Impact of Delirium Onset and Duration on Mortality in Patients With Cancer Admitted to the ICU.

BACKGROUND: Little is known on the effects of delirium onset and duration on outcome in critically ill patients with cancer. OBJECTIVES: To determine the impact of delirium onset and duration on intensive care unit (ICU) and hospital mortality and length of stay (LOS) in patients with cancer. METHODS: Of the 915 ICU patients admitted in 2018, 371 were included for analysis after excluding for terminal disease, <24-h ICU stay, lack of active cancer and delirium. Delirium was defined as early if onset was within 2 days of ICU admission, late if onset was on day 3 or later, short if duration was 2 days or less, and long if duration was 3 days or longer. Patients were placed into 4 combination groups: early-short, early-long, late-short, and late-long delirium. Multivariate analysis controlling for sex, age, metastatic disease, and predelirium hospital LOS was performed to determine ICU and hospital mortality and LOS. Exploratory analysis of long-term survival was also performed. Restricted cubic splines were performed to confirm the use of 2 days to distinguish between early versus late onset and short versus long duration. RESULTS: A total of 32.9% (n = 122) patients had early-short, 39.1% (n = 145) early-long, 16.2% (n = 60) late-short, and 11.9% (n = 44) late-long delirium. Late-long delirium was independently associated with increased ICU (OR 4.45, CI 1.92-10.30; P < .001) and hospital (OR 2.91, CI 1.37-6.19; P = .005) mortality and longer ICU (OR 1.97, CI 1.58-2.47; P < .001) LOS compared to early-short delirium. Early delirium had better overall survival at 18 months than late delirium. Long-term survival further improved when delirium duration was 2 days or less. Prediction heatmaps confirm the use of a 2-day cutoff. CONCLUSION: Late delirium, especially with long duration, significantly worsens outcome in ICU patients with cancer and should be considered a harbinger of poor overall condition.

An alternative processing approach to increase CD138 intensity in flow cytometric analysis of plasma cells.

BACKGROUND: Surface median immunofluorescence intensity (MFI) of plasma cells antigens, particularly CD138, by flow cytometry underestimates plasma cell populations when compared with that estimated by morphological assessment on Wright's-stained slides. CD138 MFI using traditional sample preparation methods for flow cytometric analysis is often dim and difficult to interpret due to multiple factors. This becomes critical when diagnosing and accurately classifying plasma cell dyscrasias. METHODS: In this study, we analyzed 280 flow cytometric results collected from 2016 to 2022 for CD38 and CD138 MFI on bone marrow aspirates performed by two different methods of sample processing-traditional method of lyse-wash and the alternative method of lyse-no-wash. RESULTS: Visual examination of histograms showed a clear advantage to CD138 expression intensity with the no-wash method. Although no significant difference was observed in CD38 MFI between the two techniques (p = 0.3), considerable improvement was observed in CD138 MFI with the lyse-no-wash technique of sample processing compared with the conventional method (p = 0.003). CONCLUSIONS: We concluded that the method of lyse-no-wash is superior to traditional methods especially when it comes to handling bone marrow aspirate samples for plasma cell immunophenotyping. This alternate technique increases the sensitivity of flow cytometry to detect plasma cells resulting in bright and crisp signal intensity for surface CD138. This technique may be particularly advantageous when analyzing low tumor burden such as minimal residual disease.

Delirium education for family caregivers of patients in the intensive care unit: A pilot study.

Objectives: Delirium, an acute change in mental state, seen in hospitalized older adults is a growing public health concern with implications for both patients and caregivers; however, there is minimal research on educating caregivers about delirium. Utilizing family caregivers to assist with delirium management in acute care settings demonstrates improved health outcomes supporting the need for patient and family centered care. The primary aims of the study were to determine feasibility of implementing a delirium education video for caregivers of patients in an adult oncology intensive care unit and compare delirium knowledge to caregivers in a control group. Methods: A quasi-experimental design comprised of 31 family caregivers of adult patients in an oncology intensive care unit to determine feasibility of implementing a delirium education video. Results: The results demonstrate feasibility of implementing a caregiver education video in-person and virtually. While total delirium knowledge scores were not statistically significant, knowledge gained within the delirium presentation subgroup was significant (p = .05). Conclusion: This study demonstrates feasibility of implementing a caregiver education video and findings support further research in this area. Innovation: Collaborating with caregivers to develop virtual video education for delirium allows for a versatile approach to connect with caregivers to support their caregiving role.

The effectiveness of various strategies to improve DNA analysis of formaldehyde-damaged tissues from embalmed cadavers for human identification purposes.

Formalin-fixed tissues provide the medical and forensic communities with alternative and often last resort sources of DNA for identification or diagnostic purposes. The DNA in these samples can be highly degraded and chemically damaged, making downstream genotyping using short tandem repeats (STRs) challenging. Therefore, the use of alternative genetic markers, methods that pre-amplify the low amount of good quality DNA present, or methods that repair the damaged DNA template may provide more probative genetic information. This study investigated whether whole genome amplification (WGA) and DNA repair could improve STR typing of formaldehyde-damaged (FD) tissues from embalmed cadavers. Additionally, comparative genotyping success using bi-allelic markers, including INDELs and SNPs, was explored. Calculated random match probabilities (RMPs) using traditional STRs, INDEL markers, and two next generation sequencing (NGS) panels were compared across all samples. Overall, results showed that neither WGA nor DNA repair substantially improved STR success rates from formalin-fixed tissue samples. However, when DNA from FD samples was genotyped using INDEL and SNP-based panels, the RMP of each sample was markedly lower than the RMPs calculated from partial STR profiles. Therefore, the results of this study suggest that rather than attempting to improve the quantity and quality of severely damaged and degraded DNA prior to STR typing, a more productive approach may be to target smaller amplicons to provide more discriminatory DNA identifications. Furthermore, an NGS panel with less loci may yield better results when examining FD samples, due to more optimized chemistries that result in greater allelic balance and amplicon coverage.

Psychotropic medication use in people living with severe and persistent mental illness in the Australian community: a cross-sectional study.

BACKGROUND: Psychotropic polypharmacy and high-dose prescribing may play a role in therapy, however, with associated risks. The aim of this study was to describe current prescribing practices and use of four psychotropic medication groups (antipsychotics, antidepressants, mood stabilisers and benzodiazepines), focusing on polypharmacy (across and within groups) and high-dose prescribing in adults experiencing severe and persistent mental illness (SPMI) in the Australian community. METHODS: 318 people taking psychotropic medication for SPMI had a medication review undertaken by a community pharmacist. Participants were recruited as part of an RCT from three Australian states/territories between September 2020-July 2021. All psychotropic medication and daily doses were recorded and reviewed for alignment with current clinical guidelines. Univariate and multiple logistic regression models investigated factors associated with antipsychotic, antidepressant, and mood stabiliser polypharmacy, and antipsychotic and antidepressant high-dose therapy. Variables included age, gender, geographic location, self- reported mental illness(es), hospital admission(s) in previous 6-months and prescriber type. RESULTS: 806 psychotropic medications were prescribed for the 318 participants. Mood stabiliser polypharmacy was recorded in 19.0% of participants prescribed mood stabilisers; antipsychotic polypharmacy in 18.4% of participants prescribed antipsychotics; antidepressant polypharmacy in 11.3% of those prescribed antidepressants; and three participants (5.1%) were prescribed two benzodiazepines concurrently. Almost 18.6% of the cohort was receiving high-dose treatment; 18 participants were prescribed high-dose antipsychotics and 39 high-dose antidepressants, with two participants prescribed both. Adjusted logistic regression for polypharmacy found male gender, psychiatrist as sole prescriber, or multiple prescribers, were associated with antipsychotic polypharmacy. The adjusted model for high-dose therapy found psychiatrist as sole prescriber was significantly associated with antipsychotic and antidepressant high-dose prescribing. CONCLUSION: Psychotropic polypharmacy was common in this community cohort experiencing SPMI. Whilst polypharmacy is not always inappropriate, it is a complex construct with potential benefits alongside potential risks. Benefits and harms need to be balanced however this practice is not supported by clear guidance to assist health practitioners. This study highlights the important need for regular medication reviews and strengthened communication between consumers and all healthcare professionals involved in community mental health care, to support safe and effective use of psychotropic medications.

A scoping review of pharmacy participation in dental and oral health care.

OBJECTIVES: To explore the scope of dental and oral health care (DOHC) provided by the pharmacy profession and associated outcomes, and attitudes of pharmacy staff and other key stakeholders about pharmacy involvement in this context. METHODS: A scoping review of full-text articles describing outcomes related to pharmacy staff/student involvement in, knowledge of or attitudes towards DOHC in any setting, and stakeholder perspectives was conducted. Articles written in English were searched for using PubMed, EMBASE, EBSCO, International Pharmaceutical Abstracts, Education Resources Information Centre, Web of Science, Google Scholar, and ProQuest for Dissertations and Theses. No date restrictions were used. Key outcomes were mapped: role and practice, knowledge and attitudes, and training and education. RESULTS: Seventy studies met the inclusion criteria: 49 were conducted in developed countries; 60 were quantitative in design; and 38 involved community pharmacy settings only. Pharmacists and pharmacy support staff commonly managed DOHC inquiries (n = 13), including the provision of advice and products with or without a further referral. Integrated pharmacist-led services in dental settings (n = 4) showed improved prescribing and quality use of medicines but low community pharmacy referrals were identified in studies involving mystery shoppers with potential oral cancer (n = 7). DOHC promotion programmes delivered by pharmacy staff and collaborations with dentists were limited. There was interest from the pharmacy profession for a role in DOHC; however, knowledge gaps were reported and needs for further training identified. Consumer participant DOHC outcomes were not reported. CONCLUSIONS: Community pharmacists and pharmacy staff were interested in an expanded role in DOHC; however, this scoping review identified lack of knowledge and sub-optimal practice as potential barriers. Research on development, implementation and evaluation of DOHC-related services and practice by pharmacy staff was scarce. Further evidence of consumer-related oral health outcomes and their perceptions of the role of pharmacy is needed.

Household determinants of biocontaminant exposures in Canadian homes.

Exposure to biocontaminants, such as dust mites, animal dander, bacteria, and mold, is associated with a range of health effects. This study identified household characteristics associated with indoor biocontaminant loadings in four Canadian cities. Floor dust was collected in 290 Canadian homes in Edmonton, Halifax, Montreal, and Windsor. The dust samples were analyzed for house dust mite allergens (Der f 1 and Der p 1), cat allergen (Fel d 1), cockroach allergen (Bla g 1), beta-(1,3)-D-glucan, and endotoxin. Household information was obtained through questionnaires and home inspections. We performed univariate and multivariate analyses to identify household determinants of biocontaminant loadings and mold odor presence. We observed large regional variations for all biocontaminants, except for cockroach allergen. The ranges of the contaminants measured in loadings and concentrations were similar to that of previous Canadian studies. Household characteristics including presence of carpeting, low floor cleaning frequency, older home age, presence of pets, and indoor relative humidity above 45% were positively associated with the presence of multiple indoor biocontaminants. High floor cleaning frequency and use of dehumidifiers were negatively associated with the presence of multiple indoor biocontaminants. Mold odor was positively associated with older home age, past water damage, and visible mold growth.

Associations between respiratory and vascular function in early childhood.

BACKGROUND AND OBJECTIVE: The link between respiratory and vascular health is well documented in adult populations. Impaired lung function is consistently associated with thicker arteries and higher incidence of cardiovascular disease. However, there are limited data on this relationship in young children and the studies that exist have focussed on populations at high risk of cardiorespiratory morbidity. We determined if an association exists between respiratory and cardiovascular function in young children and, if so, whether it is confounded by known cardiorespiratory risk factors. METHODS: Respiratory and vascular data from a prospective cohort study established to evaluate the health implications 3 years after coal mine fire smoke exposure in children aged 3-5 years were used. Respiratory function was measured using the forced oscillation technique and included resistance at 5 Hz (R5 ), reactance at 5 Hz (X5 ) and area under the reactance curve (AX). Vascular health was measured by carotid intima-media thickness (ultrasound) and pulse wave velocity (arterial tonometry). Regression analyses were used to examine the relationship between the respiratory Z-scores and cardiovascular measures. Subsequent analyses were adjusted for potential confounding by maternal smoking during pregnancy, maternal education and exposure to fine particulate matter <2.5 µm in aerodynamic diameter (PM2.5 ). RESULTS: Peripheral lung function (X5 and AX), but not respiratory system resistance (R5 ), was associated with vascular function. Adjustment for maternal smoking, maternal education and early life exposure to PM2.5 had minimal effect on these associations. CONCLUSION: These observations suggest that peripheral lung stiffness is associated with vascular stiffness and that this relationship is established early in life.

Pharmacy participation in dental and oral health care: a scoping review protocol.

OBJECTIVE: The aim of the review is to identify and describe the characteristics and associated outcomes of dental and oral health advice and support provided by members of the pharmacy profession. Research exploring the role, attitudes, and knowledge of pharmacists, pharmacy students, and support staff relating to dental and oral health care, as well as stakeholder perceptions, will also be examined. INTRODUCTION: With the increasing prevalence of dental and oral health disorders and resource constraints within health care systems, other avenues for oral health promotion and care provision are warranted. Pharmacists, as primary care professionals working across various practice settings, could play a significant role in promoting good oral health. Yet, there is limited insight about the role, attitudes, and knowledge of members of the pharmacy profession towards dental and oral health care, as well as what stakeholders, such as consumers and other health care professionals, think about their role in this context. INCLUSION CRITERIA: Any full-text publication that describes outcomes related to pharmacist, pharmacy assistant, or student involvement, knowledge, or attitudes towards dental or oral health care in any setting, and stakeholder perspectives of this role, will be included. Reviews, protocols, and commentaries will be excluded, as will studies specifically focused on smoking cessation or that do not describe the related health promotion activity. METHODS: Articles published in English will be sought from health and educational databases with no date restrictions, with additional references identified via snowballing using citations and reference lists. Data searching and screening processes will follow JBI methodology, involving two independent reviewers, and data extraction presented in a narrative form.

Provision of home medicines reviews in Australia: linking population need with service provision and available pharmacist workforce.

Objective Identifying and quantifying the health needs of a population are the basis of evidence-based health policy and workforce planning. The motivation for undertaking the present study was to evaluate whether the current level of medication review services corresponds to population need, as proxied by the rate of polypharmacy, and to undertake a preliminary analysis of the sufficiency of the current workforce. This paper: (1) estimates the age- and sex-standardised rates of polypharmacy as a proxy for population need for home medicines review; (2) compares the rate of polypharmacy with current service provision of home medicines reviews; and (3) links the estimated need for services with the current number and location of pharmacist providers. Methods Age- and sex-adjusted polypharmacy rates, by state, were estimated from the National Health Survey of Australia (2017-18), service levels were estimated from national-level administrative claims data (2017-18) and the current workforce was estimated from the Australian Association of Consultant Pharmacists (2018). The current level of service provision was compared to the estimated population need for services, alongside the size of the pharmacy workforce required if need was met. Results The adjusted rate of polypharmacy in Australia, using the strictest definition of ≥10 medications and ≥3 current chronic illnesses, was 1389 per 100000 population. The illustrative needs-based analysis suggests that there may be a disconnect between the current level of service provision and population health needs. Conclusion Given that polypharmacy is a risk factor for medication-related problems, and that medication review is one of the few targeted strategies currently available to address medication-related problems in the population, service provision may be inadequate. Policy options to improve service provision could include interventions to increase workforce productivity and relaxing the current eligibility criteria for review, especially in rural and remote areas. What is known about the topic? Polypharmacy is a risk factor for medication-related problems, which can cause increased morbidity and mortality in the population. What does this paper add? This paper provides representative, population-based rates of polypharmacy in Australia and uses these rates in a needs-based analysis of service provision and workforce adequacy to provide home medicines review services. What are the implications for practitioners? Several policy options are available for consideration, including interventions to increase workforce productivity and relaxation of the current eligibility criteria for medicines review, especially in rural and remote areas.

Acute pain after breast surgery and reconstruction: A two-institution study of surgical factors influencing short-term pain outcomes.

BACKGROUND AND OBJECTIVES: Acute postoperative pain following surgery is known to be associated with chronic pain development and lower quality of life. We sought to analyze the relationship between differing breast cancer excisional procedures, reconstruction, and short-term pain outcomes. METHODS: Women undergoing breast cancer excisional procedures with or without reconstruction at two systems: an academic hospital (AH) and Veterans Health Administration (VHA) were included. Average pain scores at the time of discharge and at 30-day follow-up were analyzed across demographic and clinical characteristics. Linear mixed effects modeling was used to assess the relationship between patient/clinical characteristics and interval pain scores with a random slope to account for differences in baseline pain. RESULTS: Our study included 1402 patients at AH and 1435 at VHA, of which 426 AH and 165 patients with VHA underwent reconstruction. Pain scores improved over time and were found to be highest at discharge. Time at discharge, 30-day follow-up, and preoperative opioid use were the strongest predictors of high pain scores. Younger age and longer length of stay were independently associated with worse pain scores. CONCLUSIONS: Younger age, preoperative opioid use, and longer length of stay were associated with higher levels of postoperative pain across both sites.

Is higher psychotropic medication burden associated with involuntary treatment under the Mental Health Act? A four-year Australian cohort study.

BACKGROUND: Involuntary treatment for individuals who lack sufficient capacity to make informed decisions regarding treatment has been associated with increased rates of injectable antipsychotics, antipsychotic polytherapy, and/or high doses. However, little is known about non-antipsychotic psychotropic prescription, or psychotropic medication burden as a more encompassing approach for people treated involuntarily. The aim of this study was to examine the relationship between Mental Health Act (MHA) status and psychotropic polypharmacy and/or high-dose medication prescribing practices in an Australian inpatient mental health unit. METHODS: A retrospective cohort study of 800 adults discharged from a large metropolitan Queensland mental health unit was undertaken. Data was collected for 200 individuals, discharged on at least one psychotropic medicine, at four time periods; Cohort 1 (on or before 31st January 2014), Cohort 2 (2015), Cohort 3 (2016) and Cohort 4 (2017). The number of prescribed medicines and total daily doses were recorded and reviewed for alignment with current clinical guidelines. Participant demographics and clinical characteristics were compared by individual MHA status using chi-square test for categorical variables and analysis of variance for continuous variables. Associations between MHA status and prescribing practices (psychotropic polypharmacy and/or high-dose prescribing) were assessed using bivariate and multivariate binomial logistic regression models. Age, gender, birth country, year of admission, admissions in previous 12 months, primary diagnosis, ECT/clozapine treatment, and other psychotropic medications were adjusted as covariates. RESULTS: Regression analysis found that compared to their voluntary counterparts, individuals treated involuntarily were 2.7 times more likely to be prescribed an antipsychotic at discharge, 8.8 times more likely to be prescribed more than one antipsychotic at discharge and 1.65 times more likely to be prescribed high-dose antipsychotic treatment at discharge. The adjusted model also found that they were half as likely to be prescribed an antidepressant at discharge. CONCLUSION: Implicit review of justifications for increased psychotropic medication burden (antipsychotic polypharmacy and high-doses) in those treated involuntarily is required to ensure clinical outcomes and overall quality of life are improved in this vulnerable group. Clearly documented medication histories, reconciliation at discharge and directions for medication management after discharge are necessary to ensure quality use of medicines.

Early life exposure to coal mine fire smoke emissions and altered lung function in young children.

BACKGROUND AND OBJECTIVE: Long-term respiratory risks following exposure to relatively short periods of poor air quality early in life are unknown. We aimed to evaluate the association between exposure to a 6-week episode of air pollution from a coal mine fire in children aged <2 years, and their lung function 3 years after the fire. METHODS: We conducted a prospective cohort study. Individual exposure to 24-h average and peak concentrations of particulate matter with an aerodynamic diameter <2.5 µm in diameter (PM2.5 ) during the fire were estimated using dispersion and chemical transport modelling. Lung function was measured using the forced oscillation technique (FOT), generating standardized Z-scores for resistance and reactance at a frequency of 5 Hz (Rrs5 and Xrs5 ), and area under the reactance curve (AX). We used linear regression models to assess the associations between PM2.5 exposure and lung function, adjusted for potential confounders. RESULTS: Of the 203 infants originally recruited, 84 aged 4.3 ± 0.5 years completed FOT testing. Median (interquartile range, IQR) for average and peak PM2.5 were 7.9 (6.8-16.8) and 103.4 (60.6-150.7) µg/m3 , respectively. The mean ± SD Z-scores for Rrs5 , Xrs5 and AX were 0.56 ± 0.80, -0.76 ± 0.88 and 0.72 ± 0.92, respectively. After adjustment for potential confounders including maternal smoking during pregnancy, a 10 µg/m3 increase in average PM2.5 was significantly associated with worsening AX (ß-coefficient: 0.260; 95% CI: 0.019, 0.502), while the association between a 100-µg/m3 increase in peak PM2.5 and AX was borderline (0.166; 95% CI: -0.002, 0.334). CONCLUSION: Infant exposure to coal mine fire emissions could be associated with long-term impairment of lung reactance.

"My Surgical Success": Effect of a Digital Behavioral Pain Medicine Intervention on Time to Opioid Cessation After Breast Cancer Surgery-A Pilot Randomized Controlled Clinical Trial.

OBJECTIVE: This study aims to assess the feasibility of digital perioperative behavioral pain medicine intervention in breast cancer surgery and evaluate its impact on pain catastrophizing, pain, and opioid cessation after surgery. DESIGN AND SETTING: A randomized controlled clinical trial was conducted at Stanford University (Palo Alto, CA, USA) comparing a digital behavioral pain medicine intervention ("My Surgical Success" [MSS]) with digital general health education (HE). PARTICIPANTS: A convenience sample of 127 participants were randomized to treatment group. The analytic sample was 68 patients (N = 36 MSS, N = 32 HE). MAIN OUTCOMES: The primary outcome was feasibility and acceptability of a digital behavioral pain medicine intervention (80% threshold for acceptability items). Secondary outcomes were pain catastrophizing, past seven-day average pain intensity, and time to opioid cessation after surgery for patients who initiated opioid use. RESULTS: The attrition rate for MSS intervention (44%) was notably higher than for HE controls (18%), but it was lower than typical attrition rates for e-health interventions (60-80%). Despite greater attrition for MSS, feasibility was demonstrated for the 56% of MSS engagers, and the 80% threshold for acceptability was met. We observed a floor effect for baseline pain catastrophizing, and no significant group differences were found for postsurgical pain catastrophizing or pain intensity. MSS was associated with 86% increased odds of opioid cessation within the 12-week study period relative to HE controls (hazard ratio = 1.86, 95% confidence interval = 1.12-3.10, P = 0.016). CONCLUSIONS: Fifty-six percent of patients assigned to MSS engaged with the online platform and reported high satisfaction. MSS was associated with significantly accelerated opioid cessation after surgery (five-day difference) with no difference in pain report relative to controls. Perioperative digital behavioral pain medicine may be a low-cost, accessible adjunct that could promote opioid cessation after breast cancer surgery.

Is remaining indoors an effective way of reducing exposure to fine particulate matter during biomass burning events?

Bushfires, prescribed burns, and residential wood burning are significant sources of fine particles (aerodynamic diameter <2.5 µm; PM2.5) affecting the health and well-being of many communities. Despite the lack of evidence, a common public health recommendation is to remain indoors, assuming that the home provides a protective barrier against ambient PM2.5. The study aimed to assess to what extent houses provide protection against peak concentrations of outdoor PM2.5 and whether remaining indoors is an effective way of reducing exposure to PM2.5. The effectiveness of this strategy was evaluated by conducting simultaneous week-long indoor and outdoor measurements of PM2.5 at 21 residences in regional areas of Victoria, Australia. During smoke plume events, remaining indoors protected residents from peak outdoor PM2.5 concentrations, but the level of protection was highly variable, ranging from 12% to 76%. Housing stock (e.g., age of the house) and ventilation (e.g., having windows/doors open or closed) played a significant role in the infiltration of outdoor PM2.5 indoors. The results also showed that leaving windows and doors closed once the smoke plume abates trapped PM2.5 indoors and increased indoor exposure to PM2.5. Furthermore, for approximately 50% of households, indoor sources such as cooking activities, smoking, and burning candles or incense contributed significantly to indoor PM2.5. Implications: Smoke from biomass burning sources can significantly impact on communities. Remaining indoors with windows and doors closed is a common recommendation by health authorities to minimize exposures to peak concentrations of fine particles during smoke plume events. Findings from this study have shown that the protection from fine particles in biomass burning smoke is highly variable among houses, with information on housing age and ventilation status providing an approximate assessment on the protection of a house. Leaving windows closed once a smoke plume abates traps particles indoors and increases exposures.

Secondary use of electronic medical records for clinical research: Challenges and Opportunities.

With increasingly ubiquitous electronic medical record (EMR) implementation accelerated by the adoption of the HITECH Act, there is much interest in the secondary use of collected data to improve outcomes and promote personalized medicine. A plethora of research has emerged using EMRs to investigate clinical research questions and assess variations in both treatments and outcomes. However, whether because of genuine complexities of modeling disease physiology or because of practical problems regarding data capture, data accuracy, and data completeness, the state of current EMR research is challenging and gives rise to concerns regarding study accuracy and reproducibility. This work explores challenges in how different experimental design decisions can influence results using a specific example of breast cancer patients undergoing excision and reconstruction surgeries from EMRs in an academic hospital and the Veterans Health Administration (VHA) We discuss emerging strategies that will mitigate these limitations, including data sharing, application of natural language processing, and improved EMR user design.

The pro-inflammatory effects of particulate matter on epithelial cells are associated with elemental composition.

BACKGROUND: Adverse health effects of particulate matter (PM) vary with chemical composition; however, evidence regarding which elements are the most detrimental is limited. The roof space area provides an open and stable environment for outdoor PM to settle and deposit. Therefore, this study used roof space PM samples as a proxy of residential cumulative exposure to outdoor air pollution to investigate their pro-inflammatory effects on human lung cells and the contribution of the endotoxin and chemical content. METHODS: Roof space PM samples of 36 different homes were collected and analysed using standardised techniques. We evaluated cytotoxicity and cytokine production of BEAS-2B cells after PM exposure using MTS and ELISA, respectively. Principle component analysis (PCA) and linear regression analyses were employed to assess the associations between cytokine production and the PM components. RESULTS: PM caused significant time- and dose-dependent increases in cellular cytokine production (p < 0.05). PCA identified four factors that explained 68.33% of the variance in the chemical composition. An increase in Factor 1 (+Fe, +Al, +Mn) score and a decrease in Factor 2 (-Ca, +Pb, +PAH) score were associated with increased interleukin (IL)-6 (Factor 1; p = 0.010; Factor 2; p = 0.006) and IL-8 (Factor 1; p = 0.003; Factor 2; p = 0.020) production, however, only the association with Factor 1 was evident after correcting for endotoxin and particle size. CONCLUSIONS: Our study provides novel insight into the positive associations between pro-inflammatory effects of roof space PM samples with Fe, Al and Mn levels.

T cell receptor sequencing of early-stage breast cancer tumors identifies altered clonal structure of the T cell repertoire.

Tumor-infiltrating T cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T cells specific to each, as well as their abundance in peripheral blood. Using immune profiling of the T cell beta-chain repertoire in 16 patients with early-stage breast cancer, we show that the clonal structure of the tumor is significantly different from adjacent breast tissue, with the tumor containing ∼2.5-fold greater density of T cells and higher clonality compared with normal breast. The clonal structure of T cells in blood and normal breast is more similar than between blood and tumor, and could be used to distinguish tumor from normal breast tissue in 14 of 16 patients. Many T cell sequences overlap between tissue and blood from the same patient, including ∼50% of T cells between tumor and normal breast. Both tumor and normal breast contain high-abundance "enriched" sequences that are absent or of low abundance in the other tissue. Many of these T cells are either not detected or detected with very low frequency in the blood, suggesting the existence of separate compartments of T cells in both tumor and normal breast. Enriched T cell sequences are typically unique to each patient, but a subset is shared between many different patients. We show that many of these are commonly generated sequences, and thus unlikely to play an important role in the tumor microenvironment.

5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages.

5-Hydroxymethylcytosine (5hmC) is an important mammalian DNA epigenetic modification that has been linked to gene regulation and cancer pathogenesis. Here we explored the diagnostic potential of 5hmC in circulating cell-free DNA (cfDNA) using a sensitive chemical labeling-based low-input shotgun sequencing approach. We sequenced cell-free 5hmC from 49 patients of seven different cancer types and found distinct features that could be used to predict cancer types and stages with high accuracy. Specifically, we discovered that lung cancer leads to a progressive global loss of 5hmC in cfDNA, whereas hepatocellular carcinoma and pancreatic cancer lead to disease-specific changes in the cell-free hydroxymethylome. Our proof-of-principle results suggest that cell-free 5hmC signatures may potentially be used not only to identify cancer types but also to track tumor stage in some cancers.

A novel thermal compression device for perioperative warming: a randomized trial for feasibility and efficacy.

BACKGROUND: Inadvertent perioperative hypothermia (IPH) leads to surgical complications and increases length of stay. IPH rates are high with the current standard of care, forced air warming (FAW). Our hypothesis is that a prototype thermal compression device that heats the popliteal fossa and soles of the feet, with lower leg compression, increases perioperative temperatures and reduces IPH compared to the current standard of care. METHODS: Thirty six female breast surgery patients, at a tertiary academic hospital, were randomized to the device or intraoperative FAW (stage I) with a further 18 patients randomized to the device with a single heating area only (stage II, popliteal fossa or sole of the feet). Stage I: 37 patients recruited (final 36). Stage II: 18 patients recruited (final 18). INCLUSION CRITERIA: general anesthesia with esophageal monitoring for over 30 min, legs available and able to fit the device and no contraindications to leg heating or compression. The intervention was: Stage I: Investigational prototype thermal compression device (full device group) or intraoperative FAW. Stage II: Device with only a single heating location. Primary outcomes were perioperative temperatures and incidence of IPH. Secondary outcomes were local skin temperature, general and thermal comfort scores and presence of perioperative complications, including blood loss. RESULTS: Mean temperatures in the full device group were significantly higher than the FAW group in the pre-operative (36.7 vs 36.4 °C, p < 0.001), early intraoperative (36.3 vs 35.9 °C, p < 0.001), intraoperative (36.6 vs 36.2 °C, p < 0.001) and postoperative periods (36.8 vs 36.5 °C, p < 0.001). The incidence of IPH in the device group was also significantly lower (16.7% vs 72.0%, p = 0.001). Thermal comfort scores were significantly higher in the full device group and hypothermia associated wound complications were higher in the FAW group. CONCLUSIONS: The thermal compression device is feasible and has efficacy over the FAW. Further studies are recommended to investigate clinically significant outcomes. TRIAL REGISTRATION: clinicaltrials.gov ( NCT02155400 ).