Assessing the contributions of phylogenetic and environmental determinants of allergic cosensitization to fungi in humans.

BACKGROUND: Understanding how allergies to 1 environmental fungus can lead to cosensitization to related fungi is important for the clinical management of allergies. Cosensitization can be caused by monosensitization combined with antibody cross-reactivity, or by coexposures driving independent sensitizations. A pioneering study showed that patterns of IgE cosensitization among 17 fungal species mirror fungal phylogeny. This could reflect either epitope or habitat similarity. Thanks to an improved understanding of fungal phylogeny, larger serologic testing datasets, and environmental data on household fungi, we can now characterize the relationship between cosensitization, species similarity, and likely coexposure with greater precision. OBJECTIVE: To assess the degree to which IgE cosensitization in a group of 17 fungi can be attributed to species similarity or environmental coexposure. METHODS: Cosensitization patterns among 17 fungal species were estimated from a dataset of approximately 8 million serologic tests on 1.6 million patients. Linear regression of cosensitization on phylogenetic distance and imputed coexposure was performed. In addition, branch lengths for the phylogenetic tree were re-estimated on the basis of cosensitization and compared with corresponding phylogenetic branch lengths. RESULTS: Phylogenetic distance explains much of the observed cosensitization (adjusted r2 = .68, p < .001). Imputed environmental coexposures and test co-ordering patterns do not significantly predict cosensitization. Branch length comparisons between the cosensitization and phylogenetic trees identified several species as less cosensitizing than phylogenetic distance predicts. CONCLUSION: Combined evidence from clinical IgE testing data on fungi, along with phylogenetic and environmental exposure data, supports the hypothesis that cosensitization is caused primarily by monosensitization plus cross-reactivity, rather than multisensitization. A serologic test result should be interpreted as pointing to a group of related species that include the sensitizing agent rather than as uniquely identifying the agent. The identified patterns of cross-reactivity may help optimize test panel design.

Fungal allergen sensitization: Prevalence, risk factors, and geographic variation in the United States.

BACKGROUND: Many fungal species are associated with the pathogenesis of allergic disease, yet most epidemiologic studies on IgE-mediated fungal sensitization have only included a few species. OBJECTIVE: We investigated fungal allergen sensitization prevalence, risk factors, and geographic variation in the United States. METHODS: From 2014 to 2019, a total of 7,912,504 serum-specific IgE (sIgE) test results for 17 fungal species were measured in 1,651,203 patients aged 0-85 years by a US-wide clinical laboratory. Fungal sensitization prevalence, patterns, and relationship with demographic characteristics, clinical diagnoses, and geographic regions were analyzed. RESULTS: Twenty-two percent of patients were positive (sIgE > 0.10 kUA/L) to at least 1 fungal allergen; 13.7% were positive to >2 fungal allergens. Fungal species-specific positivity rates ranged 7.4-18.6% and were highest for Candida albicans (18.6%), Alternaria alternata (16.6%), Stemphylium herbarum (14.9%), and Aspergillus fumigatus (14.2%). Other fungi that were frequently tested had relatively low positivity rates (eg, Cladosporium herbarum 11.1%, Penicillium chrysogenum 10.7%). Independent risk factors for test positivity for all fungal species included male sex, teen age (highest in those aged 10-19 years), atopic dermatitis, and asthma. Fungal sensitization was generally higher in urban areas and ecoregions composed predominantly of grasslands and prairies compared to woodlands and forest, although there was greater variation in sensitization risk to different fungi in different ecoregions. CONCLUSION: Independent risk factors for fungal sensitization include male sex, teen ages, atopic dermatitis, asthma, and ecoregion.

Social resources, resilience, and sexual health among South African adolescent girls and young women: findings from the HERStory study.

Socioecological factors, including social resources, influence South African adolescent girls' and young women's sexual health. Few studies have explored how these multi-level social factors relate to both resilience and sexual health in this community. This study examines if social resources mediate associations between resilience and two sexual health outcomes. A weighted-sample of 7,237 South African girls and young women (aged 15-24 years) completed a cross-sectional survey conducted from 2017 to 2018 which included a validated measure of resilience, along with measures of sexual health and social resources. Using multivariable logistic regression models and bootstrapping methods, two types of social resources were assessed as potential mediators. Increased resilience was negatively associated with early sexual debut and engagement in transactional sex. Social support mediated associations between resilience and engagement in transactional sex but did not mediate associations between resilience and early sexual debut. Of all the types of social support measured, social support from a special person mediated the largest proportion of the association between resilience and transactional sex. Examining underlying social and community dynamics related to resilience and sexual health can guide the development of future contextually-relevant programming and policies.

Chemical mixture exposures during pregnancy and cognitive abilities in school-aged children.

INTRODUCTION: Gestational exposure to chemical mixtures, which is prevalent among pregnant women, may be associated with adverse childhood neurodevelopment. However, few studies have examined relations between gestational chemical mixture exposure and children's cognitive abilities. METHODS: In a cohort of 253 pregnant women and their children from Cincinnati, OH (enrolled 2003-2006), we quantified biomarker concentrations of 43 metals, phthalates, phenols, polybrominated diphenyl ethers, organophosphate and organochlorine pesticides, polychlorinated biphenyls, perfluoroalkyl substances, and environmental tobacco smoke in blood or urine. Using k-means clustering and principal component (PC) analysis, we characterized chemical mixtures among pregnant women. We assessed children's cognitive abilities using the Wechsler Preschool and Primary Scale of Intelligence-III and Wechsler Intelligence Scale for Children-IV at ages 5 and 8 years, respectively. We estimated covariate-adjusted differences in children's cognitive ability scores ]=cross clusters, and with increasing PC scores and individual biomarker concentrations. RESULTS: Geometric mean biomarker concentrations were generally highest, intermediate, and lowest among women in clusters 1, 2, and 3, respectively. Children born to women in clusters 1 and 2 had 5.1 (95% CI: 9.4,-0.8) and 2.0 (95% CI: 5.5, 1,4) lower performance IQ scores compared to children in cluster 3, respectively. PC scores and individual chemical biomarker concentrations were not associated with cognitive abilities. CONCLUSIONS: In this cohort, combined prenatal exposure to phenols, certain phthalates, pesticides, and perfluoroalkyl substances was inversely associated with children's cognition, but some individual chemical biomarker concentrations were not. Additional studies should determine if the aggregate impact of these chemicals on cognition is different from their individual effects.

Do measures of healthy eating differ in survivors of early adversity?

Early life adversity has been linked to poor health, including obesity. Understanding the role of unhealthy food intake, may elucidate the importance of self-soothing behaviors in explaining the association between early life adversity and poor health in adulthood. The purpose of this study was to assess the association between early life adversity and dietary quality in a sample of adults from the Lifestyle Influences of Family Environment study. Early life adversity, demographic, and dietary data were obtained for 145 participants using formal interviews and two days of interviewer-administered 24-h recalls. Dietary quality was measured using the 2015 Healthy Eating Index (HEI) scoring algorithm to compute total and component scores. The association between early life adversity and dietary quality was assessed through linear regression and in models adjusted for age and sex. The mean ± SD HEI score for all participants was 54.6 ± 12.8. Individuals with early life adversity had a 4.51 lower overall HEI score when compared to those without early life adversity, 95% CI (0.35, 8.68). After adjusting for age and sex, early life adversity was associated with a 4.6 lower HEI score, 95% CI (0.45, 8.73). HEI component scores indicated that individuals with early life adversity were significantly more likely to have lower whole grain (0.7 versus 2.4) and total dairy (4.3 versus 6.1) scores compared to those without early life adversity. ELA was associated with lower measures of dietary quality. Results warrant future research on dietary and behavioral factors that underly the association between early life adversity and poor health outcomes.

Neighborhood Risk and Hospital Use for Pediatric Asthma, Rhode Island, 2005-2014.

INTRODUCTION: Studies consistently show that children living in poor neighborhoods have worse asthma outcomes. The objective of our study was to assess the association between negative neighborhood factors (ie, neighborhood risk) and pediatric asthma hospital use. METHODS: This retrospective study used data from children aged 2 to 17 years in a statewide (Rhode Island) hospital network administrative database linked to US Census Bureau data. We defined an asthma visit as an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code of 493 in any diagnosis field. We used 8 highly correlated measures for each census-block group to construct an index of neighborhood risk. We used maps and linear regression to assess the association of neighborhood risk with average annual census-block-group rates of asthma emergency department visits and hospitalizations. We used multivariable analyses to identify child characteristics and neighborhood risk associated with an asthma revisit, accounting for the child's sociodemographic information, season, and multiple measurements per child. RESULTS: From 2005 through 2014, we counted 359,195 visits for 146,889 children. Of these, 12,699 children (8.6%) had one or more asthma visits. Linear regression results showed 1.18 (95% confidence interval, 1.06-1.30) more average annual emergency departments visits per 100 children and 0.41 (95% confidence interval, 0.34-0.47) more average annual hospitalizations per 100 children in neighborhoods in the highest-risk index quintile than in neighborhoods in the lowest-risk index quintile. CONCLUSION: Interventions to improve asthma outcomes among children should move beyond primary care or clinic settings and involve a careful evaluation of social context and environmental triggers.

Barriers to Postpartum Glucose Testing in Women with Gestational Diabetes Mellitus.

OBJECTIVE: To identify barriers to postpartum glucose testing in women with a history of gestational diabetes mellitus (GDM). MATERIALS AND METHODS: This is a prospective cohort study of 300 women with GDM who completed questionnaires on socioeconomic barriers and validated instruments to measure trust in their clinician and health agency. At 12 weeks' postpartum, women were recontacted and postpartum records were collected. Women who completed glucose testing between 4 and 12 weeks' postpartum were compared with women who did not with regard to modifiable and nonmodifiable barriers to care. RESULTS: Of the 373 women approached, 300 (80%) consented to participate, completed surveys on postpartum day 2, and had records retrieved at 12 weeks' postpartum. Validated instruments used showed internal consistency (Cronbach's α > 0.6). Only 126 (42%) of the participants completed postpartum glucose testing, and these women were more likely to have reliable transportation, private insurance, college degrees, and higher annual household incomes (p < 0.05). Postpartum glucose testing was also associated with trust in clinicians (p = 0.01) but not health agency (p = 0.66). The association between trust and postpartum glucose testing persisted after adjusting for nonmodifiable barriers. CONCLUSION: Maximizing trust in clinicians should be a focus of prenatal GDM care to maximize the likelihood of postpartum glucose testing.

Subjective Wellness, Acute: Chronic Workloads, and Injury Risk in College Football.

Sampson, JA, Murray, A, Williams, S, Sullivan, A, and Fullagar, HHK. Subjective wellness, acute: chronic workloads and injury risk in college football. J Strength Cond Res 33(12): 3367-3373, 2019-Acute:chronic workload ratios (ACWRs) are associated with injury risk across team sports. In this study, one season of workload and wellness data from 42 collegiate football players were retrospectively analyzed. Daily 7:21 day exponentially weighted moving average (EWMA) ACWRs were calculated, and z-score fluctuations ("normal," "better," and "worse") in sleep, soreness, energy, and overall wellness were assessed relative to the previous day ACWRs and considered as an interactive effect on the risk of noncontact injury within 0-3 days. Fifty-five noncontact injuries were observed, and injury risks were very likely higher when ACWRs were 2 SDs above (relative risk [RR]: 3.05, 90% confidence interval [CI]: 1.14-8.16) and below (RR: 2.49, 90% CI: 1.11-5.58) the mean. A high ACWR was trivially associated (p < 0.05) with "worse" wellness (r = -0.06, CI: -0.10 to -0.02), muscle soreness (r = -0.07, CI: -0.11 to -0.03), and energy (r = -0.05, CI: -0.09 to -0.01). Feelings of "better" overall wellness and muscle soreness with collectively high EWMA ACWRs displayed likely higher injury risks compared with "normal" (RR: 1.52, 90% CI: 0.91 to 2.54; RR: 1.64, 90% CI: 1.10-2.47) and likely or very likely (RR: 2.36, 90% CI: 0.83 to 674; RR: 2.78, 90% CI: 1.21-6.38) compared with "worse" wellness and soreness, respectively. High EWMA ACWRs increased injury risk and negatively impacted wellness. However, athletes reporting "better" wellness, driven by "better" muscle soreness presented with the highest injury risk when high EWMA ACWRs were observed. This suggests that practitioners are responsive to, and/or athletes are able to self-modulate workload activities.

Evidence for finely-regulated asynchronous growth of Toxoplasma gondii cysts based on data-driven model selection.

Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system. Analyzing these interactions is important for understanding the pathogenesis of this common infection. We developed a differential equation framework of cyst growth and employed Akaike Information Criteria (AIC) to determine the growth and removal functions that best describe the distribution of cyst sizes measured from the brains of chronically infected mice. The AIC strongly support models in which T. gondii cysts grow at a constant rate such that the per capita growth rate of the parasite is inversely proportional to the number of parasites within a cyst, suggesting finely-regulated asynchronous replication of the parasites. Our analyses were also able to reject the models where cyst removal rate increases linearly or quadratically in association with increase in cyst size. The modeling and analysis framework may provide a useful tool for understanding the pathogenesis of infections with other cyst producing parasites.

What impact do self-referral and direct access pathways for patients have on health inequalities?

BACKGROUND: There is increasing interest in self-referral and direct access as alternatives pathways to care to improve patient access to specialist services. The impact of these pathways on health inequalities is unknown. OBJECTIVES: The purpose of this systematic review is to explore the impact of self-referral and direct access pathways on inequalities in health care use. DESIGN: Three databases (Ovid Medline, Embase, Web of Science) and grey literature were systematically searched for articles from January 2000 to February 2023, reporting on self-referral and direct access pathways to care. Title and abstracts were screened against eligibility criteria to identify studies that evaluated the impact on health inequalities. Data were extracted from eligible studies after full text review and a quality assessment was performed using the ROBINS-I tool. RESULTS: The search strategy identified 2948 articles. Nineteen records were included, covering seven countries and six healthcare services. The impact of self-referral and direct access on inequalities was mixed, suggesting that the relationship is dependent on patient and system factors. Typically self-referral pathways and direct access pathways tend to widen health inequalities. White, younger, educated women from less deprived backgrounds are more likely to self-refer, exacerbating existing health inequalities. CONCLUSIONS: Self-referral pathways risk widening health inequalities. Further research is required to understand the context-dependent mechanisms by which this can occur, explore ways to mitigate this and even narrow health inequalities, as well as understand the impact on the wider healthcare system.

The safety and efficacy of stem cells for the treatment of severe community-acquired bacterial pneumonia: A randomized clinical trial.

PURPOSE: Evaluate the safety profile of expanded allogeneic adipose-derived mesenchymal stem cell (eASC) for the treatment of severe community-acquired bacterial pneumonia (CABP). MATERIALS AND METHODS: Randomized, multicenter, double-blind, placebo-controlled, phase 1b/2a trial. Patients with severe CABP were enrolled to receive intravenous infusions of Cx611 or placebo. The primary objective was safety including hypersensitivity reactions, thromboembolic events, and immunological responses to Cx611. The secondary endpoints included the clinical cure rate, ventilation-free days, and overall survival (Day 90). RESULTS: Eighty-three patients were randomized and received infusions (Cx611: n = 42]; placebo: n = 41]. The mean age was similar (Cx611: 61.1 [11.2] years; placebo: 63.4 [10.4] years). The number of AEs and treatment-emergent AEs were similar (243; 184 and 2; 1) in Cx611 and placebo respectively. Hypersensitivity reactions or thromboembolic events were similar (Cx611: n = 9; placebo: n = 12). Each study arm had similar anti-HLA antibody/DSA levels at Day 90. The clinical cure rate (Cx611: 86.7%; placebo: 93.8%), mean number of ventilator-free days (Cx611: 12.2 [10.29] days; placebo: 15.4 [10.75] days), and overall survival (Cx611: 71.5%; placebo: 77.0%) did not differ between study arms. CONCLUSION: Cx611 was well tolerated in severe CABP. These data provide insights for future stem cell clinical study designs, endpoints and sample size calculation. TRIAL REGISTRATION: NCT03158727 (retrospectively registered: May 09, 2017). Full study protocol: https://clinicaltrials.gov/ProvidedDocs/27/NCT03158727/Prot_000.pdf.

Determining the feasibility of calculating pancreatic cancer risk scores for people with new-onset diabetes in primary care (DEFEND PRIME): study protocol.

INTRODUCTION: Worldwide, pancreatic cancer has a poor prognosis. Early diagnosis may improve survival by enabling curative treatment. Statistical and machine learning diagnostic prediction models using risk factors such as patient demographics and blood tests are being developed for clinical use to improve early diagnosis. One example is the Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) model, which employs patients' age, blood glucose and weight changes to provide pancreatic cancer risk scores. These values are routinely collected in primary care in the UK. Primary care's central role in cancer diagnosis makes it an ideal setting to implement ENDPAC but it has yet to be used in clinical settings. This study aims to determine the feasibility of applying ENDPAC to data held by UK primary care practices. METHODS AND ANALYSIS: This will be a multicentre observational study with a cohort design, determining the feasibility of applying ENDPAC in UK primary care. We will develop software to search, extract and process anonymised data from 20 primary care providers' electronic patient record management systems on participants aged 50+ years, with a glycated haemoglobin (HbA1c) test result of ≥48 mmol/mol (6.5%) and no previous abnormal HbA1c results. Software to calculate ENDPAC scores will be developed, and descriptive statistics used to summarise the cohort's demographics and assess data quality. Findings will inform the development of a future UK clinical trial to test ENDPAC's effectiveness for the early detection of pancreatic cancer. ETHICS AND DISSEMINATION: This project has been reviewed by the University of Surrey University Ethics Committee and received a favourable ethical opinion (FHMS 22-23151 EGA). Study findings will be presented at scientific meetings and published in international peer-reviewed journals. Participating primary care practices, clinical leads and policy makers will be provided with summaries of the findings.

Examining Associations Between Resilience and Sexual Health Among South African Girls and Young Women Living With and Without HIV.

Resilience, or multilevel processes related to thriving, offers a strengths-based approach to reducing HIV and sexual risk behaviors among girls and young women. Processes of resilience may change based on the experience of living with HIV. However, little is known about how resilience and serologically verified HIV status influence sexual health. Using weighted cross-sectional data collected during 2017-2018 from South African girls and young women aged 15-24 (N = 7237), this article examines associations between resilience and three sexual risk behaviors among those living with and without HIV. Logistic regression models indicated greater resilience scores were associated with reduced odds of engaging in transactional sex and early sexual debut. Results also identified differing associations between resilience and sexual risk behaviors by HIV status. Findings provide implications for programming to prevent HIV and improve sexual health while underscoring the need for tailored resilience-promoting interventions for South African girls and young women living with HIV.

Antibody titer levels and the effect on subsequent SARS-CoV-2 infection in a large US-based cohort.

Despite a growing amount of data around the kinetics and durability of the antibody response induced by vaccination and previous infection, there is little understanding of whether or not a given quantitative level of antibodies correlates to protection against SARS-CoV-2 infection or reinfection. In this study, we examine SARS-CoV-2 anti-spike receptor binding domain (RBD) antibody titers and subsequent SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) tests in a large cohort of US-based patients. We analyzed antibody test results in a cohort of 22,204 individuals, 6.8% (n = 1,509) of whom eventually tested positive for SARS-CoV-2 RNA, suggesting infection or reinfection. Kaplan-Meier curves were plotted to understand the effect of various levels of anti-spike RBD antibody titers (classified into discrete ranges) on subsequent RT-PCR positivity rates. Statistical analyses included fitting a Cox proportional hazards model to estimate the age-, sex- and exposure-adjusted hazard ratios for S antibody titer, using zip-code positivity rates by week as a proxy for COVID-19 exposure. It was found that the best models of the temporally associated infection risk were those based on log antibody titer level (HR = 0.836 (p < 0.05)). When titers were binned, the hazard ratio associated with antibody titer >250 Binding Antibody Units (BAU) was 0.27 (p < 0.05, 95% CI [0.18, 0.41]), while the hazard ratio associated with previous infection was 0.20 (p < 0.05, 95% CI [0.10, 0.39]). Fisher exact odds ratio (OR) for Ab titers <250 BAU showed OR = 2.84 (p < 0.05; 95% CI: [2.30, 3.53]) for predicting the outcome of a subsequent PCR test. Antibody titer levels correlate with protection against subsequent SARS-CoV-2 infection or reinfection when examining a cohort of real-world patients who had the spike RBD antibody assay performed.

Single-handed versus multiple-handed General practices: A cross-sectional study of quality outcomes in England.

OBJECTIVES: As general practice increasingly moves towards large group practices, there is debate about the relative benefits, safety and sustainability of different care delivery models. This study investigates the performance of single-handed practices compared to practices with multiple doctors in England, UK. METHODS: Practices in England with more than 1000 patients were included. Workforce data and a quality control process classified practices as single-handed or multiple-handed. Outcomes were (i) GP patient survey scores measuring access, continuity, confidence in health professional and overall satisfaction; (ii) reported diabetes and hypertension outcomes; and (iii) emergency department presentation rates and cancer detection (percentage of cancers diagnosed by a 2-week wait). Generalised linear models, controlling for patient and practice characteristics, compared outcomes in single and multiple-handed practices and assessed the effect of GP age in single-handed practices. RESULTS: Single-handed practices were more commonly found in areas of high deprivation (41% compared to 20% of multiple-handed practices). Single-handed practices had higher patient-reported access, continuity and overall satisfaction but slightly lower diabetes management and cancer detection rates. Emergency department presentations were higher when controlling for patient characteristics in single-handed practices but not when also controlling for practice rurality and size. Increased deprivation was associated with lower performance in seven out of eight outcomes. CONCLUSIONS: We found single-handed practices to be associated with high patient satisfaction while performing slightly less well on selected clinical outcomes. Further research is required to better understand the association between practice size, including increasing multidisciplinary working, on patient experience and outcomes.

An agent-based model for the transmission dynamics of Toxoplasma gondii.

Toxoplasma gondii (T. gondii) is a unicellular protozoan that infects up to one-third of the world's human population. Numerous studies revealed that a latent infection of T. gondii can cause life-threatening encephalitis in immunocompromised people and also has significant effects on the behavior of healthy people and animals. However, the overall transmission of T. gondii has not been well understood although many factors affecting this process have been found out by different biologists separately. Here we synthesize what is currently known about the natural history of T. gondii by developing a prototype agent-based model to mimic the transmission process of T. gondii in a farm system. The present model takes into account the complete life cycle of T. gondii, which includes the transitions of the parasite from cats to environment through feces, from contaminated environment to mice through oocysts, from mice to cats through tissue cysts, from environment to cats through oocysts as well as the vertical transmission among mice. Although the current model does not explicitly include humans and other end-receivers, the effect of the transition to end-receivers is estimated by a developed infection risk index. The current model can also be extended to include human activities and thus be used to investigate the influences of human management on disease control. Simulation results reveal that most cats are infected through preying on infected mice while mice are infected through vertical transmission more often than through infection with oocysts, which clearly suggests the important role of mice during the transmission of T. gondii. Furthermore, our simulation results show that decreasing the number of mice on a farm can lead to the eradication of the disease and thus can lower the infection risk of other intermediate hosts on the farm. In addition, with the assumption that the relation between virulence and transmission satisfies a normal function, we show that intermediate virulent lineages (type II) can sustain the disease most efficiently, which can qualitatively agree with the fact that the evolution of the parasite favors intermediate virulence. The effects of other related factors on transmission, including the latent period and imprudent behavior of mice, and prevention strategies are also studied based on the present model.

Child and Adolescent Abuse Patterns and Incident Obesity Risk in Young Adulthood.

INTRODUCTION: Child abuse is associated with adult obesity. Yet, it is unknown how the developmental timing and combination of abuse types affect this risk. This report examined how distinct child and adolescent abuse patterns were associated with incident obesity in young adulthood. METHODS: Data came from 7,273 participants in the Growing Up Today Study, a prospective cohort study in the U.S. with 14 waves from 1996 to 2016 (data were analyzed during 2020-2021). An abuse group variable was empirically derived using latent class analysis with indicators for child (before age 11 years) and adolescent (ages 11-17 years) physical, sexual, and emotional abuse. Risk ratios for obesity developing during ages 18-30 years were estimated using modified Poisson models. Associations of abuse groups with BMI across ages 18-30 years were then examined using mixed-effects models. All models were stratified by sex. RESULTS: Among women, groups characterized by abuse had higher BMIs entering young adulthood and greater changes in BMI per year across young adulthood. Groups characterized by multiple abuse types and abuse sustained across childhood and adolescence had approximately twice the risk of obesity as that of women in a no/low abuse group. Associations were substantially weaker among men, and only a group characterized by physical and emotional abuse in childhood and adolescence had an elevated obesity risk (risk ratio=1.38; 95% CI=1.04, 1.83). CONCLUSIONS: Obesity risk in young adulthood varied by distinct abuse groups for women and less strongly for men. Women who experience complex abuse patterns have the greatest risk of developing obesity in young adulthood.

A population-based analysis of the longevity of SARS-CoV-2 antibody seropositivity in the United States.

BACKGROUND: This cross-sectional study aimed to track population-based SARS-CoV-2 antibody seropositivity duration across the United States using observational data from a national clinical laboratory registry of patients tested by nucleic acid amplification (NAAT) and serologic assays. Knowledge of antibody seropositivity and its duration may help dictate post-pandemic planning. METHODS: Using assays to detect antibodies to either nucleocapsid (N) or spike (S) proteins performed on specimens from 39,086 individuals with confirmed positive COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR) from March 2020 to January 2021, we analyzed nationwide seropositivity rates of IgG up to 300 days following patients' initial positive NAAT test. Linear regression identified trends in seropositivity rates and logistic regression tested positive predictability by age, sex, assay type and days post-infection. FINDINGS: Seropositivity of IgG antibodies to both SARS-CoV-2 S and N-proteins followed a linear trend reaching approximately 90% positivity at 21 days post-index. The rate of N-protein seropositivity declined at a sharper rate, decaying to 68·2% [95% CI: 63·1-70·8%] after 293 days, while S-antibody seropositivity maintained a rate of 87·8% [95% CI: 86·3-89·1%] through 300 days. In addition to antigen type and the number of days post-positive PCR, age and gender were also significant factors in seropositivity prediction, with those under 65 years of age showing a more sustained seropositivity rate. INTERPRETATION: Observational data from a national clinical laboratory, though limited by an epidemiological view of the U.S. population, offer an encouraging timeline for the development and sustainability of antibodies up to ten months from natural infection and could inform post-pandemic planning.

Follow-Up SARS-CoV-2 PCR Testing Outcomes From a Large Reference Lab in the US.

By analyzing COVID-19 sequential COVID-19 test results of patients across the United States, we herein attempt to quantify some of the observations we've made around long-term infection (and false-positive rates), as well as provide observations on the uncertainty of sampling variability and other dynamics of COVID-19 infection in the United States. Retrospective cohort study of a registry of RT-PCR testing results for all patients tested at any of the reference labs operated by Labcorp® including both positive, negative, and inconclusive results, from March 1, 2020 to January 28, 2021, including patients from all 50 states and outlying US territories. The study included 22 million patients with RT-PCR qualitative test results for SARS-CoV-2, of which 3.9 million had more than one test at Labcorp. We observed a minuscule <0.1% basal positive rate for follow up tests >115 days, which could account for false positives, long-haulers, and/or reinfection but is indistinguishable in the data. In observing repeat-testing, for patients who have a second test after a first RT-PCR, 30% across the cohort tested negative on the second test. For patients who test positive first and subsequently negative within 96 h (40% of positive test results), 18% of tests will subsequently test positive within another 96-h span. For those who first test negative and then positive within 96 h (2.3% of negative tests), 56% will test negative after a third and subsequent 96-h period. The sudden changes in RT-PCR test results for SARS-CoV-2 from this large cohort study suggest that negative test results during active infection or exposure can change rapidly within just days or hours. We also demonstrate that there does not appear to be a basal false positive rate among patients who test positive >115 days after their first RT-PCR positive test while failing to observe any evidence of widespread reinfection.

Characteristics and Predictors of Radiographic Local Failure in Patients With Spinal Metastases Treated With Palliative Conventional Radiation Therapy.

PURPOSE: Although local control is an important issue for longer-term survivors of spinal metastases treated with conventional external beam radiation therapy (EBRT), the literature on radiographic local failure (LF) in these patients is sparse. To inform clinical decision-making, we evaluated rates, consequences, and predictors of radiographic LF in patients with spinal metastases managed with palliative conventional EBRT alone. METHODS AND MATERIALS: We retrospectively reviewed 296 patients with spinal metastases who received palliative EBRT at a single institution (2006-2013). Radiographic LF was defined as radiologic progression within the treatment field, with death considered a competing risk. Kaplan-Meier, cumulative incidence, and Cox regression analyses determined overall survival estimates, LF rates, and predictors of LF, respectively. RESULTS: There were 182 patients with follow-up computed tomography or magnetic resonance imaging; median overall survival for these patients was 7.7 months. Patients received a median of 30 Gy in 10 fractions to a median of 4 vertebral bodies. Overall, 74 of 182 patients (40.7%) experienced LF. The 6-, 12-, and 18-month LF rates were 26.5%, 33.1%, and 36.5%, respectively, while corresponding rates of death were 24.3%, 38.1%, and 45.9%. Median time to LF was 3.8 months. Of those with LF, 51.4% had new compression fractures, 39.2% were admitted for pain control, and 35.1% received reirradiation; median time from radiation therapy (RT) to each of these events was 3.0, 5.7, and 9.2 months, respectively. Independent predictors of LF included single-fraction RT (8 Gy) (hazard ratio [HR], 2.592; 95% confidence interval [CI], 1.437-4.675; P = .002), lung histology (HR, 3.568; 95% CI, 1.532-8.309; P = .003), and kidney histology (HR, 4.937; 95% CI, 1.529-15.935; P = .008). CONCLUSIONS: Patients experienced a >30% rate of radiographic LF by 1 year after EBRT. Single-fraction RT and lung or kidney histology predicted LF. Given the high rates of LF for patients with favorable prognosis, assessing the risk of death versus LF is important for clinical decision-making.