A pilot study characterizing tetrachloroethylene exposure with exhaled breath in an impacted community.

Martinsville, Indiana overlays four groundwater contamination plumes, including a U.S. Environmental Protection Agency (EPA)-designated Superfund site. The primary contaminants are tetrachloroethylene (PCE), trichloroethylene (TCE), and other volatile organic compounds (VOCs). Martinsville represents many similar communities facing the challenge of groundwater and soil contamination and vapor intrusion, where residents are often frustrated by the lack of help in understanding and addressing the problem. The objective of this study was to evaluate PCE in exhaled breath to identify and quantify exposure to PCE and to explore the extent and level of PCE exposure among community residents. We measured chlorinated VOCs in exhaled breath samples from 38 healthy individuals who lived either in a contamination area or outside any plume area. We also measured VOCs in indoor air and tap water samples collected from 10 homes. PCE was detected in all exhaled breath samples (mean: 6.6 µg/m3; range: 1.9-44 µg/m3) and tap water samples (mean: 0.74 µg/L; range: 0.39-0.92 µg/L). PCE was detected in six of nine (66%) homes with air concentrations ranging from 1.6 to 70 µg/m3, exceeding the EPA action level of 42 µg/m3. We did not detect TCE or any other chlorinated VOCs in these samples. PCE exposure occurred among individuals living on the EPA Superfund site, as well as among those living on other plume sites and those living outside any known plumes. Preventive measures should focus on identifying highly exposed groups and reducing their exposures, followed by addressing moderately elevated exposures in the community. Our results demonstrated that PCE in exhaled breath can be used as an effective tool in community engaged environmental health research to evaluate the extent and level of community exposure, increase awareness, and promote residents' participation in research and site cleanup decision-making.

C-reactive protein levels associated with COVID-19 outcomes in the United States.

CONTEXT: COVID-19 caused a worldwide pandemic, and there are still many uncertainties about the disease. C-reactive protein (CRP) levels could be utilized as a prognosticator for disease severity in COVID-19 patients. OBJECTIVES: This study aims to determine whether CRP levels are correlated with COVID-19 patient outcomes and length of stay (LoS). METHODS: A retrospective cohort study was conducted utilizing data obtained between March and May 2020. Data were collected by abstracting past medical records through electronic medical records at 10 hospitals within CommonSpirit Health. Patients were included if they had a positive COVID-19 test from a nasopharyngeal swab sample, and if they were admitted and then discharged alive or had in-hospital mortality and were ≥18 years. A total of 541 patients had CRP levels measured and were included in this report. Patient outcome and LoS were the endpoints measured. RESULTS: The 541 patients had their CRP levels measured, as well as the demographic and clinical data required for analysis. While controlling for body mass index (BMI), number of comorbidities, and age, the first CRP was significantly predictive of mortality (p<0.001). The odds ratio for first CRP indicates that for each one-unit increase in CRP, the odds of death increased by 0.007. For LoS, the first CRP was a significant predictor (p<0.001), along with age (p=0.002). The number of comorbidities also predicted LoS (p=0.007), but BMI did not. The coefficient for the first CRP indicates that, for each one-unit increase in CRP, LoS increased 0.003 days. CONCLUSIONS: The results indicate that there is a positive correlation between the CRP levels of COVID-19 patients and their respective outcomes with regard to death and LoS.

Impact of sequential implementation of multimodal perioperative care pathways on colorectal surgical outcomes

Background: Standardized care protocols offer the potential to reduce postoperative complication rates. The purpose of this study was to determine whether there was an additive benefit associated with the sequential implementation of the evidence-based surgical site infection bundle (SSIB) and enhanced recovery after surgery (ERAS) protocols for patients undergoing colorectal surgery in a community hospital. Methods: Patients at a single institution who underwent elective colorectal surgery between Apr. 1, 2011, and Dec. 31, 2015, were identified by means of American College of Surgeons National Surgical Quality Improvement Program data. Patients were stratified into 3 groups according to the protocol implementation dates: pre-SSIB/pre-ERAS (control), post-SSIB/pre-ERAS and post-SSIB/post-ERAS. Primary outcomes assessed were length of stay and wound complication rates. We used inverse proportional weighting to control for possible differences between the groups. Results: There were 368 patients included: 94 in the control group, 95 in the post-SSIB/pre-ERAS group and 179 in the post-SSIB/post-ERAS group. In the adjusted analyses, mean length of stay (control group 7.6 d, post-SSIB/post-ERAS group 5.5 d, p = 0.04) and overall wound complication rates (14.7% and 6.5%, respectively, p = 0.049) were reduced after sequential implementation of the protocols. Conclusion: Sequential implementation of quality-improvement initiatives yielded additive benefit for patients undergoing colorectal surgery in a community hospital, with a decrease in length of stay and wound complication rates. The amount of improvement attributable to either initiative is difficult to define as they were implemented sequentially. The improved outcomes were realized after the introduction of the ERAS protocol in adjusted analyses.

Contexte: Les protocoles de soins standardisés offrent la possibilité de réduire les taux de complications postopératoires. Le but de cette étude était de déterminer s'il y a un avantage additif associé à l'application séquentielle des protocoles fondés sur des données probantes SSIB (surgical site infection bundle) et ERAS (enhanced recovery after surgery) chez des patients soumis à une chirurgie colorectale dans un hôpital communautaire. Méthodes: Les patients d'un seul établissement ayant subi une chirurgie colorectale non urgente entre le 1er avril 2011 et le 31 décembre 2015 ont été recensés à partir des données du Programme national d'amélioration de la qualité chirurgicale de l'American College of Surgeons. Les patients ont été stratifiés en 3 groupes selon les dates d'application des protocoles : pré-SSIB/pré-ERAS (témoin), post-SSIB/pré-ERAS et post-SSIB/post-ERAS. Les paramètres principaux évalués étaient la durée du séjour hospitalier et les taux de complications de plaies. Nous avons utilisé une pondération proportionnelle inverse pour tenir compte des possibles différences entre les groupes. Résultats: Nous avons inclus 368 patients, 94 dans le groupe témoin, 95 dans le groupe post-SSIB/pré-ERAS et 179 dans le groupe post-SSIB/post-ERAS. Dans les analyses ajustées, la durée moyenne des séjours (groupe témoin 7,6 j, groupe post-SSIB/post-ERAS 5,5 j, p = 0,04) et les taux globaux de complications de plaies (14,7 % et 6,5 % respectivement, p = 0,049) ont diminué après l'application séquentielle des protocoles. Conclusion: L'application séquentielle des initiatives d'amélioration de la qualité a donné lieu à des bienfaits additifs chez les patients soumis à une chirurgie colorectale dans un hôpital communautaire, avec abrègement du séjour hospitalier et diminution du taux de complications de plaies. Le degré d'amélioration attribuable à chacune des initiatives est difficile à préciser puisqu'elles ont été appliquées séquentiellement. L'amélioration des paramètres a été obtenue après l'introduction du protocole ERAS dans des analyses ajustées.

International evolution of fat, oil and grease (FOG) waste management - A review.

In recent years, issues relating to fat, oil and grease (FOG) in sewer systems have intensified. In the media, sewer blockages caused by FOG waste deposits, commonly referred to as 'fatbergs', are becoming a reminder of the problems that FOG waste can cause when left untreated. These FOG blockages lead to sanitary sewer overflows, property flooding and contamination of water bodies with sewage. Despite these financial and environmentally detrimental effects, a homogenous FOG waste management method has not been developed internationally. However, some successful enduring FOG management programmes have been established, such as in Dublin city and in Scandinavian countries. The aim of this paper is to carry out a review on existing FOG research and management approaches. FOG management involves comprehending: (1) FOG deposition factors in the sewer, (2) FOG prevention and awareness tactics undertaken internationally and (3) potential utilisation methods for FOG waste. This review will highlight that preventing FOG from entering the sewer is the most common approach, often through simple awareness campaigns. The diverted FOG is rarely valorised to bioenergy or biomaterials, despite its potential. Thus, all facets of the FOG waste lifecycle must be identified and managed. Advancements in processes and techniques must be assessed to best determine the future evolution of FOG waste management to assist in achieving a sustainable urban environment.

Low immunogenicity of tocilizumab in patients with rheumatoid arthritis.

OBJECTIVE: Subcutaneous (SC) and intravenous formulations of tocilizumab (TCZ) are available for the treatment of patients with rheumatoid arthritis (RA), based on the efficacy and safety observed in clinical trials. Anti-TCZ antibody development and its impact on safety and efficacy were evaluated in adult patients with RA treated with intravenous TCZ (TCZ-IV) or TCZ-SC as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). METHODS: Data from 5 TCZ-SC and 8 TCZ-IV phase III clinical trials and 1 TCZ-IV clinical pharmacology safety study (>50 000 samples) were pooled to assess the immunogenicity profile of TCZ-SC and TCZ-IV (8974 total patients). The analysis included antidrug antibody (ADA) measurement following TCZ-SC or TCZ-IV treatment as monotherapy or in combination with csDMARDs, after dosing interruptions or in TCZ-washout samples, and the correlation of ADAs with clinical response, adverse events or pharmacokinetics (PK). RESULTS: The proportion of patients who developed ADAs following TCZ-SC or TCZ-IV treatment was 1.5% and 1.2%, respectively. ADA development was also comparable between patients who received TCZ monotherapy and those who received concomitant csDMARDs (0.7-2.0%). ADA development did not correlate with PK or safety events, including anaphylaxis, hypersensitivity or injection-site reactions, and no patients who developed ADAs had loss of efficacy. CONCLUSIONS: The immunogenicity risk of TCZ-SC and TCZ-IV treatment was low, either as monotherapy or in combination with csDMARDs. Anti-TCZ antibodies developed among the small proportion of patients had no evident impact on PK, efficacy or safety.

Five-year Efficacy and Safety of Tocilizumab Monotherapy in Patients with Rheumatoid Arthritis Who Were Methotrexate- and Biologic-naive or Free of Methotrexate for 6 Months: the AMBITION Study.

OBJECTIVE: To report on the 5-year efficacy and safety results of the AMBITION (Actemra versus Methotrexate double-Blind Investigative Trial In mONotherapy) monotherapy study (ClinicalTrials.gov: NCT00109408, NCT00720798). METHODS: Patients with rheumatoid arthritis for whom biologics had not failed or who did not discontinue methotrexate because of lack of efficacy or tolerability were followed up for 5 years to assess the efficacy and serious adverse events (SAE) of tocilizumab (TCZ) monotherapy. RESULTS: Longterm efficacy results showed that efficacy was maintained or improved for up to 264 weeks in patients receiving TCZ monotherapy. Serious infection was the most frequent SAE; no new safety signals were reported. CONCLUSION: Longterm monotherapy with TCZ demonstrated continuing efficacy and safety.

Long-Term Safety and Efficacy of Subcutaneously Administered Tocilizumab for Adult Rheumatoid Arthritis: A Multicenter Phase 3b Long-term Extension Study.

INTRODUCTION: To assess the long-term safety and efficacy of subcutaneous tocilizumab (TCZ-SC) in US patients with rheumatoid arthritis (RA) who rolled over from the two global phase 3 studies, SUMMACTA (NCT01194414) and BREVACTA (NCT1232569), into this open-label, single-arm, phase 3b study. METHODS: Patients continued to receive TCZ-SC 162 mg weekly or every other week or switched from intravenous TCZ to TCZ-SC 162 mg qw for up to 84 weeks. The primary endpoint was the proportion of patients with serious adverse events (SAEs). Secondary endpoints included clinical efficacy, laboratory abnormalities, and immunogenicity. RESULTS: Of the 217 patients treated, 76.5% were female, and the mean age was 58.4 years. A total of 23 patients (10.6%) had ≥1 SAE. The most common SAEs were infections (3.7%). Alanine aminotransferase elevations (38.2%) were not associated with hepatic injury. Grade 3/4 neutropenia (3%) was transient and not associated with serious infections. Immunogenicity was low (<1%) and not associated with SAEs. No anaphylaxis or deaths occurred. Thirteen patients (6.0%) withdrew due to safety reasons. Mean Clinical Disease Activity Index and Disease Activity Score in 28 joints remained stable throughout the trial. CONCLUSIONS: The long-term safety of TCZ-SC during the long-term extension period was consistent with the safety profiles from SUMMACTA and BREVACTA, with no new safety signals. Efficacy improvements observed from baseline remained stable over time. These results demonstrated the durability of the safety and efficacy responses, and low immunogenicity, with long-term exposure to TCZ-SC in patients with RA. FUNDING: F. Hoffmann-La Roche, Ltd. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier, NCT01662063.

A variable temperature synchrotron X-ray diffraction study of the ferroelastic double perovskite Ba2GdMoO6.

A study of the magnetic and structural properties of the double perovskite Ba2GdMoO6 has been performed. The crystal structure distorts from the ideal cubic (Fm3m) structure to the tetragonal space group I4/m at 220 K, before undergoing a second distortion to a triclinic system (I1) at 80 K. The phase transition to triclinic symmetry is also evident in magnetic susceptibility measurements. The variable temperature synchrotron powder X-ray diffraction results reveal that Ba2GdMoO6 is ferroelastic, with the onset of ferroelastic domain formation occurring at the cubic-tetragonal phase transition. A number of Rietveld refinement techniques for modelling diffuse scattering from ferroelastic domain boundaries have been explored.

Pulmonary vein contraction before and after radiofrequency ablation for atrial fibrillation.

UNLABELLED: INTRODUCTION: Cardiovascular magnetic resonance imaging (cMRI) may provide a noninvasive method to test for pulmonary vein (PV) isolation after ablation for atrial fibrillation (AF) by detecting changes in PV contraction. METHODS: PV contraction (the maximal percentage change in PV cross-sectional area [CSA] during the cardiac cycle) measured 1 month before and 2 months after PV isolation was compared in 63 PVs from 16 patients with medically refractory AF. Repeat cMRI imaging and invasive catheter mapping was performed prior to repeat PV ablation in 50 PVs from 14 additional patients with recurrent AF. Contraction in PVs with sustained isolation after the initial ablation was compared to contraction in PVs with electrical reconnection to adjacent atrium. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff PV contraction value for prediction of PV-atrial reconnection after ablation. The cutoff value was then prospectively tested in 40 PVs from 12 additional patients. RESULTS: PV contraction decreased after AF ablation (22.4 ± 10% variation in CSA before ablation vs 10.1 ± 8% variation in CSA after ablation, P < 0.00001). PVs with sustained isolation on invasive mapping contracted less than PVs with electrical reconnection to adjacent atrium (13.7 ± 10.6% vs 21.4 ± 9.3%, P = 0.021). PV contraction produced a c-index of 0.74 for prediction of PV-atrial reconnection after ablation and >17% variation in PV CSA predicted reconnection with a sensitivity of 84.6% and specificity of 66.7%. CONCLUSION: PV contraction is reduced by ablation. PV contraction measurement may provide a noninvasive method to test for PV isolation after ablation procedures.

Prevalence and clinical characteristics associated with left atrial appendage thrombus in fully anticoagulated patients undergoing catheter-directed atrial fibrillation ablation.

INTRODUCTION: Catheter-directed atrial fibrillation (AF) ablation is contraindicated among patients with left atrial appendage (LAA) thrombus. The prevalence of LAA thrombus among fully anticoagulated patients undergoing AF ablation is unknown. METHODS AND RESULTS: We retrospectively evaluated the prevalence of LAA thrombus among 192 consecutive patients undergoing AF ablation between July 2006 and January 2009. Seven of 192 patients (3.6%) had evidence of thrombus on transesophageal echocardiogram (TEE) despite being fully anticoagulated on warfarin (international normalized ratio [INR] 2-3) for 4 consecutive weeks prior to echocardiogram. Univariate analysis demonstrated that structural heart disease, large left atrial dimension, and number of AF ablations were associated with thrombus. Three patients with thrombus had paroxysmal AF with normal LV function. CONCLUSION: Despite full anticoagulation, 3.6% of patients undergoing AF ablation had LAA thrombus. We recommend that all patients, regardless of LV function or left atrial size, should undergo preprocedural TEE to exclude the presence of LAA thrombus.

Impact of left ventricular dysfunction on hospital mortality among patients undergoing elective percutaneous coronary intervention.

Many patients with systolic dysfunction undergo elective percutaneous coronary intervention (PCI) despite the unknown risk and limited data supporting its use. Therefore, the aim of this study was to evaluate the association between the severity of left ventricular (LV) systolic dysfunction and hospital mortality in patients who undergo elective PCI. A retrospective cohort study was conducted of all patients who underwent elective PCI in New York State in 1998 and 1999. Patients were stratified into 5 groups on the basis of their LV ejection fractions (EFs) before PCI (>55%, 46% to 55%, 36% to 45%, 26% to 35%, and < or =25%). Comparisons of demographic, procedural, and outcome variables were performed, and adjusted odds ratios (ORs) were calculated to evaluate the relation between the EF and hospital mortality. Among 55,709 patients who underwent elective PCI, EFs < or =25%, 26% to 35% and 36% to 45% were present in 3.4%, 7.6%, and 17.4%, respectively. Hospital mortality was 0.3%, 0.2%, 0.6%, 1.2%, and 2.7% in the groups with EFs >55%, 46% to 55%, 36% to 45%, 26% to 35%, and < or =25%, respectively (p <0.001). After multivariate adjustment, an increased risk for hospital mortality was significant for EF groups of 36% to 45% (OR 1.56, 95% confidence interval 1.06 to 2.30), 26% to 35% (OR 2.17, 95% confidence interval 1.42 to 3.31), and < or =25% (OR 3.85, 95% confidence interval 2.46 to 6.01) compared with EF >55%, respectively. In conclusion, this analysis demonstrates that elective PCI is commonly performed in patients with reduced EFs, and the risk for hospital mortality increases as the EF decreases. For patients who undergo elective PCI, an EF < or =45% is associated with higher adjusted hospital mortality. Whether elective PCI in patients with low EFs reduces morbidity and/or mortality over medical therapy alone is unknown.

An interesting case of positional hypoxia: the effect of multiple synergistic pathological conditions.

This report describes an elderly patient evaluated for generalized fatigue, dyspnea, presyncopal episodes, and positional hypoxemia. Workup revealed posturally related oxygen desaturation, a patent foramen ovale (PFO), an atrial septal aneurysm, and primary adrenal insufficiency. Normal intracardiac pressures and a right-to-left PFO shunt were present only while the patient was in the upright position. Numerous etiologies of positional right-to-left shunting associated with platypnea-orthodeoxia have been described. Despite advancements in diagnostic and treatment modalities, the pathophysiology of right-to-left shunting with normal intracardiac pressure remains elusive. This report highlights the complexity of positional right-to-left shunting in hypoxemic patients with normal intracardiac pressures and multiple synergistic medical conditions.

The challenge of defining bleeding among patients with acute coronary syndromes.

Advances in the management of patients with acute coronary syndromes (ACS), specifically, the use of combined pharmacotherapy with antithrombotic and antiplatelet therapies and routine percutaneous coronary intervention (PCI), have greatly reduced rates of thrombotic outcomes and mortality in these patients. However, these same therapies also can increase the risk of bleeding and transfusion use, which are predictive of poor outcomes in patients with ACS. Accurate assessment of the risk-to-benefit ratio for any therapy depends on the use of clinically relevant, preferably standardized, definitions of endpoint events. Unfortunately, clinical trials of antithrombotic therapies have used various definitions for bleeding, most of which were originally developed for trials of fibrinolytic therapy in acute myocardial infarction (MI). These variations in bleeding definitions have complicated cross-study comparisons and assessments of drug class effects. Further, it is unclear whether these definitions remain clinically relevant in the era of routine PCI and aggressive antithrombotic therapy for ACS. Although an argument can be made for development of a standardized bleeding definition, a more prudent approach may be to develop standardized data elements, which can then be used to tailor bleeding definitions according to the goals of future clinical investigations.

Prevalence and determinants of troponin T elevation in the general population.

BACKGROUND: The prevalence and determinants of cardiac troponin T (cTnT) elevation in the general population are unknown, and the significance of minimally increased cTnT remains controversial. Our objective was to determine the prevalence and determinants of cTnT elevation in a large, representative sample of the general population. METHODS AND RESULTS: cTnT was measured from stored plasma samples in 3557 subjects of the Dallas Heart Study, a population-based sample. cTnT elevation (> or =0.01 microg/L) was correlated with clinical variables and cardiac MRI findings. The sample weight-adjusted prevalence of cTnT elevation in the general population was 0.7%. In univariable analyses, cTnT elevation was associated with older age, black race, male sex, coronary artery calcium by electron beam CT, a composite marker of congestive heart failure (CHF), left ventricular hypertrophy (LVH), diabetes mellitus (DM), and chronic kidney disease (CKD) (P<0.001 for each). Subjects with minimally increased (0.01 to 0.029 microg/L) and increased (> or =0.03 microg/L) cTnT had a similar prevalence of these characteristics. In multivariable logistic regression analysis, LVH, CHF, DM, and CKD were independently associated with cTnT elevation. CONCLUSIONS: In the general population, cTnT elevation is rare in subjects without CHF, LVH, CKD, or DM, suggesting that the upper limit of normal for the immunoassay should be <0.01 microg/L. Even minimally increased cTnT may represent subclinical cardiac injury and have important clinical implications, a hypothesis that should be tested in longitudinal outcome studies.

The impact of race on response to RAAS inhibition.

Retrospective analyses of the Studies of Left Ventricular Dysfunction (SOLVD) and Vasodilator Heart Failure Trials (V-HeFT) have addressed the question of whether angiotensin-converting enzyme (ACE) inhibitors are equally efficacious in black patients and white patients with heart failure. In SOLVD, there was no ethnic difference in the efficacy of enalapril for reducing mortality and preventing the development of heart failure, but enalapril was more effective in whites in reducing hospitalizations. In V-HeFT II, enalapril was more efficacious than the combination of isosorbide dinitrate and hydralazine in whites in reducing mortality, but not in blacks. However, the combination of isosorbide dinitrate and hydralazine may be particularly advantageous in black patients as suggested by V-HeFT I and the recent African American Heart Failure Trial. In aggregate, the available data suggest that ACE inhibitors should remain a cornerstone of therapy for heart failure with a reduced ejection fraction in white patients and black patients.