Healthy People establishes national goals and specific measurable objectives to improve the health and well-being of the nation. An overarching goal of Healthy People 2030 is to "eliminate health ...disparities, achieve health equity, and attain health literacy to improve the health and well-being of all." To inform Healthy People 2030 health equity and health disparities content and products, the US Department of Health and Human Services (HHS) Office of Disease Prevention and Health Promotion (ODPHP), in collaboration with NORC at the University of Chicago, conducted a review of peer-reviewed and gray literature to examine how health equity is defined, conceptualized, and measured by public health professionals.
We reviewed (1) peer-reviewed literature, (2) HHS and other public health organization Web sites, and (3) state and territorial health department plans. We also conducted targeted searches of the gray literature to identify tools and recommendations for measuring health equity.
While definitions of health equity identified in the scan varied, they often addressed similar concepts, including "highest level of health for all people," "opportunity for all," and "absence of disparities." Measuring health equity is challenging; however, strategies to measure and track progress toward health equity have emerged. There are a range of tools and resources that have the potential to help decision makers address health equity, such as health impact assessments, community health improvement plans, and adapting a Health in All Policies approach. Tools that visualize health equity data also support data-driven decision making.
Using similar language when discussing health equity will help align and advance efforts to improve health and well-being for all. Healthy People objectives, measures, and targets can help public health professionals advance health equity in their work. HHS ODPHP continues to develop Healthy People tools and resources to support public health professionals as they work with cross-sector partners to achieve health equity.
The mechanisms responsible for the generation of LGI1- or CASPR2-antibodies are unknown. Binks et al. describe two strikingly dichotomous HLA-associations, most significantly in HLA-DRB1*07:01 for ...LGI1, and HLA-DRB1*11:01 for CASPR2. Prediction of antigen-specific HLA-binding peptides generates testable hypotheses for T cell identification.
Abstract
The recent biochemical distinction between antibodies against leucine-rich, glioma-inactivated-1 (LGI1), contactin-associated protein-2 (CASPR2) and intracellular epitopes of voltage-gated potassium-channels (VGKCs) demands aetiological explanations. Given established associations between human leucocyte antigen (HLA) alleles and adverse drug reactions, and our clinical observation of frequent adverse drugs reactions in patients with LGI1 antibodies, we compared HLA alleles between healthy controls (n = 5553) and 111 Caucasian patients with VGKC-complex autoantibodies. In patients with LGI1 antibodies (n = 68), HLA-DRB1*07:01 was strongly represented odds ratio = 27.6 (95% confidence interval 12.9-72.2), P = 4.1 × 10−26. In contrast, patients with CASPR2 antibodies (n = 31) showed over-representation of HLA-DRB1*11:01 odds ratio = 9.4 (95% confidence interval 4.6-19.3), P = 5.7 × 10−6. Other allelic associations for patients with LGI1 antibodies reflected linkage, and significant haplotypic associations included HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02, by comparison to DRB1*11:01-DQA1*05:01-DQB1*03:01 in CASPR2-antibody patients. Conditional analysis in LGI1-antibody patients resolved further independent class I and II associations. By comparison, patients with both LGI1 and CASPR2 antibodies (n = 3) carried yet another complement of HLA variants, and patients with intracellular VGKC antibodies (n = 9) lacked significant HLA associations. Within LGI1- or CASPR2-antibody patients, HLA associations did not correlate with clinical features. In silico predictions identified unique CASPR2- and LGI1-derived peptides potentially presented by the respective over-represented HLA molecules. These highly significant HLA associations dichotomize the underlying immunology in patients with LGI1 or CASPR2 antibodies, and inform T cell specificities and cellular interactions at disease initiation.
10.1093/brain/awy109_video1
awy109media1
5796480660001
A semiquantitative
I-metaiodobenzylguanidine (
I-MIBG) scoring method (the Curie score, or CS) was previously examined in the Children's Oncology Group (COG) high-risk neuroblastoma trial, COG A3973, ...with a postinduction CS of more than 2 being associated with poor event-free survival (EFS). The validation of the CS in an independent dataset, International Society of Paediatric Oncology European Neuroblastoma/High-Risk Neuroblastoma 1 (SIOPEN/HR-NBL1), is now reported.
A retrospective analysis of
I-MIBG scans obtained from patients who had been prospectively enrolled in SIOPEN/HR-NBL1 was performed. All patients exhibited
I-MIBG-avid, International Neuroblastoma Staging System stage 4 neuroblastoma.
I-MIBG scans were evaluated at 2 time points, diagnosis (
= 345) and postinduction (
= 330), before consolidation myeloablative therapy. Scans of 10 anatomic regions were evaluated, with each region being scored 0-3 on the basis of disease extent and a cumulative CS generated. Cut points for outcome analysis were identified by Youden methodology. CSs from patients enrolled in COG A3973 were used for comparison.
The optimal cut point for CS at diagnosis was 12 in SIOPEN/HR-NBL1, with a significant outcome difference by CS noted (5-y EFS, 43.0% ± 5.7% CS ≤ 12 vs. 21.4% ± 3.6% CS > 12,
< 0.0001). The optimal CS cut point after induction was 2 in SIOPEN/HR-NBL1, with a postinduction CS of more than 2 being associated with an inferior outcome (5-y EFS, 39.2% ± 4.7% CS ≤ 2 vs. 16.4% ± 4.2% CS > 2,
< 0.0001). The postinduction CS maintained independent statistical significance in Cox models when adjusted for the covariates of age and
gene copy number.
The prognostic significance of postinduction CSs has now been validated in an independent cohort of patients (SIOPEN/HR-NBL1), with a postinduction CS of more than 2 being associated with an inferior outcome in 2 independent large, cooperative group trials.
Childhood periodic syndromes are thought to be early life expressions of the genetic tendency for migraine. The objective of this study was to determine whether maternal migraine is associated with ...an increased risk of infant colic, because this may indicate that colic is a childhood periodic syndrome.
This was a cross-sectional study performed in general pediatric clinics. To minimize recall bias, mothers were surveyed at their infants' 2-month-old well-child visit, the age when colic is most prevalent. Colic was ascertained via parental report using modified Wessel criteria. Migraine history was obtained by having a physician diagnosis or a positive screen on ID Migraine. The primary outcome measure was difference in colic prevalence in infants with and without a maternal history of migraine.
Data from 154 infant-mother pairs were analyzed. Infants with a maternal history of migraine were 2.6 times as likely to have colic as infants without a maternal history of migraine (29% vs 11%, prevalence ratio 2.6 (95% confidence interval 1.2-5.5), p = 0.02). There was no difference in the accuracy with which migraineur mothers perceived their infants' colic status compared with that of nonmigraineur mothers. Data on paternal history of migraine were available for 93 infants. Infants with a paternal history of migraine may have a higher prevalence of colic (22% vs 10%), although the prevalence ratio 2.3 (0.6-9.4, p = 0.24) had wide confidence intervals.
Maternal migraine is associated with increased risk of infant colic. Because migraine has a strong genetic underpinning, this association suggests that colic may be an early life manifestation of migraine.
Common variable immunodeficiency (CVID) is characterized by late-onset hypogammaglobulinemia in the absence of predisposing factors. The genetic cause is unknown in the majority of cases, and less ...than 10% of patients have a family history of the disease. Most patients have normal numbers of B cells but lack plasma cells.
We used whole-exome sequencing and array-based comparative genomic hybridization to evaluate a subset of patients with CVID and low B-cell numbers. Mutant proteins were analyzed for DNA binding with the use of an electrophoretic mobility-shift assay (EMSA) and confocal microscopy. Flow cytometry was used to analyze peripheral-blood lymphocytes and bone marrow aspirates.
Six different heterozygous mutations in IKZF1, the gene encoding the transcription factor IKAROS, were identified in 29 persons from six families. In two families, the mutation was a de novo event in the proband. All the mutations, four amino acid substitutions, an intragenic deletion, and a 4.7-Mb multigene deletion involved the DNA-binding domain of IKAROS. The proteins bearing missense mutations failed to bind target DNA sequences on EMSA and confocal microscopy; however, they did not inhibit the binding of wild-type IKAROS. Studies in family members showed progressive loss of B cells and serum immunoglobulins. Bone marrow aspirates in two patients had markedly decreased early B-cell precursors, but plasma cells were present. Acute lymphoblastic leukemia developed in 2 of the 29 patients.
Heterozygous mutations in the transcription factor IKAROS caused an autosomal dominant form of CVID that is associated with a striking decrease in B-cell numbers. (Funded by the National Institutes of Health and others.).
Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of ...endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, interferon-β, and cGAS levels were elevated in the RPE in human eyes with geographic atrophy. Collectively, these data highlight an unexpected role of cGAS in responding to mobile-element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial-damage-induced inflammasome activation, expand the immune-sensing repertoire of cGAS and caspase-4 to noninfectious human disease, and identify new potential targets for treatment of a major cause of blindness.
Legislation on biofuels production in the USA and Europe is directing food crops towards the production of grain-based ethanol, which can have detrimental consequences for soil carbon sequestration, ...nitrous oxide emissions, nitrate pollution, biodiversity and human health. An alternative is to grow lignocellulosic (cellulosic) crops on 'marginal' lands. Cellulosic feedstocks can have positive environmental outcomes and could make up a substantial proportion of future energy portfolios. However, the availability of marginal lands for cellulosic feedstock production, and the resulting greenhouse gas (GHG) emissions, remains uncertain. Here we evaluate the potential for marginal lands in ten Midwestern US states to produce sizeable amounts of biomass and concurrently mitigate GHG emissions. In a comparative assessment of six alternative cropping systems over 20 years, we found that successional herbaceous vegetation, once well established, has a direct GHG emissions mitigation capacity that rivals that of purpose-grown crops (-851 ± 46 grams of CO(2) equivalent emissions per square metre per year (gCO(2)e m(-2) yr(-1))). If fertilized, these communities have the capacity to produce about 63 ± 5 gigajoules of ethanol energy per hectare per year. By contrast, an adjacent, no-till corn-soybean-wheat rotation produces on average 41 ± 1 gigajoules of biofuel energy per hectare per year and has a net direct mitigation capacity of -397 ± 32 gCO(2)e m(-2) yr(-1); a continuous corn rotation would probably produce about 62 ± 7 gigajoules of biofuel energy per hectare per year, with 13% less mitigation. We also perform quantitative modelling of successional vegetation on marginal lands in the region at a resolution of 0.4 hectares, constrained by the requirement that each modelled location be within 80 kilometres of a potential biorefinery. Our results suggest that such vegetation could produce about 21 gigalitres of ethanol per year from around 11 million hectares, or approximately 25 per cent of the 2022 target for cellulosic biofuel mandated by the US Energy Independence and Security Act of 2007, with no initial carbon debt nor the indirect land-use costs associated with food-based biofuels. Other regional-scale aspects of biofuel sustainability, such as water quality and biodiversity, await future study.
Background
Validation of the prognostic value of the SIOPEN mIBG skeletal scoring system in two independent stage 4, mIBG avid, high-risk neuroblastoma populations.
Results
The semi-quantitative ...SIOPEN score evaluates skeletal meta-iodobenzylguanidine (mIBG) uptake on a 0–6 scale in 12 anatomical regions. Evaluable mIBG scans from 216 COG-A3973 and 341 SIOPEN/HR-NBL1 trial patients were reviewed pre- and post-induction chemotherapy. The prognostic value of skeletal scores for 5-year event free survival (5 yr.-EFS) was tested in the source and validation cohorts. At diagnosis, both cohorts showed a gradual non-linear increase in risk with cumulative scores. Several approaches were explored to test the relationship between score and EFS. Ultimately, a cutoff score of ≤3 was the most useful predictor across trials. A SIOPEN score ≤ 3 pre-induction was found in 15% SIOPEN patients and in 22% of COG patients and increased post-induction to 60% in SIOPEN patients and to 73% in COG patients. Baseline 5 yr.-EFS rates in the SIOPEN/HR-NBL1 cohort for scores ≤3 were 47% ± 7% versus 26% ± 3% for higher scores at diagnosis (
p
< 0.007) and 36% ± 4% versus 14% ± 4% (
p
< 0.001) for scores obtained post-induction. The COG-A3973 showed 5 yr.-EFS rates for scores ≤3 of 51% ± 7% versus 34% ± 4% for higher scores (p < 0.001) at diagnosis and 43% ± 5% versus 16% ± 6% (
p
= 0.004) for post-induction scores. Hazard ratios (HR) significantly favoured patients with scores ≤3 after adjustment for age and MYCN-amplification. Optimal outcomes were recorded in patients who achieved complete skeletal response.
Conclusions
Validation in two independent cohorts confirms the prognostic value of the SIOPEN skeletal score. In particular, patients with an absolute SIOPEN score > 3 after induction have very poor outcomes and should be considered for alternative therapeutic strategies.
Generalized pustular psoriasis (GPP) is a chronic, orphan disease with limited epidemiological data.
To describe the clinical characteristics, treatments, longitudinal disease course, and ...disease-specific health care utilization among patients with GPP across the United States.
A retrospective longitudinal case series involving 95 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for GPP and were treated at 20 US academic dermatology practices between January 1, 2007, and December 31, 2018.
The primary outcome is to describe the patient characteristics, associated medical comorbidities, treatment patterns complications, and GPP-specific health care utilization.
Sixty-seven of 95 patients (70.5%) were women (mean age, 50.3 years SD, 16.1 years). In the initial encounter, 35 patients (36.8%) were hospitalized and 64 (67.4%) were treated with systemic therapies. In total, more than 20 different systemic therapies were tried. During the follow-up period, 19 patients (35.8%) reported hospitalizations at a median rate of 0.5 hospitalizations per year (IQR, 0.4-1.6). Women had a decreased risk of an emergency department or hospital encounter (odds ratio, 0.19; 95% CI, 0.04-0.83).
Generalized pustular psoriasis is a rare, chronic disease without standard treatment and is associated with continued health care utilization over time.
Kidney transplant patients with failing allografts have a physical and psychological symptom burden as well as high morbidity and mortality. Palliative care is underutilized in this vulnerable ...population. We described kidney transplant clinicians' perceptions of palliative care to delineate their perceived barriers to and facilitators of providing palliative care to this population.
National explanatory sequential mixed methods study including an online survey and semistructured interviews.
Kidney transplant clinicians in the United States surveyed and interviewed from October 2021 to March 2022.
Descriptive summary of survey responses, thematic analysis of qualitative interviews, and mixed methods integration of data.
A total of 149 clinicians completed the survey, and 19 completed the subsequent interviews. Over 90% of respondents agreed that palliative care can be helpful for patients with a failing kidney allograft. However, 46% of respondents disagreed that all patients with failing allografts benefit from palliative care, and two-thirds thought that patients would not want serious illness conversations. More than 90% of clinicians expressed concern that transplant patients and caregivers would feel scared or anxious if offered palliative care. The interviews identified three main themes: (1) transplant clinicians' unique sense of personal and professional responsibility was a barrier to palliative care engagement, (2) clinicians' uncertainty regarding the timing of palliative care collaboration would lead to delayed referral, and (3) clinicians felt challenged by factors related to patients' cultural backgrounds and identities, such as language differences. Many comments reflected an unfamiliarity with the broad scope of palliative care beyond end-of-life care.
Potential selection bias.
Our study suggests that multiple barriers related to patients, clinicians, health systems, and health policies may pose challenges to the delivery of palliative care for patients with failing kidney transplants. This study illustrates the urgent need for ongoing efforts to optimize palliative care delivery models dedicated to kidney transplant patients, their families, and the clinicians who serve them.
Kidney transplant patients experience physical and psychological suffering in the context of their illnesses that may be amenable to palliative care. However, palliative care is often underutilized in this population. In this mixed-methods study, we surveyed 149 clinicians across the United States, and 19 of them completed semistructured interviews. Our study results demonstrate that several patient, clinician, system, and policy factors need to be addressed to improve palliative care delivery to this vulnerable population.
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