Pressure Injuries in Nursing Homes: Investigating Racial/Ethnic Differences Using National Data

Context: In the United States, Black nursing home (NH) residents have higher rates of pressure injury (PI) than White residents. Although some studies ascribe this to a relatively high proportion of Black residents in NHs with poor outcomes and limited resources, the factors that associate with PIs and their consequences across and within NHs remain poorly understood. Also, little is known about PIs among residents of differing races and ethnicities. Objectives: Using four national datasets from 2016–2017, we evaluated U.S. NHs to characterize differences in PI-related outcomes among non-Hispanic Whites, non-Hispanic Blacks, Hispanics, Asians, American Indian or Alaska Natives, and Native Hawaiian or Other Pacific Islanders, and clarified the impact of resident-, facility-, and community-level characteristics on these outcomes. Methods: We calculated the annual incidence rate of PIs, the probability of PI healing, and the prevalence of PI-associated pain and analgesic prescription. We determined the bivariate associations between each of these outcomes and race/ethnicity, and between each outcome and multiple potential covariates. Multivariable analyses then evaluated the associations between each outcome and race/ethnicity while adjusting for covariates. Findings: In the bivariate analyses, the annual incidence rate of stage 2, 3, 4, and unstageable PIs for Whites was lower than Blacks and Hispanics, similar to American Indians or Alaska Natives, and higher than Asians and Native Hawaiians or Other Pacific Islanders. In the multivariable analyses, the PI incidence rate ratio was higher only among American Indians or Alaska Natives, and this difference was associated with a NH-level variable—the proportion of racial and ethnic minority residents. Other outcomes did not vary by race/ethnicity. An adjusted exploratory analysis was conducted to help explain the difference between the bivariate and multivariable analyses and revealed an important within-NH difference: Compared to Whites, the PI incidence rate ratios were higher in women who were Black, or American Indian or Alaska Native. Limitations: Our findings are correlational and may be impacted by unevaluated variables and the limitations of administrative data. Implications: In U.S. NHs, the annual incidence rate of PIs varies by race/ethnicity. Facility characteristics strongly influence this variation. Higher incidence rate ratios among racial and ethnic minority residents also are explained by differences within NHs and are striking among subgroups, including female residents who are Black, or American Indian or Alaska Native. Future research should evaluate the sexes separately and explore both across-NH and within-NH differences to determine whether there are structural inequities, bias, and disparate care

Benefits and Costs of Interventions to Improve Breast Cancer Outcomes in African American Women

Purpose Historically, African American women have experienced higher breast cancer mortality than white women, despite lower incidence. Our objective was to evaluate whether costs of increasing rates of screening or application of intensive treatment will be off-set by survival benefits for African American women. Methods We use a stochastic simulation model of the natural history of breast cancer to evaluate the incremental societal costs and benefits of status quo versus targeted biennial screening or treatment improvements among African Americans 40 years of age and older. Main outcome measures were number of mammograms, stage, all-cause mortality, and discounted costs per life year saved (LYS). Results At the current screening rate of 76%, there is little incremental benefit associated with further increasing screening, and the costs are high: $124,053 and$124,217 per LYS for lay health worker and patient reminder interventions, respectively, compared with the status quo. Using reminders would cost $51,537 per LYS if targeted to virtually unscreened women or$78,130 per LYS if targeted to women with a two-fold increase in baseline risk. If all patients received the most intensive treatment recommended, costs increase but deaths decrease, for a cost of $52,678 per LYS. Investments of up to$6,000 per breast cancer patient could be used to enhance treatment and still yield cost-effectiveness ratios of less than $75,000 per LYS. Conclusion Except in pockets of unscreened or high-risk women, further investments in interventions to increase screening are unlikely to be an efficient use of resources. Ensuring that African American women receive intensive treatment seems to be the most cost-effective approach to decreasing the disproportionate mortality experienced by this population

Public Health and Economic Consequences of Methyl Mercury Toxicity to the Developing Brain

Methyl mercury is a developmental neurotoxicant. Exposure results principally from consumption by pregnant women of seafood contaminated by mercury from anthropogenic (70%) and natural (30%) sources. Throughout the 1990s, the U.S. Environmental Protection Agency (EPA) made steady progress in reducing mercury emissions from anthropogenic sources, especially from power plants, which account for 41% of anthropogenic emissions. However, the U.S. EPA recently proposed to slow this progress, citing high costs of pollution abatement. To put into perspective the costs of controlling emissions from American power plants, we have estimated the economic costs of methyl mercury toxicity attributable to mercury from these plants. We used an environmentally attributable fraction model and limited our analysis to the neurodevelopmental impacts—specifically loss of intelligence. Using national blood mercury prevalence data from the Centers for Disease Control and Prevention, we found that between 316,588 and 637,233 children each year have cord blood mercury levels > 5.8 μg/L, a level associated with loss of IQ. The resulting loss of intelligence causes diminished economic productivity that persists over the entire lifetime of these children. This lost productivity is the major cost of methyl mercury toxicity, and it amounts to $8.7 billion annually (range,$2.2–43.8 billion; all costs are in 2000 US$). Of this total,$1.3 billion (range, $0.1–6.5 billion) each year is attributable to mercury emissions from American power plants. This significant toll threatens the economic health and security of the United States and should be considered in the debate on mercury pollution controls

Permanent hypothyroidism following immune checkpoint inhibitors induced thyroiditis may be associated with improved survival: results of an explanatory study

BackgroundImmune-related endocrinopathies are common after immune checkpoint inhibitor (ICI) therapy, among which destructive thyroiditis is the most prevalent. Improved survival outcomes have been associated with immune-related adverse events. We aimed to compare the clinical course and biochemical parameters of two subtypes of ICI-related destructive thyroiditis: a transient thyrotoxicosis that reverts to either euthyroidism (TT; transient thyroiditis) versus progression to permanent hypothyroidism (PH), and to identify prognostic markers in cancer patients receiving ICI therapy who developed DT.MethodsThis retrospective observational study included 124 patients who developed a transient thyrotoxicosis due to a destructive thyroiditis after ICI therapy from January 1, 2016 to April 30, 2021 at the Montefiore Medical Center. Patients were categorized as either TT or PH based on spontaneous renormalization of the TSH or the permanent need for thyroid hormone replacement, respectively. Thyroid hormone and antibody levels, serum inflammatory markers, eosinophils, and metabolic uptake of the thyroid on PET imaging, each corresponding closest to a suppressed TSH, were characterized. Survival from TT and PH were also analyzed.ResultsOf the 124 patients, 53 developed PH and 71 developed TT. The PH group developed thyrotoxicosis at a median of 42 days from the first ICI dose while the TT group took significantly longer at 56 days. Thyroidal PET uptake was increased in 18.9% of the PH group versus 6.0% of the TT group (P=0.04). Three different survival models consistently demonstrated a trend towards increased survival in the PH group, compared to the TT group.ConclusionOur results suggest that PH developing after ICI-induced destructive thyroiditis may be associated with a more robust inflammatory and antitumor response to ICI therapy. The results suggests that PH may be a potential clinical predictor of improved survival

Analysis of Breast Cancer Mortality in the US-1975 to 2019

IMPORTANCE: Breast cancer mortality in the US declined between 1975 and 2019. The association of changes in metastatic breast cancer treatment with improved breast cancer mortality is unclear. OBJECTIVE: To simulate the relative associations of breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer with improved breast cancer mortality. DESIGN, SETTING, AND PARTICIPANTS: Using aggregated observational and clinical trial data on the dissemination and effects of screening and treatment, 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models simulated US breast cancer mortality rates. Death due to breast cancer, overall and by estrogen receptor and ERBB2 (formerly HER2) status, among women aged 30 to 79 years in the US from 1975 to 2019 was simulated. EXPOSURES: Screening mammography, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer. MAIN OUTCOMES AND MEASURES: Model-estimated age-adjusted breast cancer mortality rate associated with screening, stage I to III treatment, and metastatic treatment relative to the absence of these exposures was assessed, as was model-estimated median survival after breast cancer metastatic recurrence. RESULTS: The breast cancer mortality rate in the US (age adjusted) was 48/100 000 women in 1975 and 27/100 000 women in 2019. In 2019, the combination of screening, stage I to III treatment, and metastatic treatment was associated with a 58% reduction (model range, 55%-61%) in breast cancer mortality. Of this reduction, 29% (model range, 19%-33%) was associated with treatment of metastatic breast cancer, 47% (model range, 35%-60%) with treatment of stage I to III breast cancer, and 25% (model range, 21%-33%) with mammography screening. Based on simulations, the greatest change in survival after metastatic recurrence occurred between 2000 and 2019, from 1.9 years (model range, 1.0-2.7 years) to 3.2 years (model range, 2.0-4.9 years). Median survival for estrogen receptor (ER)-positive/ERBB2-positive breast cancer improved by 2.5 years (model range, 2.0-3.4 years), whereas median survival for ER-/ERBB2- breast cancer improved by 0.5 years (model range, 0.3-0.8 years). CONCLUSIONS AND RELEVANCE: According to 4 simulation models, breast cancer screening and treatment in 2019 were associated with a 58% reduction in US breast cancer mortality compared with interventions in 1975. Simulations suggested that treatment for stage I to III breast cancer was associated with approximately 47% of the mortality reduction, whereas treatment for metastatic breast cancer was associated with 29% of the reduction and screening with 25% of the reduction

Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in Humans

Alteration of single genes involved in nutrient and lipoprotein metabolism increases longevity in several animal models. Because exceptional longevity in humans is familial, it is likely that polymorphisms in genes favorably influence certain phenotypes and increase the likelihood of exceptional longevity. A group of Ashkenazi Jewish centenarians ( n = 213), their offspring ( n = 216), and an age-matched Ashkenazi control group ( n = 258) were genotyped for 66 polymorphisms in 36 candidate genes related to cardiovascular disease (CVD). These genes were tested for association with serum lipoprotein levels and particle sizes, apolipoprotein A1, B, and C-3 levels and with outcomes of hypertension, insulin resistance, and mortality. The prevalence of homozygosity for the −641C allele in the APOC3 promoter (rs2542052) was higher in centenarians (25%) and their offspring (20%) than in controls (10%) ( p = 0.0001 and p = 0.001, respectively). This genotype was associated with significantly lower serum levels of APOC3 and a favorable pattern of lipoprotein levels and sizes. We found a lower prevalence of hypertension and greater insulin sensitivity in the −641C homozygotes, suggesting a protective effect against CVD and the metabolic syndrome. Finally, in a prospectively studied cohort, a significant survival advantage was demonstrated in those with the favorable −641C homozygote ( p < 0.0001). Homozygosity for the APOC3 −641C allele is associated with a favorable lipoprotein profile, cardiovascular health, insulin sensitivity, and longevity. Because modulation of lipoproteins is also seen in genetically altered longevity models, it may be a common pathway influencing lifespan from nematodes to humans

Personalizing Breast Cancer Screening Based on Polygenic Risk and Family History

_Background:_ We assessed the clinical utility of a first-degree breast cancer family history and polygenic risk score (PRS) to inform screening decisions among women aged 30-50 years. _Methods:_ Two established breast cancer models evaluated digital mammography screening strategies in the 1985 US birth cohort by risk groups defined by family history and PRS based on 313 single nucleotide polymorphisms. Strategies varied in initiation age and interval. The benefits and harms were compared with those seen with 3 established screening guidelines. _Results:_ Women with a breast cancer family history who initiated biennial screening at age 40 years had a 36% increase in life-years gained and 20% more breast cancer deaths averted, but 21% more overdiagnoses and 63% more false positives. Screening tailored to PRS vs biennial screening from50 to 74 years had smaller positive effects on life-years gained and breast cancer deaths averted but also smaller increases in overdiagnoses and false positives. Combined use of family history and PRS vs biennial screening from 50 to 74 years had the greatest increase in life-years gained and breast cancer deaths averted. _Conclusions:_ Our results suggest that breast cancer family history and PRS could guide screening decisions before age 50 years among women at increased risk for breast cancer but expected increases in overdiagnoses and false positives should be expected

Modeling Ductal Carcinoma In Situ (DCIS): An Overview of CISNET Model Approaches

Background. Ductal carcinoma in situ (DCIS) can be a precursor to invasive breast cancer. Since the advent of screening mammography in the 1980’s, the incidence of DCIS has increased dramatically. The value of screen detection and treatment of DCIS, however, is a matter of controversy, as it is unclear the extent to which detection and treatment of DCIS prevents invasive disease and reduces breast cancer mortality. The aim of this paper is to provide an overview of existing Cancer Intervention and Surveillance Modelling Network (CISNET) modeling approaches for the natural history of DCIS, and to compare these to other modeling approaches reported in the literature. Design. Five of the 6 CISNET models currently include DCIS. Most models assume that some, but not all, lesions progress to invasive cancer. The natural history of DCIS cannot be directly observed and the CISNET models differ in their assumptions and in the data sources used to estimate the DCIS model parameters. Results. These model differences translate into variation in outcomes, such as the amount of overdiagnosis of DCIS, with estimates ranging from 34% to 72% for biennial screening from ages 50 to 74 y. The other models described in the literature also report a large range in outcomes, with progression rates varying from 20% to 91%. Limitations. DCIS grade was not yet included in the CISNET models. Conclusion. In the future, DCIS data by grade from active surveillance trials, the development of predictive markers of progression probability, and evidence from other screening modalities, such as tomosynthesis, may be used to inform and improve the models’ representation of DCIS, and might lead to convergence of the model estimates. Until then, the CISNET model results consistently show a considerable amount of overdiagnosis of DCIS, supporting the safety and value of observational trials for low-risk DCIS