Medical Research Foundation Research Articles

Negative Age Stereotypes Associated with Older Persons' Rejection of COVID‐19 Hospitalization

During the pandemic, excess deaths (the difference between observed and expected deaths, based on mortality rates from previous years) have far exceeded the number of deaths officially attributed to COVID-19.1 This is partially due to older persons with COVID-19 avoiding hospitals and dying at home without an official diagnosis.2, 3 We examined a potential explanation for this avoidance. Specifically, the current study considered for the first time whether resistance to hospitalization can be explained by a psychosocial factor among older persons: stress-inducing negative age stereotypes (disparaging characterizations of older persons as a category) that are assimilated from society. A prevalent-negative-age-stereotype theme is inevitable debilitation.4, 5 Previous research demonstrated that these stereotypes, which engender a sense of futility, lead to risky health behaviors, delayed recovery from disability, and low will to live among older persons.4-6 According to stereotype embodiment theory, and its supporting research, negative age stereotypes have a greater impact on older persons, for whom the stereotypes are self-relevant, compared to younger persons, for whom the stereotypes are self-irrelevant.4 We expected that, compared to older persons with positive age stereotypes, older persons with negative age stereotypes would be more likely to oppose older individuals going to the hospital when extremely sick with COVID-19. We also conducted two specificity analyses. First, we expected that the age stereotypes of older persons would not be associated with their view of whether younger persons should go to the hospital when extremely sick with COVID-19. Second, we expected that among younger persons, age stereotypes would not be associated with their view of whether older or younger individuals should go to the hospital when extremely sick with COVID-19. To examine these hypotheses, we assessed 1,590 participants drawn from two online platforms: Amazon Mechanical Turk and Lucid.7 Both platforms provide data validity and reliability similar to that collected through in-person settings.7 Inclusion criteria were 18 years or older, English fluency, and U.S. residence. Forty-eight percent of the participants were in the older group (age 65 or greater). The cohort, similar to the U.S. population, was 55% female, 70% white, 19% African-American, 14% Hispanic, and 7% Asian. Participants were surveyed between April 23 and May 5, 2020, during which 28% of excess deaths were not officially reported as due to COVID-19.1, 8 Negative age stereotypes were measured with the reliable and valid 18-item Image of Aging scale.9 Views of whether hospitalization was appropriate were measured by asking participants how much they agreed with the following statements: “If older persons are extremely sick with COVID-19, they should stay at home and not go to the hospital;” and “If younger persons are extremely sick with COVID-19, they should stay at home and not go to the hospital.” Covariates included: age, sex, race, self-rated health, education, marital status or financial stress (measured by asking, “How much has the pandemic affected you financially?”). As hypothesized, negative age stereotypes significantly predicted a rejection of hospitalization for older persons who are extremely sick with COVID-19, among older participants β = .20, P = .04, but not among younger participants, β = .14, P = .24. Also as hypothesized, negative age stereotypes did not predict views of whether younger persons who are extremely sick with COVID-19 should be hospitalized, among older and younger participants, β = .17, P = .09 and, β = .19, P = .09, respectively. Despite widely-disseminated media reports about the relatively high risk of older persons for COVID-19 mortality,10 the saliency of negative age stereotypes still led to its association with their view that they should avoid hospitalization when extremely sick with COVID-19. It is notable that this association was greater than the one found among younger persons holding negative age stereotypes. Future research is needed to determine the extent to which the negative age stereotypes of older persons are among the risk factors contributing to pandemic deaths and how to best mitigate these societal-based stereotypes. The Patrick and Catherine Weldon Donaghue Medical Research Foundation supported this research with a grant to the first author. We appreciate our participants taking the time to engage in this research. The Patrick and Catherine Weldon Donaghue Medical Research Foundation. None. Becca R. Levy developed the concept and wrote the manuscript. Natalia Provolo and E-Shien Chang collected the data and provided feedback on the manuscript. Martin Slade conducted the data analysis and provided feedback on the manuscript. None.

The rebirth of lithium as the archetypal mood stabilizer.

The serendipitous discovery of lithium's efficacy for the treatment of manic excitement dates back to initial observations by the Danish psychologist Carl Lange in 1886 who theorised that patients with manic-depressive illness had "cerebral gout" for which he suggested lithium salts because lithium could dissolve urate stones. Modern use was triggered by Cade in Melbourne in 1949, while its efficacy for the management of manic episodes and for the prophylaxis of both manic and bipolar depressive episodes was empirically confirmed by Mogens Schou in Denmark.

Top 10 priorities for future infertility research: an international consensus development study† ‡.

Top 10 priorities for future infertility research: an international consensus development study† ‡.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease.

A comparative study of RIPASA and Alvarado score for the diagnosis of acute appendicitis

Background: Acute appendicitis is a common problem and can be difficult to diagnose at time. There are many scoring systems to predict the diagnosis of acute appendicitis. The most commonly used scoring system is Alvarado scoring system but, it is far from perfect. In this study we compare Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) scoring system to Alvarado scoring system in correctly diagnosing acute appendicitis.Methods: This prospective observational study was conducted in the department of general surgery, Sree Gokulam Medical College and Research Foundation. It comprised of 60 consecutive patients who were admitted with suspicion of appendicitis who had right iliac fossa pain. RIPASA and Alvarado scoring was done and compared to histopathology after surgery. Sensitivity, specificity and accuracy was calculated.Results: Majority of the patients were below 30 years of age majority were males 36 (60%). When Alvarado score predicted appendicitis in 31 (51.77%) and RIPASA in 54 (90%). When the RIPASA score was >7.5 the sensitivity was 100%, specificity 67% and accuracy was 95%.Conclusions: RIPASA scoring system is more accurate to diagnose acute appendicitis especially when RIPASA score is >7.5. literatures.

Study of parameters associated with severity of acute pancreatitis

Background: Acute pancreatitis is a condition associated with a lot of morbidity. There are several scoring systems that predict the severity of acute pancreatitis, but none are perfect. The aim of this study is to study the various predictors of severity know the association of the parameters with severity of disease.Methods: Our study is a prospective observational study conducted on 80 consecutive patients who presented with features of acute pancreatitis between 20-80 years age group, attending the department of General Surgery, Sree Gokulam Medical College and research foundation, Venjaramoodu, Trivandrum during the period of November 2012 to May 2014. The obtained data was uploaded in Microsoft excel sheet and analysed. Finally, all these variables were correlated with the severity of the disease to find out the association and significance using appropriate statistical methods like Pearson Chi-square test, ANOVA and Kruskal Wallis test.Results: In our study 59 (74%) were males and mean age was 45.78. Pulse rate, total count C-reactive protein, serum amylase, lipase, Low density lipoprotein (LDH), pH, calcium, lowering of haematocrit, Computerized tomography severity index (CTSI) and Ranson’s score had significant association with severity of pancreatitis.Conclusions: One should not wait for any single scoring system to get scored for effective treatment. A diagnosis of pancreatitis should be made using clinical, laboratory and radiological means and treatment in the form of aggressive crystalloid resuscitation should be started with intensive care monitoring at the earliest.

Karonudib Has Potent Anti-Tumor Effects in Preclinical Models of B-Cell Lymphoma

Although chemo-immunotherapy has improved survival in B-cell lymphoma patients, refractory and relapsed disease still represents a major challenge, urging for development of new therapeutics. A new approach is to target nucleotide metabolism. Karonudib (TH1579), was developed to inhibit MutT-homologue-1/Nudix hydrolase 1 (MTH1/NUDT1), an enzyme that prevents oxidized nucleotides to be incorporated into DNA. Under normal conditions with low reactive oxygen species (ROS) burden, MTH1 is not essential for cell survival. This contrasts cancer cells which frequently upregulate MTH1 to compensate for increased ROS with corresponding higher oxidized nucleotide levels, and therefore become more susceptible for MTH1 inhibition. Here, our aim was to perform preclinical testing of karonudib in B-cell lymphoma. Using two different gene expression datasets, we demonstrate that NUDT1, the gene encoding MTH1, was highly upregulated in tumor biopsies from patients with diffuse large B-cell lymphoma (DLBCL) and Burkitt's lymphoma as compared to follicular lymphoma and peripheral blood B cells from healthy donors, hence demonstrating a rationale for targeting MTH1 in aggressive B-cell lymphoma. We tested the efficacy of karonudib (0.06-1 µM) in vitro in a range of B-cell lymphoma cell lines using CellTiterGlo and by flow cytometry detection of active caspase-3 and TUNEL to identify apoptotic cells. Karonudib strongly reduced viability in all B-cell lymphoma cell lines tested (n = 12) and induced apoptosis at concentrations well tolerated by peripheral blood B cells from healthy donors. Cell cycle analysis and microscopy revealed that most cells arrested in prometaphase in the presence of karonudib. Failed spindle assembly led to mitotic arrest and subsequent apoptosis. Prometaphase arrest was seen in TP53 mutant as well as in TP53 wild type cell lines, confirming that karonudib induced apoptosis independent of TP53 mutational status. To test the efficacy of karonudib in vivo, we utilized two different lymphoma xenograft models, including an ABC DLBCL patient-derived model. Mice were treated with karonudib (90 mg/kg) or vehicle b.i.d, three times a week and tumor growth was monitored by in vivo imaging system or MR. In both models, karonudib as single agent completely controlled tumor growth, and significantly prolonged survival (p<0.0001, as compared to control mice). The specificity of MTH1 inhibitors has been debated and TH588, the first generation MTH1 inhibitor, was recently shown to bind b-tubulin and induce mitotic arrest in MTH1 knock out cell lines (Patterson et al, Cell Syst 2019). To elucidate the mechanism of karonudib in B-cell lymphoma, we generated MTH1 knock out cells using CRISPR/Cas9, and compared the functional effects of karonudib in these clones with the original lymphoma cells. We demonstrated on-target effect of the inhibitor as the MTH1 knock out clones were less sensitive towards karonudib. However, MTH1 knock out clones exhibited a similar cell cycle arrest as the wild type cells after karonudib treatment. This clearly indicates that karonudib can induce cell cycle arrest independent of MTH1, and hence has a dual mechanism of action. Our preclinical data suggest that karonudib is a promising drug with potential therapeutic use in B-cell lymphoma, and may be particular effective in aggressive lymphoma types. Disclosures Warpman Berglund: Oxcia AB: Other: shareholders; non profit Thomas Helleday Foundation for Medical Research: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Gad:Oxcia: Other: shareholder; non profit Thomas Helleday Foundation for Medical Research: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Pham:Oxcia AB: Other: Shareholder. Sanjiv:Oxcia AB: Other: Shareholder; non profit Thomas Helleday Foundation for Medical Research: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Helleday:Oxcia AB: Other: Shareholder; non profit Thomas Helleday Foundation for Medical Research: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.

Joint Imaging Platform for Federated Clinical Data Analytics.

PURPOSEImage analysis is one of the most promising applications of artificial intelligence (AI) in health care, potentially improving prediction, diagnosis, and treatment of diseases. Although scientific advances in this area critically depend on the accessibility of large-volume and high-quality data, sharing data between institutions faces various ethical and legal constraints as well as organizational and technical obstacles.METHODSThe Joint Imaging Platform (JIP) of the German Cancer Consortium (DKTK) addresses these issues by providing federated data analysis technology in a secure and compliant way. Using the JIP, medical image data remain in the originator institutions, but analysis and AI algorithms are shared and jointly used. Common standards and interfaces to local systems ensure permanent data sovereignty of participating institutions.RESULTSThe JIP is established in the radiology and nuclear medicine departments of 10 university hospitals in Germany (DKTK partner sites). In multiple complementary use cases, we show that the platform fulfills all relevant requirements to serve as a foundation for multicenter medical imaging trials and research on large cohorts, including the harmonization and integration of data, interactive analysis, automatic analysis, federated machine learning, and extensibility and maintenance processes, which are elementary for the sustainability of such a platform.CONCLUSIONThe results demonstrate the feasibility of using the JIP as a federated data analytics platform in heterogeneous clinical information technology and software landscapes, solving an important bottleneck for the application of AI to large-scale clinical imaging data.

Endothelial-specific Ablation of Non-nuclear Estrogen Receptor alpha Signaling Deteriorates Vascular Remodelling Response

Abstract Background and introduction The difference in cardiovascular disease risk between age-matched women and men narrows as transition through menopause in observational studies. Estrogen exerts complex physiological effects via its non-nuclear and nuclear actions. Experimental studies have shown that endothelial estrogen receptors mediate vasoprotection via endothelial nitric oxide production, reendothelialization, and atherosclerosis. Prior studies in vitro addressed estrogen's effects on endothelial cells and vascular smooth muscle cells, leading to vasoprotection. However, the in vivo evidences are lacking for beneficial effects of endothelium non-nuclear ERα signaling on vascular remodelling in response to injury. Purpose This study aims to clarify the impact of endothelial ERα non-nuclear signaling in the vasoprotection, using a novel mouse model lacking tissue-specific ERα non-nuclear signaling. Methods We identified the amino acids of ERα which were responsible for its binding to p85α subunit of phosphatidylinositol 3-kinase in vitro. We generated a novel mouse model in which non-nuclear signaling of ERα was ablated in endothelial cells by crossing Tie2-Cre transgenic mice with floxed ERα mutants (RR259/260AA) in which p85α and ERα interaction was disrupted. Results In endothelial cells isolated from ERαKI/KITie2 cre/+ animals, E2 failed to induce phosphorylation of Akt, confirming the absence of ERα non-nuclear signaling. Baseline characteristics at 8 to 12 weeks of age were undistinguishable between the genotypes, including body weight, systolic blood pressure, uterine weight and echocardiographic fractional shortening. We then assessed how vascular remodelling process was impacted in a carotid artery wire injury model. Histological analyses with Elastica van Gieson staining two weeks after injury revealed that estrogen dependent suppression of remodelling response (intima to medial ratio) was abolished in ERαki/kiTie2cre/+mice (P=0.0004). Masson's Trichrome staining showed that in the presence of E2 fibrosis was significantly higher in ERαki/kiTie2cre/+ mice than ERαki/kiTie2cre/− mice (P=0.0015). Conclusions We generated a novel mouse model for tissue-specific ablation of ERα non-nuclear signaling by interfering ERα-PI3K interaction. Our results demonstrate that the pivotal role for ERα non-nuclear signaling of endothelial cells in carotid arterial protection following injury with its minimal impact on baseline cardiovascular phenotype. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Japan Heart Foundation Research Grant, SENSHIN Medical Research Foundation

Utility of Hematological Scoring System in Diagnosis of Neonatal Sepsis

Background: Neonatal septicemia is defined as a clinical syndrome characterized by systemic signs and symptoms caused by a bacterial infection and gives positive blood culture in the first month of life. It is associated with high morbidity and mortality, but early diagnosis and treatment significantly improve the outcomes. The present study brings out a quick and cost- effective Hematological Scoring System that enables early diagnosis of neonatal sepsis
 Method: This study was conducted in the Department of Pathology of Sree Gokulam Medical College and Research Foundation, Venjaramoodu, Thiruvananthapuram over 1 year. Eighty neonates with clinical suspicion of sepsis were studied with respect to their peripheral smear findings, blood culture and C-reactive protein levels.
 Result: Among the eighty cases, twelve neonates were culture positive. Male gender and late- onset of sepsis were the significant risk parameters. Escherichia coli and Staphylococcus aureus were the most common isolated organisms. Of the different parameters studied I:T ratio and Absolute neutrophil count showed the highest specificity and immature neutrophil count had the highest sensitivity. Forty-one percent of neonates had a high Hematological Scoring System score. The specificity of Hematological Scoring System with a score > 5 was 92%
 Conclusion: Hematological Scoring System is a cost-effective, rapid and easy to perform screening test that can be used to rule out sepsis thus avoiding unnecessary administration of antibiotics to unaffected babies. It should be adopted as a routine screening procedure by minimally qualified rural doctors with minimal resources to ensure appropriate action immediately for children with high index of suspicion of sepsis.

A clinical profile of acute pancreatitis in a tertiary hospital in South India

Background: Acute pancreatitis is a condition that is quite prevalent in South India. It causes significant morbidity and even mortality if not treated. Aim of this study is to find out the main aetiological factors for acute pancreatitis and their association with comorbidities.Methods: Our study is a prospective observational study conducted on 80 consecutive patients who presented with features of acute pancreatitis between 20 – 80 years age group, attending the department of General Surgery, Sree Gokulam Medical College and research foundation, Venjaramoodu, Trivandrum during the period of November 2012 to May 2014. The obtained data was uploaded in Microsoft excel sheet and analysed. Finally all these variables were correlated with the severity using Pearson Chi-Square test.Results: In our study of 80 patients majority were males 59(73.75%). Majority cases were seen in between 41 to 50 years 29(36.3%). The commonest cause was alcohol induced type, 52(65%) followed by gall stone pancreatitis 17(21%). Diet, alcohol intake or gender did not corelate with severity of pancreatitis. Elderly patients with high BMI are more prone to complications.

Black Dancer by Robert Perless

Rcognizing the contribution art has had in the Mayo Clinic environment since the original Mayo Clinic Building was finished in 1914, Mayo Clinic Proceedings features some of the numerous works of art displayed throughout the buildings and grounds on Mayo Clinic campuses as interpreted by the author.

A study to determine the value of pre operative hyperbilirubinemia as a predictor of complicated appendicitis

Background: Acute appendicitis is a common acute abdominal condition that all surgeons confront. The early detection of patients who could go in for complication is critical so that appropriate treatment can be initiated to reduce mortality. There is no pre-operative investigation which accurately point out the patients who are going to develop severe disease. Hence this prospective study was done to identify whether preoperative bilirubin level can predict the severity of the disease.Methods: The study was conducted in the Department of General Surgery, Sree Gokulam Medical College and Research Foundation, Venjaramoodu, Trivandrum on 100 consecutive patients who were clinically diagnosed as acute appendicitis. These patients were evaluated with Alvarado score. In addition, preoperative bilirubin level and liver enzymes were estimated. Ultrasound abdomen was done preoperatively routinely. After surgery histopathology was studied. The parameters which showed statistically significant results for predicting complications were analyzed.Results: In this prospective study on 100 consecutive patients, acute appendicitis was found more commonly in males, 57 (57%) cases than in females, 43 (43%) cases. Among the cases 56 were acute appendicitis, 13 perforated, 11 gangrenous and 20 suppurative appendicitis. In our study, there was significant correlation of preoperative hyperbilirubinemia with complications of appendicitis.Conclusions: Patients with appendicitis with elevated bilirubin levels have more chance for complications like perforation, gangrene and suppuration.

Rosy Beginnings: Studying Peroxisomes in Drosophila.

Research using the fruit fly Drosophila melanogaster has traditionally focused on understanding how mutations affecting gene regulation or function affect processes linked to animal development. Accordingly, flies have become an essential foundation of modern medical research through repeated contributions to our fundamental understanding of how their homologs of human genes function. Peroxisomes are organelles that metabolize lipids and reactive oxygen species like peroxides. However, despite clear linkage of mutations in human genes affecting peroxisomes to developmental defects, for many years fly models were conspicuously absent from the study of peroxisomes. Now, the few early studies linking the Rosy eye color phenotype to peroxisomes in flies have been joined by a growing body of research establishing novel roles for peroxisomes during the development or function of specific tissues or cell types. Similarly, unique properties of cultured fly Schneider 2 cells have advanced our understanding of how peroxisomes move on the cytoskeleton. Here, we profile how those past and more recent Drosophila studies started to link specific effects of peroxisome dysfunction to organ development and highlight the utility of flies as a model for human peroxisomal diseases. We also identify key differences in the function and proliferation of fly peroxisomes compared to yeast or mammals. Finally, we discuss the future of the fly model system for peroxisome research including new techniques that should support identification of additional tissue specific regulation of and roles for peroxisomes.

Support for Work Requirements but Opposition to Terminating Benefits Among Medicaid Enrollees and NonEnrollees in Kentucky: Results from a Statewide Survey

More than a dozen states have sought federal approval for Section 1115 Medicaid waivers to make premiums and work requirements (ie, requirements to work, volunteer, or engage in education, or caretaking), a condition of Medicaid eligibility for adults deemed able‐bodied. Support for these waivers may differ among adults based on Medicaid participation and political affiliation. We report results from an original 2019 survey of a representative sample of adults in the Commonwealth of Kentucky investigating attitudes regarding work requirements, mandatory premiums, and program exclusions as penalties for noncompliance.We conducted a statewide survey of N = 1203 adults in Kentucky; 601 participants were contacted by phone via random digit dialing and 602 contacted as part of a standing web‐based panel of Kentucky residents. At the time, Kentucky had an approved Section 1115 waiver to establish work requirements and premiums for adults considered able‐bodied.The sample was representative of Kentucky adult population on the basis of age, gender, race/ethnicity, phone use, poverty level, internet access, and geographic region.A majority of Kentuckians (69%) supported the concept of work requirements, agreeing that “If people are able, they should be required to spend time volunteering or working to stay on Medicaid.” Support was higher among nonenrollees (73%) than Medicaid enrollees (64%). But only 43% of the general population, 48% of nonenrollees, and 36% of enrollees agreed that people who do not meet their hours “should lose their Medicaid benefits.” More than half of respondents proposed work hour thresholds that were lower than the 20 hours a week proposed by most states. Among Medicaid enrollees, support for work requirements was higher among those who were employed (versus unemployed), but there was little difference by political party. Opposition to mandatory premiums was high; only 34% of the general population, 38% of nonenrollees, and 28% of enrollees agreed that “People should be required to pay some money out of pocket each month to have Medicaid.” Among people enrolled in Medicaid, support for mandatory premiums was lower among people who were unemployed, and among Democrats compared to Republicans. Only 22% of the general population, 23% of nonenrollees, and 20% of enrollees supported the termination of benefits for people who miss premium payments.The majority of adult Kentucky residents support policies that require Medicaid beneficiaries to work or volunteer. However, a majority also oppose penalties that terminate benefits for people who do not comply. A majority disagreed with mandatory premiums in Medicaid, including program exclusion penalties for premium nonpayment.Work requirements in Medicaid are largely halted due to legal challenges and have been discontinued by executive order in Kentucky. If work requirements and premiums take effect elsewhere, policy makers and researchers should consider how enrollees’ beliefs may affect the acceptability and perceived legitimacy of Medicaid waivers, with possible impacts for compliance and enrollment. It is important to understand whether attitudes about waiver terms differ by demographic characteristics, given that these attitudes may influence compliance and continued coverage.The Patrick and Catherine Weldon Donaghue Medical Research Foundation and The Rx Foundation.

Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: a prospective test validation study

SummaryBackgroundCross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC.MethodsWe did a prospective multicentre study in adult participants (age ≥18 years) with newly diagnosed adrenal masses. We assessed the accuracy of diagnostic imaging strategies based on maximum tumour diameter (≥4 cm vs <4 cm), imaging characteristics (positive vs negative), and urine steroid metabolomics (low, medium, or high risk of ACC), separately and in combination, using a reference standard of histopathology and follow-up investigations. With respect to imaging characteristics, we also assessed the diagnostic utility of increasing the unenhanced CT tumour attenuation threshold from the recommended 10 Hounsfield units (HU) to 20 HU.FindingsOf 2169 participants recruited between Jan 17, 2011, and July 15, 2016, we included 2017 from 14 specialist centres in 11 countries in the final analysis. 98 (4·9%) had histopathologically or clinically and biochemically confirmed ACC. Tumours with diameters of 4 cm or larger were identified in 488 participants (24·2%), including 96 of the 98 with ACC (positive predictive value [PPV] 19·7%, 95% CI 16·2–23·5). For imaging characteristics, increasing the unenhanced CT tumour attenuation threshold to 20 HU from the recommended 10 HU increased specificity for ACC (80·0% [95% CI 77·9–82·0] vs 64·0% [61·4–66.4]) while maintaining sensitivity (99·0% [94·4–100·0] vs 100·0% [96·3–100·0]; PPV 19·7%, 16·3–23·5). A urine steroid metabolomics result indicating high risk of ACC had a PPV of 34·6% (95% CI 28·6–41·0). When the three tests were combined, in the order of tumour diameter, positive imaging characteristics, and urine steroid metabolomics, 106 (5·3%) participants had the result maximum tumour diameter of 4 cm or larger, positive imaging characteristics (with the 20 HU cutoff), and urine steroid metabolomics indicating high risk of ACC, for which the PPV was 76·4% (95% CI 67·2–84·1). 70 (3·5%) were classified as being at moderate risk of ACC and 1841 (91·3%) at low risk (negative predictive value 99·7%, 99·4–100·0).InterpretationAn unenhanced CT tumour attenuation cutoff of 20 HU should replace that of 10 HU for exclusion of ACC. A triple test strategy of tumour diameter, imaging characteristics, and urine steroid metabolomics improves detection of ACC, which could shorten time to surgery for patients with ACC and help to avoid unnecessary surgery in patients with benign tumours.FundingEuropean Commission, UK Medical Research Council, Wellcome Trust, and UK National Institute for Health Research, US National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.

Invasive pneumococcal disease incidence in children and adults in France during the pneumococcal conjugate vaccine era: an interrupted time-series analysis of data from a 17-year national prospective surveillance study

The long-term benefits of pneumococcal conjugate vaccines (PCVs) remain unknown because of serotype replacement. We aimed to estimate the effect of PCV implementation on invasive pneumococcal disease incidence in France. We did a quasi-experimental interrupted time-series analysis using data from a French national prospective surveillance system. We included all invasive pneumococcal disease cases in children and adults from more than 250 participating hospitals between Jan 1, 2001, and Dec 31, 2017. The primary outcome was incidence of invasive pneumococcal disease (meningitis and non-meningitis) over time, analysed by segmented regression with autoregressive error. Isolates were serotyped by latex agglutination with antiserum samples. We included 75 903 patients with invasive pneumococcal disease, including 4302 (5·7%) children younger than 2 years and 37 534 (49·4%) adults aged 65 years or older. Before PCV7 implementation, the estimated monthly incidence of invasive pneumococcal disease was 0·78 cases per 100 000 inhabitants, which did not change significantly up to May, 2010. PCV13 implementation in 2010 was followed by a significant decrease in the incidence of invasive pneumococcal disease (-1·5% per month, 95% CI -2·2 to -0·8), reaching an estimated monthly incidence of 0·52 cases per 100 000 inhabitants in December, 2014. From January, 2015, the incidence rebounded (1·8% per month, 95% CI 1·0 to 2·6), reaching an estimated monthly incidence of 0·73 cases per 100 000 inhabitants in December, 2017. The estimated monthly incidence increased from 0·93 cases per 100 000 in December, 2014, to 1·73 cases per 100 000 in December, 2017, for children younger than 2 years, and from 1·54 cases per 100 000 in December, 2014, to 2·08 cases per 100 000 in December, 2017, for adults aged 65 years or older. The main non-PCV13 serotypes involved in the increase were 24F in young children and 12F, 22F, 9N, and 8 in adults aged 65 years or older. PCV13 implementation led to a major reduction in the incidence of invasive pneumococcal disease. However, a rebound in cases among children and adults since 2015, driven by several emerging non-PCV13 serotypes, jeopardises the long-term PCV benefits. These findings, if confirmed in the coming years, should be considered in the development of next-generation PCVs and might guide policy makers in the selection of future pneumococcal vaccines. Foundation for Medical Research; Pfizer, BioMérieux, Sanofi for the Regional Observatory of Pneumococci.

Identifying Triad Risk Factors In Ultramarathon Runners

Ultramarathon running has gained popularity in the past decade, necessitating a better understanding of the health benefits and risks of this sport. The Female Athlete Triad (Triad) and a similar condition reported in males are common in endurance athletes, but the prevalence of triad risk factors in ultramarathon runners is unknown PURPOSE: To identify the prevalence of Triad risk in ultramarathon runners. METHODS: Runners who qualified to compete in a 100-mile endurance race were recruited pre-race to complete a survey assessing eating behaviors, menstrual history, training, and injury history; and dual-energy x-ray absorptiometry to assess bone mineral density (BMD). A cumulative Triad risk score was calculated using energy availability, body mass index (BMI), age of menarche and oligomenorrhea (for women), BMD, and history of bone stress injury. RESULTS: 123 runners (40 female and 83 male) participants had a mean age, respectively, of 41.8 and 46.2 years. 57.5% of females and 26.5% of males received moderate cumulative risk scores; 5.0% of females and 4.8% of males were classified as high risk. 62.5% of females and 39.7% of males scored moderate or high risk for low energy availability, with 13% reporting a history of clinical eating disorders. Mean female and male BMI was, respectively 21.2 kg/m2(SD=2.1) and 22.9 kg/m2 (SD=2.6). 15% of females and 0% of males scored moderate or high risk for low BMI, determined to be anything less than 18.5 kg/m2. 15% of females and 28.9% of males had BMD Z-score<-1.0, and 6.0% of males had a Z-score<-2.0. 37.5% of females and 79.5% of males reported at least one prior bone stress injury. CONCLUSIONS: Triad risk factors were common among ultramarathoners, particularly in men. ACKNOWLEDGEMENTS: Supported with grants from the Western States Endurance Run Foundation and the Napa Medical Research Foundation. Laboratory testing was done in partnership with InsideTracker

Upping The Ante: Can Agility Performance Differentiate Previously Concussed From Healthy Controls?

Returning to sport or active duty has the potential to put athletes or service members at risk. Yet, post-concussion assessments primarily rely on subjective reporting or simple clinical tests - tasks that lack ecologic validity in comparison with sport or combat environments. Both environments may require fast-paced movements such as turning, which involves the integration of oculomotor and vestibular information, as well as cognitive control for execution. Testing anticipated and unanticipated turns during agility tasks performed at high speeds may provide a more valid test setting, and help to quantify differences between previously concussed and healthy persons performing more complex movement tasks. PURPOSE: To compare performance on unanticipated and anticipated agility tasks between previously concussed and healthy controls. METHODS: We tested agility performance, defined by peak turning velocity (yaw, °/s), in previously concussed and healthy controls in two participant samples: athletes (concussed n=5, control n=5) and a general population (concussed n=8, controls n=10). Athletes completed unanticipated turns cued by a light stimulus, and the general population completed anticipated turns using a modified Illinois Agility task (IAT). Peak turning velocity was extracted from a waist worn inertial sensor. Athlete and general population data were compared separately. Cohen’s d effect size was used to evaluate between-group differences due to small sample sizes. RESULTS: The concussed athletes (mean(SD); 239(46) °/s) turned slower than the control athletes (300(37) °/s; d = -1.45, large effect) completing unanticipated turns. In the general population performing anticipated turns, the concussed group (220(23) °/s) turned slower than the healthy controls (237(33) °/s; d = -0.57, medium effect). CONCLUSION: Findings suggest differences between groups in both samples, despite using different agility tasks. Moving forward, we plan to evaluate anticipated turns performance in an active military duty population. However, unanticipated turn tasks, which require a movement coupled in response to stimulus are an interesting area for future exploration. Supported by the Assistant Secretary of Defense for Health Affairs (#W81XWH-18-2-0049) and the Medical Research Foundation of Oregon.