Last data update: May 20, 2024. (Total: 46824 publications since 2009)
Records 1-30 (of 57 Records) |
Query Trace: Holbrook J [original query] |
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A systematic review and meta-analysis of chemical exposures and attention-deficit/hyperactivity disorder in children
Dimitrov LV , Kaminski JW , Holbrook JR , Bitsko RH , Yeh M , Courtney JG , O'Masta B , Maher B , Cerles A , McGowan K , Rush M . Prev Sci 2023 Exposure to certain chemicals prenatally and in childhood can impact development and may increase risk for attention-deficit/hyperactivity disorder (ADHD). Leveraging a larger set of literature searches conducted to synthesize results from longitudinal studies of potentially modifiable risk factors for childhood ADHD, we present meta-analytic results from 66 studies that examined the associations between early chemical exposures and later ADHD diagnosis or symptoms. Studies were eligible for inclusion if the chemical exposure occurred at least 6 months prior to measurement of ADHD diagnosis or symptomatology. Included papers were published between 1975 and 2019 on exposure to anesthetics (n = 5), cadmium (n = 3), hexachlorobenzene (n = 4), lead (n = 22), mercury (n = 12), organophosphates (n = 7), and polychlorinated biphenyls (n = 13). Analyses are presented for each chemical exposure by type of ADHD outcome reported (categorical vs. continuous), type of ADHD measurement (overall measures of ADHD, ADHD symptoms only, ADHD diagnosis only, inattention only, hyperactivity/impulsivity only), and timing of exposure (prenatal vs. childhood vs. cumulative), whenever at least 3 relevant effect sizes were available. Childhood lead exposure was positively associated with ADHD diagnosis and symptoms in all analyses except for the prenatal analyses (odds ratios (ORs) ranging from 1.60 to 2.62, correlation coefficients (CCs) ranging from 0.14 to 0.16). Other statistically significant associations were limited to organophosphates (CC = 0.11, 95% confidence interval (CI): 0.03-0.19 for continuous measures of ADHD outcomes overall), polychlorinated biphenyls (CC = 0.08, 95% CI: 0.02-0.14 for continuous measures of inattention as the outcome), and both prenatal and childhood mercury exposure (CC = 0.02, 95% CI: 0.00-0.04 for continuous measures of ADHD outcomes overall for either exposure window). Our findings provide further support for negative impacts of prenatal and/or childhood exposure to certain chemicals and raise the possibility that primary prevention and targeted screening could prevent or mitigate ADHD symptomatology. Furthermore, these findings support the need for regular review of regulations as our scientific understanding of the risks posed by these chemicals evolves. |
Systematic review and meta-analysis of the relationship between exposure to parental substance use and attention-deficit/hyperactivity disorder in children
Maher BS , Bitsko RH , Claussen AH , O'Masta B , Cerles A , Holbrook JR , Mahmooth Z , Chen-Bowers N , Rojo ALA , Kaminski JW , Rush M . Prev Sci 2023 Attention-deficit/hyperactivity disorder (ADHD) is characterized by persistent patterns of inattention, hyperactivity, and impulsiveness. Among US children and adolescents aged 3-17 years, 9.4% have a diagnosis of ADHD. Previous research suggests possible links between parental substance use and ADHD among children. We conducted a systematic review and meta-analysis of 86 longitudinal or retrospective studies of prenatal or postnatal alcohol, tobacco, or other parental substance use and substance use disorders and childhood ADHD and its related behavioral dimensions of inattention and hyperactivity-impulsivity. Meta-analyses were grouped by drug class and pre- and postnatal periods with combined sample sizes ranging from 789 to 135,732. Prenatal exposure to alcohol or tobacco and parent substance use disorders were consistently and significantly associated with ADHD among children. Other parental drug use exposures resulted in inconsistent or non-significant findings. Prevention and treatment of parental substance use may have potential for impacts on childhood ADHD. |
A population-based study of the utility of screening for tics and the relative contribution of tics and psychiatric comorbidity to academic and social impairment in adolescents
Smith JN , Owens JS , Evans SW , Bitsko RH , Holbrook JR . Evid Based Pract Child Adolesc Ment Health 2023 This study examined the performance of a brief screening tool for tics in adolescents. Academic and social impairment in students by tic screen status and emotional/behavioral problem status were examined. Data were collected as part of an epidemiologic study, the Project to Learn about Youth–Mental Health. Participants were 2,312 secondary school students at the Ohio site (47.4% female; 94.4% non-Hispanic white) and their teachers. Students completed 6 items from the Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey (MOVES-6) and the Strengths and Difficulties Questionnaire (SDQ). Teachers completed the Proxy Report Questionnaire for tics and SDQ. Based on responses to the MOVES-6, 11.1% of students screened positive for tics. Internal consistency was adequate (α = 0.76); inter-rater consistency between teachers and students was low (0.03). Based on student self-report, those who screened positive for tics self-reported more academic and social impairment than students who screened negative for tics; teacher-report of impairment was similar between those with a positive or negative tic screen. Students who screened positive for tics and reported internalizing difficulties reported more academic and social impairment than students with only a positive tic screen. Teachers perceived those screening positive for tics and externalizing difficulties as the most socially impaired. In conclusion, a positive self-reported tic screen was associated with self-reported academic and social impairment. Findings reveal the independent contribution of tics to impairment, even when internalizing and externalizing problems are present, and the potential utility of a school-based screening for tics in adolescents. © 2023 Society of Clinical Child & Adolescent Psychology. |
Severe acute respiratory disease in American mink (Neovison vison) experimentally infected with SARS-CoV-2 (preprint)
Adney DR , Lovaglio J , Schulz JE , Yinda CK , Avanzato VA , Haddock E , Port JR , Holbrook MG , Hanley PW , Saturday G , Scott D , Spengler JR , Tansey C , Cossaboom CM , Wendling NM , Martens C , Easley J , Yap SW , Seifert SN , Munster VJ . bioRxiv 2022 24 An animal model that fully recapitulates severe COVID-19 presentation in humans has been a top priority since the discovery of SARS-CoV-2 in 2019. Although multiple animal models are available for mild to moderate clinical disease, a non-transgenic model that develops severe acute respiratory disease has not been described. Mink experimentally infected with SARS-CoV-2 developed severe acute respiratory disease, as evident by clinical respiratory disease, radiological, and histological changes. Virus was detected in nasal, oral, rectal, and fur swabs. Deep sequencing of SARS-CoV-2 from oral swabs and lung tissue samples showed repeated enrichment for a mutation in the gene encoding for nonstructural protein 6 in open reading frame 1a/1ab. Together, these data indicate that American mink develop clinical features characteristic of severe COVID19 and as such, are uniquely suited to test viral countermeasures. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1.
van Doremalen N , Bushmaker T , Morris DH , Holbrook MG , Gamble A , Williamson BN , Tamin A , Harcourt JL , Thornburg NJ , Gerber SI , Lloyd-Smith JO , de Wit E , Munster VJ . medRxiv 2020 A novel human coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, referred to as HCoV-19 here) that emerged in Wuhan, China in late 2019 is now causing a pandemic1. Here, we analyze the aerosol and surface stability of HCoV-19 and compare it with SARS-CoV-1, the most closely related human coronavirus.2 We evaluated the stability of HCoV-19 and SARS-CoV-1 in aerosols and on different surfaces and estimated their decay rates using a Bayesian regression model (see Supplementary Appendix). All experimental measurements are reported as mean across 3 replicates. |
Validation of the Diagnostic Interview Schedule For Children (DISC-5) tic disorder and attention-deficit/hyperactivity disorder modules
Bitsko RH , Holbrook JR , Fisher PW , Lipton C , van Wijngaarden E , Augustine EF , Mink JW , Vierhile A , Piacentini J , Walkup J , Firchow B , Ali AR , Badgley A , Adams HR . Evid Based Pract Child Adolesc Mental Heal 2023 Effective methods to assess mental disorders in children are necessary for accurate prevalence estimates and to monitor prevalence over time. This study assessed updates of the tic disorder and attention-deficit/hyperactivity disorder (ADHD) modules of the Diagnostic Interview Schedule for Children, Version 5 (DISC-5) that reflect changes in diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders (Fifth edition, DSM-5). The DISC-5 tic disorder and ADHD parent- and child-report modules were compared to expert clinical assessment for 100 children aged 6–17 years (40 with tic disorder alone, 17 with tic disorder and ADHD, 9 with ADHD alone, and 34 with neither) for validation. For the tic disorder module, parent-report had high (>90%) sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, while the youth-report had high specificity and PPV, moderate accuracy (81.4%), and lower sensitivity (69.8%) and NPV (67.3%). The ADHD module performed less well: parent-report had high NPV (91.4%), moderate sensitivity (80.8%), and lower specificity (71.6%), PPV (50.0%), and accuracy (74.0%); youth-report had moderate specificity (82.8%) and NPV (88.3%), and lower sensitivity (65.0%), PPV (54.2%), and accuracy (78.6%). Adding teacher-report of ADHD symptoms to DISC-5 parent-report of ADHD increased sensitivity (94.7%) and NPV (97.1%), but decreased specificity (64.2%), PPV (48.7%), and accuracy (72.2%). These findings support the use of the parent-report tic disorder module alone or in combination with the child report module in future research and epidemiologic studies; additional validation studies are warranted for the ADHD module. © 2023 Society of Clinical Child & Adolescent Psychology. |
Clinical characteristics of children with Tourette syndrome with and without sleep disorder
Ricketts EJ , Wolicki SB , Holbrook JR , Rozenman M , McGuire JF , Charania SN , Piacentini J , Mink JW , Walkup JT , Woods DW , Claussen AH . Pediatr Neurol 2023 141 18-24 BACKGROUND: Sleep problems are common in children with Tourette Syndrome (TS). However, research regarding their demographic and clinical profile is limited. METHODS: We examined characteristics of 114 children aged five to 17 years with a lifetime diagnosis of TS and compared children with sleep disorder (n = 32) and without sleep disorder (n = 82). Parent report from the 2014 National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome provided demographics and clinical information, other diagnosed disorders, medication use, TS severity, and impairment. RESULTS: More children with TS with sleep disorder were from households with lower parental education (P < 0.01) and poverty (P = 0.04); had other diagnoses (P = 0.03), including obsessive-compulsive disorder (P < 0.01), oppositional defiant disorder or conduct disorder (P < 0.01), attention-deficit/hyperactivity disorder (ADHD) (P = 0.02), and autism (P = 0.03); and had ever used TS medication (P = 0.01) than children with TS without sleep disorder. More children with TS with sleep disorder had severe TS symptoms (P <0.01), tic-related impairment (P<0.01), and severe ADHD symptoms (P < 0.01) compared with children with TS without sleep disorder. CONCLUSIONS: Findings suggest greater parent-reported impact and tic-related interference in children with TS with sleep disorder compared with TS without sleep disorder. Results underscore the importance of monitoring and intervention for TS exacerbations, other diagnosed disorders, and medication use, and consideration of socioeconomic context in sleep disorder management and prevention in children with TS. |
Post-COVID conditions and healthcare utilization among adults with and without disabilities-2021 Porter Novelli Fall Styles survey
Miller MJ , Feldstein LR , Holbrook J , Plumb ID , Accorsi EK , Zhang QC , Cheng Q , Ko JY , Wanga V , Konkle S , Dimitrov LV , Bertolli J , Saydah S . Disabil Health J 2022 16 (2) 101436 BACKGROUND: Adults with disabilities are at increased risk for SARS-CoV-2 infection and severe disease; whether adults with disabilities are at an increased risk for ongoing symptoms after acute SARS-CoV-2 infection is unknown. OBJECTIVES: To estimate the frequency and duration of long-term symptoms (>4 weeks) and health care utilization among adults with and without disabilities who self-report positive or negative SARS-CoV-2 test results. METHODS: Data from a nationwide survey of 4510 U.S. adults administered from September 24, 2021-October 7, 2021, were analyzed for 3251 (79%) participants who self-reported disability status, symptom(s), and SARS-CoV-2 test results (a positive test or only negative tests). Multivariable models were used to estimate the odds of having ≥1 COVID-19-like symptom(s) lasting >4 weeks by test result and disability status, weighted and adjusted for socio-demographics. RESULTS: Respondents who tested positive for SARS-CoV-2 had higher odds of reporting ≥1 long-term symptom (with disability: aOR = 4.50 [95% CI: 2.37, 8.54] and without disability: aOR = 9.88 [95% CI: 7.13, 13.71]) compared to respondents testing negative. Among respondents who tested positive, those with disabilities were not significantly more likely to experience long-term symptoms compared to respondents without disabilities (aOR = 1.65 [95% CI: 0.78, 3.50]). Health care utilization for reported symptoms was higher among respondents with disabilities who tested positive (40%) than among respondents without disabilities who tested positive (18%). CONCLUSIONS: Ongoing symptoms among adults with and without disabilities who also test positive for SARS-CoV-2 are common; however, the frequency of health care utilization for ongoing symptoms is two-fold among adults with disabilities. |
Severe acute respiratory disease in American mink experimentally infected with SARS-CoV-2.
Adney DR , Lovaglio J , Schulz JE , Yinda CK , Avanzato VA , Haddock E , Port JR , Holbrook MG , Hanley PW , Saturday G , Scott D , Shaia C , Nelson AM , Spengler JR , Tansey C , Cossaboom CM , Wendling NM , Martens C , Easley J , Yap SW , Seifert SN , Munster VJ . JCI Insight 2022 7 (22) An animal model that fully recapitulates severe COVID-19 presentation in humans has been a top priority since the discovery of SARS-CoV-2 in 2019. Although multiple animal models are available for mild to moderate clinical disease, models that develop severe disease are still needed. Mink experimentally infected with SARS-CoV-2 developed severe acute respiratory disease, as evident by clinical respiratory disease, radiological, and histological changes. Virus was detected in nasal, oral, rectal, and fur swabs. Deep sequencing of SARS-CoV-2 from oral swabs and lung tissue samples showed repeated enrichment for a mutation in the gene encoding nonstructural protein 6 in open reading frame 1ab. Together, these data indicate that American mink develop clinical features characteristic of severe COVID-19 and, as such, are uniquely suited to test viral countermeasures. |
Health care access and use among adults with and without vision impairment: Behavioral Risk Factor Surveillance System, 2018
Cheng Q , Okoro CA , Mendez I , Lundeen EA , Saaddine JB , Stein R , Holbrook J . Prev Chronic Dis 2022 19 E70 INTRODUCTION: Adults with vision impairment may have unique needs when accessing health care to maintain good health. Our study examined the relationship between vision status and access to and use of health care. METHODS: We analyzed data on adults aged 18 years or older who participated in the 2018 Behavioral Risk Factor Surveillance System. Vision impairment was identified by a yes response to the question "Are you blind or do you have serious difficulty seeing, even when wearing glasses?" Survey questions assessed health care access over the past year (having health insurance coverage, a usual health care provider, or unmet health care needs because of cost) and use of health care during that period (routine checkup and dental visit). We estimated age-adjusted prevalence of our outcomes of interest and used bivariate analyses to compare estimates of the outcomes by vision impairment status. RESULTS: The prevalence of self-reported vision impairment was 5.3%. Compared with adults without impaired vision, adults with vision impairment had a lower prevalence of having health insurance coverage (80.6% vs 87.6%), a usual health care provider (71.9% vs 75.7%), or a dental visit in the past year (52.9% vs 67.2%) and a higher prevalence of having an unmet health care need in the past year because of cost (29.2% vs 12.6%). CONCLUSION: Adults with vision impairment reported lower access to and use of health care than those without. Further research can better identify and understand barriers to care to improve access to and use of health care among this population. |
Surveillance of ADHD among children in the United States: Validity and reliability of parent report of provider diagnosis
Cree RA , Bitsko RH , Danielson ML , Wanga V , Holbrook J , Flory K , Kubicek LF , Evans SW , Owens JS , Cuffe SP . J Atten Disord 2022 27 (2) 10870547221131979 OBJECTIVE: To evaluate the appropriateness of parent-reported diagnosis of ADHD as a surveillance tool. METHOD: We assessed agreement over time and concordance of parent-reported diagnosis against Diagnostic and Statistical Manual (DSM)-based criteria. We compared concordance of diagnosis and DSM-based criteria by child characteristics, including treatment. RESULTS: Among parents who reported their child had ADHD, 95.7% reported it again 2 years later. Comparing diagnosis with DSM-based criteria, specificity and negative predictive value were high, sensitivity was moderate, and positive predictive value was low. Most children with an ADHD diagnosis who did not meet DSM-based criteria met sub-threshold criteria or took medication for ADHD. Concordance differed by child characteristics and treatment. CONCLUSION: Parent-reported diagnosed ADHD is reliable over time. Although differences in parent-reported diagnosis and DSM-based criteria were noted, these may reflect children with milder symptoms or treated ADHD. Parent-report of child ADHD ever diagnosis may be a good single-item indicator for prevalence. |
Discovery of substituted benzyloxy-benzylamine inhibitors of acetyltransferase Eis and their anti-mycobacterial activity
Pang AH , Green KD , Chandrika NT , Garzan A , Punetha A , Holbrook SYL , Willby MJ , Posey JE , Tsodikov OV , Garneau-Tsodikova S . Eur J Med Chem 2022 242 114698 A clinically significant mechanism of tuberculosis resistance to the aminoglycoside kanamycin (KAN) is its acetylation catalyzed by upregulated Mycobacterium tuberculosis (Mtb) acetyltransferase Eis. In search for inhibitors of Eis, we discovered an inhibitor with a substituted benzyloxy-benzylamine scaffold. A structure-activity relationship study of 38 compounds in this structural family yielded highly potent (IC(50) 1M) Eis inhibitors, which did not inhibit other acetyltransferases. Crystal structures of Eis in complexes with three of the inhibitors showed that the inhibitors were bound in the aminoglycoside binding site of Eis, consistent with the competitive mode of inhibition, as established by kinetics measurements. When tested in Mtb cultures, two inhibitors (47 and 55) completely abolished resistance to KAN of the highly KAN-resistant strain Mtb mc(2) 6230 K204, likely due to Eis inhibition as a major mechanism. Thirteen of the compounds were toxic even in the absence of KAN to Mtb and other mycobacteria, but not to non-mycobacteria or to mammalian cells. This, yet unidentified mechanism of toxicity, distinct from Eis inhibition, will merit future studies along with further development of these molecules as anti-mycobacterial agents. |
Childhood physical health and attention deficit/hyperactivity disorder: A systematic review and meta-analysis of modifiable factors
So M , Dziuban EJ , Pedati CS , Holbrook JR , Claussen AH , O'Masta B , Maher B , Cerles AA , Mahmooth Z , MacMillan L , Kaminski JW , Rush M . Prev Sci 2022 Although neurobiologic and genetic factors figure prominently in the development of attention deficit/hyperactivity disorder (ADHD), adverse physical health experiences and conditions encountered during childhood may also play a role. Poor health is known to impact the developing brain with potential lifelong implications for behavioral issues. In attempt to better understand the relationship between childhood physical health and the onset and presence of ADHD symptoms, we summarized international peer-reviewed articles documenting relationships between a select group of childhood diseases or health events (e.g., illnesses, injuries, syndromes) and subsequent ADHD outcomes among children ages 0-17years. Drawing on a larger two-phase systematic review, 57 longitudinal or retrospective observational studies (1978-2021) of childhood allergies, asthma, eczema, head injury, infection, or sleep problems and later ADHD diagnosis or symptomatology were identified and subjected to meta-analysis. Significant associations were documented between childhood head injuries, infections, and sleep problems with both dichotomous and continuous measures of ADHD, and between allergies with dichotomous measures of ADHD. We did not observe significant associations between asthma or eczema with ADHD outcomes. Heterogeneity detected for multiple associations, primarily among continuously measured outcomes, underscores the potential value of future subgroup analyses and individual studies. Collectively, these findings shed light on the importance of physical health in understanding childhood ADHD. Possible etiologic links between physical health factors and ADHD are discussed, as are implications for prevention efforts by providers, systems, and communities. |
Stability of mental disorder prevalence estimates among school-aged children and adolescents: Findings from the community-based Project to Learn About Youth-Mental Health (PLAY-MH) and Replication-PLAY-MH (Re-PLAY-MH), 2014-2017
Wanga V , Danielson ML , Bitsko RH , Holbrook JR , Lipton C , Claussen AH , Siceloff ER , Flory K . Ann Epidemiol 2022 72 82-90 PURPOSE: This study evaluated the stability over time of prevalence estimates of mental disorders among school-aged children from the same community. METHODS: We compared screening status and weighted prevalence of selected mental disorders from the two-stage school-based South Carolina Project to Learn About Youth-Mental Health (Time 1) and its replication study (Time 2) conducted between 2014 and 2017. During stage 1, two teacher screeners were used to group students into high or low risk for a mental disorder. During stage 2, parents of selected students completed a structured diagnostic interview to assess whether their child met criteria for specific disorders. RESULTS: For stage 1, 19.9% of students screened as high risk for a mental disorder at Time 2 compared to 17.8% at Time 1. Among students included at both timepoints, 9.1% screened as high risk at both timepoints while screening status changed for 20.7%. The overall prevalence of included mental disorders was approximately 18% at both timepoints. There were no differences (p-values>0.05) in prevalence of individual mental disorders between Time 1 (range:0.3%-6.7%) and Time 2 (range:1.2%-7.7%). CONCLUSIONS: Study findings demonstrate that similar methodology yielded similar prevalence estimates of mental disorders and can inform community-level planning for improving mental health in children. |
A systematic review and meta-analysis of parental depression, antidepressant usage, antisocial personality disorder, and stress and anxiety as risk factors for attention-deficit/hyperactivity disorder (ADHD) in children
Robinson LR , Bitsko RH , O'Masta B , Holbrook JR , Ko J , Barry CM , Maher B , Cerles A , Saadeh K , MacMillan L , Mahmooth Z , Bloomfield J , Rush M , Kaminski JW . Prev Sci 2022 Poor parental mental health and stress have been associated with children's mental disorders, including attention-deficit/hyperactivity disorder (ADHD), through social, genetic, and neurobiological pathways. To determine the strength of the associations between parental mental health and child ADHD, we conducted a set of meta-analyses to examine the association of parent mental health indicators (e.g., parental depression, antidepressant usage, antisocial personality disorder, and stress and anxiety) with subsequent ADHD outcomes in children. Eligible ADHD outcomes included diagnosis or symptoms. Fifty-eight articles published from 1980 to 2019 were included. We calculated pooled effect sizes, accounting for each study's conditional variance, separately for test statistics based on ADHD as a dichotomous (e.g., diagnosis or clinical cutoffs) or continuous measurement (e.g., symptoms of ADHD subtypes of inattentiveness and hyperactivity/impulsivity). Parental stress and parental depression were significantly associated with increased risk for ADHD overall and both symptoms and diagnosis. Specifically, maternal stress and anxiety, maternal prenatal stress, maternal depression, maternal post-partum depression, and paternal depression were positively associated with ADHD. In addition, parental depression was associated with symptoms of ADHD inattentive and hyperactive/impulsive subtypes. Parental antisocial personality disorder was also positively associated with ADHD overall and specifically ADHD diagnosis. Prenatal antidepressant usage was associated with ADHD when measured dichotomously only. These findings raise the possibility that prevention strategies promoting parental mental health and addressing parental stress could have the potential for positive long-term impacts on child health, well-being, and behavioral outcomes. |
State-level estimates of the prevalence of parent-reported ADHD diagnosis and treatment among U.S. children and adolescents, 2016 to 2019
Danielson ML , Holbrook JR , Bitsko RH , Newsome K , Charania SN , McCord RF , Kogan MD , Blumberg SJ . J Atten Disord 2022 26 (13) 10870547221099961 OBJECTIVE: To provide state-level estimates of diagnosed ADHD and associated treatment among children in the United States in 2016 to 2019. METHOD: This study used the National Survey of Children's Health to produce national and state-level estimates of lifetime diagnosis and current ADHD among all children aged 3 to 17 years (n=114,476), and national and state-level estimates of medication and behavioral treatment use among children with current ADHD. RESULTS: The state-level estimates of diagnosed ADHD ranged from 6.1% to 16.3%. Among children with current ADHD, state-level estimates of ADHD medication usage ranged from 37.8% to 81.4%, and state-level estimates of behavioral treatment ranged from 38.8% to 61.8%. CONCLUSION: There was substantial state-level variation for indicators of ADHD diagnosis and associated treatment. These state-level results can be used by policymakers, public health practitioners, health care providers, and other stakeholders to help address the service needs of children with ADHD in their states. |
All in the family A systematic review and meta-analysis of parenting and family environment as risk factors for attention-deficit/hyperactivity disorder (ADHD) in children
Claussen AH , Holbrook JR , Hutchins HJ , Robinson LR , Bloomfield J , Meng L , Bitsko RH , O'Masta B , Cerles A , Maher B , Rush M , Kaminski JW . Prev Sci 2022 1-23 Parenting and family environment have significant impact on child development, including development of executive function, attention, and self-regulation, and may affect the risk of developmental disorders including attention-deficit/hyperactivity disorder (ADHD). This paper examines the relationship of parenting and family environment factors with ADHD. A systematic review of the literature was conducted in 2014 and identified 52 longitudinal studies. A follow-up search in 2021 identified 7 additional articles, for a total of 59 studies that examined the association of parenting factors with ADHD outcomes: ADHD overall (diagnosis or symptoms), ADHD diagnosis specifically, or presence of the specific ADHD symptoms of inattention and hyperactivity/impulsivity. For parenting factors that were present in three or more studies, pooled effect sizes were calculated separately for dichotomous or continuous ADHD outcomes, accounting for each study's conditional variance. Factors with sufficient information for analysis were parenting interaction quality (sensitivity/warmth, intrusiveness/reactivity, and negativity/harsh discipline), maltreatment (general maltreatment and physical abuse), parental relationship status (divorce, single parenting), parental incarceration, and child media exposure. All factors showed a significant direct association with ADHD outcomes, except sensitivity/warmth which had an inverse association. Parenting factors predicted diagnosis and overall symptoms as well as inattentive and hyperactive symptoms when measured, but multiple factors showed significant heterogeneity across studies. These findings support the possibility that parenting and family environment influences ADHD symptoms and may affect a child's likelihood of being diagnosed with ADHD. Prevention strategies that support parents, such as decreasing parenting challenges and increasing access to parent training in behavior management, may improve children's long-term developmental health. |
Factors associated with bullying victimization and bullying perpetration in children and adolescents with ADHD: 2016 to 2017 National Survey of Children's Health
Cuba Bustinza C , Adams RE , Claussen AH , Vitucci D , Danielson ML , Holbrook JR , Charania SN , Yamamoto K , Nidey N , Froehlich TE . J Atten Disord 2022 26 (12) 10870547221085502 OBJECTIVE: To identify characteristics associated with bullying involvement in pediatric ADHD. METHODS: Data from the 2016 to 2017 National Survey of Children's Health for children aged 6 to 17 years with ADHD were evaluated to assess the association between parent-reported bullying victimization or perpetration and the following potential predictors: demographic characteristics, family factors, school factors, and child conditions/behaviors. RESULTS: Among children with ADHD, 46.9% were bullying victims and 16.2% were perpetrators. Factors associated with victimization included having family financial strain, developmental delay or intellectual disability, friendship difficulties, and school reports about problems. Factors linked to perpetration included being male, receiving government assistance, lack of school engagement, school reports about problems, and having difficulties with friendships, staying calm, and arguing. CONCLUSIONS: Children with ADHD frequently were bullying victims and sometimes bullying perpetrators. Factors related to family financial strain, developmental disabilities, emotional regulation, peer relationships, and school functioning may help to identify risk for bullying and opportunities for anti-bullying interventions. |
Defining the risk of SARS-CoV-2 variants on immune protection.
DeGrace MM , Ghedin E , Frieman MB , Krammer F , Grifoni A , Alisoltani A , Alter G , Amara RR , Baric RS , Barouch DH , Bloom JD , Bloyet LM , Bonenfant G , Boon ACM , Boritz EA , Bratt DL , Bricker TL , Brown L , Buchser WJ , Carreo JM , Cohen-Lavi L , Darling TL , Davis-Gardner ME , Dearlove BL , Di H , Dittmann M , Doria-Rose NA , Douek DC , Drosten C , Edara VV , Ellebedy A , Fabrizio TP , Ferrari G , Florence WC , Fouchier RAM , Franks J , Garca-Sastre A , Godzik A , Gonzalez-Reiche AS , Gordon A , Haagmans BL , Halfmann PJ , Ho DD , Holbrook MR , Huang Y , James SL , Jaroszewski L , Jeevan T , Johnson RM , Jones TC , Joshi A , Kawaoka Y , Kercher L , Koopmans MPG , Korber B , Koren E , Koup RA , LeGresley EB , Lemieux JE , Liebeskind MJ , Liu Z , Livingston B , Logue JP , Luo Y , McDermott AB , McElrath MJ , Meliopoulos VA , Menachery VD , Montefiori DC , Mhlemann B , Munster VJ , Munt JE , Nair MS , Netzl A , Niewiadomska AM , O'Dell S , Pekosz A , Perlman S , Pontelli MC , Rockx B , Rolland M , Rothlauf PW , Sacharen S , Scheuermann RH , Schmidt SD , Schotsaert M , Schultz-Cherry S , Seder RA , Sedova M , Sette A , Shabman RS , Shen X , Shi PY , Shukla M , Simon V , Stumpf S , Sullivan NJ , Thackray LB , Theiler J , Thomas PG , Trifkovic S , Treli S , Turner SA , Vakaki MA , vanBakel H , VanBlargan LA , Vincent LR , Wallace ZS , Wang L , Wang M , Wang P , Wang W , Weaver SC , Webby RJ , Weiss CD , Wentworth DE , Weston SM , Whelan SPJ , Whitener BM , Wilks SH , Xie X , Ying B , Yoon H , Zhou B , Hertz T , Smith DJ , Diamond MS , Post DJ , Suthar MS . Nature 2022 605 (7911) 640-652 The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced following infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases (NIAID) within the National Institutes of Health (NIH) established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants potentially impacting transmission, virulence, and resistance to convalescent and vaccine-induced immunity. The SAVE program serves as a critical data-generating component of the United States Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines, and therapeutics and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity, and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models, and pivotal findings facilitated by this collaborative approach and identify future challenges. This program serves as a template for the response against rapidly evolving pandemic pathogens by monitoring viral evolution in the human population to identify variants that could erode the effectiveness of countermeasures. |
A systematic review and meta-analysis of prenatal, birth, and postnatal factors associated with attention-deficit/hyperactivity disorder in children
Bitsko RH , Holbrook JR , O'Masta B , Maher B , Cerles A , Saadeh K , Mahmooth Z , MacMillan LM , Rush M , Kaminski JW . Prev Sci 2022 Previous studies have shown mixed results on the relationship between prenatal, birth, and postnatal ("pregnancy-related") risk factors and attention-deficit/hyperactivity disorder (ADHD). We conducted meta-analyses to identify potentially modifiable pregnancy-related factors associated with ADHD. A comprehensive search of PubMed, Web of Science, and EMBASE in 2014, followed by an updated search in January 2021, identified 69 articles published in English on pregnancy-related risk factors and ADHD for inclusion. Risk factors were included in the meta-analysis if at least three effect sizes with clear pregnancy-related risk factor exposure were identified. Pooled effect sizes were calculated for ADHD overall, ADHD diagnosis, inattention, and hyperactivity/impulsivity. Odds ratios (OR) were calculated for dichotomous measures and correlation coefficients (CC) for continuous measures. Prenatal factors (pre-pregnancy weight, preeclampsia, pregnancy complications, elevated testosterone exposure), and postnatal factors (Apgar score, neonatal illness, no breastfeeding) were positively associated with ADHD overall; the findings for ADHD diagnosis were similar with the exception that there were too few effect sizes available to examine pre-pregnancy weight and lack of breastfeeding. Prenatal testosterone was significantly associated with inattention and hyperactivity/impulsivity. Effect sizes were generally small (range 1.1-1.6 ORs, -0.16-0.11 CCs). Risk factors occurring at the time of birth (perinatal asphyxia, labor complications, mode of delivery) were not significantly associated with ADHD. A better understanding of factors that are consistently associated with ADHD may inform future prevention strategies. The findings reported here suggest that prenatal and postnatal factors may serve as potential targets for preventing or mitigating the symptoms of ADHD. |
Structure-based design of haloperidol analogues as inhibitors of acetyltransferase Eis from Mycobacterium tuberculosis to overcome kanamycin resistance
Punetha A , Green KD , Garzan A , Thamban Chandrika N , Willby MJ , Pang AH , Hou C , Holbrook SYL , Krieger K , Posey JE , Parish T , Tsodikov OV , Garneau-Tsodikova S . RSC Med Chem 2021 12 (11) 1894-1909 Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a deadly bacterial disease. Drug-resistant strains of Mtb make eradication of TB a daunting task. Overexpression of the enhanced intracellular survival (Eis) protein by Mtb confers resistance to the second-line antibiotic kanamycin (KAN). Eis is an acetyltransferase that acetylates KAN, inactivating its antimicrobial function. Development of Eis inhibitors as KAN adjuvant therapeutics is an attractive path to forestall and overcome KAN resistance. We discovered that an antipsychotic drug, haloperidol (HPD, 1), was a potent Eis inhibitor with IC(50) = 0.39 ± 0.08 μM. We determined the crystal structure of the Eis-haloperidol (1) complex, which guided synthesis of 34 analogues. The structure-activity relationship study showed that in addition to haloperidol (1), eight analogues, some of which were smaller than 1, potently inhibited Eis (IC(50) ≤ 1 μM). Crystal structures of Eis in complexes with three potent analogues and droperidol (DPD), an antiemetic and antipsychotic, were determined. Three compounds partially restored KAN sensitivity of a KAN-resistant Mtb strain K204 overexpressing Eis. The Eis inhibitors generally did not exhibit cytotoxicity against mammalian cells. All tested compounds were modestly metabolically stable in human liver microsomes, exhibiting 30-60% metabolism over the course of the assay. While direct repurposing of haloperidol as an anti-TB agent is unlikely due to its neurotoxicity, this study reveals potential approaches to modifying this chemical scaffold to minimize toxicity and improve metabolic stability, while preserving potent Eis inhibition. |
How do I… facilitate a rapid response to a public health emergency requiring plasma collection with a public-private partnership?
Miller MJ , Skrzekut A , Kracalik I , Jones JM , Lofy KH , Konkle BA , Haley NR , Duvenhage M , Bonnett T , Holbrook M , Higgs E , Basavaraju SV , Paranjape S . Transfusion 2021 61 (10) 2814-2824 In March 2020, there were no treatment options for COVID-19. Passive immune therapy including anti-SARS-CoV-2 hyperimmune globulin (hIVIG) was a logical candidate for COVID-19 therapeutic trials, given past success treating emerging pathogens with endogenous neutralizing antibodies. We established a plasma collection protocol for persons recovered from COVID-19. To speed recruitment in the first U.S. hotspot, Seattle, Washington, federal and state public health agencies collaborated with Bloodworks Northwest to collect convalescent plasma (CP) for manufacturing hIVIG. During March-December 2020, we identified and recruited prospective CP donors via letters to persons recovered from COVID-19 with laboratory-confirmed SARS-CoV-2 infection. Prospective donors were pre-screened and administered a medical history survey. Anti-SARS-CoV-2 neutralizing antibody (NAb) titers were classified as qualifying (≥1:80) or non-qualifying (<1:80) for enrollment based on a live virus neutralization assay. Generalized estimating equations were used to identify characteristics of donors associated with qualifying versus nonqualifying NAb titers. Overall, 21,359 letters resulted in 3207 inquiries, 2159 prescreenings with laboratory-confirmed SARS-CoV-2 infection, and 573 donors (27% of all pre-screenings with confirmed infection) who provided a screening plasma donation. Of 573 donors screened, 254 (44%) provided plasma with qualifying NAb titers, resulting in 1284 units for hIVIG manufacture. In a multivariable model, after adjusting for other factors, time (60 days) from COVID-19 symptom onset to screening was associated with lower odds of qualifying NAb (adjusted odds ratio = 0.67, 95% CI: 0.48-0.94). The collaboration facilitated a rapid response to develop and provide hIVIG for clinical trials and CP for transfusion. Only 1 in 12 donor inquiries resulted in a qualifying plasma donation. Challenges included recruitment and the relatively low percentage of persons with high NAb titers and limited screening capacity. This resource-intensive collaboration may not be scalable but informs preparedness and response strategies for plasma collection in future epidemics. Operational readiness plans with templates for screening, consent, and data collection forms are recommended. |
Factors associated with self-regulation in a nationally representative sample of children ages 3-5 years: United States, 2016
Claussen AH , Robinson LR , Kaminski JW , Charania S , Holbrook JR , So M , Ghandour R , Smith C , Satterfield-Nash A , Peacock G , Boyle C . Matern Child Health J 2020 25 (1) 27-37 OBJECTIVE: The aim of the present study was to describe self-regulation (the ability to influence or control one's thoughts or behavior in response to situational demands and social norms) in children ages 3-5 years using a nationally representative sample and examine risk and protective factors to identify opportunities to support children and families. METHODS: Using a cross-sectional design, we examined data from a parent-reported pilot measure of self-regulation from the 2016 National Survey of Children's Health (NSCH). We compared U.S. children aged 3-5 years who were described by parents as "on track" with self-regulation development with children who were not. In addition, we described how health care and developmental services, community, family, and child health and development factors are associated with children's self-regulation. RESULTS: The majority of children (4 of 5) were described by their parents to be developmentally on track with self-regulation. Compared to children described as not on track, children described as on track more often lived in financially and socially advantaged environments and less often experienced family adversity. They also had other positive health and development indicators, whether or not they were receiving developmental services. However, only half of children not on track received developmental surveillance, and only 1 in 4 children described as not on track received educational, mental health, or developmental services. CONCLUSION: The findings are a step towards using self-regulation as an indicator of healthy child development and as a potential strategy to identify groups of children who may need additional support. |
Treatment use among children with Tourette syndrome living in the United States, 2014
Wolicki SB , Bitsko RH , Holbrook JR , Danielson ML , Zablotsky B , Scahill L , Walkup JT , Woods DW , Mink JW . Psychiatry Res 2020 293 113400 Treatment of Tourette syndrome (TS) can be complicated by changes over time in tic expression, severity, and co-occurring disorders. Using the 2014 National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome, this study provides descriptive estimates of the use of behavioral interventions and medication among children living with TS. Parent-reported data on 115 children aged 5-17 years ever diagnosed with TS were analyzed to provide descriptive, unweighted results. Overall, 77.4% of children had current or past use of any TS treatment; 59.1% ever used behavioral interventions and 56.1% had ever taken TS medication. Children with "moderate" or "severe" versus "mild" TS, ≥1 co-occurring disorders, and tics that interfered with functioning were significantly more likely to have used one or more TS treatments. Side effects were reported for 84.4% of children who took TS medication. Most parents of children with current TS (87.2%) were satisfied with the management of their child's TS. However, parents of children with "moderate" or "severe" current TS were significantly more dissatisfied compared to parents of children with "mild" TS. Findings from this study could be used to inform efforts to support children living with TS and their families. |
Community-based prevalence of externalizing and internalizing disorders among school-aged children and adolescents in four geographically dispersed school districts in the United States
Danielson ML , Bitsko RH , Holbrook JR , Charania SN , Claussen AH , McKeown RE , Cuffe SP , Owens JS , Evans SW , Kubicek L , Flory K . Child Psychiatry Hum Dev 2020 52 (3) 500-514 The Project to Learn About Youth-Mental Health (PLAY-MH; 2014-2018) is a school-based, two-stage study designed to estimate the prevalence of selected mental disorders among K-12 students in four U.S.-based sites (Colorado, Florida, Ohio, and South Carolina). In Stage 1, teachers completed validated screeners to determine student risk status for externalizing or internalizing problems or tics; the percentage of students identified as being at high risk ranged from 17.8% to 34.4%. In Stage 2, parents completed a structured diagnostic interview to determine whether their child met criteria for fourteen externalizing or internalizing disorders; weighted prevalence estimates of meeting criteria for any disorder were similar in three sites (14.8%-17.8%) and higher in Ohio (33.3%). PLAY-MH produced point-in-time estimates of mental disorders in K-12 students, which may be used to supplement estimates from other modes of mental disorder surveillance and inform mental health screening and healthcare and educational services. |
Structure-guided optimization of inhibitors of acetyltransferase Eis from Mycobacterium tuberculosis
Punetha A , Ngo HX , Holbrook SYL , Green KD , Willby MJ , Bonnett SA , Krieger K , Dennis EK , Posey JE , Parish T , Tsodikov OV , Garneau-Tsodikova S . ACS Chem Biol 2020 15 (6) 1581-1594 The enhanced intracellular survival (Eis) protein of Mycobacterium tuberculosis (Mtb) is a versatile acetyltransferase that multiacetylates aminoglycoside antibiotics abolishing their binding to the bacterial ribosome. When overexpressed as a result of promoter mutations, Eis causes drug resistance. In an attempt to overcome the Eis-mediated kanamycin resistance of Mtb, we designed and optimized structurally unique thieno[2,3-d]pyrimidine Eis inhibitors toward effective kanamycin adjuvant combination therapy. We obtained 12 crystal structures of enzyme-inhibitor complexes, which guided our rational structure-based design of 72 thieno[2,3-d]pyrimidine analogues divided into three families. We evaluated the potency of these inhibitors in vitro as well as their ability to restore the activity of kanamycin in a resistant strain of Mtb, in which Eis was upregulated. Furthermore, we evaluated the metabolic stability of 11 compounds in vitro. This study showcases how structural information can guide Eis inhibitor design. |
Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1.
van Doremalen N , Bushmaker T , Morris DH , Holbrook MG , Gamble A , Williamson BN , Tamin A , Harcourt JL , Thornburg NJ , Gerber SI , Lloyd-Smith JO , de Wit E , Munster VJ . N Engl J Med 2020 382 (16) 1564-1567 To the Editor: A novel human coronavirus that is now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (formerly called HCoV-19) emerged in Wuhan, China, in late 2019 and is now causing a pandemic.1 We analyzed the aerosol and surface stability of SARS-CoV-2 and compared it with SARS-CoV-1, the most closely related human coronavirus.2 | | We evaluated the stability of SARS-CoV-2 and SARS-CoV-1 in aerosols and on various surfaces and estimated their decay rates using a Bayesian regression model (see the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). SARS-CoV-2 nCoV-WA1-2020 (MN985325.1) and SARS-CoV-1 Tor2 (AY274119.3) were the strains used. Aerosols (<5 μm) containing SARS-CoV-2 (105.25 50% tissue-culture infectious dose [TCID50] per milliliter) or SARS-CoV-1 (106.75-7.00 TCID50 per milliliter) were generated with the use of a three-jet Collison nebulizer and fed into a Goldberg drum to create an aerosolized environment. The inoculum resulted in cycle-threshold values between 20 and 22, similar to those observed in samples obtained from the upper and lower respiratory tract in humans. |
Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents
Wolraich ML , Hagan JFJr , Allan C , Chan E , Davison D , Earls M , Evans SW , Flinn SK , Froehlich T , Frost J , Holbrook JR , Lehmann CU , Lessin HR , Okechukwu K , Pierce KL , Winner JD , Zurhellen W . Pediatrics 2019 144 (4) Attention-deficit/hyperactivity disorder (ADHD) is 1 of the most common neurobehavioral disorders of childhood and can profoundly affect children's academic achievement, well-being, and social interactions. The American Academy of Pediatrics first published clinical recommendations for evaluation and diagnosis of pediatric ADHD in 2000; recommendations for treatment followed in 2001. The guidelines were revised in 2011 and published with an accompanying process of care algorithm (PoCA) providing discrete and manageable steps by which clinicians could fulfill the clinical guideline's recommendations. Since the release of the 2011 guideline, the Diagnostic and Statistical Manual of Mental Disorders has been revised to the fifth edition, and new ADHD-related research has been published. These publications do not support dramatic changes to the previous recommendations. Therefore, only incremental updates have been made in this guideline revision, including the addition of a key action statement related to diagnosis and treatment of comorbid conditions in children and adolescents with ADHD. The accompanying process of care algorithm has also been updated to assist in implementing the guideline recommendations. Throughout the process of revising the guideline and algorithm, numerous systemic barriers were identified that restrict and/or hamper pediatric clinicians' ability to adopt their recommendations. Therefore, the subcommittee created a companion article (available in the Supplemental Information) on systemic barriers to the care of children and adolescents with ADHD, which identifies the major systemic-level barriers and presents recommendations to address those barriers; in this article, we support the recommendations of the clinical practice guideline and accompanying process of care algorithm. |
Children with Tourette Syndrome in the United States: Parent-reported diagnosis, co-occurring disorders, severity, and influence of activities on tics
Wolicki SB , Bitsko RH , Danielson ML , Holbrook JR , Zablotsky B , Walkup JT , Woods DW , Mink JW . J Dev Behav Pediatr 2019 40 (6) 407-414 OBJECTIVE: Describe the diagnostic process for Tourette syndrome (TS) based on parent report, as well as TS severity and associated impairment; the influence of common daily activities on tics; and the presence of co-occurring mental, behavioral, and developmental disorders among children in the United States. METHODS: Parent-report data from the 2014 National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome on 115 children ever diagnosed with TS were analyzed. Descriptive, unweighted analyses included frequencies and percentages, and means and standard deviations. Fisher's exact test and t-tests were calculated to determine statistically significant differences. RESULTS: The mean age that tics were first noticed was 6.3 years, and, on average, TS was diagnosed at 7.7 years. The time from initially noticing tics to TS diagnosis averaged 1.7 years. The mean age when TS symptoms were most severe was 9.3 years. Tic severity was associated with impaired child functioning but not tic noticeability. Almost 70% of parents reported that fatigue and major transitions made their child's tics worse. Children with ever-diagnosed TS had a mean of 3.2 ever-diagnosed co-occurring mental, behavioral, or developmental disorders; a quarter (26.9%) had 5 or more co-occurring disorders. DISCUSSION: In this sample of children with TS, the time to diagnosis averaged less than 2 years from when tics were initially noticed. More severe TS was associated with greater functional impairment, and co-occurring disorders were common among children with TS. This study provides insight into the current experiences of children with TS in the United States and their families. |
Health care, family, and community factors associated with mental, behavioral, and developmental disorders and poverty among children aged 2-8 years - United States, 2016
Cree RA , Bitsko RH , Robinson LR , Holbrook JR , Danielson ML , Smith C , Kaminski JW , Kenney MK , Peacock G . MMWR Morb Mortal Wkly Rep 2018 67 (50) 1377-1383 Childhood mental, behavioral, and developmental disorders (MBDDs) are associated with adverse outcomes that can persist into adulthood (1,2). Pediatric clinical settings are important for identifying and treating MBDDs (3). Early identification and treatment of MBDDs can promote healthy development for all children (4), especially those living in poverty who are at increased risk for MBDDs (3,5) but might have reduced access to care (6). CDC analyzed data from the 2016 National Survey of Children's Health (NSCH) on MBDDs, risk factors, and use of federal assistance programs (e.g., Supplemental Nutrition Assistance Program [SNAP]) to identify points to reach children in poverty. In line with previous research (3,6), compared with children in higher-income households, those in lower-income households more often had ever received a diagnosis of an MBDD (22.1% versus 13.9%), and less often had seen a health care provider in the previous year (80.4% versus 93.8%). Among children living below 200% of the federal poverty level (FPL) who did not see a health care provider in the previous year, seven of 10 were in families receiving at least one public assistance benefit. Public assistance programs might offer collaboration opportunities to provide families living in poverty with information, co-located screening programs or services, or connection to care. |
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