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Objectives: We undertook time-stratified analyses of the National Health and Nutrition Examination Survey in the US to assess time trends (1999-2020) in the associations of blood lead (BL) with blood pressure, mortality, the BL-associated population attributable fraction (PAF)., Methods: Vital status of participants, 20-79 years old at enrolment, was ascertained via the National Death Index. Regressions, mediation analyses and PAF were multivariable adjusted and standardized to 2020 US Census data., Results: In time-stratified analyses, BL decreased from 1.76 μg/dl in 1999-2004 to 0.93 μg/dl in 2017-2020, while the proportion of individuals with BL < 1 μg/dl increased from 19.2% to 63.0%. Total mortality was unrelated to BL (hazard ratio (HR) for a fourfold BL increment: 1.05 [95% confidence interval, CI: 0.93-1.17]). The HR for cardiovascular death was 1.44 (1.01-2.07) in the 1999-2000 cycle, but lost significance thereafter. BL was directly related to cardiovascular mortality, whereas the indirect BL pathway via BP was not significant. Low socioeconomic status (SES) was directly related to BL and cardiovascular mortality, but the indirect SES pathway via BL lost significance in 2007-2010. From 1999-2004 to 2017-2020, cardiovascular PAF decreased ( P  < 0.001) from 7.80% (0.17-14.4%) to 2.50% (0.05-4.68%) and number of lead-attributable cardiovascular deaths from 53 878 (1167-99 253) to 7539 (160-14 108)., Conclusion: Due to implementation of strict environmental policies, lead exposure is no longer associated with total mortality, and the mildly increased cardiovascular mortality is not associated with blood lead via blood pressure in the United States., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Gluteal augmentation with autologous fat grafting, colloquially referred to as Brazilian butt lift (BBL), is an increasingly common procedure with a highly reported complication profile., Objectives: In this study we aimed to analyze the prevalence and characteristics of complications that accompanied these surgeries at ambulatory surgery facilities., Methods: Adults patients who experienced fat grafting complications from 2019 to 2021 were identified in QUAD A, formerly known as the American Association for Accreditation of Ambulatory Surgery Facilities (AAAASF, Highland Park, IL, USA), database. Patients and complications were analyzed based on sociodemographic, surgery-, and facility-specific variables with descriptive statistics and logistic regression., Results: Overall, 436 fat grafting procedures with complications were reported to QUAD A, with an overall complication rate of 0.94%. Of these complications, 164 (37.6%) were confirmed to be from gluteal augmentation procedures. Notably, the number of gluteal augmentation with fat grafting complications decreased from the year 2019 (48) to 2020 (36), then nearly doubled from 2020 to 2021 (69). The majority of patients were female (96.7%), with a mean age of 42.0 years and a mean BMI of 28.3 kg/m2. Wound infection was the most commonly documented complication (22.3%). Of the patients who experienced complications, 35.9% presented to a hospital for their complications and 12.6% required reoperation. Four deaths were described. There was no association between sociodemographic or surgical variables and increased odds of readmission or reoperation (P > .05), except for increasing surgeon number and reoperation (P = .02)., Conclusions: Gluteal augmentation accounts for a large proportion of complications from fat grafting procedures. Increased reporting requirements may aid in future determination of incidences of complications and improve patient safety., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To introduce 2 R-packages that facilitate conducting health economics research on OMOP-based data networks, aiming to standardize and improve the reproducibility, transparency, and transferability of health economic models., Materials and Methods: We developed the software tools and demonstrated their utility by replicating a UK-based heart failure data analysis across 5 different international databases from Estonia, Spain, Serbia, and the United States., Results: We examined treatment trajectories of 47 163 patients. The overall incremental cost-effectiveness ratio (ICER) for telemonitoring relative to standard of care was 57 472 €/QALY. Country-specific ICERs were 60 312 €/QALY in Estonia, 58 096 €/QALY in Spain, 40 372 €/QALY in Serbia, and 90 893 €/QALY in the US, which surpassed the established willingness-to-pay thresholds., Discussion: Currently, the cost-effectiveness analysis lacks standard tools, is performed in ad-hoc manner, and relies heavily on published information that might not be specific for local circumstances. Published results often exhibit a narrow focus, central to a single site, and provide only partial decision criteria, limiting their generalizability and comprehensive utility., Conclusion: We created 2 R-packages to pioneer cost-effectiveness analysis in OMOP CDM data networks. The first manages state definitions and database interaction, while the second focuses on Markov model learning and profile synthesis. We demonstrated their utility in a multisite heart failure study, comparing telemonitoring and standard care, finding telemonitoring not cost-effective., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Ventricular tachycardia (VT) and ventricular fibrillation (VF) are life-threatening conditions and can be refractory to conventional drug and device interventions. Stellate ganglion blockade (SGB) has been described as an adjunct, temporizing intervention in patients with refractory ventricular arrhythmia. We examined the association of SGB with VT/VF in a multicenter registry., Objectives: This study examined the efficacy of SGB for treatment/temporization of refractory VT/VF., Methods: The authors present the first analysis from a multicenter registry of patients treated for refractory ventricular arrhythmia at a clinical site in the Czech Republic and the United States. Data were collected between 2016 and 2022. SGB was performed at the bedside by anesthesiologists and/or cardiologists. Outcomes of interest were VT/VF burden and defibrillations at 24 hours before and after SGB., Results: In total, there were 117 patients with refractory ventricular arrhythmias treated with SGB at Duke (n = 49) and the Institute for Clinical and Experimental Medicine (n = 68). The majority of patients were male (94.0%), were White (87.2%), and had an implantable cardioverter-defibrillator (70.1%). The most common etiology of heart disease was ischemic cardiomyopathy (52.1%), and monomorphic VT was the most common morphology (70.1%). Within 24 hours before SGB (0-24 hours), the median episodes of VT/VF were 7.5 (Q1-Q3: 3.0-27.0), and 24 hours after SGB, the median decreased to 1.0 (Q1-Q3: 0.0-4.5; P < 0.001). At 24 hours before SGB, the median defibrillation events were 2.0 (Q1-Q3: 0.0-8.0), and 24 hours after SGB, the median decreased to 0.0 (Q1-Q3: 0.0-1.0; P < 0.001)., Conclusions: In the largest cohort of patients with treatment-refractory ventricular arrhythmia, we demonstrate that SGB use was associated with a reduction in the ventricular arrhythmia burden and need for defibrillation therapy., Competing Interests: Funding Support and Author Disclosures Dr Piccini is a consultant for Abbott, Biotronik, Boston Scientific, Medtronic, and Philips; has received grants for clinical research from Abbott, the American Heart Association, Boston Scientific, and Philips; and is supported by R01AG074185 from the National Institutes of Aging. Dr Fudim has been supported by the American Heart Association (20IPA35310955), Doris Duke, and Bodyport and has received consulting fees from Abbott, Boston Scientific, Presidio, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

Objective: The objective of this study was to evaluate trends, qualifications, race/ethnicity, and gender of applicants to integrated cardiothoracic (CT I-6) residency programs and compare them with other competitive surgical subspecialties., Methods: Data were collected from the National Residency Matching Program, Electronic Residency Application Service, and Association of American Medical Colleges for thoracic surgery, orthopedic surgery, neurological surgery, otolaryngology (ENT), plastic surgery, and vascular surgery for 2010 t0 2020. Applicant gender, race/ethnicity, Alpha Omega Alpha (AOA) membership, United States Medical Licensing Examination scores, research productivity, and graduation from a top-40 medical school were analyzed., Results: From 2010 to 2020, CT I-6 experienced growth in postgraduate year 1 positions (280.0%), total applicants (62.2%), and US senior applicants (59.2%). No growth in CT I-6 positions (38) or programs (29) occurred from 2016 to 2020. CT I-6 had the lowest match rates among total applicants (31.7%) and US seniors (41.0%) in 2020. CT I-6 had fewer female applicants compared with ENT (P < .001) and plastic surgery (P < .001), but more than orthopedic surgery (P < .001). Although most CT I-6 US applicants self-identified as White (75.0%), there were more Asian applicants compared with applicants for orthopedic surgery (P < .001), ENT (P < .001), plastic surgery (P < .001), and neurological surgery (P < .01). Matched applicants averaged the highest Step 2-Clinical Knowledge scores (255.1), AOA membership (48.5%), and graduation rates from top-40 medical schools (54.5%)., Conclusions: Despite tremendous growth in positions, CT I-6 has consistently been the most difficult surgical subspecialty to match. CT I-6 has recently attracted an increasingly diverse applicant pool. For the 2019 to 2020 National Residency Matching Program Match Cycle, successful applicants had the highest Step 2-Clinical Knowledge scores, AOA membership rates, and graduation rates from a top-40 medical school among all surgical subspecialties examined., (Copyright © 2022 The American Association for Thoracic Surgery. All rights reserved.)

Marie Skłodowska-Curie Symposia on Cancer Research and Care (MSCS-CRC) promote collaborations between cancer researchers and care providers in the United States, Canada and Central and Eastern European Countries (CEEC), to accelerate the development of new cancer therapies, advance early detection and prevention, increase cancer awareness, and improve cancer care and the quality of life of patients and their families. The third edition of MSCS-CRC, held at Roswell Park Comprehensive Cancer Center, Buffalo, NY, in September 2023, brought together 137 participants from 20 academic institutions in the US, Poland, Ukraine, Lithuania, Croatia and Hungary, together with 16 biotech and pharma entities. The key areas of collaborative opportunity identified during the meeting are a) creating of a database of available collaborative projects in the areas of early-phase clinical trials, preclinical development, and identification of early biomarkers; b) promoting awareness of cancer risks and efforts at cancer prevention; c) laboratory and clinical training; and d) sharing experience in cost-effective delivery of cancer care and improving the quality of life of cancer patients and their families. Examples of ongoing international collaborations in the above areas were discussed. Participation of the representatives of the Warsaw-based Medical Research Agency, National Cancer Institute (NCI) of the United States, National Cancer Research Institutes of Poland and Lithuania, New York State Empire State Development, Ministry of Health of Ukraine and Translational Research Cancer Center Consortium of 13 cancer centers from the US and Canada, facilitated the discussion of available governmental and non-governmental funding initiatives in the above areas.

Background: The European Association of Endoscopic Surgery (EAES) fellowship programme was established in 2014, allowing nine surgeons annually to obtain experience and skills in minimally invasive surgery (MIS) from specialist centres across the Europe and United States. It aligns with the strategic focus of EAES Education and Training Committee on enabling Learning Mobility opportunities. To assess the impact of the programme, a survey was conducted aiming to evaluate the experience and impact of the programme and receive feedback for improvements., Methods: A survey using a 5-point Likert scale was used to evaluate clinical, education and research experience. The impact on acquisition of new technical skills, change in clinical practice and ongoing collaboration with the host institute was assessed. The fellows selected between 2014 and 2018 were included. Ratings were analysed in percentage; thematic analysis was applied to the free-text feedbacks using qualitative analysis., Results: All the fellows had good access to observing in operating theatres and 70.6% were able to assist. 91.2% participated in educational activities and 23.5% were able to contribute through teaching. 44.1% participated in research activities and 41.2% became an author/co-author of a publication from the host. 97.1% of fellows stated that their operative competency had increased, 94.3% gained new surgical skills and 85.7% was able to introduce new techniques in their hospitals. 74.29% agreed that the clinical experience led to a change in their practices. The most commonly suggested improvements were setting realistic target in clinical and research areas, increasing fellowship duration, and maximising theatre assisting opportunities. Nevertheless, 100% of fellows would recommend the fellowship to their peers., Conclusion: EAES fellowship programme has shown a positive impact on acquiring and adopting new MIS techniques. To further refine the programme, an individualised approach should be adopted to set achievable learning objectives in clinical skills, education and research., (© 2021. The Author(s).)

Obesity is a chronic disease associated with increased metabolic and cardiovascular risk, excessive morbidity and mortality worldwide. The authors of the present consensus, clinicians representing medical specialties related to the treatment of obesity and its complications, reviewed a number of European and American guidelines, published mostly in 2019-2021, and summarized the principles of obesity management to provide a practical guidance considering the impact that increased adiposity poses to health. From a clinical perspective, the primary goal of obesity treatment is to prevent or slow down the progression of diseases associated with obesity, reduce metabolic and cardiovascular risk, and improve the quality of life by achieving adequate and stable weight reduction. However, obesity should be not only considered a disease requiring treatment in an individual patient, but also a civilization disease requiring preventive measures at the populational level. Despite the evident benefits, obesity management within the health care system-whether through pharmacotherapy or bariatric surgery-is only a symptomatic treatment, with all its limitations, and will not ultimately solve the problem of obesity. The important message is that available treatment options fail to correct the true drivers of the obesity pandemic. To this end, new solutions and efforts to prevent obesity in the populations are needed.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women and a major cause of anovulatory infertility. A diagnosis of PCOS is established based the presence of two out of three clinical symptoms, which are criteria accepted by the ESHRE/ASRM (European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine). Gonadotropin-releasing hormone (GnRH) is responsible for the release of luteinizing hormone, and follicle stimulating hormone from the pituitary and contributes a leading role in controlling reproductive function in humans. The goal of this review is to present the current knowledge on neuroendocrine determinations of PCOS. The role of such neurohormones as GnRH, and neuropeptides kisspeptin, neurokinin B, phoenixin-14, and galanin is discussed in this aspect. Additionally, different neurotransmitters (gamma-aminobutyric acid (GABA), glutamate, serotonin, dopamine, and acetylcholine) can also be involved in neuroendocrine etiopathogenesis of PCOS. Studies have shown a persistent rapid GnRH pulse frequency in women with PCOS present during the whole ovulatory cycle. Other studies have proved that patients with PCOS are characterized by higher serum kisspeptin levels. The observations of elevated serum kisspeptin levels in PCOS correspond with the hypothesis that overactivity in the kisspeptin system is responsible for hypothalamic-pituitary-gonadal axis overactivity. In turn, this causes menstrual disorders, hyperandrogenemia and hyperandrogenism. Moreover, abnormal regulation of Neurokinin B (NKB) is also suspected of contributing to PCOS development, while NKB antagonists are used in the treatment of PCOS leading to reduction in Luteinizing hormone (LH) concentration and total testosterone concentration. GnRH secretion is regulated not only by kisspeptin and neurokinin B, but also by other neurohormones, such as phoenixin-14, galanin, and Glucagon-like peptide-1 (GLP-1), that have favorable effects in counteracting the progress of PCOS. A similar process is associated with the neurotransmitters such as GABA, glutamate, serotonin, dopamine, and acetylcholine, as well as the opioid system, which may interfere with secretion of GnRH, and therefore, influence the development and severity of symptoms in PCOS patients. Additional studies are required to explain entire, real mechanisms responsible for PCOS neuroendocrine background.

Importance: Emergency departments (EDs) are increasingly initiating treatment for patients with untreated opioid use disorder (OUD) and linking them to ongoing addiction care. To our knowledge, patient perspectives related to their ED visit have not been characterized and may influence their access to and interest in OUD treatment., Objective: To assess the experiences and perspectives regarding ED-initiated health care and OUD treatment among US patients with untreated OUD seen in the ED., Design, Setting, and Participants: This qualitative study, conducted as part of 2 studies (Project ED Health and ED-CONNECT), included individuals with untreated OUD who were recruited during an ED visit in EDs at 4 urban academic centers, 1 public safety net hospital, and 1 rural critical access hospital in 5 disparate US regions. Focus groups were conducted between June 2018 and January 2019., Main Outcomes and Measures: Data collection and thematic analysis were grounded in the Promoting Action on Research Implementation in Health Services (PARIHS) implementation science framework with evidence (perspectives on ED care), context (ED), and facilitation (what is needed to promote change) elements., Results: A total of 31 individuals (mean [SD] age, 43.4 [11.0] years) participated in 6 focus groups. Twenty participants (64.5%) identified as male and most 13 (41.9%) as White; 17 (54.8%) reported being unemployed. Themes related to evidence included patients' experience of stigma and perceived minimization of their pain and medical problems by ED staff. Themes about context included the ED not being seen as a source of OUD treatment initiation and patient readiness to initiate treatment being multifaceted, time sensitive, and related to internal and external patient factors. Themes related to facilitation of improved care of patients with OUD seen in the ED included a need for on-demand treatment and ED staff training., Conclusions and Relevance: In this qualitative study, patients with OUD reported feeling stigmatized and minimized when accessing care in the ED and identified several opportunities to improve care. The findings suggest that strategies to address stigma, acknowledge and treat pain, and provide ED staff training should be implemented to improve ED care for patients with OUD and enhance access to life-saving treatment.

Background: Despite the advancement of electrocardiogram (ECG) monitoring methods, the most important factor influencing diagnostic yield (DY) may still be monitoring duration. Ambulatory ECG monitoring, typically with 24-48 hours duration, is widely used but may result in underdiagnosis of rare arrhythmias., Aims: This study aimed to examine the relationship between the DY and monitoring duration in a large patient cohort and investigate sex and age differences in the presentation of arrhythmias., Methods: The study population consisted of 25 151 patients (57.8% women; median [interquartile range, IQR], 71 [64-78] years), who were examined with mobile cardiac telemetry during 2017 in the United States, using the PocketECGTM that continuously transmits a signal on a beat-to-beat basis. We investigated the occurrence of atrial fibrillation at a burden of both ≤1% (atrial fibrillation [AF], ≤1%) and ≤10% (AF ≤10%), premature ventricular contractions (PVC; >10 000 per 24 hours), non-sustained ventricular tachycardias (nsVT), sustained ventricular tachycardias (VT ≥30 seconds), atrioventricular blocks (AVB), pauses of >3 seconds duration, and bradycardia (heart rate <40 beats per minute for ≥60 seconds)., Results: The median (IQR) recording duration was 15.4, 8.2-28.2) days. The DY increased gradually with monitoring duration for all types of investigated arrhythmias. Compared to DY after up to 30 days of monitoring, a standard 24 hours monitoring resulted in DY for males/females of 20%/18% for AF ≤1%, 29%/28% for AF ≤10%, 45%/40% for PVCs, 17%/11% for nsVT, 17%/11% for VT ≥30 seconds, 49%/42 for AVB, 27%/20% for pauses, 36%/29% for bradycardia., Conclusion: A substantial number of patients suffering from arrhythmias may remain undiagnosed due to insufficient ECG monitoring time.

In collaboration with the American College of Veterinary Pathologists.

Following the emergency use authorization of the mRNA-1273 vaccine on the 18 th of December 2020, two mRNA vaccines are in current use for the prevention of coronavirus disease 2019 (COVID-19). For both mRNA vaccines, the phase III pivotal trials excluded individuals with a history of allergy to vaccine components. Immediately after the initiation of vaccination in the United Kingdom, Canada, and the United States, anaphylactic reactions were reported. While the culprit trigger requires investigation, initial reports suggested the excipient polyethylene glycol 2000 (PEG-2000)-contained in both vaccines as the PEG-micellar carrier system-as the potential culprit. Surface PEG chains form a hydrate shell to increase stability and prevent opsonization. Allergic reactions to such PEGylated lipids can be IgE-mediated, but may also result from complement activation-related pseudoallergy (CARPA) that has been described in similar liposomes. In addition, mRNA-1273 also contains tromethamine (trometamol), which has been reported to cause anaphylaxis to substances such as gadolinium-based contrast media. Skin prick, intradermal and epicutaneous tests, in vitro sIgE assessment, evaluation of sIgG/IgM, and basophil activation tests are being used to demonstrate allergic reactions to various components of the vaccines., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objective: We sought to explore the technical and legal readiness of healthcare institutions for novel data-sharing methods that allow clinical information to be extracted from electronic health records (EHRs) and submitted securely to the Food and Drug Administration's (FDA's) blockchain through a secure data broker (SDB)., Materials and Methods: This assessment was divided into four sections: an institutional EHR readiness assessment, legal consultation, institutional review board application submission, and a test of healthcare data transmission over a blockchain infrastructure., Results: All participating institutions reported the ability to electronically extract data from EHRs for research. Formal legal agreements were deemed unnecessary to the project but would be needed in future tests of real patient data exchange. Data transmission to the FDA blockchain met the success criteria of data connection from within the four institutions' firewalls, externally to the FDA blockchain via a SDB., Discussion: The readiness survey indicated advanced analytic capability in hospital institutions and highlighted inconsistency in Fast Healthcare Interoperability Resources format utilitzation across institutions, despite requirements of the 21st Century Cures Act. Further testing across more institutions and annual exercises leveraging the application of data exchange over a blockchain infrastructure are recommended actions for determining the feasibility of this approach during a public health emergency and broaden the understanding of technical requirements for multisite data extraction., Conclusion: The FDA's RAPID (Real-Time Application for Portable Interactive Devices) program, in collaboration with Discovery, the Critical Care Research Network's PREP (Program for Resilience and Emergency Preparedness), identified the technical and legal challenges and requirements for rapid data exchange to a government entity using the FDA blockchain infrastructure., (© Copyright AAMI 2021. Copying, networking, and distribution prohibited.)

The security of the Internet of Things (IoT) is a very important aspect of everyday life for people and industries, as well as hospitals, military, households and cities. Unfortunately, this topic is still too little researched and developed, which results in exposing users of Internet of Things to possible threats. One of the areas which should be addressed is the creation of a database of information about vulnerabilities and exploits in the Internet of Things; therefore, the goal of our activities under the VARIoT (Vulnerability and Attack Repository for IoT) project is to develop such a database and make it publicly available. The article presents the results of our research aimed at building this database, i.e., how the information about vulnerabilities is obtained, standardized, aggregated and correlated as well as the way of enhancing and selecting IoT related data. We have obtained and proved that existing databases provide various scopes of information and because of that a single and most comprehensive source of information does not exist. In addition, various sources present information about a vulnerability at different times-some of them are faster than others, and the differences in publication dates are significant. The results of our research show that aggregation of information from various sources can be very beneficial and has potential to enhance actionable value of information. We have also shown that introducing more sophisticated concepts, such as trust management and metainformation extraction based on artificial intelligence, could ensure a higher level of completeness of information as well as evaluate the usefulness and reliability of data.

Mastocytosis is a neoplasm characterized by an accumulation of mast cells in various organs and increased risk for severe anaphylaxis in patients with concomitant allergies. Coronavirus disease 2019 (COVID-19) is a pandemic that is associated with a relatively high rate of severe lung disease and mortality. The mortality is particularly high in those with certain comorbidities and increases with age. Recently, several companies have developed an effective vaccination against COVID-19. Although the reported frequency of severe side effects is low, there is an emerging discussion about the safety of COVID-19 vaccination in patients with severe allergies and mastocytosis. However, even in these patients, severe adverse reactions are rare. We therefore recommend the broad use of COVID-19 vaccination in patients with mastocytosis on a global basis. The only well-established exception is a known or suspected allergy against a constituent of the vaccine. Safety measures, including premedication and postvaccination observation, should be considered in all patients with mastocytosis, depending on the individual personal risk and overall situation in each case. The current article provides a summary of published data, observations, and expert opinion that form the basis of these recommendations., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Countries worldwide have adopted various strategies to minimize the socio-economic impact of the ongoing COVID-19 pandemic. Stringency of imposed measures universally reflects the standpoint from which protecting public health and avoiding damage to economy are seen as contradictory objectives. Based on epidemic trajectories of 25 highly developed countries and 10 US states in the (mobility reduction)-(reproduction number) plane we showed that delay in imposition of nation-wide quarantine elevates the number of infections and deaths, surge of which inevitably has to be suppressed by stringent and sustained lockdown. As a consequence, cumulative mobility reduction and population-normalized cumulative number of COVID-19-associated deaths are significantly correlated and this correlation increases with time. Overall, we demonstrated that, as long as epidemic suppression is the aim, the trade-off between the death toll and economic loss is illusory: high death toll correlates with deep and long-lasting lockdown causing a severe economic downturn.

Childhood obesity is one of the most serious public health problems. The prevalence of obesity among children is increasing and may negatively affect their immediate health, but it can also lead to obesity in adulthood. The aim of the study was to compare BMI cut-off points by examining three main international references: the World Health Organization (WHO), the International Task Force Obesity (IOTF) and the US Center for Disease Control and Prevention (CDC). Ultimately, the study group consisted of 18,144 children and adolescents aged 6.5-17.5 years. Body mass was measured on medical scales with an accuracy of ± 100 g and height measurement was taken using a height meter with an accuracy of ± 0.1 cm three times. Underweight, overweight and obesity were calculated according to WHO, IOTF and CDC BMI international references. There were differences in the incidence of underweight between the classifications: 16.8% according to IATF, 5.3% according to WHO and 9.9% according to CDC. There were also differences in the incidence of overweight and obesity between the classifications: 13% according to IOTF, 19.7% according to WHO and 14.1% according to CDC. In the CDC and WHO studies, a significantly higher prevalence of childhood obesity (4.0% and 4.7%, respectively) was observed compared with IOTF (2.1%). The prevalence of overweight and obesity in this study was higher among boys compared to girls. However, estimates of prevalence of overweight and obesity differ in methods and reference cut-off points. Higher prevalence was obtained in IOTF classification, followed by the WHO and CDC classification., Competing Interests: The authors have declared that no competing interests exist.

Objective: Early survival after lung transplantation has improved in the last decade. Mechanically ventilated recipients are known to be at greater risk for early post-transplant mortality. We hypothesized that post-transplant survival in mechanically ventilated recipients has improved over time., Methods: Using a national registry, we compared hazard of death at 30 days, 4 and 14 months, 3 and 5 years, and overall for adults on mechanical ventilation who underwent lung or heart-lung transplantation from May 4, 2011, to April 4, 2018 (modern group) with those undergoing transplantation from May 4, 2005, to May 3, 2011 (early group). We quantified the impact of mechanical ventilation on survival using population-attributable fractions. We also compared mechanically ventilated recipients with nonmechanically ventilated recipients., Results: Mechanically ventilated recipients from the modern group had lower hazard of death than recipients in the early group at all time-points, lowest at 30-days post-transplant (hazard ratio, 0.04; 95% confidence interval, 0.02-0.08). In the modern period, mechanically ventilated recipients had greater hazard of death than nonmechanically ventilated recipients at 30 days' post-transplant (9.53; 4.57-19.86). For mechanically ventilated recipients, the population attributable fraction was lower in the modern group compared to the earlier group (0.6% vs 5.7%)., Conclusions: While mechanically ventilated recipients remain at high risk, survival in this patient population has improved over time. This may reflect improvements in perioperative recipient management., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To record the definition and management of Very Early Medical Abortion (VEMA) in different countries., Study Design: An Internet survey was circulated internationally among providers of medical abortion via a website. The questionnaire focused on reasons for performing or delaying medical abortion at a very early gestational age and the perceived advantages and disadvantages of VEMA., Results: Out of 220 completed questionnaires, 50 % came from European abortion providers (n = 110). Most respondents (72 %) defined VEMA as abortion performed in the presence of a positive hCG pregnancy test but with an empty uterine cavity or a gestational sac-like structure, and no signs or symptoms of ectopic pregnancy. A total of 74 % of respondents thought it was not necessary to wait for a diagnosis of intrauterine pregnancy before starting medical abortion. Equally, 74 % were aware of the possibility of an ectopic pregnancy., Conclusion: According to European providers of medical abortion, waiting for the diagnosis of an intrauterine pregnancy is not necessary and does not improve treatment of ectopic pregnancy. Providers should know that medical abortion can be performed effectively and safely as soon as the woman has decided. There is no lower gestational age limit., Competing Interests: Declaration of Competing Interest The authors were all members of the external scientific advisory board of Exelgyn at the time of this study. Christian Fiala has served on an ad hoc basis as an invited lecturer for Exelgyn. Aubert Agostini is a board member at Nordic Pharma and MSD, and an investigator for some Nordic Pharma studies. Teresa Bombas is a member of advisory boards for Merck and HRA, has an occasional consultancy relationship with Exelgyn and Nordic, and is a speaker at conferences/symposiums organized by Bayer, Merck, HRA, Gedeon, and Exelgyn. Roberto Lertxundi has a financial relationship (member of advisory boards, lecturer, and/or consultant) with Exelgyn, Nordic-Pharma, Exeltis, Bayer-Pharma, and Teva. Marek Lubusky has an occasional consultancy relationship with Exelgyn and Nordic. Mirella Parachini has an occasional consultancy relationship with Exelgyn and Nordic. Kristina Gemzell-Danielsson has served on an ad hoc basis as an invited lecturer for Exelgyn, Line Pharma, and Gynuity, and as an investigator in clinical trials conducted by Concept Foundation/SunPharma. Laurence Saya is an employee of Altius Pharma CS, and as such was indirectly paid by Exelgyn for help in medical writing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: His-bundle pacing (HBP) provides physiological ventricular activation. Observational studies have demonstrated the techniques' feasibility; however, data have come from a limited number of centers., Objectives: We set out to explore the contemporary global practice in HBP focusing on the learning curve, procedural characteristics, and outcomes., Methods: This is a retrospective, multicenter observational study of patients undergoing attempted HBP at seven centers. Pacing indication, fluoroscopy time, HBP thresholds, and lead reintervention and deactivation rates were recorded. Where centers had systematically recorded implant success rates from the outset, these were collated., Results: A total of 529 patients underwent attempted HBP during the study period (2014-19) with a mean follow-up of 217 ± 303 days. Most implants were for bradycardia indications. In the three centers with the systematic collation of all attempts, the overall implant success rate was 81%, which improved to 87% after completion of 40 cases. All seven centers reported data on successful implants. The mean fluoroscopy time was 11.7 ± 12.0 minutes, the His-bundle capture threshold at implant was 1.4 ± 0.9 V at 0.8 ± 0.3 ms, and it was 1.3 ± 1.2 V at 0.9 ± 0.2 ms at last device check. HBP lead reintervention or deactivation (for lead displacement or rise in threshold) occurred in 7.5% of successful implants. There was evidence of a learning curve: fluoroscopy time and HBP capture threshold reduced with greater experience, plateauing after approximately 30-50 cases., Conclusion: We found that it is feasible to establish a successful HBP program, using the currently available implantation tools. For physicians who are experienced at pacemaker implantation, the steepest part of the learning curve appears to be over the first 30-50 cases., (© 2019 The Authors Journal of Cardiovascular Electrophysiology Published by Wiley Periodicals, Inc.)

Exposome research can improve the understanding of the mechanistic connections between exposures and health to help mitigate adverse health outcomes across the life span. The exposomic approach provides a risk profile instead of single predictors and thus is particularly applicable to allergic diseases and asthma. Under the PRACTALL collaboration between the European Academy of Allergy and Clinical Immunology (EAACI) and the American Academy of Allergy, Asthma, and Immunology (AAAAI), we evaluated the current concepts and the unmet needs on the role of the exposome in allergic diseases and asthma., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Introduction: There is currently a paucity of health utility data describing the consequences of haemophilia and related complications., Aim: To quantify the impact of distinct stages of severity of haemophilia and disease-related complications on health-related quality of life, expressed as health utilities in Europe and the United States., Methods: Nine health state descriptions were developed based on literature review and interviews with haematologists and haemophilia patients. Three descriptions characterized the impact of mild, moderate and severe haemophilia without inhibitors. Six descriptions characterized disease-related complications added to the moderate haemophilia description (arthroscopic synovectomy, prosthetic joint replacement, chronic pain, spontaneous bleed, traumatic bleed and end-stage joint disease). Time trade-off (TTO) interviews were conducted with 100 adults from the general public in the UK, France, Germany, Italy, Sweden and the United States. Mean TTO-derived utility values were expressed on a scale from 0 (death) to 1 (full health)., Results: Utility values obtained for the health states corresponding to mild (0.73-0.86), moderate (0.68-0.76) and severe (0.64-0.71) haemophilia followed the increase in severity. The addition of a complication to the "moderate" state leads to a decrease in the associated utility value. The most severe disutility (0.23-0.36) across all countries was associated with the burden of end-stage joint disease., Conclusions: This study underlines the value that the French, Italian, German, Swedish, United States and UK populations ascribe to the avoidance of disease progression in haemophilia without inhibitors. Improved treatment options hold a potential for important benefits to haemophilia patients., (© 2018 John Wiley & Sons Ltd.)

As part of the American Society of Anesthesiology Brain Health Initiative goal of improving perioperative brain health for older patients, over 30 experts met at the fifth International Perioperative Neurotoxicity Workshop in San Francisco, CA, in May 2016, to discuss best practices for optimizing perioperative brain health in older adults (ie, >65 years of age). The objective of this workshop was to discuss and develop consensus solutions to improve patient management and outcomes and to discuss what older adults should be told (and by whom) about postoperative brain health risks. Thus, the workshop was provider and patient oriented as well as solution focused rather than etiology focused. For those areas in which we determined that there were limited evidence-based recommendations, we identified knowledge gaps and the types of scientific knowledge and investigations needed to direct future best practice. Because concerns about perioperative neurocognitive injury in pediatric patients are already being addressed by the SmartTots initiative, our workshop discussion (and thus this article) focuses specifically on perioperative cognition in older adults. The 2 main perioperative cognitive disorders that have been studied to date are postoperative delirium and cognitive dysfunction. Postoperative delirium is a syndrome of fluctuating changes in attention and level of consciousness that occurs in 20%-40% of patients >60 years of age after major surgery and inpatient hospitalization. Many older surgical patients also develop postoperative cognitive deficits that typically last for weeks to months, thus referred to as postoperative cognitive dysfunction. Because of the heterogeneity of different tools and thresholds used to assess and define these disorders at varying points in time after anesthesia and surgery, a recent article has proposed a new recommended nomenclature for these perioperative neurocognitive disorders. Our discussion about this topic was organized around 4 key issues: preprocedure consent, preoperative cognitive assessment, intraoperative management, and postoperative follow-up. These 4 issues also form the structure of this document. Multiple viewpoints were presented by participants and discussed at this in-person meeting, and the overall group consensus from these discussions was then drafted by a smaller writing group (the 6 primary authors of this article) into this manuscript. Of course, further studies have appeared since the workshop, which the writing group has incorporated where appropriate. All participants from this in-person meeting then had the opportunity to review, edit, and approve this final manuscript; 1 participant did not approve the final manuscript and asked for his/her name to be removed.

Background & Aims: The aim of the study was to evaluate the applicability of the ESPEN 16-category clinical classification of chronic intestinal failure, based on patients' intravenous supplementation (IVS) requirements for energy and fluids, and to evaluate factors associated with those requirements., Methods: ESPEN members were invited to participate through ESPEN Council representatives. Participating centers enrolled adult patients requiring home parenteral nutrition for chronic intestinal failure on March 1st 2015. The following patient data were recorded though a structured database: sex, age, body weight and height, intestinal failure mechanism, underlying disease, IVS volume and energy need., Results: Sixty-five centers from 22 countries enrolled 2919 patients with benign disease. One half of the patients were distributed in 3 categories of the ESPEN clinical classification. 9% of patients required only fluid and electrolyte supplementation. IVS requirement varied considerably according to the pathophysiological mechanism of intestinal failure. Notably, IVS volume requirement represented loss of intestinal function better than IVS energy requirement. A simplified 8 category classification of chronic intestinal failure was devised, based on two types of IVS (either fluid and electrolyte alone or parenteral nutrition admixture containing energy) and four categories of volume., Conclusions: Patients' IVS requirements varied widely, supporting the need for a tool to homogenize patient categorization. This study has devised a novel, simplified eight category IVS classification for chronic intestinal failure that will prove useful in both the clinical and research setting when applied together with the underlying pathophysiological mechanism of the patient's intestinal failure., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Each year, the annual hospitalization rates of traumatic brain injury (TBI) in children in the United States are 57.7 per 100K in the <5 years of age and 23.1 per 100K in the 5-14 years age group. Despite this, little is known about the pathophysiology of TBI in children and how to manage it most effectively. Historically, TBI management has been guided by clinical examination. This has been assisted progressively by clinical imaging, intracranial pressure (ICP) monitoring, and finally a software that can calculate optimal brain physiology. Multimodality monitoring affords clinicians an early indication of secondary insults to the recovering brain including raised ICP and decreased cerebral perfusion pressure. From variables such as ICP and arterial blood pressure, correlations can be drawn to determine parameters of cerebral autoregulation (pressure reactivity index) and "optimal cerebral perfusion pressure" at which the vasculature is most reactive. More recently, significant advances using both direct and near-infrared spectroscopy-derived brain oxygenation plus cerebral microdialysis to drive management have been described. Here in, we provide a perspective on the state-of-the-art techniques recently implemented in clinical practice for pediatric TBI.

Objective: Overall about 10 to 20% of pheochromocytomas/paragangliomas (PHEOs/PGLs) are metastatic, with higher metastatic potential observed in succinate dehydrogenase subunit B/fumarate hydratase (SDHB/FH)-related tumors. Due to the improved availability of biochemical and genetic testing and the frequent use of anatomical/functional imaging, there is currently a higher detection rate of metastatic PHEO/PGL., Methods: A retrospective analysis of 132 patients (27 children, 105 adults) with metastatic PHEO/PGL diagnosed and treated from 2000 to 2014 was conducted., Results: Seventy-seven (58%) males and 55 (42%) females were included; 39 (30%) have died, with no sex preference. Seventy-three (55%) patients had SDHB mutations; 59 (45%) patients had apparently sporadic tumors (AST). SDHB patients had an average age at primary tumor diagnosis of 31 ± 16 years compared to 40 ± 15 years in AST patients (P<.001). The average metastatic interval (MI) decreased with increasing age in both SDHB and AST patients (P = .013 for both). Only 16% of all primary tumors were smaller than 4.5 cm. Eleven percent of patients had biochemically silent disease, more with SDHB. Of SDHB patients, 23% had metastatic tumors at first diagnosis, compared to 15% of AST patients. Five- and 10-year survival rates were significantly better for metastatic AST than SDHB patients (P = .01). Overall survival was significantly different between children and adults (P = .037); this was mostly attributed to the SDHB patients, in whom children had statistically significantly longer survival than adults (P = .006). The deceased patients all died due to the PHEO/PGL and mainly had noradrenergic phenotypes., Conclusion: In children, metastatic PHEOs/PGLs are mainly due to SDHB mutations; in adults they are equally distributed between in SDHB mutations and AST, with better 5- and 10-year survival rates for ASTs. In SDHB patients, children survive longer than adults. Primary metastatic tumors, most presenting as noradrenergic PGLs, are larger than 4.5 cm in >80% of patients. The frequency of metastatic tumors from primary AST increases with age, including a decreased MI compared to SDHB tumors. These results support several recommendations that are summarized in the Discussion.

The search for drugs with anorectic activity, acting within the adrenergic system has attracted the interest of researchers. Partial α2-adrenoceptor agonists might offer the potential for effective and safe treatment of obesity. We compared the effectiveness and safety of α2-adrenoceptor ligands in reducing body mass. We also analyzed if antagonist and partial agonists of α2-adrenoceptor--yohimbine and guanfacine--act similarly, and determined which course of action is connected with anorectic activity. We tested intrinsic activity and effect on the lipolysis of these compounds in cell cultures, evaluated their effect on meal size, body weight in Wistar rats with high-fat diet-induced obesity, and determined their effect on blood pressure, heart rate, lipid profile, spontaneous locomotor activity, core temperature and glucose, as well as glycerol and cortisol levels. Both guanfacine and yohimbine showed anorectic activity. Guanfacine was much more effective than yohimbine. Both significantly reduced the amount of intraperitoneal adipose tissue and had a beneficial effect on lipid profiles. Decreased response of α2A-adrenoceptors and partial stimulation of α2B-receptors seem to be responsible for the anorectic action of guanfacine. The stimulation of α1-adrenoceptors by guanfacine is responsible for cardiovascular side effects but may also be linked with improved anorexic effect. α1-adrenoceptor blockade is connected with the side effects of yohimbine, but it is also associated with the improvement of lipid profiles. Guanfacine has been approved by the Food and Drug Administration (FDA) to treat hypertension and conduct disorder, but as it reduces body weight, it is worth examining its effectiveness and safety in models of obesity.

Objectives: This study sought to test the hypothesis that end-systolic volume (ESV), as a marker of severity of left ventricular (LV) remodeling, influences the relationship between myocardial viability and survival in patients with coronary artery disease and LV systolic dysfunction., Background: Retrospective studies of ischemic LV dysfunction suggest that the severity of LV remodeling determines whether myocardial viability predicts improved survival with surgical compared with medical therapy, with coronary artery bypass grafting (CABG) only benefitting patients with viable myocardium who have smaller ESV. However, this has not been tested prospectively., Methods: Interactions of end-systolic volume index (ESVI), myocardial viability, and treatment with respect to survival were assessed in patients in the prospective randomized STICH (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease) trial of CABG versus medical therapy who underwent viability assessment (n = 601; age 61 ± 9 years; ejection fraction ≤35%), with a median follow-up of 5.1 years. Median ESVI was 84 ml/m(2). Viability was assessed by single-photon emission computed tomography or dobutamine echocardiography using pre-specified criteria., Results: Mortality was highest among patients with larger ESVI and nonviability (p < 0.001), but no interaction was observed between ESVI, viability status, and treatment assignment (p = 0.491). Specifically, the effect of CABG versus medical therapy in patients with viable myocardium and ESVI ≤84 ml/m(2) (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.56 to 1.29) was no different than in patients with viability and ESVI >84 ml/m(2) (HR: 0.87; 95% CI: 0.57 to 1.31). Other ESVI thresholds yielded similar results, including ESVI ≤60 ml/m(2) (HR: 0.87; 95% CI: 0.44 to 1.74). ESVI and viability assessed as continuous rather than dichotomous variables yielded similar results (p = 0.562)., Conclusions: Among patients with ischemic cardiomyopathy, those with greater LV ESVI and no substantial viability had worse prognosis. However, the effect of CABG relative to medical therapy was not differentially influenced by the combination of these 2 factors. Lower ESVI did not identify patients in whom myocardial viability predicted better outcome with CABG relative to medical therapy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Recreational waters contaminated with human fecal pollution are a public health concern, and ensuring the safety of recreational waters for public use is a priority of both the Environmental Protection Agency (EPA) and the Centers for Disease Control and Prevention (CDC). Current recreational water standards rely on fecal indicator bacteria (FIB) levels as indicators of human disease risk. However present evidence indicates that levels of FIB do not always correspond to the presence of other potentially harmful organisms, such as viruses. Thus, enteric viruses are currently tested as water quality indicators, but have yet to be successfully implemented in routine monitoring of water quality. This study utilized enteric viruses as possible alternative indicators of water quality to examine 18 different fresh and offshore recreational waters on O'ahu, Hawai'i, by using newly established laboratory techniques including highly optimized PCR, real time PCR, and viral infectivity assays. All sample sites were detected positive for human enteric viruses by PCR including enterovirus, norovirus genogroups I and II, and male specific FRNA coliphage. A six time-point seasonal study of enteric virus presence indicated significant variation in virus detection between the rainy and dry seasons. Quantitative PCR detected the presence of norovirus genogroup II at levels at which disease risk may occur, and there was no correlation found between enteric virus presence and FIB counts. Under the present laboratory conditions, no infectious viruses were detected from the samples PCR-positive for enteric viruses. These data emphasize both the need for additional indicators for improved monitoring of water quality, and the feasibility of using enteric viruses as these indicators.

Background and Objectives: Despite advances in therapy, HIV-infected individuals remain at higher risk for kidney dysfunction than uninfected individuals. It was hypothesized that urine levels of α1-microglobulin, a biomarker of proximal tubular dysfunction, would predict kidney function decline and mortality risk in HIV-infected and uninfected women., Design, Setting, Participants, & Measurements: In the Women's Interagency HIV Study, urine α1-microglobulin and creatinine concentrations were measured in 903 HIV-infected and 287 uninfected women using stored urine from 1999 to 2000, when prevalence of tenofovir use was <1%. Participants were categorized into three categories by level of α1-microglobulin-to-creatinine ratio, and associations with kidney decline and all-cause mortality over 8 years were evaluated., Results: Urine α1-microglobulin was detectable in 60% of HIV-infected and 40% of uninfected women (P<0.001). Among HIV-infected women, there were 177 (22%), 61 (7%), and 128 (14%) patients with incident CKD, with 10% annual eGFR decline, and who died, respectively. Compared with HIV-infected women in the lowest α1-microglobulin category, HIV-infected women in the highest α1-microglobulin category had a 2.1-fold risk of incident CKD (95% confidence interval, 1.3 to 3.4), 2.7-fold risk of 10% annual eGFR decline (95% confidence interval, 1.2 to 5.9), and 1.6-fold mortality risk (95% confidence interval, 1.0 to 2.6) in models adjusting for kidney risk factors, baseline eGFR, and albuminuria. Among uninfected women, the highest α1-microglobulin category was associated with 3% (relative risk, 2.2; 95% confidence interval, 1.4 to 3.5) and 5% (relative risk, 2.2; 95% confidence interval, 1.1 to 4.3) annual eGFR decline relative to the lowest α1-microglobulin category., Conclusions: Proximal tubular dysfunction, indicated by urine α1-microglobulin, was independently associated with kidney function decline in HIV-infected and uninfected women and mortality risk among HIV-infected women., (Copyright © 2015 by the American Society of Nephrology.)

Objectives: To determine the factors associated with weapon carrying in school among Czech, Russian, and US adolescents., Methods: Logistic regression was used to analyze data drawn from the Social and Health Assessment (SAHA)., Results: Violent behavior (perpetration / victimization) was linked to adolescent weapon carrying in all countries. Substance use was associated with weapon carrying among boys in all countries. Greater parental warmth reduced the odds for weapon carrying among Czech and Russian adolescents. Associating with delinquent peers was important for weapon carrying only among US adolescents., Conclusions: Factors associated with weapon carrying in school vary among countries although violent behavior and substance use may be associated with weapon carrying across countries.

: In HIV negatives, markers of hemostasis, including D-dimer, factor VIII, plasminogen activator inhibitor-1 antigen (PAI-1), and total protein S are associated with all-cause and cardiovascular disease mortality. In HIV positives, studies of D-dimer and factor VIII with death were limited to short follow-up; associations of PAI-1 and total protein S with death have not been examined. In 674 HIV-infected women from the Women's Interagency HIV Study, markers from the first visit after enrollment were exposures of interest in multivariate analyses of death (AIDS and non-AIDS) in separate models at 5 and 16 years. There were 87 AIDS and 44 non-AIDS deaths at 5 years, and 159 AIDS and 113 non-AIDS deaths at 16 years. An inverse association of total protein S quartiles with non-AIDS deaths was observed at 5 (P trend = 0.002) and 16 years (P trend = 0.02); there was no association with AIDS deaths. The third quartile of PAI-1 was associated with AIDS deaths at 5 [hazard ratio (HR) = 4.0; 95% confidence interval (CI): 1.9 to 8.4] and 16 years (HR = 3.4; 95% CI: 1.9 to 5.9); and with non-AIDS deaths at 5 years (HR = 4.8; 95% CI: 1.6 to 13.9). D-dimer and factor VIII were not associated with AIDS or non-AIDS death at 5 or 16 years. Lower total Protein S was a consistent marker of non-AIDS death. We found no association between D-dimer with AIDS or non-AIDS death, in contrast to previous studies showing increased short-term (<5 years) mortality, which may represent sex differences or population heterogeneity. Given longer survival on highly active antiretroviral therapy, further studies of these markers are needed to determine their prognostic value.

Background & Aims: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in combination with cytopathology is the optimal method for diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) and other pancreatic lesions. Its clinical utility, however, can be limited by high rates of indeterminate or false-negative results. We aimed to develop and validate a microRNA (miRNA)-based test to improve preoperative detection of PDAC., Methods: Levels of miRNAs were analyzed in a centralized clinical laboratory by relative quantitative polymerase chain reaction in 95 formalin-fixed paraffin-embedded specimens and 228 samples collected by EUS-FNA during routine evaluations of patients with solid pancreatic masses at 4 institutions in the United States, 1 in Canada, and 1 in Poland., Results: We developed a 5-miRNA expression classifier, consisting of MIR24, MIR130B, MIR135B, MIR148A, and MIR196, that could identify PDAC in well-characterized, formalin-fixed, paraffin-embedded specimens. Detection of PDAC in EUS-FNA samples increased from 78.8% by cytology analysis alone (95% confidence interval, 72.2%-84.5%) to 90.8% when combined with miRNA analysis (95% confidence interval, 85.6%-94.5%). The miRNA classifier correctly identified 22 additional true PDAC cases among 39 samples initially classified as benign, indeterminate, or nondiagnostic by cytology. Cytology and miRNA test results each were associated significantly with PDAC (P < .001), with positive predictive values greater than 99% (95% confidence interval, 96%-100%)., Conclusions: We developed and validated a 5-miRNA classifier that can accurately predict which preoperative pancreatic EUS-FNA specimens contain PDAC. This test might aid in the diagnosis of pancreatic cancer by reducing the number of FNAs without a definitive adenocarcinoma diagnosis, thereby reducing the number of repeat EUS-FNA procedures., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Serum albumin concentrations are a strong predictor of mortality and cardiovascular disease in human immunodeficiency virus (HIV)-infected individuals. We studied the longitudinal associations between serum albumin levels and kidney function decline in a population of HIV-infected women., Study Design: Retrospective cohort analysis., Setting & Participants: Study participants were recruited from the Women's Interagency HIV Study (WIHS), a large observational study designed to understand risk factors for the progression of HIV infection in women living in urban communities. 908 participants had baseline assessment of kidney function and 2 follow-up measurements over an average of 8 years., Predictor: The primary predictor was serum albumin concentration., Outcomes: We examined annual change in kidney function. Secondary outcomes included rapid kidney function decline and incident reduced estimated glomerular filtration rate (eGFR)., Measurements: Kidney function decline was determined by cystatin C-based (eGFR(cys)) and creatinine-based eGFR (eGFR(cr)) at baseline and follow-up. Each model was adjusted for kidney disease and HIV-related risk factors using linear and relative risk regression., Results: After multivariate adjustment, each 0.5-g/dL decrement in baseline serum albumin concentration was associated with a 0.56-mL/min faster annual decline in eGFR(cys) (P < 0.001), which was attenuated only slightly to 0.55 mL/min/1.73 m(2) after adjustment for albuminuria. Results were similar whether using eGFR(cys) or eGFR(cr). In adjusted analyses, each 0.5-g/dL lower baseline serum albumin level was associated with a 1.71-fold greater risk of rapid kidney function decline (P < 0.001) and a 1.72-fold greater risk of incident reduced eGFR (P < 0.001)., Limitations: The cohort is composed of only female participants from urban communities within the United States., Conclusions: Lower serum albumin levels were associated strongly with kidney function decline and incident reduced eGFRs in HIV-infected women independent of HIV disease status, body mass index, and albuminuria., (Published by Elsevier Inc.)

Background: In parallel thorough QT (TQT) studies, it has been speculated that either baseline correction should be omitted, under the assumption that it only adds noise to the data, or a time-averaged baseline instead of a time-matched baseline correction should be considered in order to reduce the study variability., Objective: This study characterized the assumptions and implications of different baseline correction approaches in parallel TQT studies submitted for regulatory review., Data and Methods: 57 parallel TQT studies conducted between 2002 and 2009 in 5591 healthy volunteers were evaluated. Only moxifloxacin and placebo arms, including their baselines, were considered. The options of using no baseline correction, time-averaged baseline correction, and time-matched baseline correction were examined and compared., Results: QTc values exhibited a diurnal pattern, with longer QTc intervals during sleep preserved when correcting for a time-averaged baseline. Post-dose and baseline QTc values were highly correlated (mean ρ = 0.80, range 0.56-0.98 and mean ρ = 0.79, range 0.50-0.96 in the placebo and moxifloxacin groups, respectively). The variability of raw QTc values was substantially larger than that of baseline-adjusted QTc values. The difference in the point estimate of QTc differences between moxifloxacin and placebo differed by up to ± 4 ms between the time-averaged and the time-matched baseline corrections. Statistical tests indicate that assumptions of time-averaged baseline and no baseline correction are not appropriate., Conclusions: Baseline correction in parallel TQT studies leads to more precise QTc estimates. Because of possible inaccuracy introduced by time-averaged baseline correction, the time-matched baseline correction appears to be preferable for a parallel TQT study to both reduce the intrinsic variability due to circadian patterns and obtain more accurate point estimates.

Background: It is unknown whether purported benefits of off-pump coronary artery bypass grafting are patient-specific within the Society of Thoracic Surgeons National Cardiac Database or dependent on center volume or operating surgeon., Methods: The Society of Thoracic Surgeons National Cardiac Database was queried for all patients undergoing nonemergency, isolated coronary artery bypass between January 1, 2005, and December 31, 2010, who had Predicted Risk of Mortality scores and participant/surgeon identifiers. Of these 876,081 patients ("all sites"), 210,469 underwent surgery at participant sites that had performed more than 300 off-pump and 300 on-pump coronary artery bypass operations during the 6-year study period ("high-volume sites"). Operative mortality, stroke, acute renal failure, mortality or morbidity, and prolonged postoperative length of stay were analyzed with conditional logistic models for all sites and for high-volume sites, stratified by participant center and surgeon, and adjusted for 30 variables that comprise the Society of Thoracic Surgeons coronary artery bypass grafting risk models., Results: Off-pump coronary artery bypass was associated with a significant reduction in risk of death, stroke, acute renal failure, mortality or morbidity, and postoperative length of stay compared with on-pump coronary artery bypass after adjustment for 30 patient risk factors in the overall sample. This held true within high-volume centers. In the overall sample, there was a significant (P < .05) interaction between off-pump coronary artery bypass and Predicted Risk of Mortality for death, stroke, acute renal failure, and mortality or morbidity., Conclusions: Off-pump coronary artery bypass was associated with reduced adverse events compared with on-pump coronary artery bypass after adjustment for 30 patient risk factors and center and surgeon identity. Patients with higher Predicted Risk of Mortality scores had the largest apparent benefit., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Allergy immunotherapy (AIT) is an effective treatment for allergic asthma and rhinitis, as well as venom-induced anaphylaxis. In addition to reducing symptoms, AIT can change the course of allergic disease and induce allergen-specific immune tolerance. In current clinical practice immunotherapy is delivered either subcutaneously or sublingually; some allergens, such as grass pollen, can be delivered through either route, whereas others, such as venoms, are only delivered subcutaneously. Both subcutaneous and sublingual immunotherapy appear to have a duration of efficacy of up to 12 years, and both can prevent the development of asthma and new allergen sensitivities. In spite of the advances with AIT, safer and more effective AIT strategies are needed, especially for patients with asthma, atopic dermatitis, or food allergy. Novel approaches to improve AIT include use of adjuvants or recombinant allergens and alternate routes of administration. As part of the PRACTALL initiatives, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology nominated an expert team to develop a comprehensive consensus report on the mechanisms of AIT and its use in clinical practice, as well as unmet needs and ongoing developments in AIT. This resulting report is endorsed by both academies., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Coinfection with HIV and hepatitis C virus (HCV) is common. HIV infection and treatment are associated with hypercoagulability; thrombosis in HCV is underinvestigated. Proposed markers of hemostasis in HIV include higher D-dimer, Factor VIII%, and plasminogen activator inhibitor-1 (PAI-1) antigen and lower total Protein S% (TPS) but have not been examined in HCV. We assessed the independent association of HCV with these 4 measures of hemostasis in a multicenter, prospective study of HIV: the Women's Interagency HIV Study., Methods: We randomly selected 450 HCV-infected (anti-HCV+ with detectable plasma HCV RNA) and 450 HCV-uninfected (anti-HCV-) women. HCV was the main exposure of interest in regression models., Results: Four hundred forty-three HCV+ and 425 HCV- women were included. HCV+ women had higher Factor VIII% (124.4% ± 3.9% vs. 101.8% ± 3.7%, P < 0.001) and lower TPS (75.7% ± 1.1% vs. 84.3% ± 1.1%, <0.001) than HCV- women, independent of HIV infection and viral load; there was little difference in PAI-1 or log10 D-dimer. After adjustment for confounders, these inferences remained. HIV infection was independently associated with higher Factor VIII% and log10 D-dimer and lower TPS., Conclusions: HCV was independently associated with higher Factor VIII% and lower TPS consistent with hypercoagulability. Higher Factor VIII% and D-dimer and lower TPS were also strongly associated with HIV infection and levels of HIV viremia, independent of HCV infection. Further investigation is needed to determine if there is increased thrombotic risk from HCV. Studies examining hemostasis markers in HIV infection must also assess the contribution of HCV infection.

Unlabelled: Among individuals with and without concurrent human immunodeficiency virus (HIV), racial/ethnic differences in the natural history of hepatitis C virus (HCV) have been described. African Americans have lower spontaneous HCV clearance than Caucasians, yet slower rates of liver fibrosis once chronically infected. It is not clear how these differences in the natural history of hepatitis C affect mortality, in either HIV-positive or -negative individuals. We conducted a cohort study of HIV/HCV coinfected women followed in the multicenter Women's Interagency HIV Study to determine the association of self-reported race/ethnicity with all-cause and liver-related mortality. Survival analyses were performed using Cox's proportional hazards models. The eligible cohort (n = 794) included 140 Caucasians, 159 Hispanics, and 495 African Americans. There were 438 deaths and 49 liver-related deaths during a median follow-up of 8.9 years and maximum follow-up of 16 years. African-American coinfected women had significantly lower liver-related mortality, compared to Caucasian (hazard ratio [HR], 0.41; 95% confidence interval [CI]: 0.19-0.88; P = 0.022) and Hispanic coinfected women (HR, 0.38; 95% CI: 0.19-0.76; P = 0.006). All-cause mortality was similar between racial/ethnic groups (HRs for all comparisons: 0.82-1.03; log-rank test: P = 0.8)., Conclusions: African-American coinfected women were much less likely to die from liver disease, as compared to Caucasians and Hispanics, independent of other causes of death. Future studies are needed to investigate the reasons for this marked racial/ethnic discrepancy in liver-related mortality., (Copyright © 2012 American Association for the Study of Liver Diseases.)

The paper proposes tests to assess psychomotor impairment in drivers suspected of using substances acting similarly to alcohol. The authors also present a proposal for the protocol to be used in sampling and testing of saliva, blood and urine when psychoactive substance abuse has been suspected. A detailed procedure is based on the joined experience of German, U.S. and Polish police from Gdansk. The purpose of the appendix is to help police officers to perform and document tests confirming psychomotor impairment, as well as to provide the basis for saliva, urine and blood analysis.

Sophisticated modeling techniques can be powerful tools to help us understand the effects of cancer control interventions on population trends in cancer incidence and mortality. Readers of journal articles are, however, rarely supplied with modeling details. Six modeling groups collaborated as part of the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET) to investigate the contribution of U.S. tobacco-control efforts toward reducing lung cancer deaths over the period 1975-2000. The six models included in this monograph were developed independently and use distinct, complementary approaches toward modeling the natural history of lung cancer. The models used the same data for inputs, and agreed on the design of the analysis and the outcome measures. This article highlights aspects of the models that are most relevant to similarities of or differences between the results. Structured comparisons can increase the transparency of these complex models., (© 2011 Society for Risk Analysis.)

The Patient Protection and Affordable Care Act signed into law in March 2010, has led to sweeping changes to the US health care system. The ensuing pace of change in health care regulation is unparalleled and difficult for physicians to keep up with. Because of the extraordinary challenges that have arisen, the public policy committee of the Society for Surgery of the Alimentary tract conducted a symposium at their 52nd Annual Meeting in May 2011 to educate participants on the myriad of public policy changes occurring in order to best prepare them for their future. Expert speakers presented their views on policy changes affecting diverse areas including patient safety, patient experience, hospital and provider fiscal challenges, and the life of the practicing surgeon. In all areas, surgical leadership was felt to be critical to successfully navigate the new health care landscape as surgeons have a long history of providing safe, high quality, low cost care. The recognition of shared values among the diverse constituents affected by health care policy changes will best prepare surgeons to control their own destiny and successfully manage new challenges as they emerge.

Background: Considerable effort has been expended on tobacco control strategies in the United States since the mid-1950s. However, we have little quantitative information on how changes in smoking behaviors have impacted lung cancer mortality. We quantified the cumulative impact of changes in smoking behaviors that started in the mid-1950s on lung cancer mortality in the United States over the period 1975-2000., Methods: A consortium of six groups of investigators used common inputs consisting of simulated cohort-wise smoking histories for the birth cohorts of 1890 through 1970 and independent models to estimate the number of US lung cancer deaths averted during 1975-2000 as a result of changes in smoking behavior that began in the mid-1950s. We also estimated the number of deaths that could have been averted had tobacco control been completely effective in eliminating smoking after the Surgeon General's first report on Smoking and Health in 1964., Results: Approximately 795,851 US lung cancer deaths were averted during the period 1975-2000: 552,574 among men and 243,277 among women. In the year 2000 alone, approximately 70,218 lung cancer deaths were averted: 44,135 among men and 26,083 among women. However, these numbers are estimated to represent approximately 32% of lung cancer deaths that could have potentially been averted during the period 1975-2000, 38% of the lung cancer deaths that could have been averted in 1991-2000, and 44% of lung cancer deaths that could have been averted in 2000., Conclusions: Our results reflect the cumulative impact of changes in smoking behavior since the 1950s. Despite a large impact of changing smoking behaviors on lung cancer deaths, lung cancer remains a major public health problem. Continued efforts at tobacco control are critical to further reduce the burden of this disease.

Introduction: Carotid artery stenting (CAS) has become an alternative to carotid endarterectomy. Moreover, percutaneous transluminal angioplasty (PTA) allows other cephalad arteries revascularization. The aim of this study was to evaluate late outcomes of cephalad arteries PTA., Methods: This is an international multicenter registry of 434 consecutive patients in which 497 PTAs were performed. Patients with symptomatic >50% stenosis or asymptomatic >70% stenosis were enrolled. Stenting of 577 internal carotid arteries (ICA) and 13 common carotid arteries was performed, 20.7% procedures were complex in which bilateral carotid stenoses or carotid and vertebral arteries stenoses were revascularized at one stage. In 15.9% patients, one-stage coronary intervention was carried out. Distal protection devices were used in 69.6% of cases. PTAs were divided into high (n = 330) and low (n = 167) risk of major adverse coronary and cerebral events (MACCE)., Results: At 30 days, there were 15 (3.5%) cases of MACCE [0.9% deaths, 2.1% strokes, and 0.9% myocardial infarction (MI)]. TIAs were observed in 15 (3.9%) patients. There was no significant difference in stroke incidence between procedures with or without neuroprotection (1.8 vs. 3%; P = 0.66) as well as in MACCE occurrence between high and low-risk groups (4.3 vs. 2%; P = 0.34). Bilateral stenoses increased while hypertension decreased the risk of MACCE. Left ICA lesions increased the risk of cerebrovascular accidents (CVA). At 4 years (1-11 years), the mortality rate was 11.5%, 6% of patients had stroke, and 3% MIs. Restenosis occurred in 3%. There was a trend toward higher mortality rate (13.3 vs. 6.9%; P = 0.07) and MACCE risk in high-risk group (23.5 vs.14.7% P = 0.06). Age > 65 y.o. and stent length < 24 mm increased, while the statin therapy on admission decreased the risk of long-term death. Structural valve disease and stent length <30 mm increased the risk of MACCE, while implantation of Acculink stent decreased the risk of CVA., Conclusions: CAS is safe and successful procedure with low early and long-term adverse events. Special attention should be put on patients with bilateral and left ICA stenoses. If possible, longer stents should be applied., (Copyright © 2011 Wiley Periodicals, Inc.)

We estimate trends in BMI values by deciles of the US adult population by birth cohorts 1882-1986 stratified by ethnicity and gender. The highest decile increased by some 18-22 BMI units in the course of the century while the lowest ones increased by merely 1-3 BMI units. For example, a typical African American woman in the 10th percentile and 64 in. (162.6 cm) tall increased in weight by just 12 pounds (5 kg) whereas in the 90th percentile her weight would have increased by 128 pounds (58 kg). Hence, the BMI distribution became increasingly right skewed as the distance between the deciles increased considerably. The rate of change of the BMI decile curves varied greatly over time and across gender and ethnicity. The BMI deciles of white men and women experienced upswings after the two world wars and downswings during the Great Depression and also decelerated after 1970. However, among African Americans the pattern is different during the first half of the century with men's rate of increase in BMI values decreasing substantially and that of females remaining constant at a relatively high level until the Second World War. After the war, though, the rate of change of BMI values of blacks came to resemble that of whites with an accelerating phase followed by a slowdown around the 1970s., (Copyright © 2011 Elsevier B.V. All rights reserved.)