Prognostic and functional importance of both overt and subclinical left ventricular systolic dysfunction in systemic sclerosis.

OBJECTIVES: To quantify the frequency and clinical implications of systemic sclerosis (SSc)-associated left ventricular function (LV) impairment. METHODS: Australian Scleroderma Cohort Study participants meeting ACR/EULAR criteria for SSc with ≥1 echocardiographic LVEF measurement were included. Overt LV dysfunction was indicated by reduced LV ejection fraction (LVEF) and subclinical LV dysfunction was measured using impaired LV global longitudinal strain (LV-GLS>-16 %). Those with secondary causes of LV dysfunction (myocardial ischaemia, valvulopathy and pulmonary arterial hypertension) were excluded. Chi-squared tests, two-sample t-tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Generalised estimating equations(GEE) were used to model longitudinal data. Kaplan-Meier and Cox proportional hazard models were used for survival analyses. RESULTS: Of 1141 participants with no co-morbid cardiac disease, 2.4 % ever recorded a LVEF<50 %, while only 0.6 % ever recorded a LVEF≤40 %. LV-GLS data were available for 90 % of participants at one centre (n = 218). Impaired LV-GLS was detected in 21 % despite LVEF≥50 %. Those with a LVEF<50 % were more frequently male (p = 0.01) with dcSSc (p < 0.01), higher inflammatory markers (p < 0.02) and skeletal muscle disease (p < 0.05). In multivariable analyses, recording a LVEF<50 % was associated with increased mortality (HR2.3, 95 %CI1.0-4.8, p = 0.04). Impaired LV-GLS was also associated with poorer survival in univariable analyses (HR3.4, 95 %CI1.0-11.8, p = 0.05). Those with a LVEF<50 % more frequently recorded WHO Class III/IV dyspnoea (OR3.5, 95 %CI1.6-7.7, p < 0.01), with shorter six-minute walk distance (p = 0.01), higher Health Assessment Questionnaire-Disability Index scores (p < 0.01) and lower Short Form-36 Physical Component Summary scores (p = 0.02). Increased dyspnoea (WHO Class III/IV dyspnoea; OR3.6, 95 %CI1.4-9.2, p < 0.01) was also seen in those with impaired LV-GLS. CONCLUSIONS: Both overt and subclinical SSc-associated LV dysfunction are associated with worse survival and impaired physical function. The frequency of abnormal LV-GLS in those with consistently normal LVEF suggests an under-appreciated burden of subtle LV systolic dysfunction in SSc that has a significant impact on patient symptomatology.

Calcified left ventricular apical aneurysm with intramural thrombus: a case report.

Background: Left ventricular aneurysms (LVAs) are a well-appreciated complication of acute myocardial infarction. Ventricular aneurysms involving the left ventricle (LV) typically evolve as a result of anterior myocardial infarction and are associated with greater morbidity, complication rates, and hospital resource utilization. Incidence of LVA is decreasing with advent of modern reperfusion therapies; however, in the setting of excess morbidity, clinicians must maintain an appreciation for their appearance to allow timely diagnosis and individualized care. Case summary: This case report describes the clinical history, investigation, appearance, and management of a patient with calcified apical LVA with history of previous anterior ST-elevation myocardial infarction. The patient was initially admitted for elective coronary angiography in the setting of worsening exertional dyspnoea and subsequently underwent coronary artery bypass graft, aneurysm resection, and LV reconstruction. Discussion: Left ventricular aneurysms are an uncommon complication experienced in the modern era of acute myocardial infarction and current reperfusion therapies, but remain an important cause of excess morbidity and complication. Evidence-based guidelines for the diagnosis, workup, and subsequent management of LVAs are lacking. The imaging findings presented in this case serve as an important reminder of the appearance of LVAs so that timely diagnosis and individualized care considerations can be made.

Differential peripheral immune signatures elicited by vegan versus ketogenic diets in humans.

Nutrition has broad impacts on all physiological processes. However, how nutrition affects human immunity remains largely unknown. Here we explored the impact of a dietary intervention on both immunity and the microbiota by performing a post hoc analysis of a clinical trial in which each of the 20 participants sequentially consumed vegan or ketogenic diets for 2 weeks ( NCT03878108 ). Using a multiomics approach including multidimensional flow cytometry, transcriptomic, proteomic, metabolomic and metagenomic datasets, we assessed the impact of each diet, and dietary switch, on host immunity and the microbiota. Our data revealed that overall, a ketogenic diet was associated with a significant upregulation of pathways and enrichment in cells associated with the adaptive immune system. In contrast, a vegan diet had a significant impact on the innate immune system, including upregulation of pathways associated with antiviral immunity. Both diets significantly and differentially impacted the microbiome and host-associated amino acid metabolism, with a strong downregulation of most microbial pathways following ketogenic diet compared with baseline and vegan diet. Despite the diversity of participants, we also observed a tightly connected network between datasets driven by compounds associated with amino acids, lipids and the immune system. Collectively, this work demonstrates that in diverse participants 2 weeks of controlled dietary intervention is sufficient to significantly and divergently impact host immunity, which could have implications for precision nutritional interventions. ClinicalTrials.gov registration: NCT03878108 .

Contribution of Left Ventricular Diastolic Dysfunction to Survival and Breathlessness in Systemic Sclerosis-Associated Interstitial Lung Disease.

OBJECTIVE: To explore the effect of left ventricular (LV) diastolic dysfunction (LVDD) in systemic sclerosis (SSc)-associated interstitial lung disease (ILD), and to investigate SSc-specific associations and clinical correlates of LVDD. METHODS: There were 102 Australian Scleroderma Cohort Study participants with definite SSc and radiographic ILD included. Diastolic function was classified as normal, indeterminate, or abnormal according to 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines for assessment of LV diastolic function. Associations between clinical features and patient- and physician-reported dyspnea were evaluated using logistic regression. Survival analyses were performed using Kaplan-Meier survival estimates and Cox regression modeling. RESULTS: LVDD was identified in 26% of participants, whereas 19% had indeterminate and 55% had normal diastolic function. Those with ILD and LVDD had increased mortality (hazard ratio 2.4, 95% CI 1.0-5.7; P = 0.05). After adjusting for age and sex, those with ILD and LVDD were more likely to have severe dyspnea on the Borg Dyspnoea Scale (odds ratio [OR] 2.6, 95% CI 1.0-6.6; P = 0.05) and numerically more likely to record World Health Organization Function Class II or higher dyspnea (OR 4.2, 95% CI 0.9-20.0; P = 0.08). Older age (95% CI 1.0-6.4; P = 0.05), hypertension (OR 5.0, 95% CI 1.8-13.8; P < 0.01), and ischemic heart disease (OR 4.8, 95% CI 1.5-15.7; P < 0.01) were all associated with LVDD, as was proximal muscle atrophy (OR 5.0, 95% CI 1.9-13.6; P < 0.01) and multimorbidity (Charlson Comorbidity Index scores ≥ 4, OR 3.0, 95% CI 1.1-8.7; P = 0.04). CONCLUSION: LVDD in SSc-ILD is more strongly associated with traditional LVDD risk factors than SSc-specific factors. LVDD is associated with worse dyspnea and survival in those with SSc-ILD.

PGP-14 establishes a polar lipid permeability barrier within the C. elegans pharyngeal cuticle.

The cuticles of ecdysozoan animals are barriers to material loss and xenobiotic insult. Key to this barrier is lipid content, the establishment of which is poorly understood. Here, we show that the p-glycoprotein PGP-14 functions coincidently with the sphingomyelin synthase SMS-5 to establish a polar lipid barrier within the pharyngeal cuticle of the nematode C. elegans. We show that PGP-14 and SMS-5 are coincidentally expressed in the epithelium that surrounds the anterior pharyngeal cuticle where PGP-14 localizes to the apical membrane. pgp-14 and sms-5 also peak in expression at the time of new cuticle synthesis. Loss of PGP-14 and SMS-5 dramatically reduces pharyngeal cuticle staining by Nile Red, a key marker of polar lipids, and coincidently alters the nematode's response to a wide-range of xenobiotics. We infer that PGP-14 exports polar lipids into the developing pharyngeal cuticle in an SMS-5-dependent manner to safeguard the nematode from environmental insult.

Multidisciplinary team discussion: the emerging gold standard for management of cardiopulmonary complications of connective tissue disease.

Cardiopulmonary complications of connective tissue diseases (CTDs), particularly pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), are major determinants of morbidity and mortality. Multidisciplinary meetings may improve diagnostic accuracy and optimise treatment. We review the literature regarding multidisciplinary meetings in CTD-ILD and PAH and describe our tertiary centre experience of the role of the multidisciplinary meeting in managing CTD-PAH.

Combination Therapy with Trastuzumab and Niraparib: Quantifying Early Proliferative Alterations in HER2+ Breast Cancer Models.

HER2-targeted treatments have improved survival rates in HER2+ breast cancer patients, yet poor responsiveness remains a major clinical obstacle. Recently, HER2+ breast cancer cells, both resistant and responsive to HER2-targeted therapies, have demonstrated sensitivity to poly-(ADP-ribose) polymerase (PARP) inhibition, independent of DNA repair deficiencies. This study seeks to describe biological factors that precede cell viability changes in response to the combination of trastuzumab and PARP inhibition. Treatment response was evaluated in HER2+ and HER2- breast cancer cells. Further, we evaluated the utility of 3'-Deoxy-3'-[18F]-fluorothymidine positron emission tomography ([18F]FLT-PET) imaging for early response assessment in a HER2+ patient derived xenograft (PDX) model of breast cancer. In vitro, we observed decreased cell viability. In vivo, we observed decreased inhibition in tumor growth in combination therapies, compared to vehicle and monotherapy-treated cohorts. Early assessment of cellular proliferation corresponds to endpoint cell viability. Standard summary statistics of [18F]FLT uptake from PET were insensitive to early proliferative changes. Meanwhile, histogram analysis of [18F]FLT uptake indicated the potential translatability of imaging proliferation biomarkers. This study highlights the potential of combined trastuzumab and PARP inhibition in HER2+ breast cancer, while demonstrating a need for optimization of [18F]FLT-PET quantification in heterogeneous models of HER2+ breast cancer.

Metformin Reduces Tumor Growth in a Murine Flank Schwannoma Model.

HYPOTHESIS: Metformin and aspirin reduce vestibular schwannoma (VS) growth. BACKGROUND: There have been reported associations between patients with VS prescribed metformin and decreased tumor volumetric growth. Aspirin has also been associated with decreased VS growth in animal studies. METHODS: Rat schwannoma cell lines were grown and implanted into 50 athymic nude mice. Tumors were grown to 5 mm, and then mice were injected with either low- or high-dose metformin, aspirin, or saline daily. Tumors were measured until 14 days elapsed or mice demonstrated symptoms such as ulceration, inability to walk, or passed away. RESULTS: There were no significant differences in day 0 tumor sizes between the control and the treatment groups ( p = 0.73). In the low-dose, but not high-dose groups, day 7 volumes were significantly different for both metformin ( p = 0.04) and aspirin ( p = 0.02) compared with placebo. Mean tumor growth rates were 126.6 ± 65.6 mm 3 /day for saline compared with 73.7 ± 29.5 mm 3 /day for low-dose metformin ( p = 0.03) and 68.7 ± 34.8 mm 3 /day for low-dose aspirin ( p = 0.016). There were no significant differences in tumor sizes ( p = 0.59) or growth rates ( p = 0.75) between low-dose metformin and aspirin groups. Low-dose groups had treatment stopped at 14 days, with continued monitoring demonstrating significant increases in tumor growth off treatment for both aspirin ( p = 0.006) and metformin ( p = 0.048). CONCLUSIONS: Metformin treatment significantly reduced VS growth to a similar level as aspirin. Furthermore, when removing both metformin and aspirin treatment, tumor growth significantly increased.

Pericardial decompression syndrome with acute right ventricular failure: a case series.

Background: Pericardial decompression syndrome (PDS) is an uncommon complication of pericardial drainage of large pericardial effusions and cardiac tamponade characterized by paradoxical haemodynamic instability following drainage. Pericardial decompression syndrome may occur immediately, or in the days following pericardial decompression, and presents with signs and symptoms suggestive of uni-/biventricular failure or acute pulmonary oedema. Case summary: This series describes two cases of this syndrome which demonstrates acute right ventricular failure as a mechanism of PDS and provides insights into the echocardiographic findings and clinical course of this poorly understood syndrome. Case 1 describes a patient who underwent pericardiocentesis, whilst Case 2 describes a patient who underwent surgical pericardiostomy. In both patients, acute right ventricular failure was observed following the release of tamponade and is favoured to be the cause of haemodynamic instability. Discussion: Pericardial decompression syndrome is a poorly understood, likely underreported complication of pericardial drainage for cardiac tamponade associated with high morbidity and mortality. Whilst a number of hypotheses exist as to the aetiology of PDS, this case series supports haemodynamic compromise being secondary to left ventricular compression following acute right ventricular dilatation.

Selective control of parasitic nematodes using bioactivated nematicides.

Parasitic nematodes are a major threat to global food security, particularly as the world amasses 10 billion people amid limited arable land1-4. Most traditional nematicides have been banned owing to poor nematode selectivity, leaving farmers with inadequate means of pest control4-12. Here we use the model nematode Caenorhabditis elegans to identify a family of selective imidazothiazole nematicides, called selectivins, that undergo cytochrome-p450-mediated bioactivation in nematodes. At low parts-per-million concentrations, selectivins perform comparably well with commercial nematicides to control root infection by Meloidogyne incognita, a highly destructive plant-parasitic nematode. Tests against numerous phylogenetically diverse non-target systems demonstrate that selectivins are more nematode-selective than most marketed nematicides. Selectivins are first-in-class bioactivated nematode controls that provide efficacy and nematode selectivity.

Interdisciplinary practice in performance sport: A scoping review of evidence of collaboration.

Performance support teams are increasingly comprised of sub-disciplines, bringing varied expertise to support an athlete or team in achieving the desired result. With more voices in the room, however, there is a need to investigate how these individuals can effectively work together collaboratively. Accordingly, the present study reviewed empirical articles that have examined interdisciplinary practice in performance sport. In total, 22 articles met the full inclusion criteria. We discuss the four key themes that emerged from the literature linked to these contexts: namely, Theoretical frameworks, Facilitative leadership and culture, Organisational and logistical structure and processes, and Personal and interpersonal qualities. To deepen the understanding in this intricate field, conducting future research such as longitudinal studies that follow team working practices over time and delve into the lived experiences of teams, as well as the perspectives of various stakeholders, would be beneficial.

The terminology used to describe team working in elite sports is often ambiguous and interchangeable. To provide clarity, the following concise framing is proposed: multidisciplinary refers to a combination of several disciplines and methods; interdisciplinary denotes the connection between, among, and reciprocal collaboration; and transdisciplinary refers to going beyond, through, and across.For elite sports teams to reflect on their working practices, the following key areas should be considered: theoretical framework (programme philosophy), facilitative leadership and culture, organisational and logistical structures and processes, and personal and interpersonal qualities of the team.As the terminology around team working in elite sports remains ambiguous, future research should strive to uncover the lived experiences and practices of these teams. With scarce literature on the practice of interdisciplinarity within this field, other industries' models could provide a stepping stone for investigation.

Nemacol is a small molecule inhibitor of C. elegans vesicular acetylcholine transporter with anthelmintic potential.

Nematode parasites of humans and livestock pose a significant burden to human health, economic development, and food security. Anthelmintic drug resistance is widespread among parasites of livestock and many nematode parasites of humans lack effective treatments. Here, we present a nitrophenyl-piperazine scaffold that induces motor defects rapidly in the model nematode Caenorhabditis elegans. We call this scaffold Nemacol and show that it inhibits the vesicular acetylcholine transporter (VAChT), a target recognized by commercial animal and crop health groups as a viable anthelmintic target. We demonstrate that it is possible to create Nemacol analogs that maintain potent in vivo activity whilst lowering their affinity to the mammalian VAChT 10-fold. We also show that Nemacol enhances the ability of the anthelmintic Ivermectin to paralyze C. elegans and the ruminant nematode parasite Haemonchus contortus. Hence, Nemacol represents a promising new anthelmintic scaffold that acts through a validated anthelmintic target.

Molecular Imaging of Oxygenation Changes during Immunotherapy in Combination with Paclitaxel in Triple Negative Breast Cancer.

Hypoxia is a common feature of the tumor microenvironment, including that of triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with a high five-year mortality rate. Using [18F]-fluoromisonidazole (FMISO) positron emission tomography (PET) imaging, we aimed to monitor changes in response to immunotherapy (IMT) with chemotherapy in TNBC. TNBC-tumor-bearing mice received paclitaxel (PTX) ± immune checkpoint inhibitors anti-programmed death 1 and anti-cytotoxic T-lymphocyte 4. FMISO-PET imaging was performed on treatment days 0, 6, and 12. Max and mean standard uptake values (SUVmax and SUVmean, respectively), histological analyses, and flow cytometry results were compared. FMISO-PET imaging revealed differences in tumor biology between treatment groups prior to tumor volume changes. 4T1 responders showed SUVmean 1.6-fold lower (p = 0.02) and 1.8-fold lower (p = 0.02) than non-responders on days 6 and 12, respectively. E0771 responders showed SUVmean 3.6-fold lower (p = 0.001) and 2.7-fold lower (p = 0.03) than non-responders on days 6 and 12, respectively. Immunohistochemical analyses revealed IMT plus PTX decreased hypoxia and proliferation and increased vascularity compared to control. Combination IMT/PTX recovered the loss of CD4+ T-cells observed with single-agent therapies. PET imaging can provide timely, longitudinal data on the TNBC tumor microenvironment, specifically intratumoral hypoxia, predicting therapeutic response to IMT plus chemotherapy.

Disease specific determinants of cardiopulmonary fitness in systemic sclerosis.

OBJECTIVES: We aimed to quantify the burden of exercise intolerance in systemic sclerosis (SSc) and explore the disease features that contribute to impaired exercise capacity (measured as peak oxygen uptake, peak VO2) to provide novel mechanistic insights into the causes of physical disability in SSc. METHODS: Thirty-three SSc patients with no history of cardiac disease and no active myositis underwent cardiac and skeletal muscle MRI, transthoracic echocardiography, pulmonary function tests and cardiopulmonary exercise testing (CPET). CPET results were compared to an age-, sex-, and weight-matched controls with no overt cardiopulmonary disease. Native T1 and T2-mapping sequences were used to quantify diffuse fibroinflammatory myocardial disease and qualitative assessment of skeletal muscle oedema was performed. The associations between parameters of cardiorespiratory function and skeletal muscle abnormalities and peak VO2 were evaluated with linear regression analysis. RESULTS: Exercise capacity was markedly impaired in SSc and significantly reduced when compared to control subjects (percent predicted peak VO2: 70% vs 98%, p < 0⋅01). Diffuse myocardial fibroinflammatory disease (p < 0⋅01) and skeletal muscle oedema (p = 0⋅01) were significantly associated with reduced exercise capacity. There was no association between impaired exercise capacity and left ventricular ejection fraction. CONCLUSION: SSc is associated with marked functional impairment that is not explained by commonly used parameters of cardiac function such as left ventricular ejection fraction. Rather, only more sensitive measures of organ involvement are associated with impaired exercise tolerance. Our results show diffuse interstitial changes of the myocardium and skeletal muscle affect oxygen uptake and are important contributors to functional limitation in SSc.

Utility of preoperative colour flow Doppler assessment of perforator anatomy in medial sural artery perforator (MSAP) free flaps.

PURPOSE: It is known that the vascular perforators upon which the medial sural artery perforator (MSAP) flap is based are subject to considerable variation. This study seeks to evaluate the use of colour flow Doppler (CFD) as an imaging technique to establish the presence of suitable vessels, the discriminatory findings from that imaging, the rate of flap abandonment and flap complications. METHODS: All patients undergoing MSAP in our institution since 2015 had a pre-operative CFD using a standardised technique. A prior group of 22 patients not having CFD acted as a control group. Data were  collected prospectively. RESULTS: Fourteen patients had CFD. In one patient, no suitable vessels were found. In 13 patients, vessels of suitable size and position were identified, which then correlated precisely with operative findings. Three had suitable vessels in one leg only. No flaps in the CFD group were abandoned. One flap in the CFD group was partially lost. One flap in the prior control group was abandoned. CONCLUSIONS: CFD provided reliable discriminatory information to decide on flap suitability/which leg and correlated precisely with operative findings, with no flap abandonment. Flap survival rate was very high.

Development of a yeast whole-cell biocatalyst for MHET conversion into terephthalic acid and ethylene glycol.

BACKGROUND: Over the 70 years since the introduction of plastic into everyday items, plastic waste has become an increasing problem. With over 360 million tonnes of plastics produced every year, solutions for plastic recycling and plastic waste reduction are sorely needed. Recently, multiple enzymes capable of degrading PET (polyethylene terephthalate) plastic have been identified and engineered. In particular, the enzymes PETase and MHETase from Ideonella sakaiensis depolymerize PET into the two building blocks used for its synthesis, ethylene glycol (EG) and terephthalic acid (TPA). Importantly, EG and TPA can be re-used for PET synthesis allowing complete and sustainable PET recycling. RESULTS: In this study we used Saccharomyces cerevisiae, a species utilized widely in bioindustrial fermentation processes, as a platform to develop a whole-cell catalyst expressing the MHETase enzyme, which converts monohydroxyethyl terephthalate (MHET) into TPA and EG. We assessed six expression architectures and identified those resulting in efficient MHETase expression on the yeast cell surface. We show that the MHETase whole-cell catalyst has activity comparable to recombinant MHETase purified from Escherichia coli. Finally, we demonstrate that surface displayed MHETase is active across a range of pHs, temperatures, and for at least 12 days at room temperature. CONCLUSIONS: We demonstrate the feasibility of using S. cerevisiae as a platform for the expression and surface display of PET degrading enzymes and predict that the whole-cell catalyst will be a viable alternative to protein purification-based approaches for plastic degradation.

Illustration of Continuous Enrollment and Beneficiary Categorization in DoD and VA Infrastructure for Clinical Intelligence.

INTRODUCTION: The DoD and VA Infrastructure for Clinical Intelligence (DaVINCI) data-sharing initiative has bridged the gap between DoD and VA data. DaVINCI utilizes the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) to map DoD and VA-specific health care codes to a standardized terminology. Although OMOP CDM provides a standardized longitudinal view of health care concepts, it fails in capturing multiple and changing relationships beneficiaries have with DoD and VA as it has a static (vs. yearly) person characteristic table. Furthermore, DoD and VA utilize different policies and terminology to identify their respective beneficiaries, which makes it difficult to track patients longitudinally. The primary purpose of this report is to provide a methodology for categorizing beneficiaries and creating continuous longitudinal patient records to maximize the use of the joint DoD and VA data in DaVINCI. MATERIALS AND METHODS: For calendar year 2000-2020, we combined DoD and VA OMOP CDM and source databases to uniquely categorize beneficiaries into the following hierarchical groups: Active Duty, Guard, and Reserve Service Members (ADSMs); Separatees; Retirees; Veterans; and Deceased. Once the cohorts were identified, we examined calendar year 2020 health care utilization data using the OMOP VISIT_OCCURRENCE, DRUG_EXPOSURE, MEASUREMENT, and PROCEDURE tables. We also used the Defense Enrollment and Eligibility Reporting System source table to derive enrollment periods for DoD beneficiaries. As VA does not have enrollment plans, we utilized the VA's priority groups (1-5) in the SPATIENT source table to crosswalk the DoD's enrollment concept to the VA. We then assessed lengths of continuous enrollments in DoD and VA and the impact of appending the longitudinal records together. RESULTS: The majority of the ADSMs utilized the DoD system, but about 60,557 (3%) were seen in the VA for varied types of care. The market share of care provided to ADSMs by the VA varied by specialty and location. For Retirees, the split between DoD (1,625,874 [75%]) and VA (895,992 [41%]) health care utilization was more significant. The value added for utilizing DaVINCI in longitudinal studies was the highest for researchers normally limited to DoD data only. For beneficiaries who had 5 years of continuous enrollment, DaVINCI increased the potential study population by over 202% compared to using DoD data alone and by over 14% compared to VA data alone. Among beneficiaries with 20 years of continuous enrollment, DaVINCI increased the potential study population by over 133% compared to DoD data and by nearly 39% compared to VA data. CONCLUSIONS: DaVINCI has successfully combined DoD and VA data and utilized OMOP CDM to standardize health care concepts. However, to fully maximize the potential of DaVINCI's DoD and VA OMOP databases, researchers must uniquely categorize the DaVINCI cohort and build longitudinal patient records across DoD and VA. Because of the low other health insurance rates among DoD enrollees and their choice to enroll to a DoD Primary Care Manager, we believe this population to be the least censored in the DoD. Applying a similar concept through VA's priority groups (1-5) would enable researchers to follow ADSMs as they transition from the military.

Race and Sex Are Associated With Variations in Pain Management in Patients Presenting to the Emergency Department With Undifferentiated Abdominal Pain.

BACKGROUND: Pain management is critical to the management of patients in the emergency department (ED). The clinical decision-making process for prescribing medications is complicated by its subjective nature. Historically, racial and ethnic minority groups and women have not had their pain managed as aggressively as White and male patients. OBJECTIVE: The objective of this study was to determine whether race and biological sex affect the pain management process by means of evaluating data from a large hospital system with diverse patient demographic characteristics. METHODS: This was a retrospective study of adult patients who presented an ED within the hospital system and were discharged from the ED with a diagnosis of undifferentiated abdominal pain during a single year. Patient pain was classified as mild, moderate, or severe, and patients were further stratified by race, ethnicity, sex, and insurance status. Pain management was assessed by narcotic vs non-narcotic administration. RESULTS: A total of 32,676 patients were included in the study. Narcotic administration was more likely in White patients with undifferentiated abdominal pain (22%) compared with Black patients (12%; adjusted odds ratio 0.50; 95% CI 0.46-0.54). This persists across patient-reported pain scores. In addition, women (16.99%) were prescribed narcotics less often than men (19.41%; p < 0.0001). CONCLUSIONS: Although differences in pain management practices have been explored previously, this study provided a large, updated, multifacility assessment that confirmed that race- and sex-based differences in pain management persist, specifically in the decision to treat with narcotics. Further investigation is warranted to determine the root causes of these differences.

The clinical implications of left ventricular diastolic dysfunction in systemic sclerosis.

OBJECTIVES: We sought to quantify the burden of left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF) in systemic sclerosis (SSc) and assess the progression of LVDD over time and its prognostic importance. METHODS: Two-hundred and twenty-five participants enrolled in the Australian Scleroderma Cohort Study were included and LVDD was assessed according to 2016 ASE/EACVI Guidelines. Logistic regression analyses and generalised estimating equations were performed to evaluate the relationship between LVDD and SSc disease characteristics and symptoms and signs of heart failure, respectively. The relationship between LVDD and mortality was assessed using Kaplan-Meier survival estimates. RESULTS: Thirty-four (15%) participants were diagnosed with LVDD. A further 89 (40%) participants had indeterminate diastolic function. Older age (p<0.01), hypertension (p=0.02), impaired systolic function (p=0.03) and interstitial lung disease (p=0.01) were all associated with the presence of LVDD. There was no association between the presence of LVDD and clinical signs of heart failure, however, LVDD was associated with more breathlessness and worse functional class (p=0.03). LVDD was observed to progress over time, with significant worsening of parameters of left ventricular filling pressure. There was no significant relationship between LVDD and mortality (p=0.23). CONCLUSIONS: Abnormal diastolic function is a common finding in SSc, progresses over time and is associated with more severe dyspnoea. Whilst patients with LVDD are more breathless, LVDD is not clearly associated with clinical findings of heart failure demonstrating that LVDD may be of importance in explaining symptoms even in the absence of HFpEF in SSc.