Altered neural flexibility in children with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of childhood, and is often characterized by altered executive functioning. Executive function has been found to be supported by flexibility in dynamic brain reconfiguration. Thus, we applied multilayer community detection to resting-state fMRI data in 180 children with ADHD and 180 typically developing children (TDC) to identify alterations in dynamic brain reconfiguration in children with ADHD. We specifically evaluated MR derived neural flexibility, which is thought to underlie cognitive flexibility, or the ability to selectively switch between mental processes. Significantly decreased neural flexibility was observed in the ADHD group at both the whole brain (raw p = 0.0005) and sub-network levels (p < 0.05, FDR corrected), particularly for the default mode network, attention-related networks, executive function-related networks, and primary networks. Furthermore, the subjects with ADHD who received medication exhibited significantly increased neural flexibility (p = 0.025, FDR corrected) when compared to subjects with ADHD who were medication naïve, and their neural flexibility was not statistically different from the TDC group (p = 0.74, FDR corrected). Finally, regional neural flexibility was capable of differentiating ADHD from TDC (Accuracy: 77% for tenfold cross-validation, 74.46% for independent test) and of predicting ADHD severity using clinical measures of symptom severity (R2: 0.2794 for tenfold cross-validation, 0.156 for independent test). In conclusion, the present study found that neural flexibility is altered in children with ADHD and demonstrated the potential clinical utility of neural flexibility to identify children with ADHD, as well as to monitor treatment responses and disease severity.

The emergence of a functionally flexible brain during early infancy.

Adult brains are functionally flexible, a unique characteristic that is thought to contribute to cognitive flexibility. While tools to assess cognitive flexibility during early infancy are lacking, we aimed to assess the spatiotemporal developmental features of "neural flexibility" during the first 2 y of life. Fifty-two typically developing children 0 to 2 y old were longitudinally imaged up to seven times during natural sleep using resting-state functional MRI. Using a sliding window approach, MR-derived neural flexibility, a quantitative measure of the frequency at which brain regions change their allegiance from one functional module to another during a given time period, was used to evaluate the temporal emergence of neural flexibility during early infancy. Results showed that neural flexibility of whole brain, motor, and high-order brain functional networks/regions increased significantly with age, while visual regions exhibited a temporally stable pattern, suggesting spatially and temporally nonuniform developmental features of neural flexibility. Additionally, the neural flexibility of the primary visual network at 3 mo of age was significantly and negatively associated with cognitive ability evaluated at 5/6 y of age. The "flexible club," comprising brain regions with neural flexibility significantly higher than whole-brain neural flexibility, were consistent with brain regions known to govern cognitive flexibility in adults and exhibited unique characteristics when compared to the functional hub and diverse club regions. Thus, MR-derived neural flexibility has the potential to reveal the underlying neural substrates for developing a cognitively flexible brain during early infancy.

Lower Socioeconomic Position Is Associated with Greater Activity in and Integration within an Allostatic-Interoceptive Brain Network in Response to Affective Stimuli.

Socioeconomic inequities shape physical health and emotional well-being. As such, recent work has examined the neural mechanisms through which socioeconomic position (SEP) may influence health. However, there remain critical gaps in knowledge regarding the relationships between SEP and brain function. These gaps include a lack of research on: (1) the association between SEP and brain functioning in later life, (2) relationships between SEP and functioning of the whole brain beyond specific regions of interest, and (3) how neural responses to positive affective stimuli differ by SEP. The current study addressed these gaps by examining the association between SEP (i.e., education, income) and neural responses to affective stimuli among 122 mid- to late-life adults. During MRI scanning, participants viewed 30 positive, 30 negative, and 30 neutral images; activation and network connectivity analyses explored associations between SEP and neural responses to these affective stimuli. Analyses revealed that those with lower SEP showed greater neural activity to both positive and negative images in regions within the allostatic-interoceptive network, a system of regions implicated in representing and regulating physiological states of the body and the external environment. There were no positive associations between SEP and neural responses to negative or positive images. In addition, graph-theory network analyses showed that individuals with lower SEP demonstrated greater global efficiency within the allostatic-interoceptive network and executive control network, across all task conditions. The findings suggest that lower SEP is associated with enhanced neural sensitivity to affective cues that may be metabolically costly to maintain over time and suggest a mechanism by which SEP might get "under the skull" to influence mental and physical well-being.

Effects of a single-dose methylphenidate challenge on resting-state functional connectivity in stimulant-treatment naive children and adults with ADHD.

Prior studies suggest that methylphenidate, the primary pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), alters functional brain connectivity. As the neurotransmitter systems targeted by methylphenidate undergo significant alterations throughout development, the effects of methylphenidate on functional connectivity may also be modulated by age. Therefore, we assessed the effects of a single methylphenidate challenge on brain network connectivity in stimulant-treatment naïve children and adults with ADHD. We obtained resting-state functional MRI from 50 boys (10-12 years of age) and 49 men (23-40 years of age) with ADHD (DSM IV, all subtypes), before and after an oral challenge with 0.5 mg/kg methylphenidate; and from 11 boys and 12 men as typically developing controls. Connectivity strength (CS), eigenvector centrality (EC), and betweenness centrality (BC) were calculated for the striatum, thalamus, dorsal anterior cingulate cortex (dACC), and prefrontal cortex (PFC). In line with our hypotheses, we found that methylphenidate decreased measures of connectivity and centrality in the striatum and thalamus in children with ADHD, but increased the same metrics in adults with ADHD. Surprisingly, we found no major effects of methylphenidate in the dACC and PFC in either children or adults. Interestingly, pre-methylphenidate, participants with ADHD showed aberrant connectivity and centrality compared to controls predominantly in frontal regions. Our findings demonstrate that methylphenidate's effects on connectivity of subcortical regions are age-dependent in stimulant-treatment naïve participants with ADHD, likely due to ongoing maturation of dopamine and noradrenaline systems. These findings highlight the importance for future studies to take a developmental perspective when studying the effects of methylphenidate treatment.

Caregivers Systematically Overestimate Their Child's Height-for-Age Relative to Other Children in Rural Ethiopia.

BACKGROUND: Stunting affects one-quarter of children <5 y of age, yet little is known about the accuracy of caregivers' perceptions regarding their child's linear growth. Most existing quantitative research on this topic has been conducted in high-income countries and has examined perceptions of children's weight rather than height. OBJECTIVES: In rural Ethiopia where linear growth faltering is highly prevalent, this study aimed to better understand how caregivers perceive their child's growth. The objectives of this analysis were to 1) assess caregivers' perceptions of their child's height; 2) investigate whether there is a discrepancy between a child's actual height and caregivers' perceptions of their child's height; and 3) examine the factors that influence discrepancies in estimating a child's height (secondary outcomes), including the role of the average height in the community (primary outcome). METHODS: We conducted a cross-sectional analysis using data from 808 woman caregivers of children ages 6-35 mo in the Oromia region of Ethiopia. We assessed caregivers' rankings (from 1 to 10) of their child's height relative to other children their age in their village. We then converted these rankings to z scores based on an age- and region-specific distribution in order to calculate their difference with the child's actual height-for-age z score and to determine the degree of overestimation. Lastly, we used multivariate log Poisson regressions to determine factors associated with overestimating a child's height. RESULTS: Forty-three percent of caregivers scored their child's height as the median; 37% overestimated their child's height relative to other children. Regression results showed caregivers who were poorer, and had children who were female, older, and stunted, were more likely to overestimate. CONCLUSIONS: Our findings suggest that caregivers of young children in Oromia systematically overestimated their children's height, which could adversely affect child health if these misperceptions translate to insufficient care-seeking behavior or feeding choices for children.

Characteristics and perceptions associated with COVID-19 vaccination hesitancy among pregnant and postpartum individuals: A cross-sectional study.

OBJECTIVE: To assess the frequency and associated characteristics of COVID-19 vaccine hesitancy among pregnant and postpartum individuals. DESIGN: Cross-sectional study. SETTING: Prenatal care at a single academic tertiary care centre. POPULATION: Pregnant and postpartum individuals enrolled in prenatal care at a single academic tertiary care centre from 22 March 2021 to 2 April 2021, concurrent with state guidelines recommending COVID-19 vaccination in pregnancy. METHODS: We used logistic regression to identify characteristics associated with COVID-19 vaccine hesitancy, and adjusted for: age, parity, race, trimester of pregnancy, and chronic comorbidities. MAIN OUTCOME MEASURES: COVID-19 vaccine hesitancy, defined as uncertainty or refusal of the vaccine, despite the availability of vaccine services, in accordance with the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) on vaccine hesitancy. RESULTS: Of the 485 individuals screened and approached, 456 (94%) enrolled and completed the survey (435/456, 95% pregnant). The frequency of COVID-19 vaccine hesitancy was 46% (95% CI 41%-51%). Sociodemographic characteristics, including non-Hispanic Black race, younger age, lower education, public health insurance receipt, parity >1, and reported substance use, were associated with a higher odds of COVID-19 vaccine hesitancy, but not clinical risk conditions. Individuals who had a family or friend vaccinated for COVID-19, prior or planned vaccination for tetanus, diphtheria and acellular pertussis (Tdap) and/or influenza, and who perceived that vaccination benefited the baby were less likely to express COVID-19 vaccine hesitancy. CONCLUSIONS: COVID-19 vaccine hesitancy was frequent among pregnant and postpartum individuals. Those who may face barriers to accessing healthcare services were more likely to report vaccine hesitancy. These results can inform interventions to increase COVID-19 vaccine uptake in pregnancy. TWEETABLE ABSTRACT: COVID-19 vaccination hesitancy is frequent among pregnant and postpartum individuals, and those who face barriers to accessing healthcare services are more likely to report COVID-19 vaccine hesitancy.

Health care providers' knowledge of clinical protocols for postpartum hemorrhage care in Kenya: a cross-sectional study.

BACKGROUND: Postpartum hemorrhage (PPH) remains the leading cause of maternal death worldwide despite its often-preventable nature. Understanding health care providers' knowledge of clinical protocols is imperative for improving quality of care and reducing mortality. This is especially pertinent in referral and teaching hospitals that train nursing and medical students and interns in addition to managing emergency and referral cases. METHODS: This study aimed to (1) measure health care providers' knowledge of clinical protocols for risk assessment, prevention, and management of PPH in 3 referral hospitals in Kenya and (2) examine factors associated with providers' knowledge. We developed a knowledge assessment tool based on past studies and clinical guidelines from the World Health Organization and the Kenyan Ministry of Health. We conducted in-person surveys with health care providers in three high-volume maternity facilities in Nairobi and western Kenya from October 2018-February 2019. We measured gaps in knowledge using a summative index and examined factors associated with knowledge (such as age, gender, qualification, experience, in-service training attendance, and a self-reported measure of peer-closeness) using linear regression. RESULTS: We interviewed 172 providers including consultants, medical officers, clinical officers, nurse-midwives, and students. Overall, knowledge was lowest for prevention-related protocols (an average of 0.71 out of 1.00; 95% CI 0.69-0.73) and highest for assessment-related protocols (0.81; 95% CI 0.79-0.83). Average knowledge scores did not differ significantly between qualified providers and students. Finally, we found that being a qualified nurse, having a specialization, being female, having a bachelor's degree and self-reported closer relationships with colleagues were statistically significantly associated with higher knowledge scores. CONCLUSION: We found gaps in knowledge of PPH care clinical protocols in Kenya. There is a clear need for innovations in clinical training to ensure that providers in teaching referral hospitals are prepared to prevent, assess, and manage PPH. It is possible that training interventions focused on learning by doing and teamwork may be beneficial.

Impact of reliable light and electricity on job satisfaction among maternity health workers in Uganda: A cluster randomized trial.

BACKGROUND: Maintaining a motivated health workforce is critical to health system effectiveness and quality of care. Scant evidence exists on whether interventions aimed to strengthen health infrastructure in low-resource settings affect health workers. This study evaluated the impact of an intervention providing solar light and electricity to rural maternity facilities in Uganda on health workers' job satisfaction. METHODS: We used a mixed-methods design embedded in a cluster randomized trial to evaluate whether and how the We Care Solar Suitcase intervention, a solar electric system providing lighting and power, affected health workers in rural Ugandan maternity facilities with unreliable light. Facilities were randomly assigned to receive the intervention or not without blinding in a cluster-randomized controlled trial. Outcomes were assessed through two rounds of surveys with health workers. We used regression analyses to examine the intervention's impact on job satisfaction. We used an inductive approach to analyze qualitative data to understand the study context and interpret quantitative findings. RESULTS: We interviewed 85 health workers across 30 facilities, the majority of whom were midwives or nurses. Qualitative reports indicated that unreliable light made it difficult to provide care, worsened facility conditions, and harmed health workers and patients. Before the intervention, only 4% of health workers were satisfied with their access to light and electricity. After the installation, satisfaction with light increased by 76 percentage points [95% confidence interval (CI): 61-92 percentage points], although satisfaction with electricity did not change. Experience of negative impacts of lack of overhead light also significantly decreased and the intervention modestly increased job satisfaction. Qualitative evidence illustrated how the intervention may have strengthened health workers' sense of job security and confidence in providing high-quality care while pointing towards implementation challenges and other barriers health workers faced. CONCLUSIONS: Reliable access to light and electricity directly affects health workers' ability to provide maternal and neonatal care and modestly improves job satisfaction. Policy makers should invest in health infrastructure as part of multifaceted policy strategies to strengthen human resources for health and to improve maternal and newborn health services. Trial registration socialscienceregistry.org: AEARCTR-0003078. Registered June 12, 2018, https://www.socialscienceregistry.org/trials/3078 Additionally registered on: ClinicalTrials.gov: NCT03589625, Registered July 18, 2018, https://clinicaltrials.gov/ct2/show/NCT03589625 ).

Children with attention-deficit/hyperactivity disorder spend more time in hyperconnected network states and less time in segregated network states as revealed by dynamic connectivity analysis.

Previous studies in children with attention-deficit/hyperactivity disorder (ADHD) have observed functional brain network disruption on a whole-brain level, as well as on a sub-network level, particularly as related to the default mode network, attention-related networks, and cognitive control-related networks. Given behavioral findings that children with ADHD have more difficulty sustaining attention and more extreme moment-to-moment fluctuations in behavior than typically developing (TD) children, recently developed methods to assess changes in connectivity over shorter time periods (i.e., "dynamic functional connectivity"), may provide unique insight into dysfunctional network organization in ADHD. Thus, we performed a dynamic functional connectivity (FC) analysis on resting state fMRI data from 38 children with ADHD and 79 TD children. We used Hidden semi-Markov models (HSMMs) to estimate six network states, as well as the most probable sequence of states for each participant. We quantified the dwell time, sojourn time, and transition probabilities across states. We found that children with ADHD spent less total time in, and switched more quickly out of, anticorrelated states involving the default mode network and task-relevant networks as compared to TD children. Moreover, children with ADHD spent more time in a hyperconnected state as compared to TD children. These results provide novel evidence that underlying dynamics may drive the differences in static FC patterns that have been observed in ADHD and imply that disrupted FC dynamics may be a mechanism underlying the behavioral symptoms and cognitive deficits commonly observed in children with ADHD.

The maturation and cognitive relevance of structural brain network organization from early infancy to childhood.

The interactions of brain regions with other regions at the network level likely provide the infrastructure necessary for cognitive processes to develop. Specifically, it has been theorized that in infancy brain networks become more modular, or segregated, to support early cognitive specialization, before integration across networks increases to support the emergence of higher-order cognition. The present study examined the maturation of structural covariance networks (SCNs) derived from longitudinal cortical thickness data collected between infancy and childhood (0-6 years). We assessed modularity as a measure of network segregation and global efficiency as a measure of network integration. At the group level, we observed trajectories of increasing modularity and decreasing global efficiency between early infancy and six years. We further examined subject-based maturational coupling networks (sbMCNs) in a subset of this cohort with cognitive outcome data at 8-10 years, which allowed us to relate the network organization of longitudinal cortical thickness maturation to cognitive outcomes in middle childhood. We found that lower global efficiency of sbMCNs throughout early development (across the first year) related to greater motor learning at 8-10 years. Together, these results provide novel evidence characterizing the maturation of brain network segregation and integration across the first six years of life, and suggest that specific trajectories of brain network maturation contribute to later cognitive outcomes.

Associations between ACA-related policies and a clinical recommendation with HPV vaccine initiation.

PURPOSE: We examined associations between the 2010 Affordable Care Act (ACA) provisions, 2011 Advisory Committee on Immunization Practices (ACIP) recommendation, and 2014 ACA-related health insurance reforms with HPV vaccine initiation rates by sex and health insurance type. METHODS: Using 2009-2015 public and private health insurance claims for 551,764 males and females aged 9-26 years (referred to as youth) from Maine, New Hampshire, and Massachusetts, we conducted linear regression models to examine the associations between three policy changes and HPV vaccine initiation rates by sex and health insurance type. RESULTS: In 2009, HPV vaccine initiation rates for males and females were 0.003 and 0.604 per 100 enrollees, respectively. Among males, the 2010 ACA provisions and ACIP recommendation were associated with significant increases in HPV vaccine uptake among those with private plans (0.207 [0.137, 0.278] and 0.419 [0.353, 0.486], respectively) and Medicaid (0.157 [0.083, 0.230] and 0.322 [0.257, 0.386], respectively). Among females, the 2010 ACA provisions were associated with significant increases in HPV vaccine uptake among Medicaid enrollees only (0.123 [0.033, 0.214]). The ACA-related health insurance reforms were associated with significant increases in HPV vaccine uptake for male and female Medicaid enrollees (0.257 [0.137, 0.377] and 0.214 [0.102, 0.327], respectively), but no differences among privately insured youth. By 2015, there were no differences in HPV vaccine initiation rates between males (0.278) and females (0.305). CONCLUSIONS: Both ACA provisions and the ACIP recommendation were associated with significant increases in HPV vaccine initiation rates among privately and publicly insured males in three New England states, closing the gender gap. In contrast, females and youth with private insurance did not exhibit the same changes in HPV vaccine uptake over the study period.

Know-do gaps in obstetric and newborn care quality in Uganda: a cross-sectional study in rural health facilities.

OBJECTIVES: Variable and inadequate quality of maternity care is a critical factor in persistently high rates of maternal and neonatal mortality in Uganda. We investigated whether provider quality of care deviates from knowledge and the factors associated with these 'know-do gaps' in Ugandan maternity facilities. METHODS: Data were collected from 109 providers in 40 facilities. Quality was measured using direct observations of intrapartum care, and scores were based on the percentage of essential care actions provided out of a 20-item validated quality index. Knowledge was measured based on the percentage of items that providers reported knowing to do using vignette surveys. The know-do gap was the difference between knowledge and quality. Multivariable models were used to assess the association between provider- and facility-level characteristics and knowledge, quality and know-do gaps. RESULTS: The average quality score was 45%, with quality varying widely within and across providers. The mean knowledge score was 70%, yielding a mean know-do gap of 25%. Know-do gaps were largest for practices related to infection control, vitals monitoring, and prevention of postpartum haemorrhage. The association between quality and knowledge scores was positive but small (P = 0.08), so know-do gaps were largest for providers with the highest knowledge scores. Greater provider training was positively associated with knowledge (P = 0.005) but not with quality (P = 0.60). Having 10 or more years of work experience was associated with higher quality scores (5.3, 95%CI: 0.6 to 10.1), while higher patient volumes were associated with lower quality scores (-2.2, 95%CI: -3.7 to - 0.07). None of the factors of provider motivation, cadre, availability of essential medicines and supplies or facility staffing were associated with quality or know-do gaps. CONCLUSIONS: Our results indicate that, in Uganda, gaps between knowledge and quality do not appear to be explained by factors such as lack of motivation, education, training or supplies. Gaps are particularly large for essential practices related to prevention of postpartum haemorrhage, a leading cause of maternal mortality in Uganda and similar settings.

The price of quality care: cross-sectional associations between out-of-pocket payments and quality of care in six low-income countries.

OBJECTIVE: To assess the relationship between out-of-pocket (OOP) payments and primary health care quality in six low-income countries: Afghanistan, the Democratic Republic of the Congo (DRC), Haiti, Nepal, Senegal and Tanzania. METHODS: We examined the association between OOP payments and quality of care during antenatal care and sick child care visits using Service Provision Assessments data. We defined four process quality outcomes from observations of clinical care: visit duration, history-taking items asked, exam items performed, and counselling items delivered. The outcome is the total amount paid for services. We used multilevel models to test the relationship between OOP payments and each quality measure in public, private non-profit and private for-profit facilities controlling for patient, provider, and facility characteristics. RESULTS: Across the six countries, an average of 42% of the 29 677 observed clients paid for their visit. In the adjusted models, OOP payments were positively associated with the visit duration during sick child visits, with history-taking and exam items during antenatal care visits, and with counselling in private for-profit facilities for both visit types. These associations were strong particularly in Afghanistan, the DRC and Haiti; for example, a high-quality antenatal care visit in the DRC would cost approximately USD 1.12 more than a visit with median quality. CONCLUSION: Provider effort was associated with higher OOP payments for sick child and antenatal care services in the six countries studied. While many families are already spending high amounts on care, they must often spend even more to receive higher quality care.

Associations between insurance-related affordable care act policy changes with HPV vaccine completion.

BACKGROUND: Although all 11- or 12-year-olds in the US were recommended to receive a 3-dose series of the human papillomavirus (HPV) vaccine within a 12-month period prior to 2016, rates of completion of the HPV vaccine series remained suboptimal. The effects of the Affordable Care Act (ACA), including private insurance coverage with no cost-sharing and health insurance expansions, on HPV vaccine completion are largely unknown. The aim of this study was to examine the associations between the ACA's 2010 provisions and 2014 insurance expansions with HPV vaccine completion by sex and health insurance type. METHODS: Using 2009-2015 public and private health insurance claims from Maine, New Hampshire, and Massachusetts, we identified 9-to-26-year-olds who had at least one HPV vaccine dose. We conducted a logistic regression model to examine the associations between the ACA policy changes with HPV vaccine completion (defined as receiving a 3-dose series within 12 months from the date of initiation) as well as interactions by sex and health insurance type. RESULTS: Over the study period, among females and males who initiated the HPV vaccine, 27.6 and 28.0%, respectively, completed the series within 12 months. Among females, the 2010 ACA provision was associated with a 4.3 percentage point increases in HPV vaccine completion for the privately-insured (0.043; 95% CI: 0.036-0.061) and a 5.7 percentage point increase for Medicaid enrollees (0.057; 95% CI: 0.032-0.081). The 2014 health insurance expansions were associated with a 9.4 percentage point increase in vaccine completion for females with private insurance (0.094; 95% CI: 0.082-0.107) and a 8.5 percentage point increase for Medicaid enrollees (0.085; 95% CI: 0.068-0.102). Among males, the 2014 ACA reforms were associated with a 5.1 percentage point increase in HPV vaccine completion for the privately-insured (0.051; 95% CI: 0.039-0.063) and a 3.4 percentage point increase for Medicaid enrollees (0.034; 95% CI: 0.017-0.050). In a sensitivity analysis, findings were similar with HPV vaccine completion within 18 months. CONCLUSIONS: Despite low HPV vaccine completion overall, both sets of ACA provisions were associated with increases in completion among females and males. Our results suggest that expanding Medicaid across the remaining states could increase HPV vaccine completion among publicly-insured youth and prevent HPV-related cancers.

Resting-state EEG Connectivity in Young Children with ADHD.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing neurodevelopmental disorder. While early childhood is a crucial time for early intervention, it is characterized by instability of ADHD diagnosis. Neural correlates of ADHD have potential to improve diagnostic accuracy; however, minimal research has focused on early childhood. Research indicates that disrupted neural connectivity is associated with ADHD in older children. Here, we explore network connectivity as a potential neural correlate of ADHD diagnosis in early childhood.Method: We collected EEG data in 52 medication-naïve children with ADHD and in 77 typically developing controls (3-7 years). Data was collected with the EGI 128 HydroCel Sensor Net System, but to optimize the ICA, the data was down sampled to the 10-10 system. Connectivity was measured as the synchronization of the time series of each pair of electrodes. Subsequent analyses utilized graph theoretical methods to further characterize network connectivity.Results: Increased global efficiency, which measures the efficiency of information transfer across the entire brain, was associated with increased inattentive symptom severity. Further, this association was robust to controls for age, IQ, SES, and internalizing psychopathology.Conclusions: Overall, our findings indicate that increased global efficiency, which suggests a hyper-connected neural network, is associated with elevated ADHD symptom severity. These findings extend previous work reporting disruption of neural network connectivity in older children with ADHD into early childhood.

Quality of clinical management of children diagnosed with malaria: A cross-sectional assessment in 9 sub-Saharan African countries between 2007-2018.

BACKGROUND: Appropriate clinical management of malaria in children is critical for preventing progression to severe disease and for reducing the continued high burden of malaria mortality. This study aimed to assess the quality of care provided to children under 5 diagnosed with malaria across 9 sub-Saharan African countries. METHODS AND FINDINGS: We used data from the Service Provision Assessment (SPA) survey. SPAs are nationally representative facility surveys capturing quality of sick-child care, facility readiness, and provider and patient characteristics. The data set contained 24,756 direct clinical observations of outpatient sick-child visits across 9 countries, including Uganda (2007), Rwanda (2007), Namibia (2009), Kenya (2010), Malawi (2013), Senegal (2013-2017), Ethiopia (2014), Tanzania (2015), and Democratic Republic of the Congo (2018). We assessed the proportion of children with a malaria diagnosis who received a blood test diagnosis and an appropriate antimalarial. We used multilevel logistic regression to assess facility and provider and patient characteristics associated with these outcomes. Subgroup analyses with the 2013-2018 country surveys only were conducted for all outcomes. Children observed were on average 20.5 months old and were most commonly diagnosed with respiratory infection (47.7%), malaria (29.7%), and/or gastrointestinal infection (19.7%). Among the 7,340 children with a malaria diagnosis, 32.5% (95% CI: 30.3%-34.7%) received both a blood-test-based diagnosis and an appropriate antimalarial. The proportion of children with a blood test diagnosis and an appropriate antimalarial ranged from 3.4% to 57.1% across countries. In the more recent surveys (2013-2018), 40.7% (95% CI: 37.7%-43.6%) of children with a malaria diagnosis received both a blood test diagnosis and appropriate antimalarial. Roughly 20% of children diagnosed with malaria received no antimalarial at all, and nearly 10% received oral artemisinin monotherapy, which is not recommended because of concerns regarding parasite resistance. Receipt of a blood test diagnosis and appropriate antimalarial was positively correlated with being seen at a facility with diagnostic equipment in stock (adjusted OR 3.67; 95% CI: 2.72-4.95) and, in the 2013-2018 subsample, with being seen at a facility with Artemisinin Combination Therapies (ACTs) in stock (adjusted OR 1.60; 95% CI:1.04-2.46). However, even if all children diagnosed with malaria were seen by a trained provider at a facility with diagnostics and medicines in stock, only a predicted 37.2% (95% CI: 34.2%-40.1%) would have received a blood test and appropriate antimalarial (44.4% for the 2013-2018 subsample). Study limitations include the lack of confirmed malaria test results for most survey years, the inability to distinguish between a diagnosis of uncomplicated or severe malaria, the absence of other relevant indicators of quality of care including dosing and examinations, and that only 9 countries were studied. CONCLUSIONS: In this study, we found that a majority of children diagnosed with malaria across the 9 surveyed sub-Saharan African countries did not receive recommended care. Clinical management is positively correlated with the stocking of essential commodities and is somewhat improved in more recent years, but important quality gaps remain in the countries studied. Continued reductions in malaria mortality will require a bigger push toward quality improvements in clinical care.

BRCA1/2 Testing in Massachusetts Among Women With Private Insurance or Medicaid, 2011-2015.

PURPOSE: Testing for BRCA1/2 mutations has increased among privately insured women in the United States. However, little is known about testing rates or trends among women with Medicaid. We sought to determine whether BRCA1/2 testing rates differed between women with private insurance compared with women with Medicaid in a state where both insurance types cover the test, and to compare testing trends from 2011 to 2015. METHODS: We conducted a retrospective cohort study of medical claims from January 2011 through June 2015. We included Massachusetts women aged 18-64 with private insurance or Medicaid and at least 12 months of continuous enrollment. We used multivariable linear regression to examine the association of insurance type, age, and time with testing rates. RESULTS: Mean monthly BRCA1/2 testing rates were lower among women with Medicaid compared with those with private insurance. Among privately insured women, mean monthly rates rose from 9.3 per 100,000 in 2011 to 18.4 per 100,000 in 2015, while among Medicaid-insured women, rates increased from 3.7 to 14.7. There was no difference in the monthly rate of increase in both groups (P=0.07). In adjusted analyses, rates were lower among Medicaid-insured women (7 fewer tests per month than privately insured women, P<0.001), and differed by age, with women aged 44-54 most likely to receive testing and women 18-34 the least likely. CONCLUSION: BRCA1/2 testing rates were lower among women insured by Medicaid compared with those with private insurance, though rates increased from 2011 to 2015 among both groups of women at a similar rate.

Did a quality improvement intervention improve quality of maternal health care? Implementation evaluation from a cluster-randomized controlled study.

OBJECTIVE: To test the success of a maternal healthcare quality improvement intervention in actually improving quality. DESIGN: Cluster-randomized controlled study with implementation evaluation; we randomized 12 primary care facilities to receive a quality improvement intervention, while 12 facilities served as controls. SETTING: Four districts in rural Tanzania. PARTICIPANTS: Health facilities (24), providers (70 at baseline; 119 at endline) and patients (784 at baseline; 886 at endline). INTERVENTIONS: In-service training, mentorship and supportive supervision and infrastructure support. MAIN OUTCOME MEASURES: We measured fidelity with indictors of quality and compared quality between intervention and control facilities using difference-in-differences analysis. RESULTS: Quality of care was low at baseline: the average provider knowledge test score was 46.1% (range: 0-75%) and only 47.9% of women were very satisfied with delivery care. The intervention was associated with an increase in newborn counseling (ß: 0.74, 95% CI: 0.13, 1.35) but no evidence of change across 17 additional indicators of quality. On average, facilities reached 39% implementation. Comparing facilities with the highest implementation of the intervention to control facilities again showed improvement on only one of the 18 quality indicators. CONCLUSIONS: A multi-faceted quality improvement intervention resulted in no meaningful improvement in quality. Evidence suggests this is due to both failure to sustain a high-level of implementation and failure in theory: quality improvement interventions targeted at the clinic-level in primary care clinics with weak starting quality, including poor infrastructure and low provider competence, may not be effective.

Contraceptive Counseling in the Postpartum Period: Could Pediatricians Have a Role?

INTRODUCTION: Unplanned pregnancies lead to adverse health outcomes and contribute to economic burdens. A lack of continuity and consistency in immediate postpartum care may be a contributor. The most frequent postpartum medical encounters occur with the child's pediatric health care provider, which represents an opportunity to discuss postpartum contraception. Therefore, our objective was to evaluate postpartum family planning knowledge and behavior in women, and to assess the potential acceptability of a pediatrician-delivered intervention to improve knowledge of and convenient access to contraception among postpartum women. METHODS: This was a non-interventional pilot study that employed survey and interview methodology. RESULTS: Women attending pediatric visits for their newborn or infant (N = 346) were surveyed; 35 were interviewed. On average, respondents were 27 years old (SD = 6), 6 months postpartum (SD = 5), and resumed sex 8 weeks after delivery (SD = 6). Of those who had resumed sex, 68% were not using contraception at the time. However, only 18% of survey respondents wanted to have another child. Few exhibited accurate knowledge of birth spacing or long acting reversible contraception. Most interviewees (86%) supported the idea of pediatricians providing contraceptive counseling. Concerns identified included whether it was "allowable" and pediatrician's lack of knowledge of complex maternal health histories. DISCUSSION: This study highlights a gap between contraceptive need and provision in postpartum women. However, the findings suggest women's willingness to engage in conversations with their child's pediatrician about family planning. Future research should assess the feasibility and impact of integrating postpartum counseling into pediatric visits.

CRISPR-delivery particles targeting nuclear receptor-interacting protein 1 (Nrip1) in adipose cells to enhance energy expenditure.

RNA-guided, engineered nucleases derived from the prokaryotic adaptive immune system CRISPR-Cas represent a powerful platform for gene deletion and editing. When used as a therapeutic approach, direct delivery of Cas9 protein and single-guide RNA (sgRNA) could circumvent the safety issues associated with plasmid delivery and therefore represents an attractive tool for precision genome engineering. Gene deletion or editing in adipose tissue to enhance its energy expenditure, fatty acid oxidation, and secretion of bioactive factors through a "browning" process presents a potential therapeutic strategy to alleviate metabolic disease. Here, we developed "CRISPR-delivery particles," denoted CriPs, composed of nano-size complexes of Cas9 protein and sgRNA that are coated with an amphipathic peptide called Endo-Porter that mediates entry into cells. Efficient CRISPR-Cas9-mediated gene deletion of ectopically expressed GFP by CriPs was achieved in multiple cell types, including a macrophage cell line, primary macrophages, and primary pre-adipocytes. Significant GFP loss was also observed in peritoneal exudate cells with minimum systemic toxicity in GFP-expressing mice following intraperitoneal injection of CriPs containing Gfp-targeting sgRNA. Furthermore, disruption of a nuclear co-repressor of catabolism, the Nrip1 gene, in white adipocytes by CriPs enhanced adipocyte browning with a marked increase of uncoupling protein 1 (UCP1) expression. Of note, the CriP-mediated Nrip1 deletion did not produce detectable off-target effects. We conclude that CriPs offer an effective Cas9 and sgRNA delivery system for ablating targeted gene products in cultured cells and in vivo, providing a potential therapeutic strategy for metabolic disease.