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ADHD Diagnosis and Treatment in Children and Adolescents

Author/s: 
Peterson, BS, Trampush, J, Maglione, M, Bolshakova, M, Brown, M., Rozelle, M

Objective. The systematic review assessed evidence on the diagnosis, treatment, and monitoring of attention deficit hyperactivity disorder (ADHD) in children and adolescents to inform a planned update of the American Academy of Pediatrics (AAP) guidelines.

Data sources. We searched PubMed®, Embase®, PsycINFO®, ERIC, clinicaltrials.gov, and prior reviews for primary studies published since 1980. The report includes studies published to June 15, 2023.

Review methods. The review followed a detailed protocol and was supported by a Technical Expert Panel. Citation screening was facilitated by machine learning; two independent reviewers screened full text citations for eligibility. We abstracted data using software designed for systematic reviews. Risk of bias assessments focused on key sources of bias for diagnostic and intervention studies. We conducted strength of evidence (SoE) and applicability assessments for key outcomes. The protocol for the review has been registered in PROSPERO (CRD42022312656).

Results. Searches identified 23,139 citations, and 7,534 were obtained as full text. We included 550 studies reported in 1,097 publications (231 studies addressed diagnosis, 312 studies addressed treatment, and 10 studies addressed monitoring). Diagnostic studies reported on the diagnostic performance of numerous parental ratings, teacher rating scales, teen/child self-reports, clinician tools, neuropsychological tests, EEG approaches, imaging, and biomarkers. Multiple approaches showed promising diagnostic performance (e.g., using parental rating scales), although estimates of performance varied considerably across studies and the SoE was generally low. Few studies reported estimates for children under the age of 7. Treatment studies evaluated combined pharmacological and behavior approaches, medication approved by the Food and Drug Administration, other pharmacologic treatment, psychological/behavioral approaches, cognitive training, neurofeedback, neurostimulation, physical exercise, nutrition and supplements, integrative medicine, parent support, school interventions, and provider or model-of-care interventions. Medication treatment was associated with improved broadband scale scores and ADHD symptoms (high SoE) as well as function (moderate SoE), but also appetite suppression and adverse events (high SoE). Psychosocial interventions also showed improvement in ADHD symptoms based on moderate SoE. Few studies have evaluated combinations of pharmacological and youth-directed psychosocial interventions, and we did not find combinations that were systematically superior to monotherapy (low SoE). Published monitoring approaches for ADHD were limited and the SoE is insufficient.

Conclusion. Many diagnostic tools are available to aid the diagnosis of ADHD, but few monitoring strategies have been studied. Medication therapies remain important treatment options, although with a risk of side effects, as the evidence base for psychosocial therapies strengthens and other nondrug treatment approaches emerge.

Association Between Plant and Animal Protein Intake and Overall and Cause-Specific Mortality

Author/s: 
Huang, J., Liao, L.M., Weinstein, S.J., Sinha, R., Graubard, B.I., Albanes, D.

Importance: Although emphasis has recently been placed on the importance of high-protein diets to overall health, a comprehensive analysis of long-term cause-specific mortality in association with the intake of plant protein and animal protein has not been reported.

Objective: To examine the associations between overall mortality and cause-specific mortality and plant protein intake.

Design, setting, and participants: This prospective cohort study analyzed data from 416 104 men and women in the US National Institutes of Health-AARP Diet and Health Study from 1995 to 2011. Data were analyzed from October 2018 through April 2020.

Exposures: Validated baseline food frequency questionnaire dietary information, including intake of plant protein and animal protein.

Main outcomes and measures: Hazard ratios and 16-year absolute risk differences for overall mortality and cause-specific mortality.

Results: The final analytic cohort included 237 036 men (57%) and 179 068 women. Their overall median (SD) ages were 62.2 (5.4) years for men and 62.0 (5.4) years for women. Based on 6 009 748 person-years of observation, 77 614 deaths (18.7%; 49 297 men and 28 317 women) were analyzed. Adjusting for several important clinical and other risk factors, greater dietary plant protein intake was associated with reduced overall mortality in both sexes (hazard ratio per 1 SD was 0.95 [95% CI, 0.94-0.97] for men and 0.95 [95% CI, 0.93-0.96] for women; adjusted absolute risk difference per 1 SD was -0.36% [95% CI, -0.48% to -0.25%] for men and -0.33% [95% CI, -0.48% to -0.21%] for women; hazard ratio per 10 g/1000 kcal was 0.88 [95% CI, 0.84-0.91] for men and 0.86 [95% CI, 0.82-0.90] for women; adjusted absolute risk difference per 10 g/1000 kcal was -0.95% [95% CI, -1.3% to -0.68%] for men and -0.86% [95% CI, -1.3% to -0.55%] for women; all P < .001). The association between plant protein intake and overall mortality was similar across the subgroups of smoking status, diabetes, fruit consumption, vitamin supplement use, and self-reported health status. Replacement of 3% energy from animal protein with plant protein was inversely associated with overall mortality (risk decreased 10% in both men and women) and cardiovascular disease mortality (11% lower risk in men and 12% lower risk in women). In particular, the lower overall mortality was attributable primarily to substitution of plant protein for egg protein (24% lower risk in men and 21% lower risk in women) and red meat protein (13% lower risk in men and 15% lower risk in women).

Conclusions and relevance: In this large prospective cohort, higher plant protein intake was associated with small reductions in risk of overall and cardiovascular disease mortality. Our findings provide evidence that dietary modification in choice of protein sources may influence health and longevity.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Adolescent Opioid Misuse Attributable to Adverse Childhood Experiences

Author/s: 
Swedo, E.A., Sumner, S.A., Fijter, S., Werhan, L., Norris, K., Beauregard, J.L., Montgomery, M.P., Rose, E.B., Hillis, S. D., Massetti, G.M.

Objectives

To estimate the proportion of opioid misuse attributable to adverse childhood experiences (ACEs) among adolescents.

Study design

A cross-sectional survey was administered to 10,546 7th‒12th grade students in northeastern Ohio in Spring 2018. Study measures included self-reported lifetime exposure to 10 ACEs and past 30 day use of nonmedical prescription opioid or heroin. Using generalized estimating equations, we evaluated associations between recent opioid misuse, individual ACEs, and cumulative number of ACEs. We calculated population attributable fractions (PAF) to determine the proportion of adolescents’ recent opioid misuse attributable to ACEs.

Results

Nearly one in 50 adolescents reported opioid misuse within 30 days (1.9%); ∼60% of youth experienced ≥1 ACE; 10.2% experienced ≥5 ACEs. Cumulative ACE exposure demonstrated a significant graded relationship with opioid misuse. Compared with youth with zero ACEs, youth with 1 ACE (adjusted odds ratio [AOR]: 1.9, 95% confidence interval [CI]: 0.9‒3.9), 2 ACEs (AOR: 3.8, CI: 1.9‒7.9), 3 ACEs (AOR: 3.7, CI: 2.2‒6.5), 4 ACEs (AOR: 5.8, CI: 3.1‒11.2), and ≥5 ACEs (AOR: 15.3, CI: 8.8‒26.6) had higher odds of recent opioid misuse. The population attributable fraction of recent opioid misuse associated with experiencing ≥1 ACE was 71.6% (CI: 59.8–83.5).

Conclusions

There was a significant graded relationship between number of ACEs and recent opioid misuse among adolescents. Over 70% of recent adolescent opioid misuse in our study population was attributable to ACEs. Efforts to decrease opioid misuse could include programmatic, policy, and clinical practice interventions to prevent and mitigate the negative effects of ACEs.

Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017

Author/s: 
Osei , A.D., Mirbolouk, M., Orimoloye, O.A., Dzaye, O.

Introduction: The association between e-cigarette use and chronic bronchitis, emphysema, and
chronic obstructive pulmonary disease has not been studied thoroughly, particularly in populations
defined by concomitant combustible smoking status.

Methods: Using pooled 2016 and 2017 data from the Behavioral Risk Factor Surveillance System,
investigators studied 705,159 participants with complete self-reported information on e-cigarette use,
combustible cigarette use, key covariates, and chronic bronchitis, emphysema, or chronic obstructive
pulmonary disease. Current e-cigarette use was the main exposure, with current use further classified
as daily or occasional use. The main outcome was defined as reported ever having a diagnosis of

chronic bronchitis, emphysema, or chronic obstructive pulmonary disease. For all the analyses, multi-
variable adjusted logistic regression was used, with the study population stratified by combustible ciga-
rette use status (never, former, or current). All the analyses were conducted in 2019.

Results: Of 705,159 participants, 25,175 (3.6%) were current e-cigarette users, 64,792 (9.2%) current
combustible cigarette smokers, 207,905 (29.5%) former combustible cigarette smokers, 432,462

(61.3%) never combustible cigarette smokers, and 14,036 (2.0%) dual users of e-cigarettes and combus-
tible cigarettes. A total of 53,702 (7.6%) participants self-reported chronic bronchitis, emphysema, or

chronic obstructive pulmonary disease. Among never combustible cigarette smokers, current e-ciga-
rette use was associated with 75% higher odds of chronic bronchitis, emphysema, or chronic obstruc-
tive pulmonary disease compared with never e-cigarette users (OR=1.75, 95% CI=1.25, 2.45), with

daily users of e-cigarettes having the highest odds (OR=2.64, 95% CI=1.43, 4.89). Similar associations
between e-cigarette use and chronic bronchitis, emphysema, or chronic obstructive pulmonary disease
were noted among both former and current combustible cigarette smokers.
Conclusions: The results suggest possible e-cigarette−related pulmonary toxicity across all thecategories of combustible cigarette smoking status, including those who had never smoked combus-
tible cigarettes.

Keywords 

Association of household secondhand smoke exposure and mortality risk in patients with heart failure

Author/s: 
He, X, Zhao, J, He, J, Dong, Y, Liu, C

BACKGROUND:

Secondhand smoke (SHS) exposure is a well-established cardiovascular risk factor, yet association between SHS and prognosis of heart failure remains uncertain.

METHOD:

Data were obtained from the US National Health and Nutrition Examination Surveys III from 1988 to 1994. Currently nonsmoking adults with a self-reported history of heart failure were included. Household SHS exposure was assessed by questionnaire. Participants were followed up through December 31, 2011. Cox proportional-hazards models were used to assess the association of household SHS exposure and mortality risk. Potential confounding factors were adjusted.

RESULTS:

Of 572 currently nonsmoking patients with heart failure, 88 were exposed to household SHS while 484 were not. There were totally 475 deaths during follow-up. In univariate analysis, household SHS was not associated with mortality risk (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.76-1.26, p = 0.864). However, after adjustment for demographic variables, socioeconomic variables and medication, heart failure patients in exposed group had a 43% increase of mortality risk compared with those in unexposed group (HR: 1.43, 95% CI: 1.10-1.86, p = 0.007). Analysis with further adjustment for general health status and comorbidities yielded similar result (HR: 1.47, 95% CI: 1.13-1.92, p = 0.005).

CONCLUSION:

Household SHS exposure was associated with increased mortality risk in heart failure patients.

The Primary Care PTSD Screen (PC-PTSD)

Author/s: 
Prins, Annabel, Bovin, Michelle J., Smolenski, Derek J., Marx, Brian P., Kimmerling, Rachel, Jenkins-Guarnieri, Michael A., Kaloupek, Danny G.

BACKGROUND

Posttraumatic Stress Disorder (PTSD) is associated with increased health care utilization, medical morbidity, and tobacco and alcohol use. Consequently, screening for PTSD has become increasingly common in primary care clinics, especially in Veteran healthcare settings where trauma exposure among patients is common.

OBJECTIVE

The objective of this study was to revise the Primary Care PTSD screen (PC-PTSD) to reflect the new Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for PTSD (PC-PTSD-5) and to examine both the diagnostic accuracy and the patient acceptability of the revised measure.

DESIGN

We compared the PC-PTSD-5 results with those from a brief psychiatric interview for PTSD. Participants also rated screening preferences and acceptability of the PC-PTSD-5.

PARTICIPANTS

A convenience sample of 398 Veterans participated in the study (response rate = 41 %). Most of the participants were male, in their 60s, and the majority identified as non-Hispanic White.

MEASURES

The PC-PTSD-5 was used as the screening measure, a modified version of the PTSD module of the MINI-International Neuropsychiatric Interview was used to diagnose DSM-5 PTSD, and five brief survey items were used to assess acceptability and preferences.

KEY RESULTS

The PC-PTSD-5 demonstrated excellent diagnostic accuracy (AUC = 0.941; 95 % C.I.: 0.912– 0.969). Whereas a cut score of 3 maximized sensitivity (κ[1]) = 0.93; SE = .041; 95 % C.I.: 0.849–1.00), a cut score of 4 maximized efficiency (κ[0.5] = 0.63; SE = 0.052; 95 % C.I.: 0.527–0.731), and a cut score of 5 maximized specificity (κ[0] = 0.70; SE = 0.077; 95 % C.I.: 0.550–0.853). Patients found the screen acceptable and indicated a preference for administration by their primary care providers as opposed to by other providers or via self-report.

CONCLUSIONS

The PC-PTSD-5 demonstrated strong preliminary results for diagnostic accuracy, and was broadly acceptable to patients.

Generalized Anxiety Disorder 7-Item Scale

Author/s: 
Spitzer, Robert L., Kroenke, Kurt, Williams, Janet B. W.

BACKGROUND:

Generalized anxiety disorder (GAD) is one of the most common mental disorders; however, there is no brief clinical measure for assessing GAD. The objective of this study was to develop a brief self-report scale to identify probable cases of GAD and evaluate its reliability and validity.

METHODS:

A criterion-standard study was performed in 15 primary care clinics in the United States from November 2004 through June 2005. Of a total of 2740 adult patients completing a study questionnaire, 965 patients had a telephone interview with a mental health professional within 1 week. For criterion and construct validity, GAD self-report scale diagnoses were compared with independent diagnoses made by mental health professionals; functional status measures; disability days; and health care use.

RESULTS:

A 7-item anxiety scale (GAD-7) had good reliability, as well as criterion, construct, factorial, and procedural validity. A cut point was identified that optimized sensitivity (89%) and specificity (82%). Increasing scores on the scale were strongly associated with multiple domains of functional impairment (all 6 Medical Outcomes Study Short-Form General Health Survey scales and disability days). Although GAD and depression symptoms frequently co-occurred, factor analysis confirmed them as distinct dimensions. Moreover, GAD and depression symptoms had differing but independent effects on functional impairment and disability. There was good agreement between self-report and interviewer-administered versions of the scale.

CONCLUSION:

The GAD-7 is a valid and efficient tool for screening for GAD and assessing its severity in clinical practice and research.

The World Health Organization Adult Attention-Deficit/Hyperactivity Disorder Self-Report Screening Scale for DSM-5

Author/s: 
Ustun, Berk, Adler, Lenard A., Rudin, Cynthia, Faraone, Stephen V., Spencer, Thomas J., Berglund, Patricia, Gruber, Michael J., Kessler, Ronald C.

IMPORTANCE:

Recognition that adult attention-deficit/hyperactivity disorder (ADHD) is common, seriously impairing, and usually undiagnosed has led to the development of adult ADHD screening scales for use in community, workplace, and primary care settings. However, these scales are all calibrated to DSM-IV criteria, which are narrower than the recently developed DSM-5 criteria.

OBJECTIVES:

To update for DSM-5 criteria and improve the operating characteristics of the widely used World Health Organization AdultADHD Self-Report Scale (ASRS) for screening.

DESIGN, SETTING, AND PARTICIPANTS:

Probability subsamples of participants in 2 general population surveys (2001-2003 household survey [n = 119] and 2004-2005 managed care subscriber survey [n = 218]) who completed the full 29-question self-report ASRS, with both subsamples over-sampling ASRS-screened positives, were blindly administered a semistructured research diagnostic interview for DSM-5 adult ADHD. In 2016, the Risk-Calibrated Supersparse Linear Integer Model, a novel machine-learning algorithm designed to create screening scales with optimal integer weights and limited numbers of screening questions, was applied to the pooled data to create a DSM-5 version of the ASRS screening scale. The accuracy of the new scale was then confirmed in an independent 2011-2012 clinical sample of patients seeking evaluation at the New York University Langone Medical Center Adult ADHD Program (NYU Langone) and 2015-2016 primary care controls (n = 300). Data analysis was conducted from April 4, 2016, to September 22, 2016.

MAIN OUTCOMES AND MEASURES:

The sensitivity, specificity, area under the curve (AUC), and positive predictive value (PPV) of the revised ASRS.

RESULTS:

Of the total 637 participants, 44 (37.0%) household survey respondents, 51 (23.4%) managed care respondents, and 173 (57.7%) NYU Langone respondents met DSM-5 criteria for adult ADHD in the semistructured diagnostic interview. Of the respondents who met DSM-5 criteria for adult ADHD, 123 were male (45.9%); mean (SD) age was 33.1 (11.4) years. A 6-question screening scale was found to be optimal in distinguishing cases from noncases in the first 2 samples. Operating characteristics were excellent at the diagnostic threshold in the weighted (to the 8.2% DSM-5/Adult ADHD Clinical Diagnostic Scale population prevalence) data (sensitivity, 91.4%; specificity, 96.0%; AUC, 0.94; PPV, 67.3%). Operating characteristics were similar despite a much higher prevalence (57.7%) when the scale was applied to the NYU Langone clinical sample (sensitivity, 91.9%; specificity, 74.0%; AUC, 0.83; PPV, 82.8%).

CONCLUSIONS AND RELEVANCE:

The new ADHD screening scale is short, easily scored, detects the vast majority of general population cases at a threshold that also has high specificity and PPV, and could be used as a screening tool in specialty treatment settings.

Keywords 
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