Fine particulate matter pollution and risk of community-acquired sepsis

While air pollution has been associated with health complications, its effect on sepsis risk is unknown. We examined the association between fine particulate matter (PM2.5) air pollution and risk of sepsis hospitalization. We analyzed data from the 30,239 community-dwelling adults in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort linked with satellite-derived measures of PM2.5 data. We defined sepsis as a hospital admission for a serious infection with ≥2 systemic inflammatory response (SIRS) criteria. We performed incidence density sampling to match sepsis cases with 4 controls by age (±5 years), sex, and race. For each matched group we calculated mean daily PM2.5 exposures for short-term (30-day) and long-term (one-year) periods preceding the sepsis event. We used conditional logistic regression to evaluate the association between PM2.5 exposure and sepsis, adjusting for education, income, region, temperature, urbanicity, tobacco and alcohol use, and medical conditions. We matched 1386 sepsis cases with 5544 non-sepsis controls. Mean 30-day PM2.5 exposure levels (Cases 12.44 vs. Controls 12.34 µg/m3; p = 0.28) and mean one-year PM2.5 exposure levels (Cases 12.53 vs. Controls 12.50 µg/m3; p = 0.66) were similar between cases and controls. In adjusted models, there were no associations between 30-day PM2.5 exposure levels and sepsis (4th vs. 1st quartiles OR: 1.06, 95% CI: 0.85–1.32). Similarly, there were no associations between one-year PM2.5 exposure levels and sepsis risk (4th vs. 1st quartiles OR: 0.96, 95% CI: 0.78–1.18). In the REGARDS cohort, PM2.5 air pollution exposure was not associated with risk of sepsis

Family history of breast cancer and mammographic breast density in premenopausal women

Importance: Family history of breast cancer (FHBC) and mammographic breast density are independent risk factors for breast cancer, but the association of FHBC and mammographic breast density in premenopausal women is not well understood. Objectives: To investigate the association of FHBC and mammographic breast density in premenopausal women using both quantitative and qualitative measurements. Design, Setting, and Participants: This single-center cohort study examined 2 retrospective cohorts: a discovery set of 375 premenopausal women and a validation set of 14 040 premenopausal women. Data from women in the discovery set was collected between December 2015 and October 2016, whereas data from women in the validation set was collected between June 2010 and December 2015. Data analysis was performed between June 2018 and June 2020. Exposures: Family history of breast cancer (FHBC). Main Outcomes and Measures: The primary outcomes were mammographic breast density measured quantitatively as volumetric percent density using Volpara (discovery set) and qualitatively using BI-RADS (Breast Imaging Reporting and Data System) breast density (validation set). Multivariable regressions were performed using a log-transformed normal distribution for the discovery set and a logistic distribution for the validation set. Results: Of 14 415 premenopausal women included in the study, the discovery set and validation set had similar characteristics (discovery set with FHBC: mean [SD] age, 47.1 [5.6] years; 15 [17.2%] were Black or African American women and 64 [73.6%] were non-Hispanic White women; discovery set with no FHBC: mean [SD] age, 47.7 [4.5] years; 87 [31.6%] were Black or African American women and 178 [64.7%] were non-Hispanic White women; validation set with FHBC: mean [SD] age, 46.8 [7.3] years; 720 [33.4%] were Black or African American women and 1378 [64.0%] were non-Hispanic White women]; validation set with no FHBC: mean [SD] age, 47.5 [6.1] years; 4572 [38.5%] were Black or African American women and 6632 [55.8%] were non-Hispanic White women]). In the discovery set, participants who had FHBC were more likely to have a higher mean volumetric percent density compared with participants with no FHBC (11.1% vs 9.0%). In the multivariable-adjusted model, volumetric percent density was 25% higher (odds ratio [OR], 1.25 ;95% CI, 1.12-1.41) in women with FHBC compared with women without FHBC; and 24% higher (OR, 1.24; 95% CI, 1.10-1.40) in women who had 1 affected relative, but not significantly higher in women who had at least 2 affected relatives (OR, 1.40; 95% CI, 0.95-2.07) compared with women with no relatives affected. In the validation set, women with a positive FHBC were more likely to have dense breasts (BI-RADS 3-4) compared with women with no FHBC (BI-RADS 3: 41.1% vs 38.8%; BI-RADS 4: 10.5% vs 7.7%). In the multivariable-adjusted model, the odds of having dense breasts (BI-RADS 3-4) were 30% higher (OR, 1.30; 95% CI, 1.17-1.45) in women with FHBC compared with women without FHBC; and 29% higher (OR, 1.29; 95% CI, 1.14-1.45) in women who had 1 affected relative, but not significantly higher in women who had at least 2 affected relatives (OR, 1.38; 95% CI, 0.85-2.23) compared with women with no relatives affected. Conclusions and Relevance: In this cohort study, having an FHBC was positively associated with mammographic breast density in premenopausal women. Our findings highlight the heritable component of mammographic breast density and underscore the need to begin annual screening early in premenopausal women with a family history of breast cancer

Breast cancer mortality hot spots among Black women with de novo metastatic breast cancer

Background: Black women living in southern states have the highest breast cancer mortality rate in the United States. The prognosis of de novo metastatic breast cancer is poor. Given these mortality rates, we are the first to link nationally representative data on breast cancer mortality hot spots (counties with high breast cancer mortality rates) with cancer mortality data in the United States and investigate the association of geographic breast cancer mortality hot spots with de novo metastatic breast cancer mortality among Black women. Methods: We identified 7292 Black women diagnosed with de novo metastatic breast cancer in Surveillance, Epidemiology, and End Results (SEER). The county-level characteristics were obtained from 2014 County Health Rankings and linked to SEER. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for mortality between hot spot and non-hot spot counties. Results: Among 7292 patients, 393 (5.4%) resided in breast cancer mortality hot spots. Women residing in hot spots had similar risks of breast cancer-specific mortality (aHR = 0.99, 95% CI = 0.85 to 1.15) and all-cause mortality (aHR = 0.97, 95% CI = 0.84 to 1.11) as women in non-hot spots after adjusting for individual and tumor-level factors and treatments. Additional adjustment for county-level characteristics did not impact mortality. Conclusion: Living in a breast cancer mortality hot spot was not associated with de novo metastatic breast cancer mortality among Black women. Future research should begin to examine variation in both individual and population-level determinants, as well as in molecular and genetic determinants that underlie the aggressive nature of de novo metastatic breast cancer

Racial and ethnic differences in rural-urban trends in 5-year survival of patients with lung, prostate, breast, and colorectal cancers: 1975-2011 Surveillance, Epidemiology, and End Results (SEER)

Importance: Considering reported rural-urban cancer incidence and mortality trends, rural-urban cancer survival trends are important for providing a comprehensive description of cancer burden. Furthermore, little is known about rural-urban differences in survival trends by racial and ethnic groups. Objective: To examine national rural-urban trends in 5-year cancer-specific survival probabilities for lung, prostate, breast, and colorectal cancers in a diverse sample of racial and ethnic groups. Design, Setting, and Participants: This cross-sectional study used an epidemiologic assessment with 1975 to 2016 Surveillance, Epidemiology, and End Results (SEER) data to analyze patients diagnosed no later than 2011. Patients were classified as living in rural and urban counties based on the 2013 Rural-Urban Continuum Codes. Main Outcomes and Measures: The 5-year cancer-specific survival probability of urban and rural patients for each cancer type was estimated by fitting Cox proportional hazard regression models accounting for race, ethnicity, tumor characteristics, and other sociodemographic characteristics. A generalized linear regression model was used to estimate the mean estimated probability of survival for each stratum. Joinpoint regression analysis estimated periods of significant change in survival. Results: In this study, data from 3 659 417 patients with cancer (median [IQR] age, 67 [58-76]; 1 918 609 [52.4%] male; 237 815 [6.5%] Hispanic patients; 396 790 [10.8%] Black patients; 2 825 037 [77.2%] White patients) were analyzed, including 888 338 patients with lung cancer (24.3%), 750 704 patients with colorectal cancer (20.5%), 987 826 patients with breast cancer (27.0%) breast, and 1 023 549 patients with prostate cancer (28.0%). There were 430 353 rural patients (11.8%). Overall, there was an equal representation of rural and urban men. Rural patients were likely to be non-Hispanic White individuals, have more cases of distant tumors, and be older. Rural and non-Hispanic Black patients for all cancer types often had shorter survival. From 1975 to 2016, the 5-year lung cancer survival rate was shorter for non-Hispanic Black rural patients in 1975 at 48%, while increasing to 57% for both non-Hispanic Black urban and rural patients in 2011, but still the shortest among all cancer types. In 1975, the longest survival rate was observed in urban Asian and Pacific Islander patients with breast cancer at 86%, and in 2011, the longest survival rate was observed in urban non-Hispanic White patients with XX cancer at 92%. Conclusions and Relevance: Even after accounting for sociodemographic and tumor characteristics, these findings suggest that non-Hispanic Black patients with cancer are particularly vulnerable to cancer burden, and resources are urgently needed to reverse decades-old survival trends

Pre-Diagnostic Biomarkers of Metabolic Dysregulation and Cancer Mortality

INTRODUCTION: The obesogenic milieu is a pro-tumorigenic environment that promotes tumor initiation, angiogenesis and metastasis. In this prospective cohort, we examined the association between pre-diagnostic metabolic biomarkers, plasma adiponectin, resistin, leptin and lipoprotein (a), and the risk of cancer mortality. METHODS: Prospective data was obtained from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of Blacks and Whites followed from 2003 through 2012 for cancer mortality. We determined the association between metabolism biomarkers (log-transformed and tertiles) and risk of cancer mortality using Cox Proportional Hazards models with robust sandwich estimators to calculate the 95% confidence intervals (CIs), and adjusted for baseline covariates, including age, gender, income, education, physical activity, BMI, smoking status, alcohol use, and comorbidity score. RESULTS: Among 1764 participants with available biomarker data, each SD higher log-leptin was associated with a 54% reduced risk of total cancer mortality (HR: 0.46, 95% CI: 0.23 - 0.92) and obesity-related cancer mortality (HR: 0.55, 95% CI: 0.39-0.79). Among Blacks only, each SD higher log-resistin was associated with a nearly 7-fold increased risk of cancer mortality (adjusted HR: 6.68, 95% CI: 2.10 - 21.21). There were no significant associations of adiponectin or Lp(a) and cancer mortality. CONCLUSIONS: Leptin is involved in long-term regulation of energy balance, while resistin is involved in chronic inflammation and LDL production. These findings highlight the biological mechanisms linking metabolic dysregulation with cancer mortality, and the influence of resistin on cancer mortality only among Blacks suggests that this hormone may be a useful biomarker of racial differences in cancer mortality that deserves further study. IMPACT: Our observed increased risk of cancer mortality associated with higher serum resistin levels among Blacks suggests that if validated in larger cohorts, clinical strategies focused on resistin control may be a promising cancer prevention strategy

Gravitational Lorentz Violations from M-Theory

In an attempt to bridge the gap between M-theory and braneworld phenomenology, we present various gravitational Lorentz-violating braneworlds which arise from p-brane systems. Lorentz invariance is still preserved locally on the braneworld. For certain p-brane intersections, the massless graviton is quasi-localized. This also results from an M5-brane in a C-field. In the case of a p-brane perturbed from extremality, the quasi-localized graviton is massive. For a braneworld arising from global AdS_5, gravitons travel faster when further in the bulk, thereby apparently traversing distances faster than light.Comment: 13 pages, 1 figure, LaTeX, references added, minor corrections and addition

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Correction for Johansson et al., An open challenge to advance probabilistic forecasting for dengue epidemics.

Correction for “An open challenge to advance probabilistic forecasting for dengue epidemics,” by Michael A. Johansson, Karyn M. Apfeldorf, Scott Dobson, Jason Devita, Anna L. Buczak, Benjamin Baugher, Linda J. Moniz, Thomas Bagley, Steven M. Babin, Erhan Guven, Teresa K. Yamana, Jeffrey Shaman, Terry Moschou, Nick Lothian, Aaron Lane, Grant Osborne, Gao Jiang, Logan C. Brooks, David C. Farrow, Sangwon Hyun, Ryan J. Tibshirani, Roni Rosenfeld, Justin Lessler, Nicholas G. Reich, Derek A. T. Cummings, Stephen A. Lauer, Sean M. Moore, Hannah E. Clapham, Rachel Lowe, Trevor C. Bailey, Markel García-Díez, Marilia Sá Carvalho, Xavier Rodó, Tridip Sardar, Richard Paul, Evan L. Ray, Krzysztof Sakrejda, Alexandria C. Brown, Xi Meng, Osonde Osoba, Raffaele Vardavas, David Manheim, Melinda Moore, Dhananjai M. Rao, Travis C. Porco, Sarah Ackley, Fengchen Liu, Lee Worden, Matteo Convertino, Yang Liu, Abraham Reddy, Eloy Ortiz, Jorge Rivero, Humberto Brito, Alicia Juarrero, Leah R. Johnson, Robert B. Gramacy, Jeremy M. Cohen, Erin A. Mordecai, Courtney C. Murdock, Jason R. Rohr, Sadie J. Ryan, Anna M. Stewart-Ibarra, Daniel P. Weikel, Antarpreet Jutla, Rakibul Khan, Marissa Poultney, Rita R. Colwell, Brenda Rivera-García, Christopher M. Barker, Jesse E. Bell, Matthew Biggerstaff, David Swerdlow, Luis Mier-y-Teran-Romero, Brett M. Forshey, Juli Trtanj, Jason Asher, Matt Clay, Harold S. Margolis, Andrew M. Hebbeler, Dylan George, and Jean-Paul Chretien, which was first published November 11, 2019; 10.1073/pnas.1909865116. The authors note that the affiliation for Xavier Rodó should instead appear as Catalan Institution for Research and Advanced Studies (ICREA) and Climate and Health Program, Barcelona Institute for Global Health (ISGlobal). The corrected author and affiliation lines appear below. The online version has been corrected

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

Background: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non-OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction