An integrated molecular risk score early in life for subsequent childhood asthma risk.

BACKGROUND: Numerous children present with early wheeze symptoms, yet solely a subgroup develops childhood asthma. Early identification of children at risk is key for clinical monitoring, timely patient-tailored treatment, and preventing chronic, severe sequelae. For early prediction of childhood asthma, we aimed to define an integrated risk score combining established risk factors with genome-wide molecular markers at birth, complemented by subsequent clinical symptoms/diagnoses (wheezing, atopic dermatitis, food allergy). METHODS: Three longitudinal birth cohorts (PAULINA/PAULCHEN, n = 190 + 93 = 283, PASTURE, n = 1133) were used to predict childhood asthma (age 5-11) including epidemiological characteristics and molecular markers: genotype, DNA methylation and mRNA expression (RNASeq/NanoString). Apparent (ap) and optimism-corrected (oc) performance (AUC/R2) was assessed leveraging evidence from independent studies (Naïve-Bayes approach) combined with high-dimensional logistic regression models (LASSO). RESULTS: Asthma prediction with epidemiological characteristics at birth (maternal asthma, sex, farm environment) yielded an ocAUC = 0.65. Inclusion of molecular markers as predictors resulted in an improvement in apparent prediction performance, however, for optimism-corrected performance only a moderate increase was observed (upto ocAUC = 0.68). The greatest discriminate power was reached by adding the first symptoms/diagnosis (up to ocAUC = 0.76; increase of 0.08, p = .002). Longitudinal analysis of selected mRNA expression in PASTURE (cord blood, 1, 4.5, 6 years) showed that expression at age six had the strongest association with asthma and correlation of genes getting larger over time (r = .59, p < .001, 4.5-6 years). CONCLUSION: Applying epidemiological predictors alone showed moderate predictive abilities. Molecular markers from birth modestly improved prediction. Allergic symptoms/diagnoses enhanced the power of prediction, which is important for clinical practice and for the design of future studies with molecular markers.

Associations of Historical Redlining With BMI and Waist Circumference in Coronary Artery Risk Development in Young Adults.

Introduction: Historical maps of racialized evaluation of mortgage lending risk (i.e., redlined neighborhoods) have been linked to adverse health outcomes. Little research has examined whether living in historically redlined neighborhoods is associated with obesity, differentially by race or gender. Methods: This is a cross-sectional study to examine whether living in historically redlined neighborhoods is associated with BMI and waist circumference among Black and White adults in 1985-1986. Participants' addresses were linked to the 1930s Home Owners' Loan Corporation maps that evaluated mortgage lending risk across neighborhoods. The authors used multilevel linear regression models clustered on Census tract, adjusted for confounders to estimate main effects, and stratified, and interaction models by (1) race, (2) gender, and (3) race by gender with redlining differentially for Black versus White adults and men versus women. To better understand strata differences, they compared Census tract-level median household income across race and gender groups within Home Owners' Loan Corporation grade. Results: Black adults (n=2,103) were more likely than White adults (n=1,767) to live in historically rated hazardous areas and to have higher BMI and waist circumference. Redlining and race and redlining and gender interactions for BMI and waist circumference were statistically significant (p<0.10). However, in stratified analyses, the only statistically significant associations were among White participants. White participants living in historically rated hazardous areas had lower BMI (ß=-0.63 [95% CI= -1.11, -0.15]) and lower waist circumference (ß=-1.50 [95% CI= -2.62, -0.38]) than those living in declining areas. Within each Home Owners' Loan Corporation grade, residents in White participants' neighborhoods had higher incomes than those living in Black participants' neighborhoods (p<0.0001). The difference was largest within historically redlined areas. Covariate associations differed for men, women, Black, and White adults, explaining the difference between the interaction and the stratified models. Race by redlining interaction did not vary by gender. Conclusions: White adults may have benefitted from historical redlining, which may have reinforced neighborhood processes that generated racial inequality in BMI and waist circumference 50 years later.

Tolerance induction through early feeding to prevent food allergy in infants and children with sensitization against food allergens (TIFFANI): rationale, study design, and methods of a randomized controlled trial.

BACKGROUND: Children with sensitization against foods have to be orally food-challenged before eating these foods for the first time. However, the waiting time for an oral food challenge (OFC) in Germany is about 3-6 months. In contrast, there are hints that an early introduction of allergenic foods might be protective regarding the development of food allergy. The aim of this clinical trial is therefore to investigate, whether an introduction and regular consumption of small amounts of food allergens is safe and will result in an increase of tolerance in children with sensitization against food allergens with unknown clinical relevance. METHODS: In this randomized, placebo-controlled, double-blind, single-center trial, 138 children (8 months to 4 years of age) sensitized to the target allergen(s) hen's egg, cow's milk, peanuts, and/or hazelnuts with unknown clinical relevance will be randomized in a 1:1 ratio to either an active or a placebo group, daily receiving a rusk-like biscuit powder with or without the target allergen(s) for 3-6 months until an OFC will be performed in routine diagnostics. The primary endpoint is an IgE-mediated food allergy to the primary target allergen, after the interventional period. DISCUSSION: Children with sensitization against food allergens with unknown clinical relevance often have to avoid the corresponding foods for several months until an OFC is performed. Therefore, the "window of opportunity" for an early preventive introduction of allergenic foods might be missed. This trial will assess whether an introduction of small allergen amounts will favor tolerance development in these children. TRIAL REGISTRATION: German Clinical Trials Register DRKS00032769. Registered on 02 October 2023.

Tolerance development in cow's milk-allergic children receiving amino acid-based formula with synbiotics: 36-Months follow-up of a randomized controlled trial (PRESTO Study).

The objective of the present study is to assess the rates of acquired tolerance to cow's milk (CM) after 36 months in subjects who consumed amino acid-based formula with synbiotics (AAF-S) or amino acid-based formula without synbiotics (AAF) during a 1-year intervention period in early life as part of the PRESTO study (Netherlands Trial Register number NTR3725). Differences in CM tolerance development between groups were analysed using a logistic regression model. Results show that the proportion of subjects (mean [±SD] age, 3.8 ± 0.27 years) who developed CM tolerance after 36 months was similar in the group receiving AAF-S (47/60 [78%]) and in the group receiving AAF (49/66 [74%]) (p = 0.253), that is, figures comparable to natural outgrowth of CM allergy. Our data suggest that the consumption of AAF and absence of exposure to CM peptides do not slow down CM tolerance acquisition.

Examining the role of social relationships on health and health behaviors in African American men with prostate cancer: a qualitative analysis.

PURPOSE: Cancer survivor cohort studies document the positive impact of health behaviors on cancer survivorship by influencing quality of life, comorbidity burden, and cancer recurrence. Social networks can be instrumental in supporting health behavior changes. This study used qualitative interviews to explore how social networks may impact health and health behaviors of African American Prostate Cancer Survivors (AAPCS) enrolled in Men Moving Forward (MMF), a lifestyle intervention designed with and for AAPCS. Specifically, we sought to understand how different relationships within social networks influence health and health behaviors, and to identify potential mechanisms for this influence. METHODS: Eighteen men who completed the MMF intervention participated in a semi-structured interview which explored social connections, health and health behaviors, stress, and the cancer experience. Interviews were recorded and transcribed, and thematic analysis was performed by two coders. RESULTS: Participants described robust social networks of friends and family. Four distinct yet overlapping themes were identified that described how relationships influence health and health behaviors among AAPCS: (1) provision of knowledge, (2) health and behavior history, (3) encouragement and support, and (4) shared behavior. CONCLUSIONS: These results provide initial insight into the types of relationships that influence health, and the intersecting and multifaceted mechanisms through which this influence occurs.

The impact of environmental conditions on non-communicable diseases in sub-Saharan Africa: A scoping review of epidemiologic evidence.

Background: The burden of non-communicable diseases (NCDs) in sub-Saharan Africa (SSA) is increasing. Environmental conditions such as heavy metals and air pollution have been linked with the incidence and mortality of chronic diseases such as cancer, as well as cardiovascular and respiratory diseases. We aimed to scope the current state of evidence on the impact of environmental conditions on NCDs in SSA. Methods: We conducted a scoping review to identify environmental conditions linked with NCDs in SSA by identifying studies published from January 1986 through February 2023. We searched African Index Medicus, Ovid Medline, Scopus, Web of Science, and Greenfile. Using the PICOS study selection criteria, we identified studies conducted in SSA focussed on physical environmental exposures and incidence, prevalence, and mortality of NCDs. We included only epidemiologic or quantitative studies. Results: We identified 6754 articles from electronic database searches; only 36 met our inclusion criteria and were qualitatively synthesised. Two studies were conducted in multiple SSA countries, while 34 were conducted across ten countries in SSA. Air pollution (58.3%) was the most common type of environmental exposure reported, followed by exposure to dust (19.4%), meteorological variables (13.8%), heavy metals (2.7%), soil radioactivity (2.7%), and neighbourhood greenness (2.7%). The examined NCDs included respiratory diseases (69.4%), cancer (2.7%), stroke (5.5%), diabetes (2.7%), and two or more chronic diseases (19.4%). The study results suggest an association between environmental exposures and NCDs, particularly for respiratory diseases. Only seven studies found a null association between environmental conditions and chronic diseases. Conclusions: There is a growing body of research on environmental conditions and chronic diseases in the SSA region. Although some cities in SSA have started implementing environmental monitoring and control measures, there remain high levels of environmental pollution. Investment can focus on improving environmental control measures and disease surveillance.

Asthma as a Risk Factor for Hospitalization in Children and Youth With COVID-19: A Retrospective Cohort Study.

BACKGROUND: Studies examining the association between asthma and hospitalization among children and youth with coronavirus disease 2019 (COVID-19) have yielded mixed results. Both asthma and COVID-19 hospitalization are characterized by racial, ethnic and socioeconomic disparities which also pattern geographically, yet no studies to date have adjusted for neighborhood context in the assessment of this association. METHODS: Mixed effects logistic regression was used to estimate the association between asthma and hospitalization due to COVID-19 in a sample of 28,997 children and youth diagnosed with COVID-19 in Milwaukee County, Wisconsin, from March 1, 2020, to May 31, 2022. Models adjusted for individual-level sociodemographic factors (age, gender, race, ethnicity and city/suburb residence) and season of diagnosis were examined as moderators. Random intercepts by census tract accounted for geographic variation in neighborhood factors and census tract-level measures of education, health and environment, and social and economic factors were assessed via childhood opportunity indices. RESULTS: Asthma history was statistically significantly associated with hospitalization due to COVID-19 among children and youth. Hospitalization rates varied statistically significantly by census tract, and results were unchanged after accounting for childhood opportunity indices and census tract. Season of diagnosis was not found to moderate the effect of asthma history on COVID-19 hospitalization. CONCLUSION: Our study suggests that asthma history is a risk factor for hospitalization in the context of COVID-19 infection among children and youth, warranting observation and follow-up of children with asthma as well as continued measures to prevent COVID-19 in this population.

Disparities in Cardiovascular Disease-Related Outcomes Among Cancer Survivors in the United States: A Systematic Review of the Literature.

BACKGROUND: Cancer and cardiovascular disease (CVD) are major causes of morbidity and mortality in the United States (US). Cancer survivors have increased risks for CVD and CVD-related mortality due to multiple factors including cancer treatment-related cardiotoxicity. Disparities are rooted in differential exposure to risk factors and social determinants of health (SDOH), including systemic racism. This review aimed to assess SDOH's role in disparities, document CVD-related disparities among US cancer survivors, and identify literature gaps for future research. METHODS: Following the Peer Review of Electronic Search Strategies (PRESS) guidelines, MEDLINE, PsycINFO, and Scopus were searched on March 15, 2021, with an update conducted on September 26, 2023. Articles screening was performed using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, a pre-defined Population, Exposure, Comparison, Outcomes, and Settings (PECOS) framework, and the Rayyan platform. A modified version of the Newcastle-Ottawa Scale was used to assess the risk of bias, and RAW Graphs for alluvial charts. This review is registered with PROSPERO under ID #CRD42021236460. RESULTS: Out of 7,719 retrieved articles, 24 were included, and discussed diverse SDOH that contribute to CVD-related disparities among cancer survivors. The 24 included studies had a large combined total sample size (n=7,704,645; median=19,707). While various disparities have been investigated, including rural-urban, sex, socioeconomic status, and age, a notable observation is that non-Hispanic Black cancer survivors experience disproportionately adverse CVD outcomes when compared to non-Hispanic White survivors. This underscores historical racism and discrimination against non-Hispanic Black individuals as fundamental drivers of CVD-related disparities. CONCLUSIONS: Stakeholders should work to eliminate the root causes of disparities. Clinicians should increase screening for risk factors that exacerbate CVD-related disparities among cancer survivors. Researchers should prioritise the investigation of systemic factors driving disparities in cancer and CVD and develop innovative interventions to mitigate risk in cancer survivors.

Healthcare provider experiences interacting with survivors of intimate partner violence: a qualitative study to inform survivor-centered approaches.

BACKGROUND: Intimate partner violence (IPV) remains a pervasive form of gender-based violence (GBV) that is largely undisclosed, especially among women seeking healthcare services in Uganda. Prioritizing survivor needs may improve IPV disclosure. This study explores healthcare worker experiences from provider-patient interactions with survivors seeking antenatal care services (ANC) in Uganda. METHODS: In-depth interviews were conducted among twenty-eight experienced healthcare providers in a rural and an urban-based ANC clinic in Eastern and Central Uganda. Providers were asked what they viewed as the needs and fears of women identified as having experienced any form of IPV. Iterative, inductive/deductive thematic analysis was conducted to discover themes regarding perceived needs, fears, and normalizing violence experienced by IPV survivors. RESULTS: According to healthcare providers, IPV survivors are unaware of available support services, and have need for support services. Providers reported that some survivors were afraid of the consequences of IPV disclosure namely, community stigma, worries about personal and their children's safety, retaliatory abuse, fear of losing their marriage, and partners' financial support. Women survivors also blamed themselves for IPV. Contextual factors underlying survivor concerns included the socio-economic environment that 'normalizes' violence, namely, some cultural norms condoning violence, and survivors' unawareness of their human rights due to self-blame and shame for abuse. CONCLUSIONS: We underscore a need to empower IPV survivors by prioritizing their needs. Results highlight opportunities to create a responsive healthcare environment that fosters IPV disclosure while addressing survivors' immediate medical and psychosocial needs, and safety concerns. Our findings will inform GBV prevention and response strategies that integrate survivor-centered approaches in Uganda.

The impact of the COVID-19 pandemic on cancer care including innovations implemented in Sub-Saharan Africa: A systematic review.

Background: The coronavirus 2019 (COVID-19) pandemic has caused disruptions in the delivery and utilisation of cancer services. The impact of these interruptions is disproportionately borne by low- and middle-income countries in Sub-Saharan Africa (SSA). There are speculations of increased late-stage presentation and mortality as services are returning to the pre-pandemic state. This review aims to explore the extent to which the COVID-19 pandemic impacted cancer services across SSA and to identify innovations implemented across SSA to mitigate the impacts. Methods: Using database-specific search strategies, a systematic literature search was conducted in PubMed, Ovid (MedLine), Web of Science, and African Index Medicus. Eligible studies included original research, reports, perspectives and summaries of national or regional outcomes published in the English language. The primary outcome was changes in the delivery and utilisation of cancer prevention and screening, diagnosis, treatment and follow-up services. The secondary outcome was to identify implemented innovations to mitigate the impact of the pandemic on service delivery. Results: Out of the 167 articles identified in the literature search, 46 were included in the synthesis. A majority (95.7%) of the included articles described suspension and/or delay of screening, diagnosis, and treatment services, although two studies (4.3%) described the continuation of services despite the lockdown. Care was additionally impacted by transportation limitations, shortages of staff and personal protective equipment, disruption of the medication supply chain and patients' fears and stigma associated with contracting COVID-19. A major innovation was the use of telemedicine and virtual platforms for patient consultation and follow-up during the pandemic in SSA. Furthermore, drones and mobile applications were used for sample collection, medication delivery and scheduling of treatment. In some instances, medication routes and treatment protocols were changed. Conclusions: The delivery and utilisation of cancer services decreased substantially during the pandemic. Cancer centres initiated innovative methods of care delivery, including telehealth and drone use, with long-term potential to mitigate the impact of the pandemic on service delivery. Cancer centres in SSA must explore sustainable, facility or country-specific innovations as services return to the pre-pandemic state. Registration: The review was registered in PROSPERO with registration number CRD42022351455.

Intimate partner violence and antenatal care utilization predictors in Uganda: an analysis applying Andersen's behavioral model of healthcare utilization.

BACKGROUND: Optimal utilization of antenatal care (ANC) services improves positive pregnancy experiences and birth outcomes. However, paucity of evidence exists on which factors should be targeted to increase ANC utilization among women experiencing intimate partner violence (IPV) in Uganda. OBJECTIVE: To determine the independent association between IPV exposure and ANC utilization as well as the predictors of ANC utilization informed by Andersen's Behavioral Model of Healthcare Utilization. METHODS: We analyzed 2016 Uganda Demographic and Health Survey data that included a sample of 1,768 women with children aged 12 to 18 months and responded to both ANC utilization and IPV items. Our outcome was ANC utilization, a count variable assessed as the number of ANC visits in the last 12 months preceding the survey. The key independent variable was exposure to any IPV form defined as self-report of having experienced physical, sexual and/or emotional IPV. Covariates were grouped into predisposing (age, formal education, religion, problem paying treatment costs), enabling (women's autonomy, mass media exposure), need (unintended pregnancy, parity, history of pregnancy termination), and healthcare system/environmental factors (rural/urban residence, spatial accessibility to health facility). Poisson regression models tested the independent association between IPV and ANC utilization, and the predictors of ANC utilization after controlling for potential confounders. RESULTS: Mean number of ANC visits (ANC utilization) was 3.71 visits with standard deviation (SD) of ± 1.5 respectively. Overall, 60.8% of our sample reported experiencing any form of IPV. Any IPV exposure was associated with lower number of ANC visits (3.64, SD ± 1.41) when compared to women without IPV exposure (3.82, SD ± 1.64) at p = 0.013. In the adjusted models, any IPV exposure was negatively associated with ANC utilization when compared to women with no IPV exposure after controlling for enabling factors (Coef. -0.03; 95%CI -0.06,-0.01), and healthcare system/environmental factors (Coef. -0.06; 95%CI -0.11,-0.04). Predictors of ANC utilization were higher education (Coef. 0.27; 95%CI 0.15,0.39) compared with no education, high autonomy (Coef. 0.12; 95%CI 0.02,0.23) compared to low autonomy, and partial media exposure (Coef. 0.06; 95%CI 0.01,0.12) compared to low media exposure. CONCLUSION: Addressing enabling and healthcare system/environmental factors may increase ANC utilization among Ugandan women experiencing IPV. Prevention and response interventions for IPV should include strategies to increase girls' higher education completion rates, improve women's financial autonomy, and mass media exposure to improve ANC utilization in similar populations in Uganda.

Spatial accessibility to health facilities among pregnant women with and without exposure to intimate partner violence in Uganda.

BACKGROUND: Poor physical access to health facilities could increase the likelihood of undetected intimate partner violence (IPV) during pregnancy. We aimed to determine sub-regional differences and associations between spatial accessibility to health facilities and IPV among pregnant women in Uganda. METHOD: Weighted cross-sectional analyses were conducted using merged 2016 Uganda Demographic and Health Survey and 2014 Uganda Bureau of Statistics health facility datasets. Our study population were 986 women who self-reported being currently pregnant and responded to IPV items. Outcome was spatial accessibility computed as the near point linear distance [< 5 km (optimal) vs. ≥ 5 km (low)] between women's enumeration area and health facility according to government reference cutoffs. Primary independent variable (any IPV) was defined as exposure to at least one of physical, emotional, and sexual IPV forms. Logistic regression models were sequentially adjusted for covariates in blocks based on Andersen's behavioral model of healthcare utilization. Covariates included predisposing (maternal age, parity, residence, partner controlling behavior), enabling (wealth index, occupation, education, economic empowerment, ANC visit frequency), and need (wanted current pregnancy, difficulty getting treatment money, afraid of partner, and accepted partner abuse) factors. RESULTS: Respondents' mean age was 26.1 years with ± 9.4 standard deviations (SD), mean number of ANC visits was 3.8 (± 1.5 SD) and 492/986 (49.9%) pregnant women experienced IPV. Median spatial accessibility to the nearest health facility was 4.1 km with interquartile range (IQR) from 0.2 to 329.1 km. Southwestern, and Teso subregions had the highest average percentage of pregnant women experiencing IPV (63.8-66.6%) while Karamoja subregion had the highest median spatial accessibility (7.0 to 9.3 km). In the adjusted analysis, pregnant women exposed to IPV had significantly higher odds of low spatial accessibility to nearest health facilities when compared to pregnant women without IPV exposure after controlling for enabling factors in Model 2 (aOR 1.6; 95%CI 1.2, 2.3) and need factors in Model 3 (aOR 1.5; 95%CI 1.1, 3.8). CONCLUSIONS: Spatial accessibility to health facilities were significantly lower among pregnant women with IPV exposure when compared to those no IPV exposure. Improving proximity to the nearest health facilities with ANC presents an opportunity to intervene among pregnant women experiencing IPV. Focused response and prevention interventions for violence against pregnant women should target enabling and need factors.

EAACI guidelines on the diagnosis of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance.

Efficacy and safety of peanut epicutaneous immunotherapy in patients with atopic comorbidities.

Background: Co-occurring atopic conditions are common in children with peanut allergy. As such, it is important to examine the safety and efficacy of epicutaneous immunotherapy with Viaskin Peanut 250 µg patch (VP250) in peanut-allergic children with these conditions. Objective: We sought to compare efficacy and safety of VP250 versus placebo in peanut-allergic children with/without ongoing atopic conditions at baseline, including asthma, atopic dermatitis/eczema, or concomitant food allergy. Methods: A subgroup analysis of peanut-allergic children aged 4 to 11 years enrolled in PEPITES (12 months) and REALISE (6 months) randomized, placebo-controlled, phase 3 trials was conducted. The efficacy outcome measure was the difference in prespecified responder rate between placebo and VP250 groups at month 12 based on eliciting dose of peanut protein using double-blind, placebo-controlled food challenge in PEPITES. Safety profiles were evaluated by baseline concomitant disease subgroup in all randomized subjects who received 1 or more dose of the study drug in PEPITES and REALISE pooled data. Results: Responder rates were significantly (P < .05, all comparisons) greater with VP250 compared with placebo treatment regardless of whether subjects had other atopic conditions. Safety and tolerability profiles were generally similar across subgroups, with no new safety concerns detected. A trend for both higher responder rates and rates of local reactions was observed in subjects with baseline atopic dermatitis versus those without. In subjects with concomitant food allergy at baseline, higher rates of treatment-emergent adverse events, but not study discontinuations or overall rates of anaphylaxis, were observed. Conclusions: The results support the safety and efficacy of VP250 for treating peanut-allergic children with or without concomitant atopic conditions.

Redlining-associated methylation in breast tumors: the impact of contemporary structural racism on the tumor epigenome.

Purpose: Place-based measures of structural racism have been associated with breast cancer mortality, which may be driven, in part, by epigenetic perturbations. We examined the association between contemporary redlining, a measure of structural racism at the neighborhood level, and DNA methylation in breast tumor tissue. Methods: We identified 80 Black and White women diagnosed and treated for a first-primary breast cancer at Emory University Hospitals (2008-2017). Contemporary redlining was derived for census tracts using the Home Mortgage Disclosure Act database. Linear regression models were used to calculate the association between contemporary redlining and methylation in breast tumor tissue. We also examined epigenetic age acceleration for two different metrics, regressing ß values for each cytosine-phosphate-guanine dinucleotide (CpG) site on redlining while adjusting for covariates. We employed multivariable Cox-proportional hazards models and 95% confidence intervals (CI) to estimate the association between aberrant methylation and mortality. Results: Contemporary redlining was associated with 5 CpG sites after adjustment for multiple comparisons (FDR<0.10). All genes were implicated in breast carcinogenesis, including genes related to inflammation, immune function and stress response (ANGPT1, PRG4 and PRG4). Further exploration of the top 25 CpG sites, identified interaction of 2 sites (MRPS28 and cg11092048) by ER status and 1 site (GDP1) was associated with all-cause mortality. Contemporary redlining was associated with epigenetic age acceleration by the Hannum metric (ß=5.35; CI 95%=0.30,10.4) and showed positive but non-significant correlation with the other clock. Conclusion: We identified novel associations between neighborhood contemporary redlining and the breast tumor DNA methylome, suggesting that racist policies leading to inequitable social and environmental exposures, may impact the breast tumor epigenome. Additional research on the potential implications for prognosis is needed.

Isolation and survival: The impact of local and MSA isolation on survival among non-Hispanic Black women diagnosed with breast cancer in the United States using a SEER-Medicare cohort.

BACKGROUND: Residential segregation is an important factor that negatively impacts cancer disparities, yet studies yield mixed results and complicate clear recommendations for policy change and public health intervention. In this study, we examined the relationship between local and Metropolitan Statistical Area (MSA) measures of Black isolation (segregation) and survival among older non-Hispanic (NH) Black women with breast cancer (BC) in the United States. We hypothesized that the influence of local isolation on mortality varies based on MSA isolation-specifically, that high local isolation may be protective in the context of highly segregated MSAs, as ethnic density may offer opportunities for social support and buffer racialized groups from the harmful influences of racism. METHODS: Local and MSA measures of isolation were linked by Census Tract (CT) with a SEER-Medicare cohort of 5,231 NH Black women aged 66-90 years with an initial diagnosis of stage I-IV BC in 2007-2013 with follow-up through 2018. Proportional and cause-specific hazards models and estimated marginal means were used to examine the relationship between local and MSA isolation and all-cause and BC-specific mortality, accounting for covariates (age, comorbidities, tumor stage, and hormone receptor status). FINDINGS: Of 2,599 NH Black women who died, 40.0% died from BC. Women experienced increased risk for all-cause mortality when living in either high local (HR = 1.20; CI = 1.08-1.33; p < 0.001) or high MSA isolation (HR = 1.40; CI = 1.17-1.67; p < 0.001). A similar trend existed for BC-specific mortality. Pairwise comparisons for all-cause mortality models showed that high local isolation was hazardous in less isolated MSAs but was not significant in more isolated MSAs. INTERPRETATION: Both local and MSA isolation are independently associated with poorer overall and BC-specific survival for older NH Black women. However, the impact of local isolation on survival appears to depend on the metropolitan area's level of segregation. Specifically, in highly segregated MSAs, living in an area with high local isolation is not significantly associated with poorer survival. While the reasons for this are not ascertained in this study, it is possible that the protective qualities of ethnic density (e.g., social support and buffering from experiences of racism) may have a greater role in more segregated MSAs, serving as a counterpart to the hazardous qualities of local isolation. More research is needed to fully understand these complex relationships. FUNDING: National Cancer Institute.

The effects of contemporary redlining on the mental health of Black residents.

Understanding how structural racism, including institutionalized practices such as redlining, influence persistent inequities in health and neighborhood conditions is still emerging in urban health research. Such research often focuses on historical practices, giving the impression that such practices are a thing of the past. However, mortgage lending bias can be readily detected in contemporary datasets and is an active form of structural racism with implications for health and wellbeing. The objective of the current study was to test for associations among multiple measures of mental health and a measure of contemporary redlining. We linked a redlining index constructed using Home Mortgage Disclosure Act data (2007-2013) to 2021 health data for Black/African American participants in the Study of Active Neighborhoods in Detroit (n = 220 with address data). We used multilevel regression models to examine the relationship between redlining and a suite of mental health outcomes (perceived stress, anxiety, depressive symptoms, and satisfaction with life), accounting for covariates including racial composition of the neighborhood. We considered three mediating factors: perceived neighborhood cohesion, aesthetics, and discrimination. Although all participants lived in redlined neighborhoods compared to the complete Detroit Metropolitan area, participants with very low income, low levels of experienced discrimination, and lower perceptions of neighborhood aesthetics resided in highly redlined neighborhoods (score ≥5). We observed that higher resident-reported neighborhood aesthetics were found in neighborhoods with lower redlining scores and were associated with higher levels of satisfaction with life. We found that lower levels of redlining were significantly associated with higher levels of perceived discrimination, which was significantly, positively associated with anxiety, depressive symptoms, and perceived stress scores. Our findings highlight that contemporary redlining practices may influence the aesthetics of the built environment because these neighborhoods experience less investment, with implications for residents' satisfaction with life. However, areas with lower redlining may be areas where Black/African American people experience increased perceived discrimination.

EAACI Molecular Allergology User's Guide 2.0.

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.

Vegan diets from an allergy point of view - Position paper of the DGAKI working group on food allergy.

Vegan diets are currently attracting a great deal of attention. However, avoiding animal-based foods restricts the diet and is associated with risks, the extent and medical implications of which are at present not sufficiently understood. Elimination diets represent the usual therapeutic long-term management in the presence of food allergy. In order to understand the risks of vegan diets and to discuss these critically from the perspective of food allergies, the expertise of a nutritionist/dietitian with expertise in this area is indispensable. This position paper deals with the incentives behind and the benefits of a plant-based diet. The knowledge required to cover macro- and micronutrient dietary requirements is presented. Using the avoidance of cow's milk as an example, the challenges of adequately meeting nutritional needs are identified and (so-called) milk alternatives are evaluated from an allergy and nutritional point of view. Finally, other plant-based (substitute) products are evaluated from the same perspective, as significant protein sources in vegan diets (e.g., legumes, nuts, and seeds) are at the same time potential and potent triggers of allergic reactions. However, the allergic potential of many substitute products cannot be fully assessed at present due to gaps in research. Wheat as the most important trigger for anaphylaxis in adults is also evaluated. Finally, the increase in ultra-processed products in the (vegan) food sector and their potential consequences for the immune system are discussed.

Post hoc analysis examining symptom severity reduction and symptom absence during food challenges in individuals who underwent oral immunotherapy for peanut allergy: results from three trials.

PURPOSE: Peanut allergy and its current management, involving peanut avoidance and use of rescue medication during instances of accidental exposure, are burdensome to patients and their caregivers and can be a source of stress, uncertainty, and restriction. Physicians may also be frustrated with a lack of effective and safe treatments other than avoidance in the current management of peanut allergy. Efficacy, determined using double-blind, placebo-controlled food challenges (DBPCFCs), of oral immunotherapy with peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; Palforzia®) was demonstrated versus placebo in children and adolescents aged 4 to 17 years in multiple phase 3 trials; continued benefit of PTAH was shown in a follow-on trial. The DBPCFC is a reproducible, rigorous, and clinically meaningful assessment accepted by regulatory authorities to evaluate the level of tolerance as an endpoint for accidental exposures to peanut in real life. It also provides useful clinical and patient-relevant information, including the amount of peanut protein an individual with peanut allergy can consume without experiencing dose-limiting symptoms, severity of symptoms, and organs affected upon ingestion of peanut protein. We explored symptoms of peanut exposure during DBPCFCs from phase 3 and follow-on trials of PTAH to further characterize treatment efficacy from a perspective relevant to patients, caregivers, and clinicians. METHODS: Symptom data recorded during screening and/or exit DBPCFCs from participants aged 4 to 17 years receiving PTAH or placebo were examined post hoc across three PTAH trials (PALISADE [ARC003], ARC004 [PALISADE follow-on], and ARTEMIS [ARC010]). The maximum peanut protein administered as a single dose during DBPCFCs was 1000 mg (PALISADE and ARTEMIS) and 2000 mg (ARC004). Symptoms were classified by system organ class (SOC) and maximum severity. Endpoints were changes in symptom severity and freedom from symptoms (ie, asymptomatic) during DBPCFC. Relative risk (RR) was calculated for symptom severity by SOC and freedom from symptoms between groups; descriptive statistics were used to summarize all other data. RESULTS: The risk of any respiratory (RR 0.42 [0.30-0.60], P < 0.0001), gastrointestinal (RR 0.34 [0.26-0.44], P < 0.0001), cardiovascular/neurological (RR 0.17 [0.08-0.39], P < 0.001), or dermatological (RR 0.33 [0.22-0.50], P < 0.0001) symptoms was significantly lower in participants treated with PTAH versus placebo upon exposure to peanut at the end of the PALISADE trial (ie, exit DBPCFC). Compared with placebo-treated participants (23.4%), the majority (76.3%) of PTAH-treated participants had no symptoms at the exit DBPCFC when tested at the peanut protein dose not tolerated (ie, reactive dose) during the screening DBPCFC. Significantly higher proportions of PTAH-treated participants were asymptomatic at doses ≤ 100 mg in the exit DBPCFC compared with placebo-treated participants (PALISADE: 69.35% vs 12.10%, RR 5.73 [95% confidence interval (CI) 3.55-9.26]; P < 0.0001; ARTEMIS: 67.42% vs 13.95%, RR 4.83 [95% CI 2.28-10.25]; P < 0.0001); findings were similar at peanut protein doses ≤ 1000 mg (PALISADE: RR 15.56 [95% CI 5.05-47.94]; P < 0.0001; ARTEMIS: RR 34.74 [95% CI 2.19-551.03]; P < 0.0001). In ARC004, as the period of PTAH maintenance became longer, greater proportions of participants were asymptomatic at doses of peanut protein ≤ 1000 mg in the exit DBPCFC (from 37.63% after ~ 6 months of maintenance treatment [exit DBPCFC of PALISADE] to 45.54% after ~ 13 months and 58.06% after ~ 20 months of overall PTAH maintenance treatment). CONCLUSIONS: PTAH significantly reduced symptom severity due to exposure to peanut, which is clinically relevant. When exposed to peanut, participants with peanut allergy treated with PTAH rarely had moderate or severe respiratory or cardiovascular/neurological symptoms. Oral immunotherapy with PTAH appears to reduce frequency and severity of allergic reactions in individuals with peanut allergy after accidental exposure to peanut and may enable them and their families to have an improved quality of life. Trial registration ClinicalTrials.gov, NCT02635776, registered 17 December 2015, https://clinicaltrials.gov/ct2/show/NCT02635776?term=AR101&draw=2&rank=7 ; ClinicalTrials.gov, NCT02993107, registered 08 December 2016, https://clinicaltrials.gov/ct2/show/NCT02993107?term=AR101&draw=2&rank=6 ; ClinicalTrials.gov, NCT03201003, registered 22 June 2017, https://clinicaltrials.gov/ct2/show/NCT03201003 ? term = AR101&draw = 2&rank = 9.