Abstract
Purpose
Structural racism could contribute to racial and ethnic disparities in cancer mortality via its broad effects on housing, economic opportunities, and health care. However, there has ...been limited focus on incorporating structural racism into simulation models designed to identify practice and policy strategies to support health equity. We reviewed studies evaluating structural racism and cancer mortality disparities to highlight opportunities, challenges, and future directions to capture this broad concept in simulation modeling research.
Methods
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review Extension guidelines. Articles published between 2018 and 2023 were searched including terms related to race, ethnicity, cancer-specific and all-cause mortality, and structural racism. We included studies evaluating the effects of structural racism on racial and ethnic disparities in cancer mortality in the United States.
Results
A total of 8345 articles were identified, and 183 articles were included. Studies used different measures, data sources, and methods. For example, in 20 studies, racial residential segregation, one component of structural racism, was measured by indices of dissimilarity, concentration at the extremes, redlining, or isolation. Data sources included cancer registries, claims, or institutional data linked to area-level metrics from the US census or historical mortgage data. Segregation was associated with worse survival. Nine studies were location specific, and the segregation measures were developed for Black, Hispanic, and White residents.
Conclusions
A range of measures and data sources are available to capture the effects of structural racism. We provide a set of recommendations for best practices for modelers to consider when incorporating the effects of structural racism into simulation models.
Inorganic nanocrystals such as quantum dots (QDs) and upconverting nanoparticles (UCNPs) are uniquely suited for quantitative live-cell imaging and are typically functionalized with ligands to study ...specific receptors or cellular targets. Antibodies (Ab) are among the most useful targeting reagents owing to their high affinities and specificities, but common nanocrystal labeling methods may orient Ab incorrectly, be reversible or denaturing, or lead to Ab-NP complexes too large for some applications. Here, we show that SpyCatcher proteins, which bind and spontaneously form covalent isopeptide bonds with cognate SpyTag peptides, can conjugate engineered Ab to nanoparticle surfaces with control over stability, orientation, and stoichiometry. Compact SpyCatcher-functionalized QDs and UCNPs may be labeled with short-chain variable fragment Ab (scFv) engineered to bind urokinase-type plasminogen activator receptors (uPAR) that are overexpressed in many human cancers. Confocal imaging of anti-uPAR scFv-QD conjugates shows the antibody mediates specific binding and internalization by breast cancer cells expressing uPAR. Time-lapse imaging of photostable scFv-UCNP conjugates shows that Ab binding causes uPAR internalization with a ∼20 min half-life on the cell surface, and uPAR is internalized to endolysosomal compartments distinct from general membrane stains and without significant recycling to the cell surface. The controlled and stable conjugation of engineered Ab to NPs enables targeting of diverse receptors for live-cell study of their distribution, trafficking, and physiology.
Asthma is one of the most common underlying diseases in women of reproductive age that can lead to potentially serious medical problems during pregnancy and lactation. A group of key stakeholders ...across multiple relevant disciplines was invited to take part in an effort to prioritize, strategize, and mobilize action steps to fill important gaps in knowledge regarding asthma medication safety in pregnancy and lactation. The stakeholders identified substantial gaps in the literature on the safety of asthma medications used during pregnancy and lactation and prioritized strategies to fill those gaps. Short-term action steps included linking data from existing complementary study designs (US and international claims data, single drug pregnancy registries, case-control studies, and coordinated systematic data systems). Long-term action steps included creating an asthma disease registry, incorporating the disease registry into electronic health record systems, and coordinating care across disciplines. The stakeholders also prioritized establishing new infrastructures/collaborations to perform research in pregnant and lactating women and to include patient perspectives throughout the process. To address the evidence gaps, and aid in populating product labels with data that inform clinical decision making, the consortium developed a plan to systematically obtain necessary data in the most efficient and timely manner.
This Article follows the path of a hypothetical college football player with aspirations to play in the National Football League, explaining from a legal and ethical perspective the health and ...performance evaluations he will likely face throughout his career. Some of these evaluations are commonplace and familiar, while others are more futuristic—and potentially of unproven value. How much information about themselves should aspiring and current professional players be expected to provide in the employment context? What are the current legal standards for employers collecting and acting on an individual's health- and performance-related information? Drawing on disability law, privacy law, and the law governing genetic testing, this Article seeks to answer those questions, as well as to provide recommendations to better protect the health and privacy of professional football players. The upshot of our analysis is that it appears that some of the existing evaluations of players, both at the NFL Scouting Combine (Combine) and once drafted and playing for a club, seem to violate existing federal employment discrimination laws. Specifically, (1) the medical examinations at the Combine potentially violate the Americans with Disabilities Act's (ADA) prohibitions on pre-employment medical exams; (2) post-offer medical examinations that are made public potentially violate the ADA's confidentiality provisions; (3) post-offer medical examinations that reveal a disability and result in discrimination—e.g., the rescission of a contract offer—potentially violate the ADA provided the player can still perform the essential job functions; (4) Combine medical examinations that include a request for a player's family medical history potentially violate the Genetic Information Nondiscrimination Act (GINA); and (5) the preseason physical's requirement that a player disclose his family medical history potentially violates GINA.
Gaps in postnatal care use represent missed opportunities to prevent maternal and neonatal death in sub-Saharan Africa. As one in every three non-facility deliveries in Nigeria is assisted by a ...traditional birth attendant (TBA), and the TBA’s advice is often adhered to by their clients, engaging TBAs in advocacy among their clients may increase maternal and neonatal postnatal care use. This study estimates the impact of monetary incentives for maternal referrals by TBAs on early maternal and neonatal postnatal care use (within 48 h of delivery) in Nigeria. Overall, 207 TBAs participated in this study: 103 in the treatment group and 104 in the control group. The intervention increased the proportion of maternal clients of TBAs that reported attending postnatal care within 48 h of delivery by 15.4 percentage points 95% confidence interval (CI): 7.9–22.9. The proportion of neonatal clients of TBAs that reportedly attended postnatal care within 48 h of delivery also increased by 12.6 percentage points 95% CI: 5.9–19.3. However, providers often did not address the issues that may have led to maternal and newborn postnatal complications during these visits. We show that motivating TBAs using monetary incentives for maternal postnatal care use can increase skilled care use after delivery among their maternal and neonatal clients, who have a higher risk of mortality because of their exposure to unskilled birth attendance. However, improving the quality of care is key to ensuring maternal and neonatal health gains from postnatal care attendance.
A cross-sectional study design was utilized to evaluate the readability of patient education materials on the newborn hearing screen from Google and major institutions.
The top 55 websites from the ...Google search “failed newborn hearing screen” and websites from major institutions (the U.S. News & World Report ranked top 10 children's hospitals, the top 5 pediatric otolaryngology fellowships as ranked by Doximity Residency Navigator, the Centers for Disease and Control, the American Academy of Pediatrics and the American Academy of Otolaryngology–Head and Neck Surgery) were compiled. Text from each website was edited to remove extraneous text. Readability grade was calculated using the Flesch-Kincaid Grade Level (FKGL), Flesch Reading Ease Score, Gunning-Fog Index (GFI), Simple Measure of Gobbledygook (SMOG), Coleman-Liau Index, and Automated Readability Index. Intra- and inter-observer reliability were assessed.
26 websites from Google and 29 websites from major institutions were evaluated. From Google, provider-oriented websites (n = 2) were more difficult to read than patient-oriented websites (n = 24) with statistical significance for FKGL (p < 0.001), GFI (p < 0.013) and SMOG (p < 0.001). From the major institutions, more than half were at a reading level that exceeded the average American adult with an average FKGL 9.71 ± 2.69. Intra- and inter-observer reliability were both excellent with an intra-class correlation coefficient for each readability tool ≥0.950 (p < 0.001).
Online patient education materials about the newborn hearing screen may be too difficult for the average reader. Revisions to these materials and redirection to more readable online resources may be necessary to benefit a more inclusive patient population.
The substantial phenotypic heterogeneity in autism limits our understanding of its genetic etiology. To address this gap, here we investigated genetic differences between autistic individuals (n
= ...12,893) based on core and associated features of autism, co-occurring developmental disabilities and sex. We conducted a comprehensive factor analysis of core autism features in autistic individuals and identified six factors. Common genetic variants were associated with the core factors, but de novo variants were not. We found that higher autism polygenic scores (PGS) were associated with lower likelihood of co-occurring developmental disabilities in autistic individuals. Furthermore, in autistic individuals without co-occurring intellectual disability (ID), autism PGS are overinherited by autistic females compared to males. Finally, we observed higher SNP heritability for autistic males and for autistic individuals without ID. Deeper phenotypic characterization will be critical in determining how the complex underlying genetics shape cognition, behavior and co-occurring conditions in autism.
IMPORTANCE: The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild to moderate symptomatic COVID-19 is unclear. OBJECTIVE: To evaluate the ...efficacy of low-dose fluvoxamine (50 mg twice daily) for 10 days compared with placebo for the treatment of mild to moderate COVID-19 in the US. DESIGN, SETTING, AND PARTICIPANTS: The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) platform randomized clinical trial was designed to test repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 participants aged 30 years or older with test-confirmed SARS-CoV-2 infection and experiencing 2 or more symptoms of acute COVID-19 for 7 days or less were enrolled between August 6, 2021, and May 27, 2022, at 91 sites in the US. INTERVENTIONS: Participants were randomized to receive 50 mg of fluvoxamine twice daily for 10 days or placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was time to sustained recovery (defined as the third day of 3 consecutive days without symptoms). There were 7 secondary outcomes, including a composite outcome of hospitalization, urgent care visit, emergency department visit, or death through day 28. RESULTS: Among 1331 participants who were randomized (median age, 47 years IQR, 38-57 years; 57% were women; and 67% reported receiving ≥2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (674 in the fluvoxamine group and 614 in the placebo group). The median time to sustained recovery was 12 days (IQR, 11-14 days) in the fluvoxamine group and 13 days (IQR, 12-13 days) in the placebo group (hazard ratio HR, 0.96 95% credible interval, 0.86-1.06, posterior P = .21 for the probability of benefit determined by an HR >1). For the composite outcome, 26 participants (3.9%) in the fluvoxamine group were hospitalized, had an urgent care visit, had an emergency department visit, or died compared with 23 participants (3.8%) in the placebo group (HR, 1.1 95% credible interval, 0.5-1.8, posterior P = .35 for the probability of benefit determined by an HR <1). One participant in the fluvoxamine group and 2 participants in the placebo group were hospitalized; no deaths occurred in either group. Adverse events were uncommon in both groups. CONCLUSIONS AND RELEVANCE: Among outpatients with mild to moderate COVID-19, treatment with 50 mg of fluvoxamine twice daily for 10 days, compared with placebo, did not improve time to sustained recovery. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04885530
This phase I/II study evaluated safety, efficacy, and pharmacokinetics of escalating, multiple doses of siltuximab, a chimeric anti-interleukin (IL)-6 monoclonal antibody derived from a new Chinese ...hamster ovary (CHO) cell line in patients with advanced/refractory solid tumors.
In the phase I dose-escalation cohorts, 20 patients with advanced/refractory solid tumors received siltuximab 2.8 or 5.5 mg/kg every 2 weeks or 11 or 15 mg/kg every 3 weeks intravenously (i.v.). In the phase I expansion (n = 24) and phase II cohorts (n = 40), patients with Kirsten rat sarcoma-2 (KRAS)-mutant tumors, ovarian, pancreatic, or anti-EGF receptor (EGFR) refractory/resistant non-small cell lung cancer (NSCLC), colorectal, or H&N cancer received 15 mg/kg every 3 weeks. The phase II primary efficacy endpoint was complete response, partial response, or stable disease >6 weeks.
Eighty-four patients (35 colorectal, 29 ovarian, 9 pancreatic, and 11 other) received a median of three (range, 1-45) cycles. One dose-limiting toxicity occurred at 5.5 mg/kg. Common grade ≥3 adverse events were hepatic function abnormalities (15%), physical health deterioration (12%), and fatigue (11%). Ten percent of patients had siltuximab-related grade ≥3 adverse events. Neutropenia (4%) was the only possibly related adverse event grade ≥3 reported in >1 patient. Serious adverse events were reported in 42%; most were related to underlying disease. The pharmacokinetic profile of CHO-derived siltuximab appears similar to the previous cell line. No objective responses occurred; 5 of 84 patients had stable disease >6 weeks. Hemoglobin increased ≥1.5 g/dL in 33 of 47 patients. At 11 and 15 mg/kg, completely sustained C-reactive protein suppression was observed.
Siltuximab monotherapy appears to be well tolerated but without clinical activity in solid tumors, including ovarian and KRAS-mutant cancers. The recommended phase II doses were 11 and 15 mg/kg every 3 weeks.
PDF
