2 Minute Medicine Rewind August 31, 2020

Hyperthyroidism is associated with breast cancer risk and mammographic and genetic risk predictors

1. Hyperthyroidism was associated with a higher rate of breast cancer among women.

2. Risk was particularly elevated for those with toxic nodular goiter.

Evidence Rating Level: 2 (Good)

Breast cancer is the most common cancer among women across the world as well as the leading cause of death among women. While much is known about the roles of thyroid hormones in cell proliferation within breast tissue, less is known about the relationship between hyperthyroidism and mammographic features of breast tissue. This national cohort study of women over the age of 20 years in Sweden (n = 3,793,492) included individuals assessed between 2002 and 2011 and sought to investigate the odds ratios of hyperthyroidism based on mammographic and genetic risk predictors. Participants had a main diagnosis of hyperthyroidism and follow-ups ended at breast cancer diagnosis, death, emigration, or final follow-up. Another 68,598 participants joined the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA, 2002-2017) for genotyping, with blood samples being obtained from a subset of 11,991 women who did not have breast cancer when they joined. Findings suggested an increase in breast cancer among patients with hyperthyroidism (incidence rate ratio [IRR] = 1.23, 95% CI 1.12 to 1.36), which was higher for toxic nodular goiter (IRR = 1.38, 95% CI 1.16 to 1.63). Hyperthyroidism was also associated with lower breastfeeding duration, higher body mass index, and early age at first birth. Higher mammographic density was found in women with toxic nodular goiter compared to those without hyperthyroidism. Among those in the KARMA group, hyperthyroidism was associated with a higher polygenic risk score overall (OR = 1.98, 95% CI 1.04 to 3.43) and estrogen receptor-positive specific PRS (OR = 1.90, 95% CI 1.04 to 3.43). Overall, this study found that hyperthyroidism was associated with an increased risk of breast cancer, with particular risk being among those with toxic nodular goiter. Further studies may explore mammographic density and genetic variants of these conditions.

 

An inflammatory cytokine signature predicts COVID-19 severity and survival

1. Serum IL-6 and TNF-α were strong, independent predictors of disease severity and death among those with suspected and confirmed SARS-CoV-2 infection.

Evidence Rating Level: 2 (Good)

Hyperinflammatory responses, or cytokine storms, are known results of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), serving as a basis for disease severity and mortality. This cohort study from Mount Sinai Health System in New York aimed to investigate predictive biomarkers of pathogenic inflammation to better understand implicated immune pathways. Participants included 1,484 patients with either suspected (median [IQR] age = 60 [49-73], 53.9% male) or confirmed (median [IQR] age = 63 [53-72], 60.1% male) SARS-CoV-2 infection, for whom health and laboratory information was extracted from medical records. Four inflammatory cytokines known to contribute to pathogenic inflammation were measured: CAR T cell-associated CRS-IL-6, IL-8, TNF-α, and IL-1β, subsequently assessing their relationships to severity and survival. A total of 1,953 specimens were analyzed, mostly upon hospital admission (median [IQR] time = 1.2 days [0.7 to 3.0] days) using the ELLA rapid detection enzyme-linked immunosorbent assay (ELISA) microfluids platform. This study found that high serum TNF-α, IL-6 and IL-8 were strong, independent predictors of patient survival (p = 0.0140, p < 0.0001, p = 0.0205, respectively). When controlling for disease severity, hypoxia and other vitals, common lab inflammation markers, comorbidities and demographics, TNF-α and IL-6 serum levels continued to be strong predictors of mortality. Overall, this study suggests that serum levels of IL-6 and TNF-α should be considered among patients with suspected or confirmed SARS-CoV-2, which may better inform treatment and disease course.

 

Association of recent stressful life events with mental and physical health in the context of genomic and exposomic liability for schizophrenia

1. Environmental liability for schizophrenia moderated the association of stressful life events with mental and physical health.

Evidence Rating Level: 2 (Good)

Schizophrenia research has elucidated the roles of environmental and genetic liability as well as stressful life events (SLEs) in schizophrenia pathogenesis. However, few studies have illustrated the interactions of these risk factors and how they impact mental and physical health. This population-based prospective cohort study investigated the prevalence, incidence, course, and consequences of psychiatric disorders in the Netherlands. A total of 6,646 (M [SD] age = 44.26 [12.54] years, 55.25% female) participants were enrolled between November 5, 2007 and July 31, 2009, being followed up with by three assessments across nine years. Follow-ups included recent SLEs and aggregate scores of environmental and genetic liabilities (polygenic risk score for schizophrenia [PRS-SCZ]; exposome score for schizophrenia [ES-SCZ]). SLEs were significantly associated with reduced mental (B = -3.68, 95% CI -4.05 to -3.32) and physical health (B = -3.22, 95% CI -3.66 to -2.79). Genetic and environmental liabilities were associated with poorer mental health (PRS-SCZ: B = -0.93, 95% CI -1.31 to -0.54; ES-SCZ: B = -3.07, 95% CI -3.35 to -2.79), with environmental liability also being associated with reduced physical health (B = -3.19, 95% CI -3.56 to -2.82). The interaction model suggested that ES-SCZ moderated the association of SLEs with physical (B = -0.64, 95% CI -1.11 to -0.17) and mental health (B = -1.08, 95% CI -1.47 to -0.69). PRS-SCZ, however, did not moderate this relationship. Overall, both genetic and environmental liabilities for schizophrenia resulted in mental health outcomes across the population. Exposure to SLEs, specifically in the context of these liabilities, were further associated with poorer health outcomes. Thus, it is important to consider the environmental factors impacting schizophrenia, such that modifiable risk factors should be targets of prevention and ongoing treatment.

 

Estimates of the association of dementia with US mortality levels using linked survey and mortality records

1. Vital statistics underestimated dementia mortality burden by a factor of 2.7.

2. Non-Hispanic Black persons demonstrated significantly greater mortality burden than non-Hispanic White persons.

Evidence Rating Level: 2 (Good)

Dementia is a leading cause of death in the US and abroad, with Alzheimer’s disease accounting for approximately 80% of dementia cases. However, vital statistics are generally the method through which we determine mortality burden. Due to evidence suggesting that dementia is often underreported on death certificates, it is important to shift focus to population-based samples. This prospective cohort study of the Health and Retirement Study assessed noninstitutionalized individuals at baseline in 2000 and follow-up until 2009. A total of 7,342 adults (60.3% female) between the ages of 70 and 99 years were interviewed and included in the study. Three ten-year age groups were established to determine the representation of the sample: 70-79 (64.0%), 80-89 (31.0%), 90-99 (5.0%). The total percentage of deaths attributable to dementia was 13.6% (95% CI 12.2 to 15.0). The mortality burden of dementia was significantly higher among adults with less than a high school education (16.2%, 95% CI 13.2 to 19.0) compared to individuals with a college education (9.8%, 95% CI 7.0 to 12.5). This burden was also significantly greater among non-Hispanic Black individuals (24.7%, 95% CI 17.3 to 31.4) compared to non-Hispanic White person (12.2%, 95% CI 10.7 to 13.6). Causes of deaths reported on death certificates (5.0%, 95% CI 4.3 to 5.8) drastically underestimated dementia’s contribution to mortality in the US by a factor of 2.7. When incorporating deaths due to cognitive impairment without dementia, underestimation of dementia mortality burden was even greater. Overall, this study suggests that the standard mortality statistics utilized to determine dementia mortality burden may be significantly underestimated, calling for a need to incorporate population-based studies and interventions.

 

Internet searches for acute anxiety during the early stages of the COVID-19 pandemic

  1. Internet searches related to acute anxiety rose significantly following the declaration of COVID-19 as a national emergency in the U.S., and returned to expected rates by April 15, 2020.

Evidence Rating Level: 3 (Average)

Mental health is a significant concern in the context of COVID-19 safety precautions. This retrospective study evaluated the association between COVID-19 and anxiety by examining internet searches indicative of concerns related to acute anxiety during the early months of the pandemic. Google Trends was utilized to monitor daily searches originating from the US between January 1, 2004 and May 4, 2020, focusing specifically on the percentage of all searches that included ‘anxiety’ or ‘panic’ in combination with ‘attack’. The key reference date was set to March 13, 2020, which was when the US declared COVID-19 as a national emergency. Following this date, acute anxiety searches were cumulatively 11% higher than anticipated (375,000 more searches) based on historical trends (95% CI 7 to 14), becoming the all-time high for the search time frame. The greatest spike in anxiety searches occurred 15 days after the declaration of the national emergency (52% increase, 95% CI 27-81). A 17% (95% CI 13 to 22) cumulative increase was noted when social-distancing guidelines were imposed, along with restrictions related to masks and the US passing Italy for the most COVID-19-related deaths. By April 15, 2020, acute anxiety queries appeared to return to the expected range. In sum, anxiety appeared to be a concern for many individuals since COVID-19 restrictions. Over time, and potentially due to people achieving what they were seeking or obtaining medical care for anxiety, these concerns have returned to normal as measured by internet searches.

 

Image: PD

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