian Gulf War, Gulf War Illness still has an unexplained symptom complex, unknown etiology and lacks definitive diagnostic criteria and effective treatments. Our recent studies have found that substantially smaller brainstem volumes and lower fiber integrity are associated with increased sleep difficulty and pain intensity in 1990-91 Persian Gulf War veterans. This study was conducted to investigate whether veterans deployed to Iraq/Afghanistan present similar brainstem damage, and whether such brainstem structural differences are associated with major symptoms as in Gulf War Illness. Methods: Here, we used structural magnetic resonance imaging and diffusion tensor imaging to measure the volumes of subcortices, brainstem subregions and white matter integrity of brainstem fiber tracts in 188 veterans including 98 Persian Gulf War veterans and 90 Iraq/Afghanistan veterans. Results: We found that compared to healthy controls, veterans of both campaigns presented with substantially smaller volumes in brainstem subregions, accompanied by greater periaqueductal gray matter volumes. We also found that all veterans had reduced integrity in the brainstem-spinal cord tracts and the brainstem-subcortical tracts. In veterans deployed during the 1990-91 Persian Gulf War, we found that brainstem structural deficits significantly correlated with increased sleep difficulties and pain intensities, but in veterans deployed to Iraq/Afghanistan, no such effect was observed. Discussion: These structural differences in the brainstem neurons and tracts may reflect autonomic dysregulation corresponding to the symptom constellation, which is characteristic of Gulf War Illness. Understanding these neuroimaging and neuropathological relationships in Gulf War and Iraq/Afghanistan veterans may improve clinical management and treatment strategies for modern war related chronic multisymptom illness.

A Delphi consensus study to identify priorities for improving and measuring medication safety for intensive care patients on transfer to a hospital ward.

BACKGROUND: Intensive care patients surviving to transfer to a lower-acuity hospital ward experience ongoing challenges to their recovery and lack a well-defined and developed care pathway. The transfer process to a hospital ward exposes intensive care patients to high rates of medication errors, which increase their risk of adverse drug events. OBJECTIVE: The aims of this study were to identify priorities for medication-related intervention components and outcome measures for improving medication safety for intensive care patients transferring to a hospital ward. METHODS: Three panels involving 129 participants covering (i) intensive care, (ii) hospital ward health-care professionals and (iii) public representatives completed an electronic Delphi survey conducted over three phases. The Delphi process comprised three sections (medication-related intervention components, medication outcomes and patient outcomes). Items were graded in their level of importance, with predefined important criteria. Item agreement required consensus across all three panels. Intervention barriers and facilitators identified in participant comments were categorized according to a socio-technical systems approach to the patient journey and patient safety (Systems Engineering Initiative for Patient Safety 3.0 model). RESULTS: Of the 129 (84.5%) participants, 109 completed all three Delphi phases. Consensus was achieved for 48 intervention components, 13 medication outcome measures and 11 patient outcome measures. Phase 1 provided 158 comments comprising >200 individual barriers and facilitators to intervention delivery. Frequently cited facilitators included clearly specified roles and responsibilities (10.7% (organizational conditions)), patient and family as agents (8.8% (care team)), medicines-related information easily accessible (7.8% (tools and technologies)) and clear medication plan and communication (7.3% (tasks)). CONCLUSIONS: Our findings provide identification of priorities for medication-related intervention components to improve medication safety for intensive care patients transferring to a hospital ward. Prioritization is complemented by the identification and socio-technical categorization of barriers and facilitators to intervention delivery. The identified important medication and patient outcomes to measure will inform the design of a future patient medication safety intervention study.

Elevated water lead levels in schools using water from on-site wells.

Only 8% of US public schools operate their own community water systems, and thus are subject to the federal Lead and Copper Rule's regulation of water lead levels (WLLs). To date, the absence of parallel water testing data for all other schools has prevented the comparison of WLLs with schools that do not face federal regulation. This study compiled and analyzed newly available school-level WLL data that included water source (on-site well water or public utility) and pipe material data for public schools in New York State located outside of New York City. Despite direct federal regulation, schools that used water from on-site wells had a substantially higher percentage of water fixtures with elevated WLLs. Schools that used both on-site well water and iron pipes in their water distribution system had the highest percentage of elevated fixtures. Variation in water treatment practices was identified as a potential contributing mechanism, as schools that used on-site well water were less likely to implement corrosion control. The study concluded that information about water source and premise plumbing material may be useful to policymakers targeting schools for testing and remediation.

Functional proteomics of patient derived head and neck squamous cell carcinoma cells reveal novel applications of trametinib.

In this study, we report a differential response of mitogen-activated protein kinase-kinase (MEK) inhibitor trametinib in 20 head and neck squamous cell carcinoma (HNSCC) patients' tumor-derived cell cultures. Relatively sensitive and resistant cases to trametinib were identified using high throughput metabolic assays and validated in extended dose response studies in vitro. High throughput metabolic assays exploring combination therapies with trametinib were subjected to synergy models and maximal synergistic dose analyses. These yielded several candidates, including axtinib, GDC-0032, GSK-690693, and SGX-523. The combination regimen of trametinib and AXL/MET/VEGFR inhibitor glesatinib showed initial efficacy both in vitro and in vivo (92% reduction in tumor volume). Sensitivity was validated in vivo in a patient-derived xenograft (PDX) model in which trametinib as a single agent effected reduction in tumor volume up to 72%. Reverse Phase Protein Arrays (RPPA) demonstrated differentially expressed proteins and phosphoproteins upon trametinib treatment. Furthermore, resistant cell lines showed a compensatory mechanism via increases in MAPK and non-MAPK pathway proteins that may represent targets for future combination regimens. Intrinsic-targeted options have potential to address paucity of medical treatment options for HNSCC cancer patients, enhance response to extrinsic targeted agents, and/or reduce morbidity as neoadjuvant to surgical treatments.

Medication-related interventions to improve medication safety and patient outcomes on transition from adult intensive care settings: a systematic review and meta-analysis.

BACKGROUND: Patients recovering from an episode in an intensive care unit (ICU) frequently experience medication errors on transition to the hospital ward. Structured handover recommendations often underestimate the challenges and complexity of ICU patient transitions. For adult ICU patients transitioning to a hospital ward, it is currently unclear what interventions reduce the risks of medication errors.The aims were to examine the impact of medication-related interventions on medication and patient outcomes on transition from adult ICU settings and identify barriers and facilitators to implementation. METHODS: The systematic review protocol was preregistered on PROSPERO. Six electronic databases were searched until October 2020 for controlled and uncontrolled study designs that reported medication-related (ie, de-prescribing; medication errors) or patient-related outcomes (ie, mortality; length of stay). Risk of bias (RoB) assessment used V.2.0 and ROBINS-I Cochrane tools. Where feasible, random-effects meta-analysis was used for pooling the OR across studies. The quality of evidence was assessed by Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: Seventeen studies were eligible, 15 (88%) were uncontrolled before-after studies. The intervention components included education of staff (n=8 studies), medication review (n=7), guidelines (n=6), electronic transfer/handover tool or letter (n=4) and medicines reconciliation (n=4). Overall, pooled analysis of all interventions reduced risk of inappropriate medication continuation at ICU discharge (OR=0.45 (95% CI 0.31 to 0.63), I2=55%, n=9) and hospital discharge (OR=0.39 (95% CI 0.2 to 0.76), I2=75%, n=9). Multicomponent interventions, based on education of staff and guidelines, demonstrated no significant difference in inappropriate medication continuation at the ICU discharge point (OR 0.5 (95% CI 0.22 to 1.11), I2=62%, n=4), but were very effective in increasing de-prescribing outcomes on hospital discharge (OR 0.26 (95% CI 0.13 to 0.55), I2=67%, n=6)). Facilitators to intervention delivery included ICU clinical pharmacist availability and participation in multiprofessional ward rounds, while barriers included increased workload associated with the discharge intervention process. CONCLUSIONS: Multicomponent interventions based on education of staff and guidelines were effective at achieving almost four times more de-prescribing of inappropriate medication by the time of patient hospital discharge. Based on the findings, practice and policy recommendations are made and guidance is provided on the need for, and design of theory informed interventions in this area, including the requirement for process and economic evaluations.

Reducing lead exposure in school water: Evidence from remediation efforts in New York City public schools.

Following the Flint Water Crisis, many states passed legislation requiring schools to measure and remediate lead in school drinking water. In this study, we present new evidence on the level and distribution of lead in school drinking water by examining the case of New York City, which tested water from every public school fixture in the 2016-17 school year, remediated fixtures that showed elevated levels of lead above 15 ppb, and retested a sample of fixtures in 2018-19. Prior to remediation, 8 % of fixtures showed elevated levels of lead; after remediation, 5 % of fixtures did. In both pre- and post-remediation periods, Black children attended schools with a higher proportion of elevated fixtures than White, Asian, and Hispanic children. We observe post-remediation lead exposure reductions that were largest for Black children, though racial disparities in exposure remained. Together, our results show that New York City's remediation efforts significantly reduced lead in its schools' drinking water in a short period of time, providing evidence of the promise of such efforts. However, the continued presence of lead in school drinking water and persistent racial disparities in exposure demonstrate the ongoing challenges to eradicating lead exposure in schools.

Brainstem damage is associated with poorer sleep quality and increased pain in gulf war illness veterans.

AIMS: Gulf War Illness (GWI) is manifested as multiple chronic symptoms, including chronic pain, chronic fatigue, sleep problems, neuropsychiatric disorders, respiratory, gastrointestinal, and skin problems. No single target tissue or unifying pathogenic process has been identified that accounts for this variety of symptoms. The brainstem has been suspected to contribute to this multiple symptomatology. The aim of this study was to assess the role of the brainstem in chronic sleep problems and pain in GWI veterans. MATERIALS AND METHODS: We enrolled 90 veterans (Age = 50 ± 5, 87% Male) who were deployed to the 1990-91 Gulf War and presented with GWI symptoms. Sleep quality was evaluated using the global Pittsburgh Sleep Quality Index. Pain intensities were obtained with the Brief Pain Inventory sum score. Volumes in cortical, subcortical, brainstem, and brainstem subregions and diffusion tensor metrics in 10 bilateral brainstem tracts were tested for correlations with symptom measures. KEY FINDINGS: Poorer sleep quality was significantly correlated with atrophy of the whole brainstem and brainstem subregions (including midbrain, pons, medulla). Poorer sleep quality also significantly correlated with lower fractional anisotropy in the nigrostriatal tract, medial forebrain tract, and the dorsal longitudinal fasciculus. There was a significant correlation between increased pain intensity and decreased fractional anisotropy in the dorsal longitudinal fasciculus. These correlations were not altered after controlling for age, sex, total intracranial volumes, or additional factors, e.g., depression and neurological conditions. SIGNIFICANCE: These findings suggest that the brainstem plays an important role in the aberrant neuromodulation of sleep and pain symptoms in GWI.

Yoga is effective in treating symptoms of Gulf War illness: A randomized clinical trial.

Many Veterans of the 1990-1991 Gulf War report symptoms of Gulf War Illness, a condition involving numerous chronic symptoms including pain, fatigue, and mood/cognition symptoms. Little is known about this condition's etiology and treatment. This study reports outcomes from a randomized controlled single-blind trial comparing yoga to cognitive behavioral therapy for chronic pain and other symptoms of Gulf War Illness. Participants were Veterans with symptoms of GWI: chronic pain, fatigue and cognition-mood symptoms. Seventy-five Veterans were randomized to treatment via selection of envelopes from a bag (39 yoga, 36 cognitive behavioral therapy), which consisted of ten weekly group sessions. The primary outcomes of pain severity and interference (Brief Pain Inventory- Short Form) improved in the yoga condition (Cohen's d = .35, p = 0.002 and d = 0.69, p < 0.001, respectively) but not in the CBT condition (d = 0.10, p = 0.59 and d = 0.25 p = 0.23). However, the differences between groups were not statistically significant (d = 0.25, p = 0.25; d = 0.43, p = 0.076), though the difference in an a-priori-defined experimental outcome variable which combines these two variables into a total pain variable (d = 0.47, p = 0.047) was significant. Fatigue, as indicated by a measure of functional exercise capacity (6-min walk test) was reduced significantly more in the yoga group than in the CBT group (between-group d = .27, p = 0.044). Other secondary outcomes of depression, wellbeing, and self-reported autonomic nervous system symptoms did not differ between groups. No adverse events due to treatment were reported. Yoga may be an effective treatment for core Gulf War Illness symptoms of pain and fatigue, making it one of few treatments with empirical support for GWI. Results support further evaluation of yoga for treating veterans with Gulf War Illness. CLINICAL TRIAL REGISTRY: clinicaltrials.gov Registration Number NCT02378025.

Diffusion tensor tractography of brainstem fibers and its application in pain.

Evaluation of brainstem pathways with diffusion tensor imaging (DTI) and tractography may provide insights into pathophysiologies associated with dysfunction of key brainstem circuits. However, identification of these tracts has been elusive, with relatively few in vivo human studies to date. In this paper we proposed an automated approach for reconstructing nine brainstem fiber trajectories of pathways that might be involved in pain modulation. We first performed native-space manual tractography of these fiber tracts in a small normative cohort of participants and confirmed the anatomical precision of the results using existing anatomical literature. Second, region-of-interest pairs were manually defined at each extracted fiber's termini and nonlinearly warped to a standard anatomical brain template to create an atlas of the region-of-interest pairs. The resulting atlas was then transformed non-linearly into the native space of 17 veteran patients' brains for automated brainstem tractography. Lastly, we assessed the relationships between the integrity levels of the obtained fiber bundles and pain severity levels. Fractional anisotropy (FA) measures derived using automated tractography reflected the respective tracts' FA levels obtained via manual tractography. A significant inverse relationship between FA and pain levels was detected within the automatically derived dorsal and medial longitudinal fasciculi of the brainstem. This study demonstrates the feasibility of DTI in exploring brainstem circuitries involved in pain processing. In this context, the described automated approach is a viable alternative to the time-consuming manual tractography. The physiological and functional relevance of the measures derived from automated tractography is evidenced by their relationships with individual pain severities.

Targeted Identification of Protein Interactions in Eukaryotic mRNA Translation.

To identify protein-protein interactions and phosphorylated amino acid sites in eukaryotic mRNA translation, replicate TAP-MudPIT and control experiments are performed targeting Saccharomyces cerevisiae genes previously implicated in eukaryotic mRNA translation by their genetic and/or functional roles in translation initiation, elongation, termination, or interactions with ribosomal complexes. Replicate tandem affinity purifications of each targeted yeast TAP-tagged mRNA translation protein coupled with multidimensional liquid chromatography and tandem mass spectrometry analysis are used to identify and quantify copurifying proteins. To improve sensitivity and minimize spurious, nonspecific interactions, a novel cross-validation approach is employed to identify the most statistically significant protein-protein interactions. Using experimental and computational strategies discussed herein, the previously described protein composition of the canonical eukaryotic mRNA translation initiation, elongation, and termination complexes is calculated. In addition, statistically significant unpublished protein interactions and phosphorylation sites for S. cerevisiae's mRNA translation proteins and complexes are identified.

ADHD remission, inclusive special education, and socioeconomic disparities.

To understand how institutional environments and socioeconomic backgrounds may influence health outcomes, we examined the relationship among special education environments, socioeconomic status (SES), and likelihood of ADHD remission in children. While the majority of children experience remission by adulthood, the likelihood of remission varies across different SES levels and education environments. We find that for low SES children the likelihood of remission is higher in states that have more inclusive special education regimes. In contrast, for more advantaged children, the odds of remission do not depend on the level of special education inclusivity. Our findings suggest that providing more inclusive education can reduce disparities in behavioral disorders and are particularly important for less advantaged children. In doing so, this study contributes to the fundamental cause and health inequality literature by adding to a growing body of work showing how institutional environments can affect socioeconomic gradients in health treatment and outcomes.

Reducing medication errors in critical care patients: pharmacist key resources and relationship with medicines optimisation.

BACKGROUND: Medication errors are the most common type of medical errors critical care patients experience. Critical care units utilise a variety of resources to reduce medication errors; it is unknown which resources or combinations thereof are most effective in improving medication safety. OBJECTIVES: To obtain UK critical care pharmacist group consensus on the most important interventions/resources that reduce medication errors. To then classify units that participated in the PROTECTED UK study to investigate if there were significant differences in the reported pharmacist prescription intervention type, clinical impact and rates according to unit resource classification. METHODS: An e-Delphi process (three rounds) obtained pharmacist consensus on which interventions/resources were most important in the reduction of medication errors in critical care patients. The 21 units involved in the PROTECTED UK study (multicentre study of UK critical care pharmacist medicines interventions), were categorised as high-, medium- and low-resource units based on routine delivery of the final Top 5 interventions/ resources. High and low units were compared according to type, clinical impact and rate of medication interventions reported during the PROTECTED UK study. KEY FINDINGS: Consensus on the Top 5 combined medication error reduction resources was established: advanced-level clinical pharmacist embedded in critical care being ranked most important. Pharmacists working on units with high resources made significantly more clinically significant medicines optimisations compared to those on low-resourced units (OR 3.09; P = 0.035). CONCLUSIONS: Critical care pharmacist group consensus on the most important medication error reduction resources was established. Pharmacists working on high-resourced units made more clinically significant medicines optimisations.

Measure for Measure: How Proficiency-Based Accountability Systems Affect Inequality in Academic Achievement.

How do proficiency-based accountability systems affect inequality in academic achievement? This paper reconciles mixed findings in the literature by demonstrating that three factors jointly determine accountability's impact. First, by analyzing student-level data from a large urban school district, we find that when educators face accountability pressure, they focus attention on students closest to proficiency. We refer to this practice as educational triage, and show that the difficulty of the proficiency standard affects whether lower or higher performing students gain most on high-stakes tests used to evaluate schools. Less difficult proficiency standards decrease inequality in high-stakes achievement, while more difficult ones increase it. Second, we show that educators emphasize test-specific skills with students near proficiency, a practice that we refer to as instructional triage. As a result, the effects of accountability pressure differ across high and low-stakes tests; we find no effects on inequality in low-stakes reading and math tests of similar skills. Finally, we provide suggestive evidence that instructional triage is most pronounced in the lowest performing schools. We conclude by discussing how these findings shape our understanding of accountability's impacts on educational inequality.