Children And The Opioid Epidemic: Age-Stratified Exposures And Harms.
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ABSTRACT:
SUBMITTER: Brown KW
PROVIDER: S-EPMC8157201 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVES:To estimate health outcomes of policies to mitigate the opioid epidemic. METHODS:We used dynamic compartmental modeling of US adults, in various pain, opioid use, and opioid addiction health states, to project addiction-related deaths, life years, and quality-adjusted life years from 2016 to 2025 for 11 policy responses to the opioid epidemic. RESULTS:Over 5 years, increasing naloxone availability, promoting needle exchange, expanding medication-assisted addiction treatment, and increasing psychosocial treatment increased life years and quality-adjusted life years and reduced deaths. Other policies reduced opioid prescription supply and related deaths but led some addicted prescription users to switch to heroin use, which increased heroin-related deaths. Over a longer horizon, some such policies may avert enough new addiction to outweigh the harms. No single policy is likely to substantially reduce deaths over 5 to 10 years. CONCLUSIONS:Policies focused on services for addicted people improve population health without harming any groups. Policies that reduce the prescription opioid supply may increase heroin use and reduce quality of life in the short term, but in the long term could generate positive health benefits. A portfolio of interventions will be needed for eventual mitigation.
| S-EPMC6137764 | biostudies-literature
Project description:Compartmental models enable the analysis and prediction of an epidemic including the number of infected, hospitalized and deceased individuals in a population. They allow for computational case studies on non-pharmaceutical interventions thereby providing an important basis for policy makers. While research is ongoing on the transmission dynamics of the SARS-CoV-2 coronavirus, it is important to come up with epidemic models that can describe the main stages of the progression of the associated COVID-19 respiratory disease. We propose an age-stratified discrete compartment model as an alternative to differential equation based S-I-R type of models. The model captures the highly age-dependent progression of COVID-19 and is able to describe the day-by-day advancement of an infected individual in a modern health care system. The fully-identified model for Switzerland not only predicts the overall histories of the number of infected, hospitalized and deceased, but also the corresponding age-distributions. The model-based analysis of the outbreak reveals an average infection fatality ratio of 0.4% with a pronounced maximum of 9.5% for those aged ≥ 80 years. The predictions for different scenarios of relaxing the soft lockdown indicate a low risk of overloading the hospitals through a second wave of infections. However, there is a hidden risk of a significant increase in the total fatalities (by up to 200%) in case schools reopen with insufficient containment measures in place.
| S-EPMC7718912 | biostudies-literature
Project description:Tuberculosis (TB) in young children differs from adult TB in that the risk of rapid progression to active TB (aTB) is higher in children than in adults. The reasons for this increased risk are not fully understood. Early differentiation remains difficult between children at risk to develop aTB from those who will remain healthy and develop a latent TB infection (LTBI). Biomarkers to differentiate aTB from LTBI in children, especially in very young children, are urgently needed. To identify M. tuberculosis-specific functional T cell subsets related to clinical manifestations in children, we enrolled 87 children exposed to M. tuberculosis. After standard clinical assessment, the children were classified as aTB, LTBI, or uninfected. Their CD4+ T cell cytokine profiles (IFN-?, TNF-?, IL-2, IL-17) were analyzed at the single-cell level by flow cytometry after stimulation with three mycobacterial antigens, purified protein derivative (PPD), early-secreted-antigenic target-6 (ESAT-6), or heparin-binding hemagglutinin (HBHA). This approach identified age-related discriminative markers between aTB and LTBI. Whereas among the 3- to 15-year-old children, an excellent discrimination between aTB and LTBI was provided by comparing the ratio between the proportions of ESAT-6-induced IFN-?single+ and ESAT-6-induced TNF-?single+CD4+ T lymphocytes, this was not the case for children younger than 3?years. By contrast, in this group (<3years), the analysis of HBHA-induced IL-17single+CD4+ T lymphocytes allowed us to identify children with LTBI by the high proportion of this cellular lymphocyte subset, whereas this was not the case for children with aTB. The analysis at the single-cell level of T cell immune responses induced by mycobacterial antigens are, thus, different in infected children younger or older than 3?years of age. HBHA-induced IL-17 production by CD4+ T lymphocytes was associated with protection only in children under 3?years who are at high risk for rapid progression to aTB. This suggests that the HBHA-induced IL-17 production by CD4+ T lymphocytes is a potential new correlate of protection against M. tuberculosis in humans, and that the distinction between children with LTBI and those with aTB is possible based on age-related diagnostic markers.
| S-EPMC5591888 | biostudies-literature
Project description:BACKGROUND:Polybrominated diphenyl ethers (PBDEs) reduce serum thyroid hormone concentrations in animal studies, but few studies have examined the impact of early-life PBDE exposures on thyroid hormone disruption in childhood. METHODS:We used data from 162 mother-child pairs from the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, OH). We measured PBDEs in maternal serum at 16 ± 3 weeks gestation and in child serum at 1-3 years. Thyroid hormones were measured in serum at 3 years. We used multiple informant models to investigate associations between prenatal and early-life PBDE exposures and thyroid hormone levels at age 3 years. RESULTS:Prenatal PBDEs were associated with decreased thyroid stimulating hormone (TSH) levels at age 3 years. A 10-fold increase in prenatal ∑PBDEs (BDE-28, -47, -99, -100, and -153) was associated with a 27.6% decrease (95% CI -40.8%, -11.3%) in TSH. A ten-fold increase in prenatal ∑PBDEs was associated with a 0.25 pg/mL (0.07, 0.43) increase in free triiodothyronine (FT3). Child sex modified associations between prenatal PBDEs and thyroid hormones, with significant decrements in TSH among females and decreased free T4 (FT4) in males. Prenatal ∑PBDEs were not associated with TT4, FT4, or total T3. CONCLUSIONS:These findings suggest an inverse relationship between prenatal ∑PBDEs and TSH at 3 years. Associations may be sexually dimorphic, with an inverse relationship between prenatal BDE-47 and -99 and TSH in females and null associations among males.
| S-EPMC5997562 | biostudies-literature
Project description:The United States opioid epidemic is a nationwide public health crisis. Initially driven by increased consumption and availability of pharmaceutical opioids, an increasing number of opioid overdoses are now related to heroin and illicitly manufactured fentanyl and fentanyl analogs. Addressing this epidemic requires addressing the stigma associated with opioid use disorders and its treatment, improving access to efficacious treatment options, specifically methadone and buprenorphine, and reducing opioid overdose fatalities with distribution of the opioid antagonist and overdose reversal agent naloxone.
| S-EPMC6578581 | biostudies-literature
Project description:Opioid use in the United States and in many parts of the world has reached epidemic proportions. This has led to excess mortality as well as significant changes in the epidemiology of liver disease. Herein, we review the impact of the opioid epidemic on liver disease, focusing on the multifaceted impact this epidemic has had on liver disease and liver transplantation. In particular, the opioid crisis has led to a significant shift in incident hepatitis C virus infection to younger populations and to women, leading to changes in screening recommendations. Less well characterized are the potential direct and indirect hepatotoxic effects of opioids, as well as the changes in the incidence of hepatitis B virus infection and alcohol abuse that are likely rising in this population as well. Finally, the opioid epidemic has led to a significant rise in the proportion of organ donors who died due to overdose. These donors have led to an overall increase in donor numbers, but also to new considerations about the better use of donors with perceived or actual risk of disease transmission, especially hepatitis C. Clearly, additional efforts are needed to combat the opioid epidemic. Moreover, better understanding of the epidemiology and underlying pathophysiology will help to identify and treat liver disease in this high-risk population.
| S-EPMC7001546 | biostudies-literature
Project description:BackgroundMechanisms that facilitate early infection and inflammation in cystic fibrosis (CF) are unclear. We previously showed that young CF children with secondhand smoke exposure (SHSe) have increased susceptibility to respiratory infections. We aimed to define the impact of SHSe and other external factors upon the fecal bacteriome in early CF.MethodsTwenty CF infants and children were enrolled, clinical data recorded, and hair nicotine measured as an objective surrogate of SHSe. Fecal samples were collected at clinic visits and bacteriome 16S rRNA gene sequencing performed.ResultsSHSe was associated with increased alpha diversity and increased relative abundance of Acinetobacter and Akkermansia, along with decreased Bifidobacterium and Lactobacillus. Recent antibiotic exposure predicted bacterial population structure in children less than 2 years of age and was associated with decreased Bacteroides relative abundance. Age was the strongest predictor of overall fecal bacterial composition and positively associated with Blautia and Parabacteroides. Weight for length was negatively associated with Staphylococcus relative abundance.ConclusionsSHSe and other external factors such as antibiotics appear to alter fecal bacterial composition in young CF children, but the strongest predictor of overall composition was age. These findings have implications for understanding the intestinal microbiome in young CF children.
| S-EPMC7593804 | biostudies-literature
Project description:Background and objectivesAlthough opioid pain relievers are commonly prescribed in pregnancy, their association with neonatal outcomes is poorly described. Our objectives were to identify neonatal complications associated with antenatal opioid pain reliever exposure and to establish predictors of neonatal abstinence syndrome (NAS).MethodsWe used prescription and administrative data linked to vital statistics for mothers and infants enrolled in the Tennessee Medicaid program between 2009 and 2011. A random sample of NAS cases was validated by medical record review. The association of antenatal exposures with NAS was evaluated by using multivariable logistic regression, controlling for maternal and infant characteristics.ResultsOf 112,029 pregnant women, 31,354 (28%) filled ? 1 opioid prescription. Women prescribed opioid pain relievers were more likely than those not prescribed opioids (P < .001) to have depression (5.3% vs 2.7%), anxiety disorder (4.3% vs 1.6%) and to smoke tobacco (41.8% vs 25.8%). Infants with NAS and opioid-exposed infants were more likely than unexposed infants to be born at a low birth weight (21.2% vs 11.8% vs 9.9%; P < .001). In a multivariable model, higher cumulative opioid exposure for short-acting preparations (P < .001), opioid type (P < .001), number of daily cigarettes smoked (P < .001), and selective serotonin reuptake inhibitor use (odds ratio: 2.08 [95% confidence interval: 1.67-2.60]) were associated with greater risk of developing NAS.ConclusionsPrescription opioid use in pregnancy is common and strongly associated with neonatal complications. Antenatal cumulative prescription opioid exposure, opioid type, tobacco use, and selective serotonin reuptake inhibitor use increase the risk of NAS.
| S-EPMC4411781 | biostudies-literature
Project description:BackgroundStudies conducted in Swedish populations have shown that men with lowest prostate-specific antigen (PSA) levels at ages 44-50 years and 60 years have very low risk of future distant metastasis or death from prostate cancer. This study investigates benefits and harms of screening strategies stratified by PSA levels.MethodsPSA levels and diagnosis patterns from two microsimulation models of prostate cancer progression, detection, and mortality were compared against results of the Malmö Preventive Project, which stored serum and tracked subsequent prostate cancer diagnoses for 25 years. The models predicted the harms (tests and overdiagnoses) and benefits (lives saved and life-years gained) of PSA-stratified screening strategies compared with biennial screening from age 45 years to age 69 years.ResultsCompared with biennial screening for ages 45-69 years, lengthening screening intervals for men with PSA less than 1.0 ng/mL at age 45 years led to 46.8-47.0% fewer tests (range between models), 0.9-2.1% fewer overdiagnoses, and 3.1-3.8% fewer lives saved. Stopping screening when PSA was less than 1.0 ng/mL at age 60 years and older led to 12.8-16.0% fewer tests, 5.0-24.0% fewer overdiagnoses, and 5.0-13.1% fewer lives saved. Differences in model results can be partially explained by differences in assumptions about the link between PSA growth and the risk of disease progression.ConclusionRelative to a biennial screening strategy, PSA-stratified screening strategies investigated in this study substantially reduced the testing burden and modestly reduced overdiagnosis while preserving most lives saved. Further research is needed to clarify the link between PSA growth and disease progression.
| S-EPMC7566340 | biostudies-literature
Project description:Executive function is a critical behavioral trait rarely studied in relation to potential neurotoxicants. Prenatal exposure to polybrominated diphenyl ethers (PBDEs) and perfluoroalkyl substances (PFASs) has been associated with adverse neurodevelopment, but there is limited research on executive function. Data from 256 mother-child pairs in the Health Outcomes and Measures of the Environment Study, a prospective birth cohort (2003-2006, Cincinnati, OH), was used to examine maternal serum PBDEs and PFASs and executive function in children ages 5 and 8 years. Maternal serum PBDEs and PFASs were measured at 16±3 weeks gestation. Executive function was assessed with the parent-rated Behavior Rating Inventory of Executive Function (BRIEF), which yields composite measures: behavioral regulation index, metacognition index, and global executive composite. Higher BRIEF scores indicate executive function impairments. Linear mixed models and generalized estimating equations were used to estimate covariate-adjusted associations between PBDEs and PFASs and executive function. A 10-fold increase in BDE-153 was associated with poorer behavior regulation (?=3.23, 95% CI 0.60, 5.86). Higher odds of having a score ?60 in behavior regulation (OR=3.92, 95% CI 1.76, 8.73) or global executive functioning (OR=2.34, 95% CI 1.05, 5.23) was observed with increased BDE-153. Each ln-unit increase in perfluorooctane sulfonate (PFOS) was associated with poorer behavior regulation (?=3.14, 95% CI 0.68, 5.61), metacognition (?=3.10, 95% CI 0.62, 5.58), and global executive functioning (?=3.38, 95% CI 0.86, 5.90). However, no association was observed between perfluorooctanoate (PFOA) and executive function. Prenatal exposures to BDE-153 and PFOS may be associated with executive function deficits in school-age children.
| S-EPMC4821747 | biostudies-literature