Principles for Primary Care Screening in the Context of Population Health.

A key component of primary care pediatrics is health promotion through screening: applying a test or procedure to detect a previously unrecognized disease or disease risk. How do we decide whether to screen? In 1965, Wilson and Jungner published an influential set of screening principles focused on the health problem's importance, the screening tool's performance, and the evidence for treatment efficacy. However, if we want realistic estimates of the population effects of routine screening, we must also account for the health care system's real-world functioning and disparities in care. We offer revised principles to guide discussions about routine screening in the primary care setting. We add to Wilson and Jungner's principles: 1. A focus on life course epidemiology and its consequences for population health, 2. A need to screen for the early stages of chronic health problems, 3. A concern for screening's acceptability to providers and the community, 4. A recommendation for estimating the uncertainty in benefits and harms in evaluating screening, 5. Inclusion of systematic plans for population data collection and monitoring, and 6. Recognition that achieving population health improvement requires a high-performing system with sufficient throughput and monitoring to deliver accessible, affordable, and effective care, especially for the groups experiencing the greatest inequities in access. Above all, instead of assuming best practices in treatment delivery and monitoring after screening, we argue for realism about the health care system functioning in routine practice.

Impact of COVID-19 pandemic on prescription stimulant use among children and youth: a population-based study.

COVID-19 associated public health measures and school closures exacerbated symptoms in some children and youth with attention-deficit hyperactivity disorder (ADHD). Less well understood is how the pandemic influenced patterns of prescription stimulant use. We conducted a population-based study of stimulant dispensing to children and youth ≤ 24 years old between January 1, 2013, and June 30, 2022. We used structural break analyses to identify the pandemic month(s) when changes in the dispensing of stimulants occurred. We used interrupted time series models to quantify changes in dispensing following the structural break and compare observed and expected stimulant use. Our main outcome was the change in the monthly rate of stimulant use per 100,000 children and youth. Following an initial immediate decline of 60.1 individuals per 100,000 (95% confidence interval [CI] - 99.0 to - 21.2), the monthly rate of stimulant dispensing increased by 11.8 individuals per 100,000 (95% CI 10.0-13.6), with the greatest increases in trend observed among females, individuals in the highest income neighbourhoods, and those aged 20 to 24. Observed rates were between 3.9% (95% CI 1.7-6.2%) and 36.9% (95% CI 34.3-39.5%) higher than predicted among females from June 2020 onward and between 7.1% (95% CI 4.2-10.0%) and 50.7% (95% CI 47.0-54.4%) higher than expected among individuals aged 20-24 from May 2020 onward. Additional research is needed to ascertain the appropriateness of stimulant use and to develop strategies supporting children and youth with ADHD during future periods of long-term stressors.

Mortality in adolescents and young adults following a first presentation to the emergency department for alcohol.

BACKGROUND AND METHODS: We conducted a population-based, retrospective cohort study of first-time emergency department (ED) visits in adolescents and young adults (AYA) due to alcohol and compared mortality to AYA with nonalcohol ED visits between 2009 and 2015 using standardized all-cause mortality ratios (age, sex, income, and rurality). We described the cause of death for AYA and examined the association between clinical factors and mortality rates in the alcohol cohort using proportional hazard models. RESULTS: A total of 71,776 AYA had a first-time ED visit due to alcohol (56.1% male, mean age 20.7 years) between 2009 and 2015, representing 3.3% of the 2,166,838 AYA with an ED visit in this time period. At 1 year, there were 2396 deaths, 248 (10.3%) following an ED visit related to alcohol. First-time alcohol ED visits were associated with a threefold higher risk in mortality at 1 year (0.35% vs. 0.10%, adjusted hazard ratio [aHR] 3.07, 95% confidence interval [CI] 2.69-3.51). Mortality was associated with age 25-29 years (aHR 3.88, 95% CI 2.56-5.86), being male (aHR 1.98, 95% CI 1.49-2.62), having a history of mental health or substance use (aHR 3.22, 95% CI 1.64-6.32), cause of visit being withdrawal/dependence (aHR 2.81, 95% CI 1.96-4.02), and having recurrent ED visits (aHR 1.97, 95% CI 1.27-3.05). Trauma (42.7%), followed by poisonings from drugs other than opioids (38.3%), and alcohol (28.6%) were the most common contributing causes of death. CONCLUSION: Incident ED visits due to alcohol in AYA are associated with a high risk of 1-year mortality, especially in young adults, those with concurrent mental health or substance use disorders, and those with a more severe initial presentation. These findings may help inform the need and urgency for follow-up care in this population.

Impact of the COVID-19 pandemic on antidepressant and antipsychotic use among children and adolescents: a population-based study.

Background: The COVID-19 pandemic was associated with increases in the prevalence of depression, anxiety and behavioural problems among children and youth. Less well understood is the influence of the pandemic on antidepressant and antipsychotic use among children. This is important, as it is possible that antidepressants and antipsychotics were used as a "stop-gap" measure to treat mental health symptoms when in-person access to outpatient care and school-based supportive services was disrupted. Furthermore, antipsychotics and antidepressants have been associated with harm in children and youth. We examined trends in dispensing of these medications two years following the pandemic among children 18 years of age and under in Ontario, Canada. Methods: We conducted a population-based time-series study of antidepressant and antipsychotic medication dispensing to children and adolescents ≤18 years old between September 1, 2014, and March 31, 2022. We measured monthly population-adjusted rates of antidepressant and antipsychotics obtained from the IQVIA Geographic Prescription Monitor (GPM) database. We used structural break analyses to identify the pandemic month(s) when changes in the dispensing of antidepressants and antipsychotics occurred. We used interrupted time series models to quantify changes in dispensing following the structural break and compare observed and expected use of these drugs. Results: Overall, we found higher-than-expected dispensing of antidepressants and antipsychotics in children and youth. Specifically, we observed an immediate step decrease in antidepressant dispensing associated with a structural break in April 2020 (-55.8 units per 1,000 individuals; 95% confidence intervals [CI] CI: -117.4 to 5.8), followed by an increased monthly trend in the rate of antidepressant dispensing of 13.0 units per 1,000 individuals (95% CI: 10.2-15.9). Antidepressant dispensing was consistently greater than predicted from September 2020 onward. Antipsychotic dispensing increased immediately following a June 2020 structural break (26.4 units per 1,000 individuals; 95% CI: 15.8-36.9) and did not change appreciably thereafter. Antipsychotic dispensing was higher than predicted at all time points from June 2020 onward. Conclusion: We found higher-than-expected dispensing of antidepressants and antipsychotics in children and youth. These increases were sustained through nearly two years of observation and are especially concerning in light of the potential for harm with the long-term use of antipsychotics in children. Further research is required to understand the clinical implications of these findings.

New and continuing physician-based outpatient mental health care among children and adolescents during the COVID-19 pandemic in Ontario, Canada: a population-based study.

Objective: To assess physician-based mental health care utilization during the COVID-19 pandemic among children and adolescents new to care and those already engaged with mental health services, and to evaluate differences by sociodemographic factors. Study design: We performed a population-based repeated cross-sectional study using linked health and administrative databases in Ontario, Canada among all children and adolescents 3-17 years. We examined outpatient visit rates per 1,000 population for mental health concerns for those new to care (no physician-based mental healthcare for ≥1 year) and those with continuing care needs (any physician-based mental healthcare <1 year) following onset of the pandemic. Results: Among ~2.5 million children and adolescents (48.7% female, mean age 10.1 ± 4.3 years), expected monthly mental health outpatient visits were 1.5/1,000 for those new to mental health care and 5.4/1,000 for those already engaged in care. Following onset of the pandemic, visit rates for both groups were above expected [adjusted rate ratio (aRR) 1.22, 95% CI 1.17, 1.27; aRR 1.10, 95% CI 1.07, 1.12] for new and continuing care, respectively. The greatest increase above expected was among females (new: aRR 1.33, 95% CI 1.25, 1.42; continuing: aRR 1.22 95% CI 1.17, 1.26) and adolescents ages 13-17 years (new: aRR 1.31, 95% CI 1.27, 1.34; continuing: aRR 1.15 95% CI 1.13, 1.17). Mood and anxiety concerns were prominent among those new to care. Conclusion: In the 18 months following onset of the pandemic, outpatient mental health care utilization increased for those with new and continuing care needs, especially among females and adolescents.

Impact of a publicly-funded pharmacare program policy on benzodiazepine dispensing among children and youth: a population-based natural experiment.

BACKGROUND: In January 2018, the Government of Ontario, Canada, initiated a universal pharmacare program (OHIP+) for all individuals aged 24 years and younger. In April 2019, the program was amended to cover only children and youth without private insurance. Because benzodiazepines are commonly prescribed to children and youth despite their potential hazards, we examined whether changes in publicly-funded drug coverage influenced benzodiazepine dispensing trends in this demographic. METHODS: We conducted a population-based natural experiment study of benzodiazepine dispensing to children and youth in Ontario between January 2013 and March 2020. We used interventional autoregressive integrated moving average models to estimate the impact of OHIP + and its subsequent modification on these trends. RESULTS: The implementation of OHIP + was associated with an immediate increase in the monthly rate of benzodiazepine dispensing of 12.9 individuals per 100,000 population (95% confidence interval [CI]; 7.5 to 18.3 per 100,000). Benzodiazepine dispensing rates rose from 214.2 to 241.5 per 100,000 from December 2017 to March 2019, a 12.8% (95% CI 9.6-16.0%) increase. In stratified analyses, increases were most pronounced among females, children and youth living in the lowest income neighbourhoods and individuals aged 20 to 24. The April 2019 modification to OHIP + was not associated with changes in monthly benzodiazepine dispensing trends (0.39 individuals per 100,000; 95% CI -1.3 to 2.1 per 100,000). However, rates remained elevated relative to the period preceding OHIP + implementation. CONCLUSIONS: Implementation of a publicly-funded pharmacare program resulted in more children and youth being prescribed benzodiazepines.

Effect of clear aligner attachment design on extrusion of maxillary lateral incisors: A multicenter, single-blind randomized clinical trial.

INTRODUCTION: Extrusion of maxillary lateral incisors during aligner treatment is a difficult movement to achieve accurately. Despite recommendations regarding attachment design, few studies and no prospective trials compare predictability among attachments. This study aimed to compare the efficacy between optimized and horizontal attachment designs for achieving maxillary lateral incisor extrusion during clear aligner treatment. METHODS: The study included maxillary lateral incisors in 3 orthodontic practices requiring at least 0.3 mm of extrusion during the first series of 20-25 aligners in patients aged ≥16 years who were scheduled to begin clear aligner treatment (Invisalign; Align Technology, San Jose, Calif). Teeth were randomly assigned to receive optimized (O), rectangular horizontal nonbeveled (H), rectangular horizontal incisally-beveled (HIB), or rectangular horizontal gingivally-beveled (HGB) attachments. After the first series, a blinded evaluator measured extrusion using superimpositions with initial and predicted models. Linear models determined the difference in the predicted extrusion percentage achieved on the basis of attachment design. Other covariates were patient age, sex, number of trays, and self-reported compliance. RESULTS: Forty patients (74 teeth) were enrolled, and 38 patients (71 teeth) completed the study. Intraexaminer and interexaminer reliability for extrusion measurements was high (intraclass correlation coefficient, 0.985 and 0.991, respectively). The achieved extrusion was significantly less than predicted (mean, 73%; P <0.0001). The average achieved extrusion was 62%, 79%, 78%, and 78% for O, H, HIB, and HGB attachments, respectively, with H significantly more effective than O (P = 0.0403). Horizontal attachments (H, HIB, and HGB combined) were significantly more effective than O attachments (P = 0.0060), with an average difference in achieved extrusion of 14% of the predicted amount (95% confidence interval, 4-23; estimated 76% vs 62%). Horizontal attachments were an estimated 22% more effective than O attachments for extruding maxillary lateral incisors. CONCLUSIONS: Horizontal attachments are more effective than O attachments for predicted maxillary lateral incisor extrusion between 0.3 and 2.5 mm. The 3 horizontal attachment designs evaluated performed similarly for achieving predicted extrusion. TRIAL REGISTRATION: This randomized clinical trial was registered and reported at clinicaltrials.gov (NCT04968353). PROTOCOL: The protocol was not published before trial commencement. FUNDING: This study was funded in part by the Alexander Fellowship of the Virginia Commonwealth University School of Dentistry, the Southern Association of Orthodontists, and the Virginia Orthodontic Education and Research Foundation. No funding source influenced the study design, the collection, analysis or interpretation of data, writing of the report, or the decision to submit the article for publication.

Trends in Office-Based Anxiety Treatment Among US Children, Youth, and Young Adults: 2006-2018.

BACKGROUND AND OBJECTIVES: Anxiety disorder diagnoses in office-based settings increased for children through the mid-2010s, but recent changes in diagnosis and treatment are not well understood. The objectives of the current study were to evaluate recent trends in anxiety disorder diagnosis and treatment among children, adolescents, and young adults. METHODS: This study used serial cross-sectional data from the National Ambulatory Medical Care Survey (2006-2018), a nationally representative annual survey of US office-based visits. Changes in anxiety disorder diagnosis and 4 treatment categories (therapy alone, therapy and medications, medications alone, or neither) are described across 3 periods (2006-2009, 2010-2013, 2014-2018). Multinomial logistic regression compared differences in treatment categories, adjusting for age group, sex, and race/ethnicity, contrasting the last and middle periods with the first. RESULTS: The overall proportion of office visits with an anxiety disorder diagnosis significantly increased from 1.4% (95% confidence interval [CI] 1.2-1.7; n = 9 246 921 visits) in 2006 to 2009 to 4.2% (95% CI 3.4-5.2; n = 23 120 958 visits) in 2014 to 2018. The proportion of visits with any therapy decreased from 48.8% (95% CI 40.1-57.6) to 32.6% (95% CI 24.5-41.8), but there was no significant change in the overall use of medications. The likelihood of receiving medication alone during office visits was significantly higher in the last, relative to the first period (relative risk ratio = 2.42, 95% CI 1.24-4.72). CONCLUSIONS: The proportion of outpatient visits that included a diagnosis of anxiety increased over time, accompanied by a decrease in the proportion of visits with therapy.

Adherence to antipsychotic laboratory monitoring guidelines in children and youth: a population-based study.

Background: In 2011, the Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) published guidelines for the metabolic monitoring of antipsychotic-treated children and youth. Population-based studies examining adherence to these guidelines are needed to ensure the safe use of antipsychotics in children and youth. Methods: We conducted a population-based study of all Ontario residents aged 0 to 24 who were newly dispensed an antipsychotic between April 1, 2018, and March 31, 2019. We estimated prevalence ratios (PRs) and 95% confidence intervals (CI) associating sociodemographic characteristics with the receipt of baseline and follow-up (3- and 6-month) laboratory testing using log-Poisson regression models. Results: Overall, 6,505 of 27,718 (23.5%) children and youth newly dispensed an antipsychotic received at least one guideline-recommended baseline test. Monitoring was more prevalent among individuals aged 10 to 14 years (PR 1.20; 95% CI 1.04 to 1.38), 15 to 19 years (PR 1.60; 95% CI 1.41 to 1.82), and 20 to 24 years (PR 1.71; 95% CI 1.50 to 1.94) compared to children under the age of 10. Baseline monitoring was associated with mental health-related hospitalizations or emergency department visits in the year preceding therapy (PR 1.76; 95% CI 1.65 to 1.87), a prior diagnosis of schizophrenia (PR 1.20; 95% CI 1.14 to 1.26) or diabetes (PR 1.35; 95% CI 1.19 to 1.54), benzodiazepine use (PR 1.13; 95% CI 1.04 to 1.24), and receipt of a prescription from a child and adolescent psychiatrist or developmental pediatrician versus a family physician (PR 1.41; 95% CI 1.34 to 1.48). Conversely, monitoring was less frequent in individuals co-prescribed stimulants (PR 0.83; 95% CI 0.75 to 0.91). The prevalence of any 3- and 6-month follow-up monitoring among children and youth receiving continuous antipsychotic therapy at these time points was 13.0% (1,179 of 9,080) and 11.4% (597 of 5,261), respectively. Correlates of follow-up testing were similar to those of baseline monitoring. Conclusion: Most children initiating antipsychotic therapy do not receive guideline-recommended metabolic laboratory monitoring. Further research is needed to understand reasons for poor guideline adherence and the role of clinician training and collaborative service models in promoting best monitoring practices.

Impact of a Publicly-Funded Pharmacare Program on Prescription Stimulant use Among Children and Youth: A Population-Based Observational Natural Experiment.

OBJECTIVE: Stimulants are first-line pharmacotherapy for individuals with attention-deficit hyperactivity disorder. However, disparities in drug coverage may contribute to inequitable treatment access. In January 2018, the government of Ontario, Canada, implemented a publicly-funded program (OHIP+) providing universal access to medications at no cost to children and youth between the ages of 0 and 24. In April 2019, the program was amended to cover only children and youth without private insurance. We studied whether these policy changes were associated with changes in prescription stimulant dispensing to Ontario children and youth. METHODS: We conducted a population-based observational natural experiment study of stimulant dispensing to children and youth in Ontario between January 2013 and March 2020. We used interventional autoregressive integrated moving average models to estimate the association between OHIP+ and its subsequent modification with stimulant dispensing trends. RESULTS: The implementation of OHIP+ was associated with a significant immediate increase in the monthly rate of stimulant dispensing of 53.6 individuals per 100,000 population (95% confidence interval [CI], 36.8 to 70.5 per 100,000) and a 14.2% (95% CI, 12.8% to 15.6%) relative percent increase in stimulant dispensing rates between December 2017 and March 2019 (1198.6 vs. 1368.7 per 100,000 population). The April 2019 OHIP+ program amendment was associated with an increase in monthly stimulant dispensing trends of 10.2 individuals per 100,000 population (95% CI, 5.0 to 15.5), with rates increasing 7.5% (95% CI, 6.2% to 8.7%) between March 2019 and March 2020 (1368.7 vs. 1470.8 per 100,000 population). These associations were most pronounced among males, children and youth living in the highest income neighbourhoods and individuals aged 20 to 24. CONCLUSION: A publicly-funded pharmacare program was associated with more children and youth being dispensed stimulants.

Sociodemographic Differences in Physician-Based Mental Health and Virtual Care Utilization and Uptake of Virtual Care Among Children and Adolescents During the COVID-19 Pandemic in Ontario, Canada: A Population-Based Study.

OBJECTIVE: We sought to evaluate the relationship between social determinants of health and physician-based mental healthcare utilization and virtual care use among children and adolescents in Ontario, Canada, during the COVID-19 pandemic. METHODS: This population-based repeated cross-sectional study of children and adolescents (3-17 years; N = 2.5 million) used linked health and demographic administrative data in Ontario, Canada (2017-2021). Multivariable Poisson regressions with generalized estimating equations compared rates of outpatient physician-based mental healthcare use during the first year of the COVID-19 pandemic with expected rates based on pre-COVID patterns. Analyses were conducted by socioeconomic status (material deprivation quintiles of the Ontario Marginalization index), urban/rural region of residence, and immigration status. RESULTS: Overall, pediatric physician-based mental healthcare visits were 5% lower than expected (rate ratio [RR] = 0.95, 95% confidence interval [CI], 0.92 to 0.98) among those living in the most deprived areas in the first year of the pandemic, compared with the least deprived with 4% higher than expected rates (RR = 1.04, 95% CI, 1.02 to 1.06). There were no differences in overall observed and expected visit rates by region of residence. Immigrants had 14% to 26% higher visit rates compared with expected from July 2020 to February 2021, whereas refugees had similarly observed and expected rates. Virtual care use was approximately 65% among refugees, compared with 70% for all strata. CONCLUSION: During the first year of the pandemic, pediatric physician-based mental healthcare utilization was higher among immigrants and lower than expected among those with lower socioeconomic status. Refugees had the lowest use of virtual care. Further work is needed to understand whether these differences reflect issues in access to care or the need to help inform ongoing pandemic recovery planning.

Geographic variation and sociodemographic correlates of prescription psychotropic drug use among children and youth in Ontario, Canada: a population-based study.

BACKGROUND: Population-based research examining geographic variability in psychotropic medication dispensing to children and youth and the sociodemographic correlates of such variation is lacking. Variation in psychotropic use could reflect disparities in access to non-pharmacologic interventions and identify potentially concerning use patterns. METHODS: We conducted a population-based study of all Ontario residents aged 0 to 24 years who were dispensed a benzodiazepine, stimulant, antipsychotic or antidepressant between January 1, 2018, and December 31, 2018. We conducted small-area variation analyses and identified determinants of dispensing using negative binomial generalized estimating equation models. RESULTS: The age- and sex-standardized rate of psychotropic dispensing to children and youth was 76.8 (range 41.7 to 144.4) prescriptions per 1000 population, with large variation in psychotropic dispensing across Ontario's census divisions. Males had higher antipsychotic [rate ratio (RR) 1.40; 95% confidence interval (CI) 1.36 to 1.44) and stimulant (RR 1.75; 95% CI 1.70 to 1.80) dispensing rates relative to females, with less use of benzodiazepines (RR 0.85; 95% CI 0.83 to 0.88) and antidepressants (RR 0.81; 95% CI 0.80 to 0.82). Lower antipsychotic dispensing was observed in the highest income neighbourhoods (RR 0.72; 95% CI 0.70 to 0.75) relative to the lowest. Benzodiazepine (RR 1.12; 95% CI 1.01 to 1.24) and stimulant (RR 1.11; 95% CI 1.01 to 1.23) dispensing increased with the density of mental health services in census divisions, whereas antipsychotic use decreased (RR 0.82; 95% CI 0.73 to 0.91). The regional density of child and adolescent psychiatrists and developmental pediatricians (RR 1.00; 95% CI 0.99 to 1.01) was not associated with psychotropic dispensing. CONCLUSION: We found significant variation in psychotropic dispensing among young Ontarians. Targeted investment in regions with long wait times for publicly-funded non-pharmacological interventions and novel collaborative service models may minimize variability and promote best practices in using psychotropics among children and youth.

Impact of COVID-19 on opioid use in those awaiting hip and knee arthroplasty: a retrospective cohort study.

BACKGROUND: COVID-19 has had a detrimental impact on access to hip and knee arthroplasty surgery. We set out to examine whether this had a subsequent impact on preoperative opioid prescribing rates for those awaiting surgery. METHODS: Data regarding patient demographics and opioid utilisation were collected from the electronic health records of included patients at a large university teaching hospital. Patients on the outpatient waiting list for primary hip and knee arthroplasty as of September 2020 (COVID-19 group) were compared with historical controls (Controls) who had previously undergone surgery. A sample size calculation indicated 452 patients were required to detect a 15% difference in opioid prescription rates between groups. RESULTS: A total of 548 patients (58.2% female) were included, 260 in the COVID-19 group and 288 in the Controls. Baseline demographics were similar between the groups. For those with data available, the proportion of patients on any opioid at follow-up in the COVID-19 group was significantly higher: 55.0% (143/260) compared with 41.2% (112/272) in the Controls (p=0.002). This remained significant when adjusted for confounding (age, gender, Scottish Index of Multiple Deprivation, procedure and wait time). The proportion of patients on a strong opioid was similar (4.2% (11/260) vs 4.8% (13/272)) for COVID-19 and Controls, respectively. The median waiting time from referral to follow-up was significantly longer in the COVID-19 group compared with the Controls (455 days vs 365 days; p<0.0001). CONCLUSION: The work provides evidence of potential for an emerging opioid problem associated with the influence of COVID-19 on elective arthroplasty services. Viable alternatives to opioid analgesia for those with end-stage arthritis should be explored, and prolonged waiting times for surgery ought to be avoided in the recovery from COVID-19 to prevent more widespread opioid use.

A scoping review of the Choice and Partnership Approach in child and adolescent mental health services.

Child and adolescent mental health (CAMH) problems are prevalent and inefficient mental health (MH) care systems can contribute to poor outcomes. The Choice and Partnership Approach (CAPA) is a MH care delivery model aiming to provide efficient, high-quality care. Although widely used, no CAPA research review exists. We conducted a scoping review to fill this gap. Medline, Embase, and PsycINFO databases were searched from inception to June 2021. Grey Matters and Google were used to search the grey literature. We identified 5322 records. Removal of duplicates left 4720 documents, which were successively screened and data extracted by pairs of co-authors. The final dataset comprised six published and three non-published studies, conducted primarily at CAMH sites in England, Scotland, Australia, or Canada. Each study had multiple research objectives, which we summarized into seven categories. Positive outcomes were reported for most objectives, but attributing causality to CAPA was hampered by research methodology. Observational designs were used in all studies and approaches to analyzing data varied considerably. Research gaps included the lack of healthcare economics studies of CAPA and no assessment of facilitators and barriers. Current research on CAPA provides intriguing findings meriting further investigation. We suggest strategies to improve future studies.

Circadian cortisol secretion in adolescent girls with conduct disorder.

Severe antisocial behavior in girls, best exemplified by conduct disorder (CD), is a serious clinical and public health problem. Treatment is difficult, particularly in girls with comorbid internalizing disorders. Identifying biological correlates may help to develop new treatments or diagnostic, prognostic, or treatment response biomarkers. Based on our earlier work and research from others occurring primarily in boys with severe antisocial behavior, it is possible that abnormalities in the hypothalamic pituitary adrenal (HPA) axis circadian cortisol cycle may be associated with female CD. Additionally, research suggests that the presence of comorbid internalizing disorders may be related to differences in cortisol secretion, compared to subjects who only have CD. Our study aimed: 1) to compare the circadian cortisol cycle in 98 girls with CD, 15-16 years of age to 47 girls without any psychiatric disorder (ND) and 2) to compare the cycle in girls with CD and comorbid internalizing disorders (CD + INT) to those without such comorbidity (CD Only). Salivary cortisol was collected over 24 h during weekdays at scheduled times, with protocol adherence measures in place. Unstructured covariance pattern modeling, controlling for effects of age, social class, IQ, and awakening time was used to analyze cortisol data. CD was associated with overall lower cortisol secretion (p = 0.03), but this difference was due to a lower volume of cortisol secreted 30 min after awakening (area under the curve with respect to ground, p = 0.01). Circadian cortisol secretion was no different in the CD+INT group compared to the CD Only group (p = 0.52). Our findings need to be replicated using current consensus guidelines for the assessment of the CAR. We also suggest two new avenues of research in this field.

The Gross Developmental Potential (GDP2): a new approach for measuring human potential and wellbeing.

Many factors influence the health and well-being of children and the adults they will become. Yet there are significant gaps in how trajectories of healthy development are measured, how the potential for leading a healthy life is evaluated, and how that information can guide upstream policies and investments. The Gross Developmental Potential (GDP2) is proposed as a new capabilities-based framework for assessing threats to thriving and understanding progress in achieving lifelong health and wellbeing. Moving beyond the Gross Domestic Product's (GDP) focus on economic productivity as a measure of progress, the GDP2 focuses on seven essential developmental capabilities for lifelong health and wellbeing. The GDP2 capability domains include Health -living a healthy life; Needs-satisfying basic human requirements; Communication-expressing and understanding thoughts and feelings; Learning-lifelong learning; Adaption -adapting to change; Connections -connecting with others; and Community -engaging in the community. The project team utilized literature reviews and meetings with the subject and technical experts to develop the framework. The framework was then vetted in focus groups of community leaders from three diverse settings. The community leaders' input refined the domains and their applications. This prototype GDP2 framework will next be used to develop specific measures and indices and guide the development of community-level GDP2 dashboards for local sense-making, learning, and application.

Peripheral and neural correlates of self-harm in children and adolescents: a scoping review.

BACKGROUND: Self-harm in children and adolescents is difficult to treat. Peripheral and neural correlates of self-harm could lead to biomarkers to guide precision care. We therefore conducted a scoping review of research on peripheral and neural correlates of self-harm in this age group. METHODS: PubMed and Embase databases were searched from January 1980-May 2020, seeking English language peer-reviewed studies about peripheral and neural correlates of self-harm, defined as completed suicide, suicide attempts, suicidal ideation, or non-suicidal self-injury (NSSI) in subjects, birth to 19 years of age. Studies were excluded if only investigating self-harm in persons with intellectual or developmental disability syndromes. A blinded multi-stage assessment process by pairs of co-authors selected final studies for review. Risk of bias estimates were done on final studies. RESULTS: We screened 5537 unduplicated abstracts, leading to the identification of 79 eligible studies in 76 papers. Of these, 48 investigated peripheral correlates and 31 examined neural correlates. Suicidality was the focus in 2/3 of the studies, with NSSI and any type of self-harm (subjects recruited with suicidality, NSSI, or both) investigated in the remaining studies. All studies used observational designs (primarily case-control), most used convenience samples of adolescent patients which were predominately female and half of which were recruited based on a disorder. Over a quarter of the specific correlates were investigated with only one study. Inter-study agreement on findings from specific correlates with more than one study was often low. Estimates of Good for risk of bias were assigned to 37% of the studies and the majority were rated as Fair. CONCLUSIONS: Research on peripheral and neural correlates of self-harm is not sufficiently mature to identify potential biomarkers. Conflicting findings were reported for many of the correlates studied. Methodological problems may have produced biased findings and results are mainly generalizable to patients and girls. We provide recommendations to improve future peripheral and neural correlate research in children and adolescents, ages 3-19 years, with self-harm.

Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden.

BACKGROUND: Group B streptococcus (GBS) colonisation during pregnancy can lead to invasive GBS disease (iGBS) in infants, including meningitis or sepsis, with a high mortality risk. Other outcomes include stillbirths, maternal infections, and prematurity. There are data gaps, notably regarding neurodevelopmental impairment (NDI), especially after iGBS sepsis, which have limited previous global estimates. In this study, we aimed to address this gap using newly available multicountry datasets. METHODS: We collated and meta-analysed summary data, primarily identified in a series of systematic reviews published in 2017 but also from recent studies on NDI and stillbirths, using Bayesian hierarchical models, and estimated the burden for 183 countries in 2020 regarding: maternal GBS colonisation, iGBS cases and deaths in infants younger than 3 months, children surviving iGBS affected by NDI, and maternal iGBS cases. We analysed the proportion of stillbirths with GBS and applied this to the UN-estimated stillbirth risk per country. Excess preterm births associated with maternal GBS colonisation were calculated using meta-analysis and national preterm birth rates. FINDINGS: Data from the seven systematic reviews, published in 2017, that informed the previous burden estimation (a total of 515 data points) were combined with new data (17 data points) from large multicountry studies on neurodevelopmental impairment (two studies) and stillbirths (one study). A posterior median of 19·7 million (95% posterior interval 17·9-21·9) pregnant women were estimated to have rectovaginal colonisation with GBS in 2020. 231 800 (114 100-455 000) early-onset and 162 200 (70 200-394 400) late-onset infant iGBS cases were estimated to have occurred. In an analysis assuming a higher case fatality rate in the absence of a skilled birth attendant, 91 900 (44 800-187 800) iGBS infant deaths were estimated; in an analysis without this assumption, 58 300 (26 500-125 800) infant deaths from iGBS were estimated. 37 100 children who recovered from iGBS (14 600-96 200) were predicted to develop moderate or severe NDI. 40 500 (21 500-66 200) maternal iGBS cases and 46 200 (20 300-111 300) GBS stillbirths were predicted in 2020. GBS colonisation was also estimated to be potentially associated with considerable numbers of preterm births. INTERPRETATION: Our analysis provides a comprehensive assessment of the pregnancy-related GBS burden. The Bayesian approach enabled coherent propagation of uncertainty, which is considerable, notably regarding GBS-associated preterm births. Our findings on both the acute and long-term consequences of iGBS have public health implications for understanding the value of investment in maternal GBS immunisation and other preventive strategies. FUNDING: Bill & Melinda Gates Foundation.

Current dichotomous metrics obscure trends in severe and extreme child growth failure.

Historically, the prevalence of child growth failure (CGF) has been tracked dichotomously as the proportion of children more than 2 SDs below the median of the World Health Organization growth standards. However, this conventional "thresholding" approach fails to recognize child growth as a spectrum and obscures trends in populations with the highest rates of CGF. Our analysis presents the first ever estimates of entire distributions of HAZ, WHZ, and WAZ for each of 204 countries and territories from 1990 to 2020 for children less than 5 years old by age group and sex. This approach reflects the continuous nature of CGF, allows us to more comprehensively assess shrinking or widening disparities over time, and reveals otherwise hidden trends that disproportionately affect the most vulnerable populations.