Search

Objective: Loneliness, when prolonged, is associated with many deleterious effects and has been shown to be highly prevalent in those with a history of stroke, yet the cognitive mechanisms underpinning this phenomenon remain unclear. Therefore, the current study aims to investigate the extent to which cognitive factors, with specific focus on processing speed, are associated with loneliness in those with a history of stroke., Method: Utilizing data from the British Cohort Study, a nationally representative dataset, we conducted secondary data analysis. A total of 7,752 participants completed relevant questions related to health, social interactions, demographics, loneliness, and cognitive assessments. Among them, 47 had experienced a stroke ("stroke," n = 47), 5,545 reported other health conditions ("ill," n = 5,545), and 2,857 were deemed healthy ("healthy," n = 2,857)., Results: Consistent with previous research, our findings confirmed a positive correlation between stroke history and heightened loneliness. However, inferential analysis revealed that processing speed, alongside other cognitive factors, had a minimal impact on loneliness, with correlations too small to draw definitive conclusions., Conclusion: This study suggests that cognitive processing speed alone is not a robust predictor of loneliness in stroke survivors. Consequently, when developing interventions to combat loneliness in this population, it is crucial to consider a broader spectrum of factors, such as social engagement, emotional wellbeing, and interpersonal relationships. This underscores the imperative need for comprehensive assessments to better comprehend the multifaceted nature of loneliness and inform more effective intervention strategies., (© The Author(s) 2024. Published by Oxford University Press.)

Aims: To assess whether the optimal mean arterial blood pressure (MAP) target after out-of-hospital cardiac arrest (OHCA) is influenced by age and a history of arterial hypertension., Methods and Results: A post hoc analysis of data from the Blood Pressure and Oxygenation Targets in Post Resuscitation Care trial. The trial included 789 comatose patients randomized to a MAP target of 63 or 77 mmHg. The primary outcome of this sub-study was 1-year all-cause mortality. Cox proportional hazards regression and restricted cubic splines were used to examine whether prevalent hypertension and age modified the effect of low vs. high MAP target on all-cause mortality. Of the 789 patients randomized, 393 were assigned to a high MAP target, and 396 to a low MAP target. Groups were well-balanced for mean age (high MAP target 63 ± 13 years vs. low 62 ± 14 years) and hypertension (45 vs. 47%, respectively). At 1 year, the primary outcome occurred in 143 patients (36%) with a high MAP target and 138 (35%) with a low MAP target. The risk of the primary outcome increased linearly with increasing age (P < 0.001). The effect of a high vs. low MAP target on the primary outcome was modified by age when tested continuously, potentially favouring a low MAP target in younger patients (P for interaction = 0.03). Prevalent hypertension did not modify the effect of a high vs. low MAP target on the primary outcome (P for interaction = 0.67)., Conclusion: Among patients resuscitated after OHCA, older patients and those with a history of hypertension did not benefit from a high MAP target., Competing Interests: Conflict of interest: C.B.: speaker’s fee: Bayer. J.K.: received funding for the BOX trial (NNF17OC0028706) and DANOHCA trial (NNF22OC0079649) from the Novo Nordisk Foundation. J.E.M.: institutional research grant outside submitted work: Abiomed and the Novo Nordic Foundation; lecture fee: Abbott, Boehringer Ingelheim, and Orion. T.B.-S.: steering committee member of the Amgen-financed GALACTIC-HF trial, Boehringer Ingelheim–financed EASi-KIDNEY trial, LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System trial; chief investigator of the Sanofi Pasteur–financed NUDGE-FLU, DANFLU-1, and DANFLU-2 trials; advisory board: Sanofi Pasteur, Amgen, CSL Seqirus, and GSK; speaker honorarium: Bayer, Novartis, Sanofi Pasteur, GE Healthcare, and GSK; research grants: GE Healthcare, AstraZeneca, Novo Nordisk, and Sanofi Pasteur; consultant appointments: Novo Nordisk, IQVIA, and Parexel. B.B. and H.S.: nothing to declare. C.H.: research grant from the Novo Nordisk Foundation, the Lundbeck Foundation, and The Danish Heart Foundation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To evaluate a strategy designed to optimize care and increase uptake of urate-lowering therapy (ULT) during hospitalizations for gout flares., Methods: We conducted a prospective cohort study to evaluate a strategy that combined optimal in-hospital gout management with a nurse-led, follow-up appointment, followed by handover to primary care. Outcomes, including ULT initiation, urate target attainment and re-hospitalization rates, were compared between patients hospitalized for flares in the 12 months post-implementation and a retrospective cohort of hospitalized patients from 12 months pre-implementation., Results: One hundred and nineteen and 108 patients, respectively, were hospitalized for gout flares in the 12 months pre- and post-implementation. For patients with 6-month follow-up data available (n = 94 and n = 97, respectively), the proportion newly initiated on ULT increased from 49.2% pre-implementation to 92.3% post-implementation (age/sex-adjusted odds ratio [aOR] 11.5; 95% CI 4.36, 30.5; P < 0.001). After implementation, more patients achieved a serum urate ≤360 μmol/l within 6 months of discharge (10.6% pre-implementation vs 26.8% post-implementation; aOR 3.04; 95% CI 1.36, 6.78; P = 0.007). The proportion of patients re-hospitalized for flares was 14.9% pre-implementation vs 9.3% post-implementation (aOR 0.53; 95% CI 0.22, 1.32; P = 0.18)., Conclusion: Over 90% of patients were initiated on ULT after implementing a strategy to optimize hospital gout care. Despite increased initiation of ULT during flares, recurrent hospitalizations were not more frequent following implementation. Significant relative improvements in urate target attainment were observed post-implementation; however, for the majority of hospitalized gout patients to achieve urate targets, closer primary-secondary care integration is still needed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Post-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due to overlapping symptoms and poorly understood pathology. Identifying inflammatory profiles may improve clinical prognostication and trial endpoints., Methods: 1,988 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative post-COVID symptom scores were included in this analysis. Among participants who reported moderate-to-severe symptoms on surveys collected 6-months post-SARS-CoV-2 infection, principal component analysis (PCA) followed by K-means clustering identified distinct clusters of symptoms., Results: Three symptom-based clusters were identified: a sensory cluster (loss of smell and/or taste), a fatigue/difficulty thinking cluster, and a difficulty breathing/exercise intolerance cluster. Individuals within the sensory cluster were all outpatients during their initial COVID-19 presentation. The difficulty breathing cluster had a higher likelihood of obesity and COVID-19 hospitalization compared to those with no/mild symptoms at 6-months post-infection. Multinomial regression linked early post-infection D-dimer and IL-1RA elevation to fatigue/difficulty thinking, and elevated ICAM-1 concentrations to sensory symptoms., Conclusions: We identified three distinct symptom-based PCC phenotypes with specific clinical risk factors and early post-infection inflammatory predictors. With further validation and characterization, this framework may allow more precise classification of PCC cases and potentially improve the diagnosis, prognostication, and treatment of PCC., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Aims: It is unclear how serial high-sensitivity troponin-I (hsTnI) concentrations affect long-term prognosis in individuals with suspected acute coronary syndrome (ACS)., Methods and Results: Subjects who underwent two hsTnI measurements (Siemens TnI Flex® Reagent) separated by 1-7 h, during a first-time hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019, were identified through Danish national registries. Individuals were stratified per their hsTnI concentration pattern (normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (<20%, >20-50%, or >50% in either direction). We calculated absolute and relative mortality risks standardized to the distributions of risk factors for the entire study population. A total of 20 609 individuals were included of whom 2.3% had died at 30 days, and an additional 4.7% had died at 365 days. The standardized risk of death was highest among persons with a persistently elevated hsTnI concentration (0-30 days: 8.0%, 31-365 days: 11.1%) and lowest among those with two normal hsTnI concentrations (0-30 days: 0.5%, 31-365 days: 2.6%). In neither case did relative hsTnI concentration changes between measurements clearly affect mortality risk. Among persons with a rising hsTnI concentration pattern, 30-day mortality was higher in subjects with a >50% rise compared with those with a less pronounced rise (2.2% vs. <0.1%)., Conclusion: Among individuals with suspected ACS, those with a persistently elevated hsTnI concentration consistently had the highest risk of death. In subjects with two normal hsTnI concentrations, mortality was very low and not affected by the magnitude of change between measurements., Competing Interests: Conflict of interest: M.P. discloses the following relationships—advisory board: AstraZeneca, Janssen-Cilag, and Novo Nordisk; grant support: Danish Cardiovascular Academy funded by the Novo Nordisk Foundation and the Danish Heart Foundation (grant number CPD5Y-2022004-HF); and speaker honorarium: AstraZeneca, Bayer, Boehringer Ingelheim, and Janssen-Cilag. M.V. has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Relypsa, and Roche Diagnostics; speaker engagements with Novartis and Roche Diagnostics; and participates on clinical endpoint committees for studies sponsored by Galmed and Novartis. C.B. discloses the following relationships—speaker honorarium: Bayer. T.B.-S. discloses the following relationships—steering committee member of the Amgen-financed GALACTIC-HF trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘NUDGE-FLU’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-1’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-2’ trial, and steering committee member of ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial; advisory board: Sanofi Pasteur, Amgen, and GSK; speaker honorarium: Novartis, Sanofi Pasteur, and GSK; and research grants: GE Healthcare and Sanofi Pasteur. M.M. is supported by a grant from the Novo Nordisk Foundation (grant number NNFOC0074083) and has received lecture and advisory board fees from Novo Nordisk. C.P.M. is supported by a grant from the National Institutes of Health (K23HL167659) and has received consulting fees/honorarium from Roche Diagnostics and Abbott Laboratories. L.K. discloses the following relationships—speaker honorarium from Novo Nordisk, Novartis, AstraZeneca, Boehringer, and Bayer. N.T.O. discloses the following relationships—research funding: Abbott and Shockwave. D.L.B. discloses the following relationships—advisory board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; board of directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); consultant: Broadview Ventures and Hims; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic, Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT Trial); honoraria: American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor, associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and US national co-leader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); other: Clinical Cardiology (deputy editor); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither I nor Brigham and Women’s Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties: Elsevier (editor, Braunwald’s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; and unfunded research: FlowCo and Takeda. The other authors report no relevant disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Comparison of humoral responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinees, those with SARS-CoV-2 infection, or combinations of vaccine/ infection ("hybrid immunity") may clarify predictors of vaccine immunogenicity., Methods: We studied 2660 US Military Health System beneficiaries with a history of SARS-CoV-2 infection-alone (n = 705), vaccination-alone (n = 932), vaccine-after-infection (n = 869), and vaccine-breakthrough-infection (n = 154). Peak anti-spike-immunoglobulin G (IgG) responses through 183 days were compared, with adjustment for vaccine product, demography, and comorbidities. We excluded those with evidence of clinical or subclinical SARS-CoV-2 reinfection from all groups., Results: Multivariable regression results indicated that vaccine-after-infection anti-spike-IgG responses were higher than infection-alone (P < .01), regardless of prior infection severity. An increased time between infection and vaccination was associated with greater post-vaccination IgG response (P < .01). Vaccination-alone elicited a greater IgG response but more rapid waning of IgG (P < .01) compared with infection-alone (P < .01). BNT162b2 and mRNA-1273 vaccine-receipt was associated with greater IgG responses compared with JNJ-78436735 vaccine-receipt (P < .01), regardless of infection history. Those with vaccine-after-infection or vaccine-breakthrough-infection had a more durable anti-spike-IgG response compared to infection-alone (P < .01)., Conclusions: Vaccine-receipt elicited higher anti-spike-IgG responses than infection-alone, although IgG levels waned faster in those vaccinated (compared to infection-alone). Vaccine-after-infection elicits a greater humoral response compared with vaccine or infection alone; and the timing, but not disease severity, of prior infection predicted these post-vaccination IgG responses. While differences between groups were small in magnitude, these results offer insights into vaccine immunogenicity variations that may help inform vaccination timing strategies., Competing Interests: Conflicts of interest. S. D. P., T. H. B., D. T., and M. P. S. report that the Uniformed Services University (USU) IDCRP, a US Department of Defense institution, and the Henry M. Jackson Foundation were funded under a cooperative research and development agreement to conduct an unrelated phase 3 COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The Henry M. Jackson Foundation, in support of the USU IDCRP, was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase 3 vaccine trial sponsored by AstraZeneca. Both of these trials were part of the US government COVID-19 response. Neither is related to the work presented here. C. M. B. reports a leadership or fiduciary role on the Infectious Diseases Society of America Clinical Affairs Committee. R. C. M. reports grants or contracts to his institution and unrelated to this work from AiCuris, Sound Pharmaceutical, and AstraZeneca; consulting fees and honorarium for advisory panel membership from the Society of Critical Care Medicine; honorarium for a lecture from the California Thoracic Society; travel support from the American Thoracic Society, American College of Chest Physicians, and Society of Critical Care Medicine; a US patent for investigational dengue vaccine candidate (no payments made or current commercial development planned); data and safety monitoring board membership (funds to author) for Trauma Insights, LLC; member of The Society of Critical Care Medicine (SCCM) Congress Program Committee (travel support for official meetings [pre-March 2020]), chair of the American College of Chest Physicians (CHEST) COVID-19 Task Force and Disaster/Global Health Section (travel support for official meetings), and member of the CHEST Scientific Program Committee (travel support for official meetings). All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Long-term prognostic implications of serial high-sensitivity troponin concentrations in subjects with suspected acute coronary syndrome are unknown., Methods and Results: Individuals with a first diagnosis of myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019 who underwent two high-sensitivity troponin-T (hsTnT) measurements 1-7 h apart were identified through Danish national registries. Absolute and relative risks for death at days 0-30 and 31-365, stratified for whether subjects had normal or elevated hsTnT concentrations, and whether these concentrations changed by <20%, > 20 to 50%, or >50% in either direction from first to second measurement, were calculated through multivariable logistic regression with average treatment effect modeling. Of the 28 902 individuals included, 2.8% had died at 30 days, whereas 4.9% of those who had survived the first 30 days died between days 31-365. The standardized risk of death was highest among subjects with two elevated hsTnT concentrations (0-30 days: 4.3%, 31-365 days: 7.2%). In this group, mortality was significantly higher in those with a > 20 to 50% or >50% rise from first to second measurement, though only at 30 days. The risk of death was very low in subjects with two normal hsTnT concentrations (0-30 days: 0.1%, 31-365 days: 0.9%) and did not depend on relative or absolute changes between measurements., Conclusions: Individuals with suspected acute coronary syndrome and two consecutively elevated hsTnT concentrations consistently had the highest risk of death. Mortality was very low in subjects with two normal hsTnT concentrations, irrespective of changes between measurements., Competing Interests: Conflict of interest: M.P. discloses the following relationships—Advisory Board: AstraZeneca, Janssen-Cilag; Grant Support: Danish Cardiovascular Academy funded by the Novo Nordisk Foundation and the Danish Heart Foundation (grant number: CPD5Y-2022004-HF); Speaker Honorarium: AstraZeneca, Bayer, Boehringer Ingelheim, Janssen-Cilag. M.V. has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health, speaker engagements with AstraZeneca, Novartis, and Roche Diagnostics, and participates on clinical trial committees for studies sponsored by Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. C.B. discloses the following relationships—speaker honorarium: Bayer. M.M. is supported by a grant from the Novo Nordisk Foundation (grant number NNFOC0074083) and has received lecture and advisory board fees from Novo Nordisk. T.B.-S. discloses the following relationships—Steering Committee member of the Amgen financed GALACTIC-HF trial, Chief investigator and steering committee chair of the Sanofi Pasteur financed ‘NUDGE-FLU’ trial, Chief investigator and steering committee chair of the Sanofi Pasteur financed ‘DANFLU-1’ trial, Chief investigator and steering committee chair of the Sanofi Pasteur financed ‘DANFLU-2’ trial, Steering Committee member of ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial, Advisory Board: Sanofi Pasteur, Amgen and GSK, speaker honorarium: Novartis, Sanofi Pasteur and GSK, Research grants: GE Healthcare and Sanofi Pasteur. L.K. discloses the following relationships—speaker honorarium from Novo Nordisk, Novartis, AstraZeneca, Boehringer, and Bayer. N.T.O. discloses the following relationships—research funding: Abbott, Shockwave. D.L.B. discloses the following relationships—advisory board: AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Takeda. The other authors report no relevant disclosures., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Despite clinical observation that stroke survivors frequently experience loneliness, there is no large-scale empirical evidence to support this observation. Therefore, the primary objective of this research was to provide the first large-scale and comprehensive estimate of loneliness in the stroke survivor population., Method: To address this issue, we completed two preregistered analyses of a nationally representative annual survey (N > 21,000). A two-phase approach was adopted combining both exploratory (Study 1) and confirmatory (Study 2) phases. The benefit of such an approach is that replication is built into the design, which considerably strengthens the inferences that can be made., Results: Across two separate cohorts, the results consistently showed that human stroke survivors report higher levels of loneliness compared with healthy individuals, and this relationship could not be accounted for by demographic factors (e.g., age, sex) or objective measures of social isolation (e.g., marital status, number of household members)., Conclusions: These findings demonstrate that elevated levels of loneliness poststroke are robust in that they replicate in large nationally representative samples and cannot be reduced to objective measures of social isolation. The work has clinical and societal relevance by suggesting that loneliness poststroke is unlikely to be adequately "treated" if only the quantity and not the quality of social experiences are considered., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Introduction: The U.S. Preventive Services Task Force (USPSTF) modified their screening guidelines for breast cancer in November 2009. Previous studies evaluated the impact of these guideline changes among privately and Medicare insured populations. Women in the military form a unique population exposed to many social, environmental, and occupational hazards that may increase breast cancer incidence. By evaluating mammography screening rates among women in the military before and after the USPSTF guideline changes, this study evaluated the impact of the USPSTF breast cancer guideline change on screening mammography use within the military population and determined whether current guidelines were followed for this high-risk population with universal health care access., Materials and Methods: This study evaluated the impact of the 2009 guideline changes among the population of universally insured military servicewomen, comparing the proportion of active duty women aged 40 to 64 receiving mammograms from fiscal years 2006 to 2015 using an interrupted time series analysis. Stratified analyses evaluated differences by age (aged 40-49, 50-64), race, military branch, and rank. This research is considered exempt by the Uniformed Services University Institutional Review Board., Results: The proportion of insured military servicewomen receiving mammograms increased from October 2005 through September 2009. A significant decrease occurred in the first quarter of 2010 following the publication of the screening guideline update. From this new baseline, the proportion of women screened increased again through September 2015. Comparative analyses showed more pronounced effects both immediately and over time among the women aged 50 to 64 compared to those aged 40 to 49 years and among older enlisted women compared with their officer counterparts. The patterns were near identical in all subgroups; however, no changes in rate were evident among Air Force and black servicewomen aged 50 to 64 and Army and Navy/Marine Corps servicewomen aged 40 to 49 years. No racial disparities in screening or impact were noted., Conclusions: The USPSTF guidelines had differential impacts among some subpopulations. While older women, aged 50 to 64 years, had a greater temporary reduction immediately after the guideline change, younger women aged 40 to 49 years had a longer-term reduction in screening following the guideline changes. No racial disparities in the proportion screened or in the impact of the guideline change were noted in this population with universal health coverage. The lack of Department of Defense standard breast cancer screening guidelines was evident from the different patterns of mammography utilization observed among military branches. To completely understand the impact of the updated screening guidelines, future studies must incorporate research focusing on changes in breast cancer morbidity and mortality as well as updated cost-benefit analyses., (© Association of Military Surgeons of the United States 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The current global pandemic of the novel coronavirus SARS-CoV2 is a threat to the health and lives of millions of people worldwide. The latest statistics from the World Health Organisation show that there have been 6,515,796 confirmed cases worldwide with 387,298 confirmed deaths (last update 5 June 2020, 10:41 CEST). The majority of critically unwell patients with SARS-CoV2 are adults and the radiological findings associated with them are consistent throughout the literature. However, the reported paediatric cases are few, and as such, there is a limited body of evidence available. More international data is needed, not only on the clinical presentation, but also the radiological findings, so that health-care providers are better able to understand and diagnose this pandemic disease. We describe a case of a previously healthy 9-year-old female who presented to the Emergency Department with symptoms suggestive of raised intracranial pressure. Her CT revealed a medulloblastoma and post-operatively she tested positive for SARS-CoV2. She had a rapid deterioration in her clinical condition and required admission to the intensive care unit (ICU). We provide the supporting radiology along her clinical course in order to demonstrate important insights into this disease in children, including the unusual pnemomediastinum complications which occurred as part of her clinical course. This case is the first reported of its kind., Competing Interests: Competing interests: The authors have no conflicts of interest to disclose., (© 2021 The Authors. Published by the British Institute of Radiology.)

Aims: The 2018 ESC/ESH guidelines for hypertension recommend differential management of patients who are <65, 65-79, and ≥80 years of age. However, it is unclear whether intensive blood pressure lowering is well-tolerated and modifies risk uniformly across the age spectrum., Methods and Results: SPRINT randomized 9361 high-risk adults without diabetes and age ≥50 years with systolic blood pressure 130-180 mmHg to either intensive or standard antihypertensive treatment. The primary efficacy endpoint was the composite of acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. The primary safety endpoint was composite serious adverse events. We assessed whether age modified the efficacy and safety of intensive vs. standard blood pressure lowering using Cox proportional-hazards regression and restricted cubic splines. In all, 3805 (41%), 4390 (47%), and 1166 (12%) were <65, 65-79, and ≥80 years. Mean age was similar between the two study groups (intensive group 67.9 ± 9.4 years vs. standard group 67.9 ± 9.5 years; P = 0.94). Median follow-up was 3.3 years. In multivariable models, age was linearly associated with the risk of stroke (P < 0.001) and non-linearly associated with the risk of primary efficacy events, death from cardiovascular causes, death from any cause, heart failure, and serious adverse events (P < 0.001). The safety and efficacy of intensive blood pressure lowering were not modified by age, whether tested continuously or categorically (P > 0.05)., Conclusion: In SPRINT, the benefits and risks of intensive blood pressure lowering did not differ according to the age categories proposed by the ESC/ESH guidelines for hypertension., Trial Registration: SPRINT (Systolic Blood Pressure Intervention Trial); ClinicalTrials.gov Identifier: NCT01206062, https://clinicaltrials.gov/ct2/show/NCT01206062., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Joubert syndrome is a genetically heterogeneous multisystem disorder typically diagnosed in childhood. Nephronophthisis is the most common renal pathology in Joubert syndrome, and renal failure usually occurs in childhood or in young adults. We report a 61-year-old female diagnosed with AHI1 -related oculorenal Joubert syndrome, who presented initially with decline in renal function in her 50s. Our report describes exceptionally late presentation of renal disease in Joubert syndrome and highlights the importance of continued renal function monitoring in older adults with Joubert syndrome., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Aims: Patients with non-ischaemic systolic heart failure often have reduced myocardial blood flow without significant coronary atherosclerosis. Likewise, patients with atrial fibrillation (AF) have reduced myocardial perfusion during AF compared with sinus rhythm. The aim of this study was to explore whether there is an additive negative effect of AF during scan on the myocardial perfusion in patients with non-ischaemic systolic heart failure., Methods and Results: We included 27 young healthy controls and 114 patients with non-ischaemic systolic heart failure to a Rubidium-82 positron emission tomography/computed tomography perfusion scan (23 with AF during scan). To obtain the myocardial flow reserve (MFR = stress flow/rest flow), patients were scanned at rest and during adenosine-induced stress. Among patients, those with AF were older [years: 73; interquartile range (IQR) 65-78 vs. 67; IQR 60-74; P = 0.03] and more were men (87% vs. 62%; P = 0.02). Distribution of sex in controls did not differ from either patient group. Patients with AF had significantly lower MFR than patients without [MFR: 1.87; 95% confidence interval (CI) 1.58-2.22 vs. 2.50; 95% CI 2.06-2.86; percent difference: -21.5%; P = 0.01]. MFR remained significantly lower in the group with AF (estimate -24.2%; 95% CI -39.6% to -4.8%; P = 0.02) in an adjusted multivariable regression analysis. Further, patients had lower MFR compared with controls: 3.46; 95% CI 3.03-3.94; P < 0.0001. Additionally, coronary vascular resistance was highest in patients with AF and lowest in controls., Conclusion: Patients with systolic heart failure had lower flow reserve than healthy controls and even lower MFR if they had AF during scan.

Introduction: Sickle cell trait (SCT), the heterozygous carrier state for hemoglobin S, is present in an estimated 1.6% of all newborns and 7.3% in black individuals in the USA. SCT has long been considered a benign condition with anticipated normal life expectancy and no increased risk for chronic diseases. The medical literature is inconclusive on the potential association between SCT and chronic medical conditions (CMC) including chronic kidney disease, venous thromboembolism, and stroke. Studies addressing these questions are lacking particularly in non-Black young adults., Materials and Methods: We conducted a retrospective cohort study among U.S. active duty, enlisted, service members who entered from 1992 to 2012 using existing Department of Defense (DoD Military Healthcare System databases). SCT positive subjects (1,323) were matched by demographic characteristics to SCT negative subjects (3,136) and followed through 2013 for CMC that included deep vein thrombosis, diabetes mellitus and hematologic, pulmonary, and renal conditions., Results: The rate of developing any of the included CMC was higher for those with SCT (incidence rate ratio = 1.71 95% CI 1.61-1.81) compared with those who were SCT negative and their healthcare utilization rate for any of CMC studied was higher for SCT positive compared with negative individuals (URR = 2.45 95% CI 2.41-2.50), with the highest rate ratios observed for hematologic and renal conditions. SCT positive compared with negative individuals were more likely to have encounter diagnoses of sickle cell disease and diabetes Type II and were less likely to have encounter diagnoses of other hemoglobinopathies and diabetes type I., Conclusion: SCT in these racially diverse, young adults increased both the incidence of and healthcare utilization for thromboembolism, diabetes mellitus type II, sickle cell disease, pulmonary, and chronic renal conditions. These findings suggest that clinicians treating young adults with SCT should exercise heightened surveillance for these CMC to ensure both early diagnosis and access to treatments.

Introduction: A number of studies have found an association between sickle cell trait (SCT) and exertional heat illnesses (EHIs) including heat stroke, a potentially fatal condition. The strength of this association varied across studies, limiting the ability to quantify potential benefits of SCT-screening policies for competitive athletics and military service members. We determined the relative rate and attributable risk of developing EHI associated with being SCT positive and the EHI health care utilization., Methods: We conducted a retrospective cohort study among U.S. enlisted, active duty service members during 1992-2012 from the Department of Defense Military Healthcare System databases. All 15,081 SCT-positive individuals and a sample of 60,320 from those considered SCT negative were followed through 2013 for EHI outcomes ranging from mild heat illness to heat stroke., Results: The adjusted hazard ratio for EHI in SCT-positive compared with SCT-negative individuals was 1.24 (95% confidence interval 1.06, 1.45). Risk factors for EHI included age over 30 yr at enlistment, female gender, Marine Corps, combat occupations, and enlistment between April and June. An estimated 216 Department of Defense enlistees (95% confidence interval: 147, 370) would need to be screened to identify and potentially prevent one case of EHI. The attributable risk of EHI due to SCT was 33% (95% confidence interval 19, 45%)., Conclusion: Our findings suggest that SCT screening will identify approximately a third of SCT individuals at risk for EHI, but does not provide definitive evidence for universal compared with selective (e.g., occupational based) in military enlistees. A cost-effectiveness analysis is needed for policy makers to assess the overall value of universal SCT screening to prevent morbidity and mortality in both the military and the collegiate athletic populations.

Introduction: Sickle cell trait (SCT) affects an estimated 5.02% of non-Hispanic blacks, 1.08% of Hispanics, and 0.1% of Whites in the U.S. military. Policies for SCT screening and occupational restrictions vary by service. Population-based studies of SCT with quantification of military-relevant outcomes are lacking., Methods: The study design was a retrospective cohort of 15,081 SCT-positive versus 60,320 SCT-negative U.S. active duty personnel enlisted from 1992 to 2012 and followed through 2013. Military-relevant outcome included number and days of deployment, length of service, and cause of death., Results: SCT-positive versus SCT-negative service members experienced more deployments (p < 0.01) and longer number of days deployed for all services, especially the Army (p < 0.001). The median length of service was longer for SCT-positive service members stratified by service and by gender (p < 0.05). The adjusted risk of length of service greater than 5 yr by SCT status was 1.37 (95% confidence interval 1.31-1.43) with greater than a three-fold higher risk in the Navy and Air Force compared with the Army. Crude mortality rate was not significantly different by SCT status, although deaths due to suicide, self-directed violence, and other non-specific causes were more common in SCT-positive service members., Conclusion: We found that SCT-positive service members deployed more frequently, for greater lengths of time, and remained in service longer. No significant difference in crude mortality ratio was discovered. Additional research on military-relevant outcomes and a cost-effectiveness analysis of SCT screening practices are needed to inform evidence-based SCT enlistment policies.

Vertebroplasty is a recognised treatment for osteoporotic and pathological compression fractures. We present the case of TF, a 70-year-old male patient with a history of poor left ventricular function presenting with refractory lower back pain, thought to be secondary to Modic Type1 changes in the L2 and L3 vertebrae, accompanying L2-L3 degenerative disc disease. He was treated conservatively for approximately 9 months without success. Following recent suggestions that vertebroplasty may provide pain relief in patients with degenerative disc change and coexistent Modic 1 changes not responding to conservative treatment, we proceeded to vertebroplasty of the affected levels. This resulted in rapid resolution of pain and return to his pre low back pain level of activity. At 1-year follow-up the patient remains pain free. We review the causes of Modic 1 change, its relationship to low back pain and a rarely used but highly effective treatment option, percutaneous cement vertebroplasty, when it is unresponsive to traditional treatment options.

Background: Estrogen plus progestin therapy increases both mammographic density and breast cancer incidence. Whether mammographic density change associated with estrogen plus progestin initiation predicts breast cancer risk is unknown., Methods: We conducted an ancillary nested case-control study within the Women's Health Initiative trial that randomly assigned postmenopausal women to daily conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg or placebo. Mammographic density was assessed from mammograms taken prior to and one year after random assignment for 174 women who later developed breast cancer (cases) and 733 healthy women (controls). Logistic regression analyses included adjustment for confounders and baseline mammographic density when appropriate., Results: Among women in the estrogen plus progestin arm (97 cases/378 controls), each 1% positive change in percent mammographic density increased breast cancer risk 3% (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.01 to 1.06). For women in the highest quintile of mammographic density change (>19.3% increase), breast cancer risk increased 3.6-fold (95% CI = 1.52 to 8.56). The effect of estrogen plus progestin use on breast cancer risk (OR = 1.28, 95% CI = 0.90 to 1.82) was eliminated in this study, after adjusting for change in mammographic density (OR = 1.00, 95% CI = 0.66 to 1.51)., Conclusions: We found the one-year change in mammographic density after estrogen plus progestin initiation predicted subsequent increase in breast cancer risk. All of the increased risk from estrogen plus progestin use was mediated through mammographic density change. Doctors should evaluate changes in mammographic density with women who initiate estrogen plus progestin therapy and discuss the breast cancer risk implications., (Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.)

Background: Population-based estimates of sickle cell trait (SCT) prevalence in the U.S. military across services and over time are lacking., Methods: SCT prevalence by service, race/ethnicity, and gender in 5-year time intervals was estimated using demographic, ambulatory, and hospital SCT encounter (International Classification of Diseases, 9th Revision, Clinical Modification 282.5) data for active duty, enlisted between 1992 and 2012 and limited SCT laboratory results., Results: Our study identified 15,081 SCT subjects. SCT prevalence varied significantly by race, year, gender, and service branch. SCT prevalence was highest for non-Hispanic blacks (5.02%; prevalence ratio = 56.33, confidence interval [CI] = 52.14-60.85; compared to non-Hispanic white) in 2005-2009 (0.40%; prevalence ratio = 10.04, CI = 9.21-10.94; compared to 1992-1994), for women (2.97%; prevalence ratio = 3.14, CI = 3.04-3.25; compared to men), and in the Navy (2.26%; prevalence ratio = 2.96, CI = 2.84-3.02; compared to Army). Among foreign born, Africans were more likely to be SCT+ (prevalence ratio = 1.68, CI = 1.39-2.04; compared to non-U.S. North American)., Conclusion: This study estimated the prevalence of SCT within U.S. military enlisted force and describes variability across services for race, time intervals, gender, and foreign-born region and will support investigation into the health effects of SCT in young adult populations., (Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.)

Herniation pits are small benign lucent oval lesions within the anterior aspect of the superolateral femoral neck and were first described in 1982 by Michael J. Pitt. They are widely believed to occur as a result of mechanical forces from the overlying capsule resulting in herniation of soft tissues and synovium through a small bony defect. More recently, there has been evidence to suggest that femeroacetabular impingement may have a role in their aetiology. We present a case of a 59 -year -old male patient who developed hip pain following a jump from a wall. MRI was performed following failure of conservative management and demonstrated a small herniation pit with surrounding bone oedema. Following flouroscopic intra-articular steroid injection there was complete resolution of the patient's symptoms and the bone oedema surrounding the herniation pit. We review the potential causes, imaging appearances and potential treatment of synovial herniation pits with an emphasis on the role of radiologically guided intra-articular steroid injection.

Background: Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001., Methods: Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0., Results: The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones., Conclusions: Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.)

Over the last quarter of a century, a huge effort has been made to develop interventions that can minimise ischaemia reperfusion injury. The most potent of these are the ischaemic conditioning strategies, which comprise ischaemic preconditioning, remote ischaemic preconditioning and ischaemic postconditioning. While much of the focus for these interventions has been on protecting the myocardium, other organs including the kidney can be similarly protected. However, translation of these beneficial effects from animal models into routine clinical practice has been less straightforward than expected. In this review, we examine the role of ischaemic conditioning strategies in reducing tissue injury from the 'bench to the bedside' and discuss the barriers to their greater translation., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

To maximize statistical power in studies of mammographic density and breast cancer, it is advantageous to combine data from several studies, but standardization of the density assessment is desirable. Using data from 4 case-control studies, we describe the process of reassessment and the resulting correlation between values, identify predictors of differences in density readings, and evaluate the strength of the association between mammographic density and breast cancer risk using different representations of density values. The pooled analysis included 1,699 cases and 2,422 controls from California (1990-1998), Hawaii (1996-2003), Minnesota (1992-2001), and Japan (1999-2003). In 2010, a single reader reassessed all images for mammographic density using Cumulus software (Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada). The mean difference between original and reassessed percent density values was -0.7% (95% confidence interval: -1.1, -0.3), with a correlation of 0.82 that varied by location (r = 0.80-0.89). Case status, weight status, age, parity, density assessment method, mammogram view, and race/ethnicity were significant determinants of the difference between original and reassessed values; in combination, these factors explained 9.2% of the variation. The associations of mammographic density with breast cancer and the model fits were similar using the original values and the reassessed values but were slightly strengthened when a calibrated value based on 100 reassessed radiographs was used.

Background: South Asian and Black ethnic minorities in the UK have higher rates of acceptance onto renal replacement therapy (RRT) than Caucasians. Registry studies in the USA and Canada show better survival; there are few data in the UK., Methods: Renal Association UK Renal Registry data were used to compare the characteristics and survival of patients starting RRT from both groups with those of Caucasians, using incident cases accepted between 1997 and 2006. Survival was analysed by multivariate Cox's proportional hazards regression split by haemodialysis and peritoneal dialysis (PD) due to non-proportionality, and without censoring at transplantation., Results: A total of 2495 (8.2%) were South Asian and 1218 (4.0%) were Black. They were younger and had more diabetic nephropathy. The age-adjusted prevalence of vascular co-morbidity was higher in South Asians and lower in Blacks; other co-morbidities were generally common in Caucasians. Late referral did not differ. They were less likely to receive a transplant or to start PD. South Asians and Blacks had significantly better survival than Caucasians both from RRT start to Day 90 and after Day 90, and for those on HD or PD at Day 90. Fully adjusted hazard ratios after Day 90 on haemodialysis were 0.70 (0.55-0.89) for South Asians and 0.56 (0.41-0.75) for Blacks., Conclusion: South Asian and Black minorities have better survival on dialysis. An understanding of the mechanisms may provide general insights for all patients on RRT.

The metabolic syndrome (MetS) represents a combination of cardiometabolic risk determinants including obesity (central adiposity), insulin resistance, glucose intolerance, dyslipidaemia, non-alcoholic fatty liver disease and hypertension. MetS is rapidly increasing in prevalence worldwide as a consequence of the continued obesity "epidemic", and as a result will have a considerable impact on the global incidence of cardiovascular disease and type 2 diabetes. Currently, there is debate concerning whether the risk of cardiovascular disease is greater in patients diagnosed with MetS than that of the sum of the individual risk factors. At present, no unifying origin that can explain the pathogenesis of MetS has been identified and therefore no unique pharmacological treatment is available. This review summarises and critically evaluates the current clinical and scientific evidence supporting the existence of MetS as a multifactorial endocrine disease, for which maternal nutrition may be a common pathogenic mechanism. In addition, we suggest that ectopic fat accumulation (such as visceral and hepatic fat accumulation) and the proinflammatory state are central to the development of the MetS.

Aims: To determine the degree of relatedness between isolates of Escherichia coli O157:H7 of human, bovine, ovine and porcine origin., Methods and Results: Escherichia coli O157:H7 isolates were compared using (i) PFGE XbaI patterns, (ii) PCR profiles of virulence genes and (iii) the DNA sequences of genes reported to play a role in pathogenicity. The 77 E. coli O157:H7 isolates demonstrated 49 different PFGE patterns of which, eight were common to multiple isolates, and the remaining 41 were distinct. Isolates of different origin did not correlate, except for one cluster consisting of two human and two beef isolates. The majority of animal isolates had the same PCR profiles of virulence genes as those isolated from clinical patients. Single nucleotide polymorphisms (SNPs) were identified in the sequence of a 255-bp region of the vtx2 subunit A gene., Conclusions: Six SNPs were detected in the vtx2A gene, defining four different haplotypes. One nonsynonymous substitution encoded for an amino acid change from glutamic to aspartic acid., Significance and Impact of the Study: Results indicate that although E. coli O157:H7 isolates of differing origin were distinct by PFGE, the DNA sequences of the main virulence genes associated with human clinical illness were conserved.

Aims: To (i) monitor the presence of Enterobacteriaceae as indicators of faecal contamination on pig carcasses, (ii) examine the potential use of chilling as a critical control point (CCP) and establish its influence on pig carcass categorization by Decision 471/EC and (iii) determine the incidence of E. coli O157:H7 in pigs., Methods and Results: Porcine faecal samples and carcass swabs were collected before and after chilling at four Irish pig abattoirs and examined for Enterobacteriaceae and E. coli O157:H7. Chilling generally reduced Enterobacteriaceae counts on carcasses, but increases were also observed, particularly in one abattoir. E. coli O157:H7 was absent from carcasses before chilling, present on 0.21% after chilling and was recovered from 0.63% of faecal samples. All of the isolates were found to contain virulence genes associated with clinical illness in humans., Conclusions: The data show that overall chilling had the capacity to reduce the numbers of carcasses positive for the presence of Enterobacteriaceae., Significance and Impact of Study: The influence of chilling on the categorization of pig carcasses suggests that it has the potential to improve the numbers of acceptable carcasses and the process could be used as a CCP within a HACCP plan.

FKBP-like (FKBPL) protein is a novel immunophilin-like protein that plays a role in the cellular stress response. Its three tetratricopeptide repeat motifs are homologous to the heat shock protein 90 interaction sites of other immunophilins that have roles in steroid hormone receptor signaling. In this study, using biomolecular complementation and coimmunoprecipitation techniques, we show that FKBPL also colocalizes and interacts with the components of the heat shock protein 90-glucocorticoid receptor (GR) complex and demonstrate that the PPIase domain of FKBPL is important for the interaction between this complex and the dynein motor protein, dynamitin. Treatment of DU145 cells with the GR ligand, dexamethasone, induced a rapid and coordinated translocation of both GR and FKBPL to the nucleus; this response was perturbed when FKBPL was knocked down with a targeted small interfering RNA. Furthermore, overexpression of FKBPL increased GR protein levels and transactivation of a luciferase reporter gene in response to dexamethasone in DU145 cells. However, these responses were cell line dependent. In summary, these data suggest that FKBPL can be classed as a new member of the FKBP protein family with a role in steroid receptor complexes and signaling.

Breast density is one of the strongest predictors of breast cancer risk, and quantitative measurement is fairly reproducible. However, to study change in breast density, other issues should also be considered. Most studies of breast density have relied on one assessment, yet the mammographic features of the breast that constitute breast density change with age and/or menopause. When measuring breast density change, issues related to assessment are of greater concern. In addition, because age-period and cohort effects are codefined, evaluation of age trends must also consider the possible explanations of period and cohort effects. The prevalence of different factors affecting breast density changed dramatically over the last 50 years. In this issue of the Journal (Am J Epidemiol 2008;167:1027-1036), Kelemen et al. evaluate how factors known to be related to breast density influence breast density change with age. These authors are to be complimented on their detailed analysis and consideration of many of these issues. They not only describe the averaged effects of age on breast density changes but also consider whether patterns of density change differ for women with different exposure histories.

Background: Mammographic density and circulating sex hormones are two well-confirmed predictors of breast cancer risk. Whether mammographic density reflects levels of endogenous sex hormones is unclear. We examined whether these predictors are independently associated with breast cancer risk in a prospective study., Methods: We conducted a nested case-control study within the Nurses' Health Study cohort of 253 case subjects with breast cancer and 520 control subjects. All participants were postmenopausal women who were not using postmenopausal hormones at the time of both blood collection and mammography. Plasma levels of estradiol, free estradiol, testosterone, and free testosterone were evaluated. Mammographic density was assessed by use of computer-assisted analysis of mammograms. Logistic regression models that were adjusted for matching variables and potential confounders were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided., Results: Levels of circulating sex steroids and mammographic density were both statistically significantly and independently associated with breast cancer risk. The relative risk of breast cancer associated with mammographic density (RR for highest quartile compared with lowest quartile = 3.8, 95% CI = 2.2 to 6.6; P(trend)<.001) changed little when the analysis was adjusted for circulating estradiol (RR = 3.9, 95% CI = 2.2 to 6.9; P(trend)<.001) or circulating testosterone (RR = 4.1, 95% CI = 2.3 to 7.2; P(trend)<.001). Circulating levels of estradiol (RR = 2.4, 95% CI = 1.4 to 4.0) and of testosterone (RR = 2.0, 95% CI = 1.2 to 3.1) were both associated with breast cancer risk, before and after adjustment for mammographic density. In a joint analysis of mammographic density and plasma testosterone, the risk of breast cancer was highest in the highest tertiles of both relative to the lowest tertiles of both (RR = 6.0, 95% CI = 2.6 to 14.0). A similar pattern was observed in the joint analysis of estradiol and mammographic density (RR = 4.1, 95% CI = 1.7 to 9.8)., Conclusions: Circulating sex steroid levels and mammographic density appear strongly and independently associated with the risk of breast cancer in postmenopausal women.

Background: To improve the discriminatory power of the Gail model for predicting absolute risk of invasive breast cancer, we previously developed a relative risk model that incorporated mammographic density (DENSITY) from data on white women in the Breast Cancer Detection Demonstration Project (BCDDP). That model also included the variables age at birth of first live child (AGEFLB), number of affected mother or sisters (NUMREL), number of previous benign breast biopsy examinations (NBIOPS), and weight (WEIGHT). In this study, we developed the corresponding model for absolute risk., Methods: We combined the relative risk model with data on the distribution of the variables AGEFLB, NUMREL, NBIOPS, and WEIGHT from the 2000 National Health Interview Survey, with data on the conditional distribution of DENSITY given other risk factors in BCDDP, with breast cancer incidence rates from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute, and with national mortality rates. Confidence intervals (CIs) accounted for variability of estimates of relative risks and of risk factor distributions. We compared the absolute 5-year risk projections from the new model with those from the Gail model on 1744 white women., Results: Attributable risks of breast cancer associated with DENSITY, AGEFLB, NUMREL, NBIOPS, and WEIGHT were 0.779 (95% CI = 0.733 to 0.819) and 0.747 (95% CI = 0.702 to 0.788) for women younger than 50 years and 50 years or older, respectively. The model predicted higher risks than the Gail model for women with a high percentage of dense breast area. However, the average risk projections from the new model in various age groups were similar to those from the Gail model, suggesting that the new model is well calibrated., Conclusions: This new model for absolute invasive breast cancer risk in white women promises modest improvements in discriminatory power compared with the Gail model but needs to be validated with independent data.

A randomized control trial completed in the Hamilton-Wentworth and Halton regions of Ontario, Canada, was created to assess the effects and expense of age-appropriate provider-initiated and subsidized versus self-directed and self-financed methods of recreation. Upon completion, this study proved that the annual per-person expenditure for the subsidized, quality recreation paid for itself by children's lower use of healthcare and social services. The children within the subsidized recreation group had lower use of physician, physiotherapy, probation, children's aid society, social work, psychologist and services in comparison with those in the non-subsidized group. The subsidized group also proved to be beneficial for the parents as well. The use of health and social services, by the parents in the subsidized group, was also decreased in comparison with those of the self-financed group. This group also proved to have improvement of the global socioeconomic status, with a 10% greater exit from the social assistance program within 1 year.

This study compared the effectiveness of carbohydrate-electrolyte (CHO-E) fluid replacement versus water (WAT) on hydration status, physiological and subjective responses, and exercise performance during a 3 x 60-minute loaded (14 kg) treadmill walk in 35 degrees C ambient temperature and 55% humidity. CHO-E did not affect urine loss, plasma volume change (WAT = -3.0 +/- 1.6% vs. CHO-E = -1.1 +/- 1.6%), dehydration (WAT = 0.4 +/- 0.3% vs. CHO-E = 0.4 +/- 0.3% of body mass), or core body temperature (Tc) and heart rate (HR) responses. Endurance time was greater but not significantly different with CHO-E (WAT = 134 +/- 9 vs. CHO-E = 146 +/- 9 minutes). CHO-E increased the frequency of task completion (WAT = 21% vs. CHO-E = 50%), elevated blood glucose, and reduced perceived exertion. CHO-E offers potential to enhance exercise capacity by elevating blood glucose and thereby preventing hypoglycemia, maintaining high rates of carbohydrate oxidation, and/or preventing central fatigue; but provided no additional benefits with regard to hydration status and physiological function during loaded walking under heat stress.

Aims: The objective of these surveys was to estimate the prevalence of faecal carriage of Salmonella in healthy pigs, cattle and sheep at slaughter, and of pig carcase contamination with Salmonella. These data can be used as a baseline against which future change in Salmonella prevalence in these species at slaughter can be monitored., Methods and Results: In this first randomized National Survey for faecal carriage of Salmonella in slaughter pigs, cattle and sheep in Great Britain, 2509 pigs, 891 cattle and 973 sheep were sampled in 34 pig abattoirs and 117 red meat abattoirs in England, Scotland and Wales. Carriage of Salmonella in 25 g caecal contents was identified in 578 (23.0% pigs) but in only 134 (5.3%) of carcase swabs. The predominant Salmonella serovars found in both types of sample were S. Typhimurium (11.1% caeca, 2.1% carcases) and S. Derby (6.3% caeca, 1.6% carcases). The main definitive phage types (DT) of S. Typhimurium found were DT104 (21.9% of caecal S. Typhimurium isolates), DT193 (18.7%), untypable strains (17.6%), DT208 (13.3%) and U302 (13.3%). Three isolates of S. Enteritidis (PTs 13A and 4) and one enrofloxacin-resistant S. Choleraesuis were also isolated. A positive 'meat-juice ELISA' was obtained from 15.2% of pigs at 40% optical density (O.D.) cut-off level and 35.7% at 10% cut-off. There was poor correlation between positive ELISA results or carcase contamination and the caecal carriage of Salmonella. The ratio of carcase contamination to caecal carriage rates was highest in abattoirs from the midland region of England and in smaller abattoirs. In cattle and sheep 1 g samples of rectal faeces were tested. Two isolates (i.e. 0.2%) were recovered from cattle, one each of S. Typhimurium, DT193 and DT12. One sheep sample (0.1%) contained a Salmonella, S. Typhimurium DT41. In a small subsidiary validation exercise using 25 g of rectal faeces from 174 cattle samples, three (1.7%) isolates of Salmonella (S. Typhimurium DT104, S. Agama, S. Derby) were found., Conclusions: The carriage rate of Salmonella in prime slaughter cattle and sheep in Great Britain was very low compared with pigs. This suggests that future control measures should be focused on reduction of Salmonella infection on pig farms and minimizing contamination of carcases at slaughter., Significance and Impact of the Study: This work has set baseline figures for Salmonella carriage in these species slaughtered for human consumption in Great Britain. These figures were collected in a representative way, which enables them to be used for monitoring trends and setting control targets.

Aims: The objective of this study was to investigate the potential value of individual and combined applications of some GRAS (generally regarded as safe) additives with freezing and pulsed electric field (PEF) application, in reducing the risks associated with the presence of E. coli O157:H7 in beef burgers., Methods and Results: Beef burgers, trimmings and filter paper were inoculated with E. coli O157:H7 and subjected to a range of chemical and physical treatments. Sequential application of 2% (v/v) lactic acid and freezing (at - 20 degrees C for 2 h) resulted in a decrease of approximately 6 log10 cfu cm(-1) in E. coli O157:H7, but only on filter paper. All other treatments were ineffective., Conclusions: Currently available methods for controlling E.coli O157:H7 in beef burgers during production are ineffective., Significance and Impact of the Study: Further research is needed to develop controls for E. coli O157:H7 during beef burger production.

Background: Women and their clinicians are increasingly encouraged to use risk estimates derived from statistical models, primarily that of Gail et al., to aid decision making regarding potential prevention options for breast cancer, including chemoprevention with tamoxifen., Methods: We evaluated both the goodness of fit of the Gail et al. model 2 that predicts the risk of developing invasive breast cancer specifically and its discriminatory accuracy at the individual level in the Nurses' Health Study. We began with a cohort of 82 109 white women aged 45-71 years in 1992 and applied the model of Gail et al. to these women over a 5-year follow-up period to estimate a 5-year risk of invasive breast cancer. All statistical tests were two-sided., Results: The model fit well in the total sample (ratio of expected [E] to observed [O] numbers of cases = 0.94; 95% confidence interval [CI] = 0.89 to 0.99). Underprediction was slightly greater for younger women (<60 years), but in most age and risk factor strata, E/O ratios were close to 1.0. The model fit equally well (E/O ratio = 0.93; 95% CI = 0.87 to 0.99) in a subset of women reporting recent screening (i.e., within 1 year before the baseline); among women with an estimated 5-year risk of developing invasive breast cancer of 1.67% or greater, the E/O ratio was 1.04 (95% CI = 0.96 to 1.12). The concordance statistic, which indicates discriminatory accuracy, for the Gail et al. model 2 when used to estimate 5-year risk was 0.58 (95% CI = 0.56 to 0.60). Only 3.3% of the 1354 cases of breast cancer observed in the cohort arose among women who fell into age-risk strata expected to have statistically significant net health benefits from prophylactic tamoxifen use., Conclusions: The Gail et al. model 2 fit well in this sample in terms of predicting numbers of breast cancer cases in specific risk factor strata but had modest discriminatory accuracy at the individual level. This finding has implications for use of the model in clinical counseling of individual women.

To compare pathologic features of the cancers arising after different types of benign breast disease (BBD), we reviewed the invasive breast cancer slides of 169 women with a previous benign biopsy result. Lesions were categorized previously as nonproliferative, proliferative without atypia, or atypical hyperplasia. Pathologic features of the cancers were evaluated without knowledge of the previous BBD category. Estrogen and progesterone receptor immunohistochemistry was performed on available tissue blocks. The median times between a benign result and cancer were 100, 124, and 92 months for women with nonproliferative lesions, proliferative lesions without atypia, and atypical hyperplasia, respectively. Cancers in the 3 groups did not differ significantly in tumor size, axillary lymph node status, or histologic grade, and there was no significant difference in the distribution of histologic types of breast cancer. Lymphatic vessel invasion, extensive intraductal component, and hormone receptor status did not differ among BBD categories. The pathologic features of breast cancers that develop in women with a previous benign biopsy result do not vary according to the histologic category of the previous BBD.

The metabolic syndrome is associated with a marked increase in risk of type 2 diabetes and atherosclerotic vascular disease (AVD). The mechanism responsible for the metabolic syndrome is uncertain, but recent evidence suggests that a combination of low birth weight and adult obesity is associated with a markedly increased prevalence. Insulin resistance is the cardinal feature of the metabolic syndrome. Several hormones, have modes of action that either potentiate or reduce the biological actions of insulin and, therefore, attenuate or induce insulin resistance. Since insulin action may be modified, these hormones potentially contribute to the pathogenesis of the metabolic syndrome. The purpose of this review is to discuss programming of hormones that modulate insulin action. The review focuses on two major endocrine pathways: (i) glucocorticoid hormone action; and (ii) the growth hormone (GH)-insulin-like growth factor (IGF-1) axis, and discusses mechanisms linking abnormal activity of these pathways with reduced early growth, adult obesity and the metabolic syndrome.

The effect of culture growth phase on induction of the heat shock response in Yersinia enterocolitica and Listeria monocytogenes, was examined. Exponential or stationary preconditioned cultures were heat shocked and survivor numbers estimated using selective and overlay/resuscitation recovery techniques. The results indicate that prior heat shock induced increased heat resistance in both micro-organisms to higher heat treatments. Heat-shocked cells of each micro-organism were able to survive much longer than non-heat-shocked cells when heated at 55 degrees C. The size of the change in heat resistance between heat-shocked and non-heat-shocked cells was greatest for exponential cultures (X:X). Results indicate that the overall relative thermal resistance of each pathogen was dependent on cell growth phase. Stationary cultures (S:S) were significantly (P < 0.01) more thermotolerant than exponential cultures (X:X) under identical processing conditions. Under most conditions, the use of an overlay/resuscitation recovery medium resulted in higher D-values (P < 0.05) compared with a selective recovery medium.

Background: There is conflicting evidence on whether stress is a risk factor for breast cancer. The present study examined prospectively the relationship between stress at work and risk of breast cancer., Methods: Participants comprised 26 936 postmenopausal women in the Nurses' Health Study ages 46-72 who were in paid employment, and who had no previous history of cancer. Multivariate-adjusted regression analysis was used to examine the relationship between job strain (measured by the Karasek Job Content Questionnaire in 1992) and risk of incident invasive and in situ breast cancer., Results: From 1992 through 1994, 219 women were diagnosed with breast cancer. No evidence was found for a relationship between job stress and risk of breast cancer. Compared with women in low strain jobs, the multivariate-adjusted relative risks of breast cancer were RR = 0.78 (95% CI : 0.52-1.16) for high-strain jobs; RR = 0.76 (95% CI : 0.49-1.17) for active jobs; and RR = 0.94 (95% CI : 0.67-1.34) for passive jobs. Although job strain was related to less breast cancer screening among women in highly demanding jobs, it was not associated with tumour size., Conclusions: Job stress was not related to an increase in the incidence of breast cancer in the present cohort of nurses.

Fresh bovine faeces were inoculated with a non-toxigenic, antibiotic resistant strain of Escherichia coli O157:H7, spread on the rump areas of 30 heifers and allowed to dry for 24 h. Ten of the cattle then entered the normal slaughter process without further treatment. The remaining cattle were washed with a powerhose for 1 min (10 animals) and 3 min (10 animals) before entering the normal slaughter process. Both washing treatments removed all visible faecal materials on the live animals although a significant reduction (P < 0.05) in E. coli O157:H7 levels on the hides was only observed on those animals which were powerhosed for 3 min. After slaughter, E. coli O157:H7 was detected on carcasses and on the knives and hands of operatives. Preslaughter washing for 3 min did not statistically reduce the numbers of E. coli O157:H7 transferred from the hide to the carcass during slaughter. However, the organism was not detected on three of the four areas of the carcass sampled, indicating that washing may be a suitable method of decontamination animal hides before slaughter and as such deserves further investigation.

The survival characteristics of a non-toxigenic, antibiotic-resistant strain of Escherichia coli O157:H7 in bovine faeces were investigated. Faecal samples were inoculated with 10(8-9) cfu g-1 of the organism and (i) stored in closed plastic containers at 10 degrees C, (ii) stored in closed plastic containers placed outside or (iii) decanted onto the surface of grazing land. Recovery and enumeration on Sorbitol MacConkey Agar (SMAC) and Tryptic Soya Agar (TSA) revealed that the E. coli O157:H7 numbers in both enclosed samples (i and ii) had decreased by 4.5-5.5 log10 cfu g-1 within 99 d. Numbers in samples decanted onto grassland (iii) decreased by 4.0-5.0 log10 cfu g-1 within 50 d but the organism was still detectable in the surrounding soil for up to 99 d. Persistence of E. coli O157:H7 in bovine faeces and contaminated pastures may therefore be an important factor in the initial infection and re-infection of cattle.