Reversing immunosuppression in the tumor microenvironment of fibrolamellar carcinoma via PD-1 and IL-10 blockade.

Fibrolamellar carcinoma (FLC) is a rare liver tumor driven by the DNAJ-PKAc fusion protein that affects healthy young patients. Little is known about the immune response to FLC, limiting rational design of immunotherapy. Multiplex immunohistochemistry and gene expression profiling were performed to characterize the FLC tumor immune microenvironment and adjacent non-tumor liver (NTL). Flow cytometry and T cell receptor (TCR) sequencing were performed to determine the phenotype of tumor-infiltrating immune cells and the extent of T cell clonal expansion. Fresh human FLC tumor slice cultures (TSCs) were treated with antibodies blocking programmed cell death protein-1 (PD-1) and interleukin-10 (IL-10), with results measured by cleaved caspase-3 immunohistochemistry. Immune cells were concentrated in fibrous stromal bands, rather than in the carcinoma cell compartment. In FLC, T cells demonstrated decreased activation and regulatory T cells in FLC had more frequent expression of PD-1 and CTLA-4 than in NTL. Furthermore, T cells had relatively low levels of clonal expansion despite high TCR conservation across individuals. Combination PD-1 and IL-10 blockade signficantly increased cell death in human FLC TSCs. Immunosuppresion in the FLC tumor microenvironment is characterized by T cell exclusion and exhaustion, which may be reversible with combination immunotherapy.

Quality improvement project to reduce medicare 1-day write-offs due to inappropriate admission orders.

BACKGROUND: We identified that Stanford Health Care had a significant number of patients who after discharge are found by the utilization review committee not to meet Center for Mediare and Medicaid Services (CMS) 2-midnight benchmark for inpatient status. Some of the charges incurred during the care of these patients are written-off and known as Medicare 1-day write-offs. This study which aims to evaluate the use of a Best Practice Alert (BPA) feature on the electronic medical record, EPIC, to ensure appropriate designation of a patient's hospitalization status as either inpatient or outpatient in accordance with Center for Medicare and Medicaid services (CMS) 2 midnight length of stay benchmark thereby reducing the number of associated write-offs. METHOD: We incorporated a best practice alert (BPA) into the Epic Electronic Medical Record (EMR) that would prompt the discharging provider and the case manager to review the patients' inpatient designation prior to discharge and change the patient's designation to observation when deemed appropriate. Patients who met the inclusion criteria (Patients must have Medicare fee-for-service insurance, inpatient length of stay (LOS) less than 2 midnights, inpatient designation as hospitalization status at time of discharge, was hospitalized to an acute level of care and belonged to one of 37 listed hospital services at the time of signing of the discharge order) were randomized to have the BPA either silent or active over a three-month period from July 18, 2019, to October 18, 2019. RESULT: A total of 88 patients were included in this study: 40 in the control arm and 48 in the intervention arm. In the intervention arm, 8 (8/48, 16.7%) had an inpatient status designation despite potentially meeting Medicare guidelines for an observation stay, comparing to 23 patients (23/40, 57.5%) patients in the control group (p = 0.001). The estimated number of write-offs in the control arm was 17 (73.9%, out of 23 inpatient patients) while in the intervention arm was 1 (12.5%, out of 8 inpatient patient) after accounting for patients who may have met inpatient criteria for other reasons based on case manager note review. CONCLUSION: This is the first time to our knowledge that a BPA has been used in this manner to reduce the number of Medicare 1-day write-offs.

Cognitive decrements in 1991 Gulf War veterans: associations with Gulf War illness and neurotoxicant exposures in the Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) cohorts.

BACKGROUND: During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant induced symptoms of Gulf War Illness (GWI), a multi-faceted condition that includes fatigue, pain and cognitive decrements. When studied empirically, both deployed veterans with exposures and those who meet the criteria for GWI are more likely to show deficits in the area of neuropsychological functioning. Although studies have shown cognitive impairments in small sample sizes, it is necessary to revisit these findings with larger samples and newer cohorts to see if other areas of deficit emerge with more power to detect such differences. A group of researchers and clinicians with expertise in the area of GWI have identified common data elements (CDE) for use in research samples to compare data sets. At the same time, a subgroup of researchers created a new repository to share these cognitive data and biospecimens within the GWI research community. METHODS: The present study aimed to compare cognitive measures of attention, executive functioning, and verbal memory in a large sample of GWI cases and healthy GW veteran controls using neuropsychological tests recommended in the CDEs. We additionally subdivided samples based on the specific neurotoxicant exposures related to cognitive deficits and compared exposed versus non-exposed veterans regardless of case criteria status. The total sample utilized cognitive testing outcomes from the newly collated Boston, Biorepository, Recruitment, and Integrative Network (BBRAIN) for GWI. RESULTS: Participants included 411 GW veterans, 312 GWI (cases) and 99 healthy veterans (controls). Veterans with GWI showed significantly poorer attention, executive functioning, learning, and short-and-long term verbal memory than those without GWI. Further, GW veterans with exposures to acetylcholinesterase inhibiting pesticides and nerve gas agents, had worse performance on executive function tasks. Veterans with exposure to oil well fires had worse performance on verbal memory and those with pyridostigmine bromide anti-nerve gas pill exposures had better verbal memory and worse performance on an attention task compared to unexposed veterans. CONCLUSIONS: This study replicates prior results regarding the utility of the currently recommended CDEs in determining impairments in cognitive functioning in veterans with GWI in a new widely-available repository cohort and provides further evidence of cognitive decrements in GW veterans related to war-related neurotoxicant exposures.

Low Back Pain Perceptions and Coping Strategies in Pre-Professional Dancers: A Qualitative Study.

AIMS: Low back pain (LBP) is a common health problem in pre-professional dancers which could hamper the dancers' professional career. However, pre-professional dancers are not often studied, although they may have their own pain perceptions and coping strategies towards LBP. Considering the biopsychosocial nature of LBP, it is important to increase the understanding of these perceptions and coping strategies. The aim of this qualitative research study was to explore the dancers' perceptions about LBP and their coping strategies when they suffered from LBP. METHODS: Eighteen pre-professional dancers with and without LBP from different dance schools in Belgium were included in this study. Participants were invited for an in-depth online video interview. These in-depth interviews were based on a topic list. Afterwards, the interview transcripts were analyzed thematically. RESULTS: Two primary themes emerged from the data: 1) perceptions of LBP and 2) coping strategies which dancers applied when they suffered from LBP. The perceptions about LBP were related to two different themes: "it's all about the body" and "it's all about the psychosocial and contextual factors." In addition, the coping strategies were divided into "active coping strategies" and "passive coping strategies," whereas the most popular coping strategies were stretching exercises and passive coping strategies such as massages or heating cream. CONCLUSION: Although LBP has clearly been shown to be a biopsychosocial phenomenon, this qualitative study showed that dancers mainly considered biomedical factors as contributing factors to LBP. Additionally, instead of relying on coping strategies aimed at directly improving pain or trying to treat LBP on the basis of a single-cause diagnosis, it is important to consider the biopsychosocial origin of LBP in the management plans.

Genetic association between the APOE ε4 allele, toxicant exposures and Gulf war illness diagnosis.

INTRODUCTION: Exposure to nerve agents, pyridostigmine bromide (PB), pesticides, and oil-well fires during the 1991 Gulf War (GW) are major contributors to the etiology of Gulf War Illness (GWI). Since the apolipoprotein E (APOE) ε4 allele is associated with the risk of cognitive decline with age, particularly in the presence of environmental exposures, and cognitive impairment is one of the most common symptoms experienced by veterans with GWI, we examined whether the ε4 allele was associated with GWI. METHODS: Using a case-control design, we obtained data on APOE genotypes, demographics, and self-reported GW exposures and symptoms that were deposited in the Boston Biorepository and Integrative Network (BBRAIN) for veterans diagnosed with GWI (n = 220) and healthy GW control veterans (n = 131). Diagnosis of GWI was performed using the Kansas and/or Center for Disease Control (CDC) criteria. RESULTS: Age- and sex-adjusted analyses showed a significantly higher odds ratio for meeting the GWI case criteria in the presence of the ε4 allele (Odds ratio [OR] = 1.84, 95% confidence interval [CI = 1.07-3.15], p ≤ 0.05) and with two copies of the ε4 allele (OR = 1.99, 95% CI [1.23-3.21], p ≤ 0.01). Combined exposure to pesticides and PB pills (OR = 4.10 [2.12-7.91], p ≤ 0.05) as well as chemical alarms and PB pills (OR = 3.30 [1.56-6.97] p ≤ 0.05) during the war were also associated with a higher odds ratio for meeting GWI case criteria. There was also an interaction between the ε4 allele and exposure to oil well fires (OR = 2.46, 95% CI [1.07-5.62], p ≤ 0.05) among those who met the GWI case criteria. CONCLUSION: These findings suggest that the presence of the ε4 allele was associated with meeting the GWI case criteria. Gulf War veterans who reported exposure to oil well fires and have an ε4 allele were more likely to meet GWI case criteria. Long-term surveillance of veterans with GWI, particularly those with oil well fire exposure, is required to better assess the future risk of cognitive decline among this vulnerable population.

Evaluation of test-day milk somatic cell count to predict intramammary infection in late lactation grazing dairy cows.

Use of selective dry cow antimicrobial therapy requires to precisely differentiate cows with an intramammary infection (IMI) from uninfected cows close to drying-off to enable treatment allocation. Milk somatic cell count (SCC) is an indicator of an inflammatory response in the mammary gland and is usually associated with IMI. However, SCC can also be influenced by cow-level variables such as milk yield, lactation number and stage of lactation. In recent years, predictive algorithms have been developed to differentiate cows with IMI from cows without IMI based on SCC data. The objective of this observational study was to explore the association between SCC and subclinical IMI, taking cognizance of cow-level predictors on Irish seasonal spring calving, pasture-based systems. Additionally, the optimal test-day SCC cut-point (maximized sensitivity and specificity) for IMI diagnosis was determined. A total of 2,074 cows, across 21 spring calving dairy herds with an average monthly milk weighted bulk tank SCC of ≤200,000 cells/mL were enrolled in the study. Quarter-level milk sampling was carried out on all cows in late lactation (interquartile range = 240-261 d in milk) for bacteriological culturing. Bacteriological results were used to define cows with IMI, when ≥1 quarter sample resulted in bacterial growth. Cow-level test-day SCC records were provided by the herd owners. The ability of the average, maximum and last test-day SCC to predict infection were compared using receiver operator curves. Predictive logistic regression models tested included parity (primiparous or multiparous), yield at last test-day and a standardized count of high SCC test-days. In total, 18.7% of cows were classified as having an IMI, with first parity cows having a higher proportion of IMI (29.3%) compared with multiparous cows (16.1%). Staphylococcus aureus accounted for the majority of these infections. The last test-day SCC was the best predictor of infection with the highest area under the curve. The inclusions of parity, yield at last test-day, and a standardized count of high SCC test-days as predictors did not significantly improve the ability of last test-day SCC to predict IMI. The cut-point for last test-day SCC which maximized sensitivity and specificity was 64,975 cells/mL. This study indicates that in Irish seasonal pasture-based dairy herds, with low bulk tank SCC control programs, the last test-day SCC (interquartile range days in milk = 221-240) is the best predictor of IMI in late lactation.

Study of dielectric breakdown in liquid xenon with XeBrA: The xenon breakdown apparatus.

Maintaining the electric fields necessary for the current generation of noble liquid time projection chambers (TPCs), with drift lengths exceeding 1 m, requires a large negative voltage applied to their cathode. Delivering such high voltage is associated with an elevated risk of electrostatic discharge and electroluminescence, which would be detrimental to the performance of the experiment. The Xenon Breakdown Apparatus (XeBrA) is a 5-l, high voltage test chamber built to investigate the contributing factors to electrical breakdown in noble liquids. In this work, we present the main findings after conducting scans over stressed electrode areas, surface finish, pressure, and high voltage ramp speed in the medium of liquid xenon. Area scaling and surface finish were observed to be the dominant factors affecting breakdown, whereas no significant changes were observed with varying pressure or ramp speed. A general rise in both the anode current and photon rate was observed in the last 30 s, leading up to a breakdown, with a marked increase in the last couple of seconds. In addition, the position of breakdowns was reconstructed with a system of high-speed cameras and a moderate correlation with the Fowler-Nordheim field emission model was found. Tentative evidence for bubble nucleation being the originating mechanism of breakdown in the liquid was also observed. We deem the results presented in this work to be of particular interest for the design of future, large TPCs, and practical recommendations are provided.

Factors associated with breast cancer mammography screening and breast self-examination in Irish women: results from the Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: BreastCheck is Ireland's breast screening service which offers biennial mammograms to women aged 50-69. Practicing regular breast self-examination (BSE) enhances women's awareness and increases their perception of their susceptibility to the risk of breast cancer, possibly increasing their likelihood of attending a screening programme which reduces breast cancer mortality. Research is needed to identify the promotors and barriers to both attending breast cancer screening and practicing BSE. PURPOSE: The aim of this study was to determine the promotors and barriers associated with attending breast cancer screening and practicing BSE in Irish women. MATERIALS AND METHODS: Data from the participants of TILDA wave 3 (2014-2015) was used, the participant population included females only (≥50 years old), a total of 3575 women. Bivariate analysis was used to identify variables that were significantly associated with having had a mammogram since the last interview (wave 2) or regularly checking their breasts for lumps (BSE). Regression analysis was then used to determine the effect the significant variables had on predicting the likelihood of participants attending breast screening or practicing BSE. RESULTS: Over half (55%) of all women over the age of 50 had a mammogram since wave 2 was completed (2012) and two thirds reported practicing regular BSE. The factors associated with having attended for breast cancer screening were: having private health insurance (OR = 1.86, 95%CI = 1.45-2.380), and practicing BSE (OR = 1.683, 95%CI = 1.344-2.107). The factors found to be associated with practicing regular BSE were: higher quality of life (OR = 1.035, 95%CI = 1.015-1.057), higher BMI (OR = 1.118, 95%CI = 1.020-1.226), being married (OR = 1.436, 95%CI = 1.190-1.732) and attending mammogram screening (OR = 1.691, 95%CI = 1.353-2.114). CONCLUSION: Regular participation in mammography screening reduces breast cancer mortality. Women eligible for BreastCheck were significantly more likely to attend screening. BSE is associated with increased attendance at screening. Health-care professionals should encourage BSE in order to increase screening uptake.

Assessment of level of care recommendations and nursing acuity scores following an appropriateness of care intervention.

BACKGROUND: As part of a multiprong intervention to eliminate waste in cost of hospital accommodations, the InterQual Level of Care (LOC) criteria was deployed by our institution to assign patients to one of three LOCs: acute care, intermediate intensive care unit (IICU) or intensive care unit (ICU). In that intervention, which sought to decrease the number of patients in a higher LOC than what was clinically necessary, patient safety balancing metrics were stable. However, nursing workload, a key balancing metric, has yet to be examined. In this study, we examine nursing workload before and after the intervention using a proprietary nursing acuity score. METHODS: A retrospective study was conducted analysing admissions at the study institution. Patient's LOC recommendation (as determined by InterQual), assigned (actual) LOC and nursing acuity scores were collected and analysed. Average nursing acuity scores were compared across patients whose InterQual recommendation aligned with actual LOC ('Acute Match' or 'IICU Match') versus patients who were recommended to be in acute care but were receiving IICU care ('Mismatch'). RESULTS: Following the intervention, the per cent of patients in the Mismatch cohort decreased from 13% to 7%. Prior to the intervention, average nursing acuity score for the Mismatch cohort was less than the IICU Match cohort and greater than Acute Match cohort in all departments analysed. After the intervention period, average acuity score in the Mismatch cohort exceeded that of the Acute Match cohort in all eight departments, but the Mismatch cohort's scores differed from the IICU Match cohort in only one department. CONCLUSION: Collectively, this study demonstrates that our intervention successfully decreased inappropriate use of the IICU LOC, and that the residual Mismatch cohort is a distinct entity, with nursing needs that exceed that of the Acute Match cohort. Thus, a higher LOC can be justified. This demonstrates that a nursing workload metric such as the nursing acuity score can be a valuable complement to clinical criteria such as the InterQual LOC criteria to objectively determine patient's true, necessary LOC and ensure that nursing staff feels adequately staffed to care for patients.

Economic evaluations of interventions against influenza at workplaces: systematic review.

BACKGROUND: The burden of influenza is mostly felt by employees and employers because of increased absenteeism rates, loss of productivity and associated direct costs. Even though interventions against influenza among working adults are effective, patronage and compliance to these measures especially vaccination are low compared to other risk groups. AIMS: This study was aimed to assess evidence of economic evaluations of interventions against influenza virus infection among workers or in the workplace setting. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guideline for systematic reviews was followed. Three databases, PubMed, Web of Science and EconLit, were searched using keywords to identify relevant articles from inception till 25 October 2020. Original peer-reviewed papers that conducted economic evaluations of influenza interventions using cost-benefit, cost-effectiveness or cost-utility analysis methods focused on working-age adults or work settings were eligible for inclusion. Two independent teams of co-authors extracted and synthesized data from identified studies. RESULTS: Twenty-four articles were included: 21 were cost-benefit analyses and 3 examined cost-effectiveness analyses. Two papers also presented additional cost-utility analysis. Most of the studies were pharmaceutical interventions (n = 23) primarily focused on vaccination programs while one study was a non-pharmaceutical intervention examining the benefit of paid sick leave. All but two studies reported that interventions against influenza virus infection at the workplace were cost-saving and cost-effective regardless of the analytic approach. CONCLUSIONS: Further cost-effectiveness research in non-pharmaceutical interventions against influenza in workplace settings is warranted. There is a need to develop standardized methods for reporting economic evaluation methods to ensure comparability and applicability of future research findings.

Hydrogeochemical mineral exploration in deeply weathered terrains: An example from Mumbwa, Zambia.

Locating mineral deposits in areas of thick or transported overburden is notoriously difficult. Post-mineral cover is prevalent in many parts of the globe and has led to prospective geological sequences being missed by traditional methods of exploration. Hydrogeochemistry is particularly applicable for the exploration of Iron Oxide Copper Gold (IOCG) deposits because, when compared to larger porphyry or sediment-hosted systems, IOCG deposits tend to be smaller and high-grade with a limited lateral footprint to intersect with grid-drilling; groundwater interactions and ion dispersion tend to produce a much larger anomaly target than regolith geochemistry alone and require fewer samples. As a case study, we examine the hydrogeochemistry of the Kitumba IOCG deposit, located in the Mumbwa district of west-central Zambia. We present physicochemical data (Eh, pH, TDS, conductivity), major and trace element concentrations, and isotopic compositions (δ98Mo, 87Sr/86Sr, and δ65Cu) from groundwaters interacting with the Kitumba deposit and surrounding prospects. A hydrogeochemical footprint of As, Mo, Fe, Mn, and Zn is dispersed from the deposit. Groundwater 87Sr/86Sr values (0.708832 to 0.731807) reflect the mixing in varying proportions of waters that have interacted with distinct lithological endmembers in the Mumbwa area, corresponding to a complicated tectonic and metamorphic history. We report fractionation of 1.34 to 1.60‰ (∆65Cugroundwater - chalcopyrite) between proximal groundwater and primary chalcopyrite, which we postulate may be related to the oxidative dissolution of primary sulfide minerals. The δ98Mo3134 values of groundwaters proximal to known ore bodies are isotopically distinct (-1.08 ± 0.18‰ 2SE to 0.64 ± 0.08‰ 2 SE) from background aquifers (2.08 ± 0.12‰ 2SE). The trace element and isotopic hydrogeochemical patterns described in this study document water-rock and water-deposit interactions and demonstrate the potential of non-traditional stable isotopes to be employed in district-scale reduction of exploration ground and vectoring towards undisturbed ore deposits similar to Kitumba.

Assessment of the microbial load of airway clearance devices used by a cohort of children with cystic fibrosis.

BACKGROUND: Positive expiratory pressure (PEP) devices are an important element of the management of cystic fibrosis, and of other respiratory diseases. Whereas there have been reports in the literature of contamination of airway clearance devices and their surfaces by microbial pathogens, there is little evidence available regarding such contamination and its contribution to respiratory infection. AIM: To establish whether pathogenic bacteria can contaminate PEP devices in the context of normal cleaning and maintenance practices. METHODS: Patients' home-use clearance devices were brought to a routine clinic appointment and collected for microbiology sampling and analysis. The patients were provided with replacement devices. Nineteen such devices were collected from 17 patients, reflecting use of multiple devices by some patients. Swabs were taken and cultured from each patient's used device, the patient's airway, as well as from new unopened and unused devices that acted as controls. RESULTS: Seven of 19 devices (37%) tested positive for presence of pathogenic bacteria. Device-cleaning methods varied among patients and non-sterilization methods were found to be ineffective at removing pathogens. Microbial species found on the devices did not correlate with those identified from airway swabs. CONCLUSION: This study demonstrates the presence of pathogens on positive expiratory pressure devices. The potential for transmission of these pathogens to the patient's airway and the risk of infection remains unclear and requires further study.

Boston biorepository, recruitment and integrative network (BBRAIN): A resource for the Gulf War Illness scientific community.

AIMS: Gulf War Illness (GWI), a chronic debilitating disorder characterized by fatigue, joint pain, cognitive, gastrointestinal, respiratory, and skin problems, is currently diagnosed by self-reported symptoms. The Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) is the collaborative effort of expert Gulf War Illness (GWI) researchers who are creating objective diagnostic and pathobiological markers and recommend common data elements for GWI research. MAIN METHODS: BBRAIN is recruiting 300 GWI cases and 200 GW veteran controls for the prospective study. Key data and biological samples from prior GWI studies are being merged and combined into retrospective datasets. They will be made available for data mining by the BBRAIN network and the GWI research community. Prospective questionnaire data include general health and chronic symptoms, demographics, measures of pain, fatigue, medical conditions, deployment and exposure histories. Available repository biospecimens include blood, plasma, serum, saliva, stool, urine, human induced pluripotent stem cells and cerebrospinal fluid. KEY FINDINGS: To date, multiple datasets have been merged and combined from 15 participating study sites. These data and samples have been collated and an online request form for repository requests as well as recommended common data elements have been created. Data and biospecimen sample requests are reviewed by the BBRAIN steering committee members for approval as they are received. SIGNIFICANCE: The BBRAIN repository network serves as a much needed resource for GWI researchers to utilize for identification and validation of objective diagnostic and pathobiological markers of the illness.

Seven-year retrospective study understanding the latent TB infection treatment cascade of care among adults in a low incidence country.

BACKGROUND: Prevention of TB is paramount to achieving elimination targets as recommended by the World Health Organization's action framework for low incidence countries striving to eliminate TB. Although the rates of TB in Canada are low, understanding the latent TB infection (LTBI) cascade is paramount to identifying gaps in care and treatment barriers, thereby increasing the effectiveness of preventive strategies. The purpose of this study was to examine the LTBI cascade of care and identify barriers to treatment completion in adults referred from primary care to a regional tertiary care TB clinic in Ottawa, Canada. METHODS: Electronic medical records between January 2010 and December 2016 were reviewed retrospectively and an LTBI cascade of care was constructed from The Ottawa Hospital TB clinic and surrounding primary care clinics. A cohort of 2207 patients with untreated LTBI was used to ascertain the associations between demographic and clinical factors for both treatment non-initiation and non-completion using log-binomial univariable and multivariable regression models. RESULTS: Of 2207 patients with untreated LTBI who were seen in the clinic during the study period, 1771 (80.2%) were offered treatment, 1203 (67.9% of those offered) started treatment, and 795 (66.1% of those started) completed treatment. In multivariable analysis, non-initiation of treatment was associated with older age (adjusted risk ratio [aRR] 1.06 per 5-year increase, 95% CI: 1.03-1.08) and female gender (aRR 1.28, 95% CI: 1.11-1.47). Non completion of treatment was associated with referral from the TB Clinic back to the primary care team following initial consult (aRR 1.62, 95% CI: 1.35-1.94) and treatment with the standard of 9 months of Isoniazid (9H) compared to 4 months of Rifampin (4R) (aRR 1.45, 95% CI:1.20-1.74). CONCLUSIONS: LTBI treatment completion was significantly decreased among patients who were referred back to primary care from the TB clinic. The 4R regimen resulted in more people completing LTBI treatment compared to 9H in keeping with a recently published RCT. Improved education, communication, and collaboration between tertiary care TB clinics and primary care teams may improve treatment completion rates and address the TB burden in low incidence communities in Canada.

Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Indentation and Transverse Diameter of the Meckel Cave: Imaging Markers to Diagnose Idiopathic Intracranial Hypertension.

BACKGROUND AND PURPOSE: Clinical and imaging manifestations of idiopathic intracranial hypertension should prompt early diagnosis and treatment to avoid complications. Multiple diagnostic imaging criteria are reported to suggest the diagnosis of idiopathic intracranial hypertension with questionable sensitivity and/or specificity. Increased intracranial pressure results in dilation of the perineural cisternal spaces such as the optic nerve sheaths and the Meckel cave. It may also cause protrusion of cisternal structures of the Meckel cave through the skull base foramina, which could result in indentation or a bilobed appearance of the Meckel cave. We investigated the changes in the Meckel cave in patients with proved idiopathic intracranial hypertension versus healthy controls. MATERIALS AND METHODS: We studied 75 patients with a diagnosis of idiopathic intracranial hypertension and 75 age-and sex-matched healthy controls. The transverse diameter of Meckel cave was measured in the axial and coronal planes of T2-weighted MR imaging sequences, and comparison was made between the 2 groups. RESULTS: The mean diameters of the Meckel cave on the coronal T2 plane in patients with idiopathic intracranial hypertension were 5.21 ± 1.22 mm on the right side and 5.16 ± 0.90 mm on the left side, while in the control group, they measured 3.89 ± 0.62 mm and 4.09 ± 0.68 mm, respectively (P value < .001). Of 75 patients with an approved diagnosis of idiopathic intracranial hypertension, 57 (76%) showed an indented Meckel cave as opposed to 21 (28%) in the control group. CONCLUSIONS: Our results confirm for the first time that the shape and size of the Meckel cave can be used as sensitive and specific diagnostic imaging markers for the diagnosis of idiopathic intracranial hypertension.

The most influential papers in mitral valve surgery; a bibliometric analysis.

This study is an analysis of the 100 most cited articles in mitral valve surgery. A bibliometric analysis is a tool to evaluate research performance in a given field. It uses the number of times a publication is cited by others as a proxy marker of its impact. The most cited paper Carpentier et al. discusses mitral valve repair in terms of restoring the geometry of the entire valve rather than simply narrowing the annulus (Carpentier, J Thorac Cardiovasc Surg 86:23-37, 1983). The first successful mitral valve repair was performed by Elliot Cutler at Brigham and Women's Hospital in 1923 (Cohn et al., Ann Cardiothorac Surg 4:315, 2015). More recently percutaneous and minimally invasive techniques that were originally designed as an option for high risk patients are being trialled in other patient groups (Hajar, Heart Views 19:160-3, 2018). Comparison of percutaneous method with open repair represents an expanding area of research (Hajar, Heart Views 19:160-3, 2018). This study will analyse the top 100 cited papers relevant to mitral valve surgery, identifying the most influential papers that guide current management, the institutions that produce them and the authors involved.

Work-Related Stress Induced Takotsubo Cardiomyopathy.

Aim To report a case of Takotsubo cardiomyopathy secondary to a verbal altercation in an employee who presented with chest pain. Methods The clinical history was obtained from the patient's occupational health record and correspondence from her treating cardiologist. Results The patient was diagnosed with Takotsubo cardiomyopathy following investigations for chest pain. Her echocardiogram was diagnostic. She was treated with beta blockers and advised to have complete rest; she remained out of work for six months. Conclusion There are few published cases of work related Takotsubo cardiomyopathy; it poses a challenge to physicians to be cognisant of this condition in a case of chest pain following emotional turmoil.

Antimicrobial use and stewardship practices on Australian beef feedlots.

OBJECTIVE: Improving antimicrobial stewardship in the livestock sector requires an understanding of the motivations for antimicrobial use and the quantities consumed. However,detailed information on antimicrobial use in livestock sectors is lacking. This cross-sectional study aimed to better understand antimicrobial use in the beef feedlot sector in Australia. DESIGN: A self-administered questionnaire asking about antimicrobial use and reasons for use was designed and mailed to beef feedlot operators in Australia. Respondents were asked to report the percentage of animals treated, purpose of use, and disease conditions targeted for 26antimicrobial agents. RESULTS: In total, 83 of 517 (16.1%) beef feedlot operators completed the survey. Monensin (61.0%of respondents) and virginiamycin (19.5%of respondents) were the most commonly reported in-feed antimicrobials. In-feed antimicrobial agents were most frequently used by respondents for treatment of gastrointestinal diseases (52.8%). Antimicrobials were used for growth promotion by 42.1% of respondents, with most (85.7%) reporting the use of ionophores(a group of compounds not used in human medicine). Short-acting penicillin(69.1%), short-acting oxytetracycline, and tulathromycin (both 57.3%) werethe most common injectable antimicrobial agents used. Injectable antimicrobials were most frequently used to treat respiratory (72.3%) and musculoskeletal (67.5%) conditions. CONCLUSION: Overall,the use of antimicrobials was appropriate for the purpose indicated, and there was a strong preference for drugs of low-importance in human medicine. The data described here stand to be a strong influence on the implementation of an antimicrobial stewardship program in the sector.

General health complaints and sleep associated with new injury within an endurance sporting population: A prospective study.

OBJECTIVES: To examine the association between subjective health complaints, sleep quantity and new injury within an endurance sport population. DESIGN: Prospective cohort study. METHODS: Ninety-five endurance sporting participants were recruited from running, triathlon, swimming, cycling and rowing disciplines. Over 52-week period participants submitted weekly data regarding subjective health complaints (SHCs) (cardiorespiratory, gastrointestinal and psychological/lifestyle), sleep quantity, training load and new injury episodes. Applying a 7- and 14-day lag period, a shared frailty model was used to explore new injury risk associations with total SHCs and sleep quantity. RESULTS: 92.6% of 95 participants completed all 52 weeks of data submission and the remainder of the participants completed ≥30 weeks. Seven-day lag psychological/lifestyle SHCs were significantly associated with new injury risk (Hazard ratio (HR)=1.32; CI 95%=1.01-1.72, p<0.04). In contrast, cardiorespiratory (HR=1.15; CI 95%=0.99-1.36, p=0.07) and gastrointestinal (HR=0.77; CI 95%=0.56-1.05, p=0.09) SHCs were not significantly associated with new injury risk. New injury risk had a significant increased association with 14-day lag <7h/day sleep quantity (HR=1.51; CI 95%=2.02-1.13, p<0.01) and a significant decreased association with >7h/day sleep quantity (HR=0.63, CI 95%=0.45-0.87, p<0.01. A secondary regression analysis demonstrated no significant association with total SHCs and training load factors (Relative Risk (RR)=0.08, CI 95%=0.04-0.21, p=0.20). CONCLUSIONS: To minimise an increased risk of new injuries within an endurance sporting population, this study demonstrates that psychological/lifestyle subjective health complaints and sleep quantity should be considered. The study also highlights a lag period between low sleep quantity and its subsequent impact on new injury risk. No association was demonstrated between subjective health complaints, sleep quantity and training load factors.