Adverse events of anti-IL-5 drugs in patients with eosinophilic asthma: a meta-analysis of randomized controlled trials and real-world evidence-based assessments.

BACKGROUND: We aimed to clarify comprehensively the safety profiles of anti-IL-5 drugs and pinpoint potential safety concerns that may arise in their post-marketing phase. METHODS: Two researchers conducted comprehensive searches of PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to September 2022. Additionally, we investigated the FDA AE Reporting System for post-marketing adverse event (AE) reports related to anti-IL-5 drugs. The outcomes fulfilled the proportional reporting rate criteria and the Bayesian confidence propagation neural network. RESULTS: We included 24 published studies in our analysis. The anti-IL-5 treatment group showed an incidence of AEs comparable to the placebo group, and it exhibited a significantly lower frequency of serious AEs. Common AEs were asthma, nasopharyngitis, headache, upper respiratory tract infection (URTI), and bronchitis. The post-marketing data included 28,478 case reports associated with the suspect drugs and 75 suspect safety observations affecting 16 system organ classes. New suspect observations included incomplete therapeutic product effect, URTIs, and pulmonary mass in reports related to mepolizumab. Reports associated with mepolizumab and benralizumab also indicated issues with incorrect technique in device usage and product issues. CONCLUSIONS: Individual anti-IL-5 drugs' safety profiles largely matched their product inserts. We identified issues like improper device usage, product issue, and URTIs as potential concerns for mepolizumab and benralizumab. Additionally, all anti-IL-5 drugs showed signs of incomplete therapeutic effects.

Incremental burden on health-related quality of life, health service utilization and direct medical expenditures associated with cognitive impairment among non-institutionalized people with diabetes aged 65 years and older.

AIMS: To quantify the incremental health and economic burden associated with cognitive impairment (CI) among non-institutionalized people with diabetes ≥65 years in the United States. MATERIALS AND METHODS: Using 2016-2019 Medical Expenditure Panel Surveys data, we identified participants ≥65 years with diabetes. We used propensity score weighting to quantify the CI-associated incremental burden on health-related quality of life measured by the 12-item Short Form Survey (SF-12), including the mental component summary score, physical component summary score and health utility. We also compared the annual health service utilization and expenditures on ambulatory visits, prescriptions, home care, emergency room (ER), hospitalizations and total annual direct medical expenditures. RESULTS: We included 5094 adults aged ≥65 with diabetes, of whom 804 had CI. After propensity score weighting, CI was associated with a lower mental component summary score (-8.4, p < .001), physical component summary score (-5.2, p < .001) and health utility (-0.12, p < .001). The CI group had more ambulatory visits (+4.4, p = .004) and prescriptions (+9.9, p < .001), with higher probabilities of having home care (+11.3%, p < .001) and ER visits (+8.2%, p = .001). People with CI spent $5441 (p < .001) more annually, $2039 (p = .002) more on prescriptions, $2695 (p < .001) more on home care and $118 (p < .001) more on ER visits. There is no statistically significant difference in the utilization and expenditure of hospitalizations. CONCLUSION: CI was associated with worse health-related quality of life, higher health service utilization and expenditures. Our findings can be used to monitor the health and economic burden of CI in non-institutionalized older persons with diabetes.

Are Home Evictions Associated with Child Welfare System Involvement? Empirical Evidence from National Eviction Records and Child Protective Services Data.

This study aimed to understand the relationship between home eviction and child welfare system involvement at the county level. Using administrative data, we examined associations of home eviction and eviction filing rates with child abuse and neglect (CAN) reports and foster care entries. We found one additional eviction per 100 renter-occupied homes in a county was associated with a 1.3% increase in the rate of CAN reports and a 1.6% increase in foster care entries. The association between eviction and foster care entries was strongest among Hispanic children with an 8.1% increase. Assisting parents in providing stable housing may reduce the risk of child welfare system involvement, including out-of-home child placement. Primary and secondary prevention strategies could include housing assistance, increasing access to affordable and safe housing, as well as providing economic support for families (e.g., tax credits, childcare subsidies) that reduce parental financial burden to access stable housing.

Prevalence of diagnosed depression, anxiety, and ADHD among youth with type 1 or type 2 diabetes mellitus.

We examined the prevalence of diagnosed depression, anxiety, and ADHD among youth by diabetes type, insurance type, and race/ethnicity. These mental disorders were more prevalent among youth with diabetes, particularly those with type 2 diabetes, with non-Hispanic White youth with Medicaid and diabetes having a higher prevalence than other races/ethnicities.

State-Specific Prevalence of Depression Among Adults With and Without Diabetes - United States, 2011-2019.

INTRODUCTION: In 2019 among US adults, 1 in 9 had diagnosed diabetes and 1 in 5 had diagnosed depression. Since these conditions frequently coexist, compounding their health and economic burden, we examined state-specific trends in depression prevalence among US adults with and without diagnosed diabetes. METHODS: We used data from the 2011 through 2019 Behavioral Risk Factor Surveillance System to evaluate self-reported diabetes and depression prevalence. Joinpoint regression estimated state-level trends in depression prevalence by diabetes status. RESULTS: In 2019, the overall prevalence of depression in US adults with and without diabetes was 29.2% (95% CI, 27.8%-30.6%) and 17.9% (95% CI, 17.6%-18.1%), respectively. From 2011 to 2019, the depression prevalence was relatively stable for adults with diabetes (28.6% versus 29.2%) but increased for those without diabetes from 15.5% to 17.9% (average annual percent change [APC] over the 9-year period = 1.6%, P = .015). The prevalence of depression was consistently more than 10 percentage points higher among adults with diabetes than those without diabetes. The APC showed a significant increase in some states (Illinois: 5.9%, Kansas: 3.5%) and a significant decrease in others (Arizona: -5.1%, Florida: -4.0%, Colorado: -3.4%, Washington: -0.9%). In 2019, although it varied by state, the depression prevalence among adults with diabetes was highest in states with a higher diabetes burden such as Kentucky (47.9%), West Virginia (47.0%), and Maine (41.5%). CONCLUSION: US adults with diabetes are more likely to report prevalent depression compared with adults without diabetes. These findings highlight the importance of screening and monitoring for depression as a potential complication among adults with diabetes.

Cogan's syndrome is more than just keratitis: a case-based literature review.

BACKGROUND: Cogan's syndrome (CS) is a rare autoimmune disorder characterized by non-syphilitic interstitial keratitis (IK) and Menière-like cochlear vestibular symptoms, which may also have systemic effects. Corticosteroids are first-line treatment. DMARDs and biologics have been used to treat ocular and systemic symptoms of CS. CASE PRESENTATION: This is a case of a 35-year-old female who reported hearing loss, eye redness and photophobia. Her condition progressed to a sudden sensorineural hearing loss, tinnitus, and constant vertigo accompanied by cephalea. CS was diagnosed after excluding other diseases. The patient still developed bilateral sensorineural hearing loss after receiving hormone, methotrexate, cyclophosphamide, and a variety of biological agents. Joint symptoms were relieved after treatment with a JAK inhibitor (tofacitinib), and hearing did not deteriorate further. CONCLUSIONS: CS should be involved in the differential diagnosis of keratitis. Early identification and intervention of this autoimmune disease can minimize disability and irreversible damage.

Lowering hemoglobin A1c level to less than 6.0% in people with type 2 diabetes may reduce major adverse cardiovascular events: a Bayesian's narrative.

Whether lowering the hemoglobin A1c to <6.0% in patients with type 2 diabetes can reduce the risk of cardiovascular disease (CVD) remains under debate. The ACCORDION and the VADT studies both found reductions in the primary CVD composite associated with intensive glycemic control, though the difference is not statistically significant. However, the lack of significance is often overinterpreted as non-effective: a p-value >.05 only implies that the study "failed to reject" the null hypothesis (i.e. lowering the A1c level to <6.0% results in no CVD benefit), which is different from concluding the null hypothesis being true. In this study, we used Bayesian analysis to reanalyze results from the ACCORDION and VADT-15 trials. Our results suggest achieving an A1c goal of <6.0% as compared to moderate control could result in a moderate risk reduction in MACE.

Change in unemployment by social vulnerability among United States counties with rapid increases in COVID-19 incidence-July 1-October 31, 2020.

OBJECTIVE: During the COVID-19 pandemic, the unemployment rate in the United States peaked at 14.8% in April 2020. We examined patterns in unemployment following this peak in counties with rapid increases in COVID-19 incidence. METHOD: We used CDC aggregate county data to identify counties with rapid increases in COVID-19 incidence (rapid riser counties) during July 1-October 31, 2020. We used a linear regression model with fixed effect to calculate the change of unemployment rate difference in these counties, stratified by the county's social vulnerability (an indicator compiled by CDC) in the two months before the rapid riser index month compared to the index month plus one month after the index month. RESULTS: Among the 585 (19% of U.S. counties) rapid riser counties identified, the unemployment rate gap between the most and least socially vulnerable counties widened by 0.40 percentage point (p<0.01) after experiencing a rapid rise in COVID-19 incidence. Driving the gap were counties with lower socioeconomic status, with a higher percentage of people in racial and ethnic minority groups, and with limited English proficiency. CONCLUSION: The widened unemployment gap after COVID-19 incidence rapid rise between the most and least socially vulnerable counties suggests that it may take longer for socially and economically disadvantaged communities to recover. Loss of income and benefits due to unemployment could hinder behaviors that prevent spread of COVID-19 (e.g., seeking healthcare) and could impede response efforts including testing and vaccination. Addressing the social needs within these vulnerable communities could help support public health response measures.

The mediating role of internalizing and externalizing symptoms in the association between child neglect and suicide attempt in adulthood.

To examine the association between child neglect and adult suicide risk as well as the underlying mechanism. Adults aged 18 or older from the National Epidemiological Survey on Alcohol and Related Conditions Wave 3 who did not have suicide attempts before 18 were included (N = 35,275). Child neglect was categorized into emotional and physical neglect. Suicide risk was captured by suicide attempt. Mediators included internalizing and externalizing symptoms. Natural effect models along with regression analyses were used to estimate the mediated models. Respondents who reported child emotional neglect had greater odds of attempting suicide than those who did not report child emotional neglect. This association was partially mediated by internalizing symptoms. Child emotional neglect is associated with greater odds of suicide attempt and internalizing symptoms partially mediate this association. These results highlight the importance of a comprehensive approach to suicide prevention which includes providing safe, stable, nurturing relationships and environments to prevent child neglect.

Cost Analysis of Community-Based Violence Prevention Programs: Manhood 2.0 and Job Skills Programs.

Purpose: Sexual violence (SV) and adolescent relationship abuse (ARA) are common in the U. S. and have strong associations with negative health and wellbeing outcomes. Manhood 2.0 is the first U.S. program designed for community settings to build bystander skills while also challenging harmful gender norms. A cluster-randomized trial comparing Manhood 2.0 to Job Skills, a job readiness training control condition, demonstrated that it is a promising strategy to prevent sexual violence and adolescent relationship abuse. Such community-based interventions may be particularly relevant in lower resource urban settings, and the costs of such prevention programs have not been considered previously. Methods: The aim of the present study is to perform systematic and standardized cost calculations associated with implementing Manhood 2.0 among adolescent males. In addition, this study provides detailed cost information of the community-based intervention program, as well as costs associated with implementing the Job Skills control program. Program implementation data were recorded throughout the study period (2015-2019) by the Manhood 2.0 study team. Results: The cost of implementing Manhood 2.0 is $4,771 per complete round of program delivery and $451 per participant, which is approximately the same cost as the control Job Skills program ($4,432 and $453 per participant). The marginal cost per additional round of Manhood 2.0 program is $3,682. Conclusion: Implementation of a community-based program requires substantial resources and collaborations with community partners especially in economically disadvantaged neighborhoods. This study provides a snapshot of the cost information of a community-based intervention program from the implementing agency's perspective, which is essential in helping decision-makers understand the costs they will incur by implementing prevention programs and ensuring program feasibility and sustainability.

Association of Online Risk Factors With Subsequent Youth Suicide-Related Behaviors in the US.

Importance: The association between online activities and youth suicide is an important issue for parents, clinicians, and policy makers. However, most information exploring potential associations is drawn from survey data and mainly focuses on risk related to overall screen time. Objective: To evaluate the association between a variety of online risk factors and youth suicide-related behavior using real-world online activity data. Design, Setting, and Participants: A matched case-control study was conducted from July 27, 2019, to May 26, 2020, with the sample drawn from more than 2600 US schools participating in an online safety monitoring program via the Bark online safety tool. For 227 youths having a severe suicide/self-harm alert requiring notification of school administrators, cases were matched 1:5 to 1135 controls on location, the amount of follow-up time, and general volume of online activity. Exposures: Eight potential online risk factors (cyberbullying, violence, drug-related, hate speech, profanity, sexual content, depression, and low-severity self-harm) through assessment of text, image, and video data. Main Outcomes and Measures: Severe suicide/self-harm alert requiring notification of school administrators; severe suicide alerts are statements by youths indicating imminent or recent suicide attempts and/or self-harm. Results: The 1362 participants had a mean (SD) age of 13.3 (2.41) years; 699 (51.3%) were male. All 8 online risk factors studied exhibited differences between case and control populations and were significantly associated with subsequent severe suicide/self-harm alerts when examining total direct and indirect pathways. These associations ranged from an adjusted odds ratio (aOR) of 1.17 (95% CI, 1.09-1.26) for drug-related content to an aOR of 1.82 (95% CI, 1.63-2.03) for depression-related content. When considering the total number of different types of online risk factors among the 8 measured, there was an exponentially larger risk of severe suicide/self-harm alerts; youths with 5 or more of the 8 risk factors present in their online activity had a more than 70-fold increased odds of subsequently having a severe suicide/self-harm alert (aOR, 78.64; 95% CI, 34.39-179.84). Conclusions and Relevance: The findings of this study suggest that many discrete types of risk factors are identifiable from online data and associated with subsequent youth suicide-related behavior. Although each risk factor carries a specific association with suicide-related behavior, the greatest risk is evident for youths demonstrating multiple types of online risk factors.

Adverse childhood experiences and stimulant use disorders among adults in the United States.

Recent data indicate a resurgence of stimulant use and harms in the United States; thus, there is a need to identify risk factors to inform development of effective prevention strategies. Prior research suggests adverse childhood experiences (ACEs) are common among individuals using stimulants and may be an important target for prevention. National Epidemiological Survey on Alcohol and Related Conditions was used to estimate prevalence of ACEs among U.S. adults using amphetamine-type stimulants (ATS), cocaine, or both. Multivariable logistic regression examined associations between ACEs and stimulant use and use disorders. Among adults reporting lifetime ATS use, 22.1% had ≥4 ACEs, 24.9% had 2-3 ACEs, 22.4% had 1 ACE, 30.6% reported no ACEs. Among adults with lifetime ATS use disorder, 29.3% reported ≥4 ACEs, 28.7% reported 2-3 ACEs, 21.6% reported 1 ACE, and 20.4% reported no ACEs. Multivariable logistic regression found a significant relationship between number of ACEs and stimulant use and use disorders. In conclusion, we found a strong relationship between increasing ACE exposures and stimulant use and use disorders. Advancing comprehensive strategies to prevent ACEs and treating underlying trauma among those using stimulants holds great promise to reduce stimulant use and its health and social consequences in the United States.

Impact of Medicaid expansion and methadone coverage as a medication for opioid use disorder on foster care entries during the opioid crisis.

Between 2012 and 2018, incidents of opioid-involved injuries surged and the number of children in foster care due to parental drug use disorder increased. Treatments for opioid use disorder (OUD) might prevent or reduce the amount of time that children spend in the child welfare system. Using administrative data, we examined the impact of Medicaid expansion and state support for methadone as a medication for opioid use disorder (MOUD) on first-time foster care placements. Results show that first-time foster care entries due to parental drug use disorder experienced a reduction of 28 per 100,000 children in Medicaid expansion states with methadone MOUD covered by their state Medicaid programs. The largest reduction was found among non-Hispanic Black children and the youngest children (age 0-1 years). Policies that increase OUD treatment access may reduce foster care placements by reducing parents' drug use, a risk factor for child abuse/neglect and subsequent home removal.

Breaking the cycle of Adverse Childhood Experiences (ACEs): Economic position moderates the relationship between mother and child ACE scores among Black and Hispanic families.

IMPORTANCE: Adverse Childhood Experiences (ACEs) are prevalent, preventable, and a public health issue that cycles from one generation to the next with serious implications for health and wellbeing, particularly. Research is needed to identify factors, including those related to economic position (i.e., wage, net family wealth, home ownership), that break the cycle of ACEs and inform decisions about policies, practices, and programs. OBJECTIVE: To determine whether economic position moderates the association between mother's ACE score and child's ACE score and whether these pathways differ by race and ethnicity. DESIGN: Conducted regression and moderation analysis using mother-child dyadic data from panel surveys, stratified by race. The simple slopes for the interactions were probed to determine the magnitude and significance of the interaction. SETTING: Secondary data analysis utilizing data from two cohorts of the National Longitudinal Surveys: 1) National Longitudinal Survey of Youth 1979; and 2) National Longitudinal Survey of Youth 1979 Children and Young Adults. PARTICIPANTS: The sample included 6,261 children and 2,967 matched mothers. MAIN OUTCOMES S AND MEASURES: The outcome variable was the child's ACE score. Mother's ACE score was the independent variable. Three economic position moderators were examined: mother's and her spouse's average wage and salary, average net family wealth, and percent of time owning a home during her child's first five years of life. RESULTS: Mother's ACE score was positively associated with her child's ACE score. Economic position was a significant moderator for Black families. Higher wages and net family wealth during children's first five years were associated with weakened associations between mother and child ACEs for Black families. For Hispanic families, higher wages and salary were significantly associated with weakened associations. Among White families, higher net family wealth was associated with stronger ACEs transmission. CONCLUSIONS AND RELEVANCE: Taken together, these findings highlight the important role that economic position may play on breaking the cycle of ACEs. This information can inform decisions about what public assistance policies, practices, and programs may be used to improve economic stability among families as an effective ACEs prevention strategy, and for whom these strategies might be most effective at reducing the cycle of ACEs.

Changing Age Distribution of the COVID-19 Pandemic - United States, May-August 2020.

As of September 21, 2020, the coronavirus disease 2019 (COVID-19) pandemic had resulted in more than 6,800,000 reported U.S. cases and more than 199,000 associated deaths.* Early in the pandemic, COVID-19 incidence was highest among older adults (1). CDC examined the changing age distribution of the COVID-19 pandemic in the United States during May-August by assessing three indicators: COVID-19-like illness-related emergency department (ED) visits, positive reverse transcription-polymerase chain reaction (RT-PCR) test results for SARS-CoV-2, the virus that causes COVID-19, and confirmed COVID-19 cases. Nationwide, the median age of COVID-19 cases declined from 46 years in May to 37 years in July and 38 in August. Similar patterns were seen for COVID-19-like illness-related ED visits and positive SARS-CoV-2 RT-PCR test results in all U.S. Census regions. During June-August, COVID-19 incidence was highest in persons aged 20-29 years, who accounted for >20% of all confirmed cases. The southern United States experienced regional outbreaks of COVID-19 in June. In these regions, increases in the percentage of positive SARS-CoV-2 test results among adults aged 20-39 years preceded increases among adults aged ≥60 years by an average of 8.7 days (range = 4-15 days), suggesting that younger adults likely contributed to community transmission of COVID-19. Given the role of asymptomatic and presymptomatic transmission (2), strict adherence to community mitigation strategies and personal preventive behaviors by younger adults is needed to help reduce their risk for infection and subsequent transmission of SARS-CoV-2 to persons at higher risk for severe illness.

Purification and characterization of glucoamylase of Aspergillus oryzae from Luzhou-flavour Daqu.

OBJECTIVE: To obtain novel glucoamylase from Daqu microbe. RESULTS: A dominant strain known as LZ2 with high activity of hydrolyzing starch was isolated from Luzhou Daqu, a Chinese traditional fermentation starter. The LZ2 was identified as Aspergillus oryzae by 18S rDNA sequence analysis. Glucoamylase from LZ2, named as GA-LZ2, was purified to homogeneity and showed a single band with expected molecular mass of 60 kD. The GA-LZ2 effectively degraded amylose, rice starch and wheat starch. Optimal temperature and pH value of enzyme were 60 °C and pH 4.0 respectively. The GA-LZ2 displayed significant thermal stability and pH stability at moderate temperature and low pH. Intriguingly, the thermostability was enhanced in the presence of starch. In addition, GA-LZ2 exhibited insensitivity to glucose, independence of metal ions and tolerance to organic solvents. The GA-LZ2 retained complete activity in the presence of 100 mM glucose and 5% ethanol and methanol. CONCLUSION: Glucoamylase GA-LZ2 displayed broad substrate specificity, strong stability and tolerance, suggesting that GA-LZ2 carry potential for industrial application in bioethanol production.

Adverse childhood experiences, internalizing/externalizing symptoms, and associated prescription opioid misuse: A mediation analysis.

Adverse childhood experiences (ACEs) are associated with mental health and substance use problems, but lesser known is how they interconnect. The objective of this study was to examine how internalizing and externalizing symptoms mediate the association of ACEs with prescription opioid misuse in order to understand how ACEs interconnect with mental health and substance use problems. Adults aged 18 or older from the National Epidemiological Survey on Alcohol and Related Conditions Wave 3 (NESARC-III) conducted in 2012-2013 were included (N = 36,309). The prescription opioid misuse outcomes examined include prescription opioid misuse status, early-onset status of prescription opioid misuse, frequency of past-year prescription opioid misuse, and opioid use disorder. A natural effect model and regression analyses were used to conduct the mediation analyses. We found that respondents with higher ACE scores had greater odds of reporting past-year and lifetime prescription opioid misuse and DSM-V-diagnosed opioid use disorder as well as early onset of prescription opioid misuse (AORs range from 1.06 to 1.12). These associations are partially mediated by internalizing and externalizing symptoms. The findings suggest that internalizing and externalizing symptoms may be potential pathways through which ACEs are associated with prescription opioid misuse. Our results underscore the importance of preventing ACEs and reducing risk for internalizing and externalizing symptoms after exposure, which may reduce later prescription opioid misuse.

Reducing the Number of Children Entering Foster Care: Effects of State Earned Income Tax Credits.

Foster care caseloads, an indicator of child maltreatment, are increasing. Children living in poverty are significantly more likely to be reported to the child welfare system and are overrepresented in foster care. Thus, it is critical to identify prevention strategies that can stem the flow of foster care entries, particularly among populations at higher risk. We used variations in the adoption and refund status of state-level Earned Income Tax Credit (EITC), a socioeconomic policy intended to reduce poverty, to examine their effect on foster care entry rates. Fixed-effects models, accounting for year- and state-fixed effects, demonstrated that a refundable EITC was associated with an 11% decrease in foster care entries compared to states without a state-level EITC after controlling for child poverty rate, racial/ethnic composition, education, and unemployment. Policies that strengthen economic supports for families may prevent child maltreatment and reduce foster care entries and associated costs.

Mothers' homeownership and children's economic success 20 years later among a sample of US citizens.

Familial economic hardship, an adverse childhood experience (ACE) that increases children's risk for exposure to additional ACEs, can derail optimal child development. A compelling area with potential for reducing economic hardship and promoting healthy child development is housing. In the US, the largest contributor to family wealth is homeownership, which may contribute to a family's ability to provide their children opportunities to do better than previous generations. The objective of the current study was to examine the influence of homeownership on children's economic outcomes in adulthood. This study used data from two surveys conducted in the US, the National Longitudinal Survey of Youth 1979 (NLSY79) and the NLSY79 Young Adult survey, to examine the association between mothers' homeownership in 1994 and children's economic outcomes 20 years later. Adults whose mothers owned homes in 1994 were over 1.5 times more likely to own homes, attained higher education, and were moderately less likely to receive public assistance in 2014 compared to adults whose mothers did not own homes. This paper highlights the potential of homeownership to break the intergenerational continuity of poverty. Programs that help families purchase affordable housing hold promise in helping ensure children reach their full potential and improving economic outcomes in future generations.