Age Continuum Research Articles

Characterising the age-dependent effects of risk factors on type 1 diabetes progression.

Age is known to be one of the most important stratifiers of disease progression in type 1 diabetes. However, what drives the difference in rate of progression between adults and children is poorly understood. Evidence suggests that many type 1 diabetes disease predictors do not have the same effect across the age spectrum. Without a comprehensive analysis describing the varying risk profiles of predictors over the age continuum, researchers and clinicians are susceptible to inappropriate assessment of risk when examining populations of differing ages. We aimed to systematically assess and characterise how the effect of key type 1 diabetes risk predictors changes with age. Using longitudinal data from single- and multiple-autoantibody-positive at-risk individuals recruited between the ages of 1 and 45years in TrialNet's Pathway to Prevention Study, we assessed and visually characterised the age-varying effect of key demographic, immune and metabolic predictors of type 1 diabetes by employing a flexible spline model. Two progression outcomes were defined: participants with single autoantibodies (n=4893) were analysed for progression to multiple autoantibodies or type 1 diabetes, and participants with multiple autoantibodies were analysed (n=3856) for progression to type 1 diabetes. Several predictors exhibited significant age-varying effects on disease progression. Amongst single-autoantibody participants, HLA-DR3 (p=0.007), GAD65 autoantibody positivity (p=0.008), elevated BMI (p=0.007) and HOMA-IR (p=0.002) showed a significant increase in effect on disease progression with increasing age. Insulin autoantibody positivity had a diminishing effect with older age in single-autoantibody-positive participants (p<0.001). Amongst multiple-autoantibody-positive participants, male sex (p=0.002) was associated with an increase in risk for progression, and HLA DR3/4 (p=0.05) showed a decreased effect on disease progression with older age. In both single- and multiple-autoantibody-positive individuals, significant changes in HR with age were seen for multiple measures of islet function. Risk estimation using prediction risk score Index60 was found to be better at a younger age for both single- and multiple-autoantibody-positive individuals (p=0.007 and p<0.001, respectively). No age-varying effect was seen for prediction risk score DPTRS (p=0.861 and p=0.178, respectively). Multivariable analyses suggested that incorporating the age-varying effect of the individual components of these validated risk scores has the potential to enhance the risk estimate. Analysing the age-varying effect of disease predictors improves understanding and prediction of type 1 diabetes disease progression, and should be leveraged to refine prediction models and guide mechanistic studies.

Successful healthcare transition for youth with special healthcare needs is a team effort.

NPs care for persons across the age continuum and transitions commonly occur. Some are unexpected, like hospitalizations for acute illness or injury. Others are an expected consequence of growing up, like moving from pediatric to adult care models. Understanding the factors impacting healthcare transition is critical for successful outcomes.

High-Flow Nasal Cannula in Transport: Process, Results, and Considerations

ObjectiveThe current coronavirus disease 2019 pandemic has increased interest in the use of high-flow nasal cannula (HFNC) in the transport setting. The purpose of this report was to outline the clinical workflow of using HFNC in transport and the results of a retrospective chart review of patients undergoing interhospital transfer on HFNC. MethodsWe conducted a retrospective chart review of all patient transfers using HFNC between January 2018 and June 2019. The primary data abstracted from patient charts included patient demographics, transport distance, HFNC settings including flow rate in liters per minute and fraction of inspired oxygen (Fio2), and vital signs. ResultsThere was a total of 220 patients, 148 pediatric and 72 adult patients. Both pediatric groups experienced statistically significant reductions in heart rate, systolic blood pressure, and diastolic blood pressure. The most common flow rate for both pediatric groups was 10 L/min and 50 L/min for adults. For pediatrics, the most common settings ranged between 30% and 50% Fio2, with the most common setting being 30% Fio2. The adult Fio2 settings ranged from 30% to 100% Fio2, with the 2 most common settings being 50% Fio2 and 80% Fio2. No patients were intubated during the transport encounter. ConclusionOur study provides evidence that HFNC is feasible and tolerated by patients and is an additional option for noninvasive ventilation in transport across the age continuum. Future studies are needed to compare HFNC with other noninvasive modalities that include assessing patient tolerance and comfort as contributing factors and to identify indications and contraindications for use in the transport setting.

Pediatric reference intervals for 32 routine biochemical markers using the siemens healthineers atellica® CH assays in healthy children and adolescents

BackgroundPediatric reference intervals are essential for test interpretation. With development of newer analytical systems, de novo reference interval establishment is of necessary importance. In the current study, pediatric reference intervals were determined for 32 analytes using Siemens Healthineers Atellica® CH assays in the CALIPER cohort of healthy children and adolescents. MethodsApproximately 600 healthy children and adolescents were recruited with informed consent and collected serum samples were analyzed on the Siemens Healthineers Atellica® CH platform. Assays studied included enzymes, proteins, lipids, electrolytes, and additional markers Reference intervals were established according to Clinical and Laboratory Standards Institute (CLSI) guidelines. ResultsOf the 32 parameters, 26 required age partitioning and 18 required sex partitioning. Reference value distributions included consistent increases, decreases, and dynamic variation across the age continuum. Chloride, LDL cholesterol, glucose, lipase, sodium, and triglyceride demonstrated no age or sex-specific differences. ConclusionThe current study expands the clinical utility of the CALIPER database to include 32 Siemens Atellica® chemistry assays. Reference value distributions for Siemens assays mirrored those observed on other comparable assays/systems with few exceptions (e.g. lipase, direct and total bilirubin). These finding support the robustness of previously derived reference intervals in the CALIPER cohort and other global cohorts.

Diversity and Inclusion in Drug Development: Rethinking Intrinsic and Extrinsic Factors with Patient Centricity.

Diversity and Inclusion in Drug Development: Rethinking Intrinsic and Extrinsic Factors with Patient Centricity.

Risk of Engraftment Syndrome after Autologous Stem Cell Transplantation for Multiple Myeloma Increases with Age and Lower Dose of CD34+ Cells, but Is Not Impacted By Immunomodulatory Chemotherapy

Background: Engraftment syndrome (ES) has been observed post autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM), and may require treatment with immunosuppressive therapies and prolonged hospitalization. Risk factors for the development of ES have not been clearly defined, with conflicting reports as to the role of CD34+ cell dose and pre-ASCT therapy. Defining risk factors could lead to the development of strategies to mitigate the risk of ES.Methods : A cohort of 496 patients who received 596 ASCT for MM between January 2005 and December 2015 was reviewed. ES was defined as a combination of at least 2 symptoms not attributed to other causes including non-infectious fever, diarrhea, skin rash, pulmonary infiltrates or hepatic dysfunction starting from 3 days prior to 10 days post-engraftment. Potential risk factors for the development of ES were analyzed, including age, pre-ASCT therapy, mobilization regimen, pre-ASCT dialysis or radiation therapy, number of CD34+ cells infused, time from diagnosis to transplantation, and disease status at the time of transplantation. Pre-ASCT therapies included lenalidomide (Len), bortezomid (Bor) and Carfilzomib (Car). High risk disease (HRD) was defined as t(14;16), t(14;20), del 17p, t(4;14) or 1q gain by FISH, del 13q, monosomy 13 or hypodiploidy by standard cytogenetics, or high risk signature gene expression profiling. Kaplan Meier and Cox proportional hazard methods were employed.Results: The median age at ASCT was 61 years (range 39-84) and 58% were male. There were 153 incidents of ES by defined criteria, with 123 patients requiring corticosteroids, 6 patients requiring the addition of tacrolimus, and one patient death attributed to ES. Pre-ASCT radiation therapy, time from diagnosis to transplantation and disease status at the time of transplantation were not significantly associated with the development of ES. Patients who received Len (p=0.8840), Bor (p=0.2458), Len and Bor combination (0.6907), or Car (p=0.6818) did not have increased risk of ES. Cyclophosphamide (Cy) for mobilization resulted in higher collection of CD34+ cells, but was not significantly associated with the risk of ES (p=0.6095). The median CD34+ cell dose infused for patients with ES was 5.22 x 10e6/kg versus 5.91 x 10e6/kg for patients without ES. Higher doses of CD34+ cells infused were protective against ES (P=0.0030). Patients with HRD had a significantly higher risk for developing ES, vs patients with standard risk disease (P=0.0041). Patients age 60 and older at the time of ASCT were more likely to develop ES (p=0.0249), and the incidence of ES increased with age up to age 75 . OS by univariate analysis was worse for patients who experienced ES (p=0.0.49). In multivariate analysis, stratified by number of transplants, patients with ES had lower overall survival than patients without ES (p=0.0179) when accounting for HRD, progression and response at ASCT.Conclusions: Pre-ASCT chemotherapy with Bor, Car and/or Len has no effect on the incidence of ES. Stem cell mobilization regimen did not impact the incidence of ES, but higher CD34+ cell doses are protective against ES. Patients without ES have improved overall survival. Older patients are at greater risk for ES, and the risk increases along the age continuum up to age 75. Infusing higher doses of CD34+ cells could be a strategy to mitigate the risk of ES in older patients. [Display omitted] DisclosuresMcKiernan:Novartis: Speakers Bureau. Siegel:Merck: Consultancy; Celgene, Takeda, Amgen Inc, Novartis and BMS: Consultancy, Speakers Bureau. Vesole:Takeda: Speakers Bureau; Celgene: Speakers Bureau. Skarbnik:Novartis: Speakers Bureau; Seattle Genetics: Speakers Bureau; Gilead: Speakers Bureau; Genentech: Speakers Bureau; Abbvie: Other: Ad board, Speakers Bureau. Biran:Celgene, Amgen: Consultancy, Speakers Bureau; Takeda: Speakers Bureau. Richter:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Pecora:COTA: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Caladrius Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Goy:Genentech: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics / J&J: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Disease and Treatment Knowledge Deficits in Patients with Mild and Moderate Hemophilia May Impact Transition Readiness

Objectives: Demonstration of age appropriate disease and treatment knowledge is important in preparing adolescents with hemophilia for transition to adult care. Our pediatric hemophilia treatment center (HTC) aimed to use quality improvement (QI) methodology to develop a tool to assess and document transition skills in order to foster medical independence in a complex healthcare environment.Methods: A standardized transition tool questionnaire was developed for adolescent/young adult patients diagnosed with hemophilia A or B followed in the Nationwide Children's Hospital HTC. Key drivers for the project included; identifying age appropriate tool elements, development of an educational resource repository, development of communication strategies and development of educational strategies to address knowledge gaps identified through tool use. The Ohio State University adult HTC actively collaborated in tool development. A final 19 item paper tool was devised to assess the knowledge and skills of adolescent patients in the domains of fundamental hemophilia knowledge (6 items) and hemophilia treatment knowledge and skills (13 items). Each item had a potential score of 0 to 2 for a total score range of 0 to 36 points. An item score of 0 indicated an incorrect, incomplete or blank answer, 1 meant the patient could answer with assistance of family or staff and 2 represented an independently derived correct answer. Patients with hemophilia A or B aged 15-21 years who were seen for comprehensive hemophilia care were eligible to complete the tool with each comprehensive visit up to twice per year. Patients with mild and moderate disease are seen once per year while those with severe disease are seen twice per year. The tool was administered by hemophilia staff using a standard script. Once the tool was completed by the patient the hemophilia staff reviewed the answers with the patient and family and provided directed education for incorrectly answered items. The tool was scored independently by a hemophilia nurse and physician. If there was a discrepancy in scoring the answer was reviewed and the score was adjudicated. The final score results were entered into a password protected data collection instrument. Scores between patient groups were compared using a Mann-Whitney test.Results: The tool was introduced into clinic April 5, 2016 and data was collected through June 5, 2017. During the review period there were 28 eligible patients seen for comprehensive care and 27 patients completed the tool. In 1 case the source document of a completed tool was lost so this patient was eliminated from analysis. Of the remaining 26 patients there were a total of 36 tools to evaluate, 18 patients completed the tool during 1 clinic visit, 6 completed the tool at 2 separate successive visits and 2 patients completed the tool at 3 successive clinic visits. Twenty-five patients were male, and 1 was female, 17 had hemophilia A and 9 had hemophilia B, 15 had severe hemophilia, 7 had moderate disease and 4 had mild disease. The median baseline score for patients with mild and moderate disease (n=15) was 14 points which was significantly lower (p=0.0156) than those with severe hemophilia (n=21) who had a median score of 27 points. Of the 8 patients with multiple assessments, 5 improved their scores by an average of 9 points, and 3 patients had decreases in scores by an average of 5 points.Conclusions: Quality improvement methodology was used to successfully develop, implement and sustain use of a standardized transition tool in a pediatric HTC. The project identified knowledge and skill gaps and targeted educational opportunities in addition to fostering improved communication between staff at the pediatric and adult HTCs regarding the important topic of transition of care. The scores highlighted that patients with milder disease were at risk for less adequate knowledge about their hemophilia care than those with severe disease. Next steps include continued utilization of the tool and ongoing evaluation of scores to determine if the tool fosters sustained improvement in disease and treatment understanding as well as development of tools to span the age continuum. Ongoing collaboration between the adult and pediatric HTCs will be needed to determine if the tool increases successful transition to adult care. DisclosuresDunn:Shire: Consultancy, Other: Unrestricted educational grant, Research Funding; Biogen: Other: Unrestricted educational grant, Research Funding; Kedrion: Other: Unrestricted educational grant; CSL Behring: Consultancy, Other: Unrestricted educational grant; Bayer: Consultancy, Other: Unrestricted educational grant; World Federation of Hemophilia USA: Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Other: Unrestricted educational grant; Octapharma: Other: Unrestricted educational grant; Alnylam: Other: Unrestricted educational grant. Casto:Shire: Speakers Bureau. Biega:Shire: Speakers Bureau.

Tumor Long Interspersed Nucleotide Element-1 (LINE-1) Hypomethylation in Relation to Age of Colorectal Cancer Diagnosis and Prognosis.

Simple SummaryThe rising incidence of early-onset cancers diagnosed before 50 years in many body sites (including the colorectum) is a growing concern. Despite the many studies of early-onset colorectal cancer, the characteristics of colorectal cancer diagnosed at age 50 or slightly after (close to age 50) have not been adequately examined. Although epigenetic alterations are considered to play a role in early-onset colorectal cancer, the association of LINE-1 hypomethylation (that reflects global DNA hypomethylation) with the age of colorectal cancer diagnosis has not been thoroughly clarified. Using a database of 1356 colorectal cancers, we found that tumor LINE-1 hypomethylation was increasingly more common with decreasing age of colorectal cancer diagnosis and was associated with higher colorectal cancer-specific mortality. Our findings support the “age continuum” model that has substantial implications in research on cancers in not only the colorectum but also many other body sites.Evidence indicates the pathogenic role of epigenetic alterations in early-onset colorectal cancers diagnosed before age 50. However, features of colorectal cancers diagnosed at age 50–54 (hereafter referred to as “intermediate-onset”) remain less known. We hypothesized that tumor long interspersed nucleotide element-1 (LINE-1) hypomethylation might be increasingly more common with decreasing age of colorectal cancer diagnosis. In 1356 colorectal cancers, including 28 early-onset and 66 intermediate-onset cases, the tumor LINE-1 methylation level measured by bisulfite-PCR-pyrosequencing (scaled 0 to 100) showed a mean of 63.6 (standard deviation (SD) 10.1). The mean tumor LINE-1 methylation level decreased with decreasing age (mean 64.7 (SD 10.4) in age ≥70, 62.8 (SD 9.4) in age 55–69, 61.0 (SD 10.2) in age 50–54, and 58.9 (SD 12.0) in age <50; p < 0.0001). In linear regression analysis, the multivariable-adjusted β coefficient (95% confidence interval (CI)) (vs. age ≥70) was −1.38 (−2.47 to −0.30) for age 55–69, −2.82 (−5.29 to −0.34) for age 50–54, and −4.54 (−8.24 to −0.85) for age <50 (Ptrend = 0.0003). Multivariable-adjusted hazard ratios (95% CI) for LINE-1 methylation levels of ≤45, 45–55, and 55–65 (vs. >65) were 2.33 (1.49–3.64), 1.39 (1.05–1.85), and 1.29 (1.02–1.63), respectively (Ptrend = 0.0005). In conclusion, tumor LINE-1 hypomethylation is increasingly more common with decreasing age of colorectal cancer diagnosis, suggesting a role of global DNA hypomethylation in colorectal cancer arising in younger adults.

Effects of Antiretroviral Therapy in the Central Nervous System: Beyond Viral Suppression.

Persistence of cognitive, behavioral and, to a lesser extent, motor dysfunction in People living with HIV (PLWH) despite viral suppression has raised the question about the potential contribution of antiretroviral (ARV) compounds themselves. Converging clinical and experimental evidence support a contribution of ARV compounds. In this issue we explore the existing clinical evidence on the impact of antiretroviral therapy (ART) on the CNS across the age continuum and in women. We further examine cell type specific effects of ARV drugs as well as the class specific effects. Finally, underlying mechanisms for the observed clinical and experimental ARV-induced effects are discussed. To improve the quality of life for PLWH who are dependent on life-long ART for viral suppression, it is critical to minimize ARV-induced cellular and tissue dysfunction in the CNS.

COVID-19, promotion and provision of palliative care: reaching out, accounting for linguistic diversity.

The combined forces of economic globalization and international migration have resulted in specific challenges to palliative care systems. The COVID-19 pandemic has and is still greatly affecting elder populations as well as those across the age continuum living with long-standing chronic conditions or with pre-existing diverse unmet needs. While health promotion and palliative care may appear to be conceptually opposing fields, we argue that palliative care can and should fit under the umbrella of the health promotion continuum. This commentary seeks to discuss the importance of linguistic literacy and communication imperatives in the context of access to palliative care, given the broad, diversified and sensitive scope of care. While the pandemic has demonstrated that the public health responses of migrant host societies are deeply intertwined with policies as well as local rules and constraints, the promotion and provision of safe, timely and appropriate palliative care can be achieved through a sensitive assessment of differential contexts of diversity. The pandemic has painfully illustrated the need for a strong, respectful and equitable working partnership within the professions as well as with the civic society in order for the palliative needs of those exposed to a sustained risk not to be forgotten.

Which Physiological Swallowing Parameters Change with Healthy Aging?

Research suggests there are age-related changes in swallowing that do not constitute impairment (“presbyphagia”). The goal of this study was to explore the influence of age on quantitative measures of healthy swallowing by controlling for the effects of sex and sip volume in order to determine the specific characteristics of presbyphagia. Videofluoroscopy recordings of thin liquid swallows from 76 healthy adults (38 male), aged 21–82 were analysed. Blinded duplicate ratings of swallowing safety, efficiency, kinematics, and timing were made using the ASPEKT method. Hierarchical regression models were used to determine the effects of age, sex, and sip-volume on swallowing. There were no age-related changes in sip volume, number of swallows per bolus, frequency or severity of penetration-aspiration, duration of the hyoid-burst (HYB)-to-upper-esophageal-sphincter (UES) opening interval, time-to-laryngeal-vestibule-closure (LVC), peak hyoid position, hyoid speed, or pharyngeal residue. Significant changes seen with increasing age included: longer swallow reaction time, UES opening duration and LVC duration; larger pharyngeal area at rest and maximum constriction; and wider UES diameter. Male participants had larger sip volume and pharyngeal area at rest. Larger sip volumes were associated with multiple swallows per bolus and shorter hyoid-burst-to-UES opening intervals. These results help to define presbyphagic changes in swallowing that can be expected in healthy older adults up to 80 years of age, and distinguish them from changes that represent impairment. Certain parameters showed changes that were opposite in direction to changes that are usually considered to reflect impairment: longer UES opening, longer LVC duration and wider UES opening. These changes may reflect possible compensations for slower bolus transit. Further research is needed to determine the points along the age continuum where observed age-related changes in swallowing begin to emerge.

Polygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum.

Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevity-associated variants. Using a cohort of centenarians with maintained cognitive health (N = 343), a population-matched cohort of older adults from 5 cohorts (N = 2905), and summary statistics data from genome-wide association studies on parental longevity, we constructed a PRS including 330 variants that significantly discriminated between centenarians and older adults. This PRS was also associated with longer survival in an independent sample of younger individuals (p = .02), leading up to a 4-year difference in survival based on common genetic factors only. We show that this PRS was, in part, able to compensate for the deleterious effect of the APOE-ε4 allele. Using an integrative framework, we annotated the 330 variants included in this PRS by the genes they associate with. We find that they are enriched with genes associated with cellular differentiation, developmental processes, and cellular response to stress. Together, our results indicate that an extended human life span is, in part, the result of a constellation of variants each exerting small advantageous effects on aging-related biological mechanisms that maintain overall health and decrease the risk of age-related diseases.

Identifying metrics of success for transitional care practices in childhood cancer survivorship: a qualitative interview study of survivors

BackgroundAdolescent and young adult (AYA) childhood cancer survivors (CCS) should be empowered to continue their survivor-focused care as they transition into adult medicine. However, the majority of AYA-aged survivors become lost to follow up around the age of typical transition to adulthood. The purpose of this study was to identify, from the patient’s perspective, key factors that facilitate successful transitions to adult-centered survivorship care.MethodsA qualitative study was conducted with AYA CCS (n = 29) from the survivorship clinic of a single institution as key informants. Data were collected through a series of structured phone interviews and subjected to thematic content analysis.ResultsFour major themes with multiple subthemes were identified: (1) transition practices need to be flexible and individually tailored; (2) effective communication is critical to a successful transition; (3) continuity in providers is needed during the transition; and (4) comprehensive care means care that also addresses psycho-social well-being.ConclusionsFrom the perspective of AYA CCS, the ideal model of transitional survivorship care could include a patient navigator who promotes provider flexibility, consistent communication, and pro-active comprehensive care that encompasses both medical and psycho-social well-being. Models of care for CCS should be built to provide, or seamlessly facilitate, continuous survivor-focused care across the age continuum. A longitudinal relationship with a survivor-focused provider can help promote the values that CCS’ report as important in transitioning care from pediatric- to adult-centered care.

Frontline Interventions: Considerations for Modifying Fluids and Foods for Management of Feeding and Swallowing Disorders Across the Life Span.

Purpose Individuals with dysphagia across the age continuum may require dietary modifications of fluids and foods for safe and adequate oral intake. Considerations of this frontline intervention are presented in this clinical forum dedicated to the discussion of dysphagia. Method This clinical focus article reviews the technical challenges of providing modified fluids and foods across the life span as well as the literature specific to its origins, efficacy, challenges and solutions to standardization, and the methods for ensuring quality service delivery. Conclusion Dietary modification is an often-used method of dysphagia management that presents unique challenges to the clinician for successful application. Speech-language pathologists in clinical practice across all settings must remain dedicated to evidence-based practice as they navigate service delivery of this strategy to individuals with dysphagia across the life span.

CXCL9 and CXCL10 display an age-dependent profile in Chagas patients: a cohort study of aging in Bambui, Brazil

BackgroundChagas disease is endemic in Latin America and still represents an important public health problem in the region. Chronic cardiomyopathy is the most significant chronic form due to its association with morbidity and mortality. The last decade has seen increasing evidence that inflammatory cytokines and chemokines are responsible for the generation of inflammatory infiltrate and tissue damage, with chronic chagasic cardiomyopathy patients presenting a pro-inflammatory immune response. Although studies have evaluated the role of chemokines in experimental T. cruzi infection, few have addressed their systemic profile, especially for human infection and in aging populations. The present work aimed to use the data from a large population based study of older adults, conducted in an endemic area for Chagas disease, to examine the association between serum levels of cytokines and chemokines, T. cruzi infection and electrocardiogram (ECG) abnormality.MethodsThe present work evaluated serum levels of CCL2, CXCL9, CXCL10, CCL5, CXCL8, IL-1β, IL-6, TNF, IL-12 and IL-10 by Flow Cytometric Bead Array assay (CBA) and the results expressed in pg/ml. The baseline survey started in January 1st 1997, with 1284 participants of an aged population-based cohort. Participants signed an informed consent at baseline and at each subsequent visit and authorized death certificate and medical records verification.ResultsOur results demonstrated that Chagas disease patients had higher serum levels of CXCL9, CXCL10 and IL-1β and lower serum levels of CCL5 than non-infected subjects. Moreover, our data demonstrated that CXCL9 and CXCL10 increased in an age-dependent profile in Chagas disease patients.ConclusionTogether, this study provided evidences that serum biomarkers increase along the age continuum and may have potential implications for establishing clinical management protocols and therapeutic intervention in Chagas disease patients.

Colonization routes, microevolutionary genetic structure and conservation concerns in a remote widespread insular endemic grass: the case of the Azorean tussock grass Deschampsia foliosa

AbstractPopulation genetic structure and diversity and phylogeographical dispersal routes were assessed for the Azorean endemic grass Deschampsia foliosa using AFLP markers. This species occurs on seven islands in the archipelago and a sampling of populations from the three main geographical groups of islands was used, covering its known distribution. Principal coordinates analyses (PCoAs), Bayesian analyses and phylogenetic networks revealed different degrees of admixture for the central group (C) populations and a clear differentiation for the western group (W) and São Miguel island (in the eastern group, E) populations. The best K values corresponded to nine and 11 genetic groups, which were also confirmed by analysis of molecular variance. A low but significant correlation between genetic data and geography was observed, with most relevant barriers to gene flow generally placed between sub-archipelagos. We suggest a west-to-east isolation by distance dispersal model across an island age continuum with Flores–Corvo (W) and Pico (C) at the extremes of the dispersal path. An alternative scenario, also supported by the genetic data, implies an initial colonization of São Jorge (C), dispersal within C and following bidirectional dispersal to the W and E. The phylogeographical framework detected might be related to island age and to highly destructive volcanic events, and it supports the occurrence of cryptic diversity within D. foliosa. Genetic diversity estimators were highest for Pico island populations (C), lowest for São Miguel (E) and Flores (W) populations, and more divergent for the Corvo population (W). Conservation measures should be taken to preserve the genetic structure found across sub-archipelagos and islands.

Effects of age, sex, race/ethnicity, and allergy status in obesity-related pediatric asthma.

Obesity in children increases the risk for new asthma. How age, sex, race/ethnicity, and allergy status affect the relationship between obesity and asthma is unclear. This study describes the relationship between high body mass index (BMI) and incident asthma. We conducted a retrospective cohort study to compare asthma incidence among normal weight, overweight, and obese 2 to 6, 7 to 11, and 12 to 17 year olds to define the effects of sex, race/ethnicity, and allergy status. Weight status was determined at baseline and asthma incidence was defined as ≥2 asthma encounters and ≥1 asthma prescriptions. We used multivariable Poisson regression to estimate adjusted incident asthma rates and risk ratios. Data from 192 843 2 to 6 year olds, 157 284 7 to 11 year olds, and 157 369 12 to 17 year olds were included. The relative risks (95% confidence interval [CI]) of new asthma among obese children in 2 to 6 year olds, 7 to 11 year olds, and 12 to 17 year olds were 1.25 (1.15, 1.37), 1.49 (1.32, 1.69) and 1.40 (1.21, 1.63), respectively. Among children with underlying allergic rhinitis, obesity did not increase the risk of new asthma. In children without allergic rhinitis, the risk for obesity-related asthma was highest in 7 to 11 year olds (risk ratio = 1.50 95% CI, 1.33, 1.60). Before age 12, females had a higher risk for obesity-related asthma; but after age 12, obese males had a higher asthma risk (interaction P-value < .05). Obesity is a major preventable risk factor for pediatric asthma that appears to vary along the pediatric age continuum and depends on sex, race/ethnicity and atopy status.

A U.S. population-based study of insurance disparities in cancer survival among adolescents and young adults.

BackgroundAdolescents and young adults (AYA), patients age 15‐39, may experience worse outcomes than pediatric and adult patients. The aim of this paper was to document survival disparities associated with insurance status across the AYA age continuum in the United States.MethodsWe utilized the Surveillance, Epidemiologic, and End Results database to identify 66 556 AYA patients between 2007 and 2014 with 10 International Classification of Childhood Cancer diagnoses and calculated the Cox proportional hazard ratios of death for those with public or no insurance status compared to private insurance. The odds ratios of having a late stage of diagnosis by insurance status were also calculated.ResultsInsurance status was a statistically significant predictor of death for lymphoid leukemia (age 15‐19, 30‐34, and 35‐39), acute myeloid leukemia (age 15‐19 and 25‐29), Hodgkin lymphoma (all ages), non‐Hodgkin lymphoma (age 20‐24, 25‐29, 30‐34, and 35‐39), astrocytomas (age 30‐34), other gliomas (age 25‐29, 30‐34, and 35‐39), hepatic carcinomas (age 25‐29), fibrosarcomas, peripheral nerve and other fibrous tumors (age 30‐34), malignant gonadal germ cell tumors (age 20‐24, 25‐29, 30‐34, and 35‐39), and other and unspecified carcinomas (age 20‐24, 25‐29, 30‐34, and 35‐39), independent of stage at diagnosis. This hazard increased with age for most cancer types. Insurance status strongly predicted the odds of a metastatic cancer diagnosis for lymphoma, fibrosarcomas (age 15‐19), germ cell tumors, and other carcinomas.ConclusionsAYA in the US experience disparities in cancer survival based on insurance status, independent of late stage of presentation. Patients age 26‐39 may be especially vulnerable to health outcomes associated with poor socioeconomic status, treatment disparities, and poor access to care.

Sexual minority female youth and substance use disparities across development

Objectives: To estimate individual and group trajectories of substance use among heterosexual and sexual minority adolescent females (SMFs) and evaluate longitudinal substance use disparities.Methods: Annual self-reported substance use data (frequency of cigarette, alcohol, and marijuana use) across ages 13–20 years were used to estimate individual and group trajectories using the Pittsburgh Girls Study—a large population-based study of urban-living adolescents. Participants were 2263 females (ages 13–16 years at baseline of current analysis) who were 60% racial/ethnic minority, and 17% sexual minority (lesbian or bisexual). Multilevel models compared SMF versus heterosexual differences in substance use over time controlling for race, single parent status, public assistance status, and caregivers’ low education status.Results: SMFs reported higher frequencies of cigarette, alcohol, and marijuana use across the entire age continuum. SMFs demonstrated more rapid escalations in substance use during early adolescence resulting in larger substance use disparities by the time they reached emerging adulthood.Conclusions: Early adolescence is a critical period of risk for increases in substance use among SMFs. Early intervention and prevention efforts may help reduce the rapid escalation in substance use and decrease substance use disparities over time.

Dynamics of Organic Anion Transporter-Mediated Tubular Secretion during Postnatal Human Kidney Development and Maturation.

The neonatal and juvenile human kidney can be exposed to a variety of potentially toxic drugs (e.g., nonsteroidal anti-inflammatory drugs, antibiotics, antivirals, diuretics), many of which are substrates of the kidney organic anion transporters, OAT1 (SLC22A6, originally NKT) and OAT3 (SLC22A8). Despite the immense concern about the consequences of drug toxicity in this vulnerable population, the developmental regulation of OATs in the immature postnatal kidney is poorly understood. Recognizing that today it is difficult to obtain rich data on neonatal kidney handling of OAT probes due to technical, logistic, and ethical considerations, multiple older physiologic studies that used the prototypical organic anion substrate para-aminohippurate (PAH) were reanalyzed in order to provide a quantitative description of OAT-mediated tubular secretion across the pediatric age continuum. Parametric and semiparametric models were evaluated for kidney function outcome variables of interest (maximum tubular secretory capacity of PAH [TmPAH], effective renal plasma flow [ERPF], and GFR). Data from 119 neonates, infants, and children ranging in age from 1 day to 11.8 years were used to fit TmPAH, ERPF, and GFR as functions of postnatal age. TmPAH is low in the immediate postnatal period and increases markedly after birth, reaching 50% of the adult value (80 mg/min) at 8.3 years of age. During the first 2 years of life, TmPAH is lower than that of GFR when viewed as the fraction of the adult value. During postnatal human kidney development, proximal tubule secretory function-as measured using PAH, a surrogate for OAT-mediated secretion of organic anion drugs, metabolites, and toxins-is low initially but increases rapidly. Despite developmental differences between species, this overall pattern is roughly consistent with animal studies. The human data raise the possibility that the acquisition of tubular secretory function may not closely parallel glomerular filtration.