Detecting Fast Progressors: Comparing a Bayesian Longitudinal Model to Linear Regression for Detecting Structural Changes in Glaucoma.

PURPOSE: Demonstrate that a novel Bayesian hierarchical spatial longitudinal (HSL) model identifies macular superpixels with rapidly deteriorating ganglion cell complex (GCC) thickness more efficiently than simple linear regression (SLR). DESIGN: Prospective cohort study. SETTING: Tertiary Glaucoma Center. SUBJECTS: One hundred eleven eyes (111 patients) with moderate to severe glaucoma at baseline and ≥4 macular optical coherence tomography scans and ≥2 years of follow-up. OBSERVATION PROCEDURE: Superpixel-patient-specific GCC slopes and their posterior variances in 49 superpixels were derived from our latest Bayesian HSL model and Bayesian SLR. A simulation cohort was created with known intercepts, slopes, and residual variances in individual superpixels. MAIN OUTCOME MEASURES: We compared HSL and SLR in the fastest progressing deciles on (1) proportion of superpixels identified as significantly progressing in the simulation study and compared to SLR slopes in cohort data; (2) root mean square error (RMSE), and SLR/HSL RMSE ratios. RESULTS: Cohort- In the fastest decile of slopes per SLR, 77% and 80% of superpixels progressed significantly according to SLR and HSL, respectively. The SLR/HSL posterior SD ratio had a median of 1.83, with 90% of ratios favoring HSL. Simulation- HSL identified 89% significant negative slopes in the fastest progressing decile vs 64% for SLR. SLR/HSL RMSE ratio was 1.36 for the fastest decile of slopes, with 83% of RMSE ratios favoring HSL. CONCLUSION: The Bayesian HSL model improves the estimation efficiency of local GCC rates of change regardless of underlying true rates of change, particularly in fast progressors.

A Bayesian Hierarchical Spatial Longitudinal Model Improves Estimation of Local Macular Rates of Change in Glaucomatous Eyes.

Purpose: Demonstrate that a novel Bayesian hierarchical spatial longitudinal (HSL) model improves estimation of local macular ganglion cell complex (GCC) rates of change compared to simple linear regression (SLR) and a conditional autoregressive (CAR) model. Methods: We analyzed GCC thickness measurements within 49 macular superpixels in 111 eyes (111 patients) with four or more macular optical coherence tomography scans and two or more years of follow-up. We compared superpixel-patient-specific estimates and their posterior variances derived from the latest version of a recently developed Bayesian HSL model, CAR, and SLR. We performed a simulation study to compare the accuracy of intercept and slope estimates in individual superpixels. Results: HSL identified a significantly higher proportion of significant negative slopes in 13/49 superpixels and a significantly lower proportion of significant positive slopes in 21/49 superpixels than SLR. In the simulation study, the median (tenth, ninetieth percentile) ratio of mean squared error of SLR [CAR] over HSL for intercepts and slopes were 1.91 (1.23, 2.75) [1.51 (1.05, 2.20)] and 3.25 (1.40, 10.14) [2.36 (1.17, 5.56)], respectively. Conclusions: A novel Bayesian HSL model improves estimation accuracy of patient-specific local GCC rates of change. The proposed model is more than twice as efficient as SLR for estimating superpixel-patient slopes and identifies a higher proportion of deteriorating superpixels than SLR while minimizing false-positive detection rates. Translational Relevance: The proposed HSL model can be used to model macular structural measurements to detect individual glaucoma progression earlier and more efficiently in clinical and research settings.

Fibroepithelial stromal polyp of bladder-a mimicker of sarcoma or angiomyxoma at uncommon location.

The fibroepithelial stromal polyp is a benign polypoid proliferation of the stroma with overlying epithelium. Because the lesion contains atypical stromal cells, sometimes it can be overdiagnosed as sarcoma or with myxoid stroma, it can be misdiagnosed as angiomyxoma. The reported locations are mainly in the lower female genital tract, urethra, and rarely extragenital sites, such as the breast, and are exceptionally rare in the bladder. We encountered a 65-year-old man who presented with two small velvety, erythematous patches on the posterior bladder wall. The final diagnosis is a fibroepithelial stromal polyp of the bladder. Familiarity with this lesion will prevent overinterpretation of this benign lesion as a malignancy.

Chromophobe Renal Cell Carcinoma with Sarcomatoid Differentiation.

Chromophobe renal cell carcinoma (chRCC) is one of the less common types of kidney cancer and generally portends a more favorable prognosis. RCC with sarcomatoid differentiation has a more aggressive clinical course with poor outcomes. Four cases of chRCC with varying degrees of sarcomatoid differentiation were retrospectively reviewed at our institution, and clinicopathologic data as well as clinical courses were reported. Patients with higher degrees of sarcomatoid differentiation and larger tumors at presentation generally had and worse overall survival. chRCC with sarcomatoid differentiation portends a poor prognosis with limited data on systemic treatment options for metastatic disease.

Preclinical optimization of a diode laser-based clamp-free partial nephrectomy in a large animal model.

Kidney cancer is a common urologic malignancy with either laparoscopic (LPN) or robotic partial nephrectomy as therapeutic options of choice for localized tumors. However, renal resection and suturing are challenging steps of the procedure that can lead to complications such as prolonged warm ischemia, bleeding, and urinary fistulas. LPN with a diode laser is an efficient technique due to its cutting and/or coagulation attributes. Surprisingly, key laser features such as wavelength and power remain undefined. Using a large porcine model, we evaluated the laser range of wavelength and power in a clamp-free LPN and compared it to the established gold-standard LPN technique (i.e., cold-cutting and suturing). By analyzing surgery duration, bleeding, presence of urine leak, tissue damage related to the resected renal fragment and the remaining organ, hemoglobin levels, and renal function, we show that an optimized experimental diode laser clamp-free LPN (wavelength, 980 nm; power, 15 W) had shorter surgery time with less bleeding, and better postoperative renal function recovery when compared to the well-established technique. Together, our data indicate that partial nephrectomy with a diode laser clamp-free LPN technique is an improved alternative to the gold-standard technique. Therefore, translational clinical trials towards human patient applications are readily feasible.

Comparing Rates of Change in Moderate to Advanced Glaucoma: Retinal Nerve Fiber Layer Versus Bruch Membrane Opening-Minimum Rim Width.

PURPOSE: To compare rates of change (RoC) of peripapillary retinal nerve fiber layer (RNFL) and Bruch membrane opening-based minimum rim width (BMO-MRW) thickness in moderate-to-advanced glaucoma. DESIGN: Prospective cohort study. METHODS: Longitudinal optical coherence tomography (OCT) optic nerve head volume scans of 113 eyes of 113 glaucoma patients with moderate-to-advanced or central damage were exported. This study estimated and compared global and sectoral RoC with linear mixed effects models and simple linear regression (SLR) of RNFL and BMO-MRW thickness. Permutation analyses were used to test significance of RoC in the SLR model. It also compared longitudinal signal-to-noise ratios (LSNR) defined as RoC divided by residual standard deviation (SD) between the two groups. RESULTS: Mean (SD) follow-up and median (IQR) OCT scan sessions were 5.2 (1.3) years and 10 (8-11), respectively. Baseline average (SD) visual field mean deviation was -9.2 (5.8) dB. Based on SLR, a higher proportion of significant negative RNFL RoC was observed compared to BMO-MRW in the inferotemporal (35% vs 20%; P = .015) and inferonasal (42% vs 17%; P < .001) sectors. Permutation analyses also demonstrated a higher proportion of worsening RNFL RoC than BMO-MRW in the inferotemporal (P = .026) and inferonasal (P < .001) sectors along with overall lower positive RoC. Longitudinal signal-to-noise ratios for RNFL were significantly more negative than for BMO-MRW globally, and in the inferotemporal, inferonasal, and superonasal sectors (P ≤ .01). CONCLUSIONS: Longitudinal RNFL OCT measurements are more likely to detect structural change and demonstrate better LSNR compared with BMO-MRW in eyes with central or moderate-to-advanced glaucoma damage at baseline.

Racial, gender, and psychosocial disparities in viral suppression trends among people receiving coordinated HIV care in Los Angeles County.

OBJECTIVE: To longitudinally evaluate differences in HIV viral suppression (<200 copies/ml) by intersections of race/ethnicity, gender, and psychosocial issues in people with HIV in the Los Angeles County Medical Care Coordination Program. DESIGN: We analyzed 74 649 viral load measurements over 10 184 people with HIV enrolled in the Medical Care Coordination Program between January 1, 2013 and March 1, 2020.Methods: We fit Bayesian logistic hierarchical random effects models to test interactions between gender, race/ethnicity, and a psychosocial acuity score on viral suppression over time from 1 year prior to program enrollment to 24 months after enrollment. RESULTS: The probability of viral suppression declined prior to enrollment, then increased and stabilized by 6 months after enrollment. Black/African American patients with low and moderate psychosocial acuity scores did not achieve the same increase in percentage of viral suppression as those in other racial/ethnic groups. Transgender women with high psychosocial acuity scores took longer (about 1 year) to achieve the same percentage of viral suppression as clients of other gender identities. CONCLUSIONS: Some racial/ethnic and gender disparities in viral suppression persisted after enrollment in the Los Angeles County Medical Care Coordination Program while accounting for psychosocial acuity score, which may be explained by factors not assessed in the program.

Association of Blood Pressure With Rates of Macular Ganglion Cell Complex Thinning in Patients With Glaucoma.

Importance: There are scarce data on the association of blood pressure measures with subsequent macular structural rates of change in patients with glaucoma. Objective: To investigate the association of baseline blood pressure measures with rates of change of the macular ganglion cell complex in patients with central or moderate to advanced glaucoma damage at baseline. Design, Setting, and Participants: This prospective cohort study, conducted from August 2021 to August 2022, used data from patients in the Advanced Glaucoma Progression Study at the University of California, Los Angeles. Participants were between 39 and 80 years of age and had more than 4 macular imaging tests and 2 or more years of follow-up. Exposures: A diagnosis of glaucoma with either central damage or a visual field mean deviation worse than -6 dB. Main Outcomes and Measures: The main outcome was the association of blood pressure measures with ganglion cell complex rates of change. Macular ganglion cell complex thickness rates of change were estimated with a bayesian hierarchical model. This model included relevant demographic and clinical factors. Blood pressure measures, intraocular pressure, and their interactions were added to the model to assess the association of baseline blood pressure measures with global ganglion cell complex rates of change. Results: The cohort included 105 eyes from 105 participants. The mean (SD) age, 10-2 visual field mean deviation, and follow-up time were 66.9 (8.5) years, -8.3 (5.3) dB, and 3.6 (0.4) years, respectively, and 67 patients (63.8%) were female. The racial and ethnic makeup of the cohort was 15 African American (14.3%), 23 Asian (21.9%), 12 Hispanic (11.4%), and 55 White (52.4%) individuals based on patient self-report. In multivariable analyses, female sex, history of taking blood pressure medications, higher intraocular pressure, thicker central corneal thickness, shorter axial length, higher contrast sensitivity at 12 cycles per degree, and higher baseline 10-2 visual field mean deviation were associated with faster ganglion cell complex thinning. Lower diastolic blood pressure was associated with faster rates of ganglion cell complex thinning at higher intraocular pressures. For intraocular pressures of 8 and of 16 mm Hg (10% and 90% quantiles, respectively), every 10 mm Hg-lower increment of diastolic blood pressure was associated with 0.011 µm/y slower and -0.130 µm/y faster rates of ganglion cell complex thinning, respectively. Conclusions and Relevance: In this cohort study, a combination of lower diastolic blood pressure and higher intraocular pressure at baseline was associated with faster rates of ganglion cell complex thinning. These findings support consideration of evaluating and addressing diastolic blood pressure as a therapeutic measure in patients with glaucoma if supported by appropriate clinical trials.

Comparison of Ganglion Cell Layer and Inner Plexiform Layer Rates of Change in Suspected and Established Glaucoma.

PURPOSE: We compared ganglion cell layer (GCL) and inner plexiform layer (IPL) rates of change (RoC) in patients with glaucoma suspect (GS) and established glaucoma (EG) to test the hypothesis that IPL thickness changes would occur earlier than GCL changes in eyes with early damage. DESIGN: Prospective, cohort study. METHODS: A total of 64 GS eyes (46 patients) and 112 EG eyes (112 patients) with ≥2 years of follow-up and ≥3 macular optical coherence tomography scans were included. GCL and IPL superpixel thickness measurements were exported. A Bayesian hierarchical model with random intercepts/slopes and random residual variances was fitted to estimate RoC in individual superpixels. Normalized RoC and proportions of superpixels with significantly negative and positive GCL and IPL RoC were compared within the groups. RESULTS: The average (SD) follow-up time and number of scans were 3.5 (0.7) years and 4.2 (1.0), respectively, in the GS group and 3.6 (0.4) years and 7.3 (1.1) in the EG group. Mean (SD) normalized RoC was faster for GCL than IPL (-0.69 [0.05] vs -0.33 [0.04]) in the GS group, whereas it was faster for IPL (-0.47 [0.03] vs -0.28 [0.02]) in EG eyes. GCL RoC were significantly negative in 24 of 36 superpixels compared with 8 of 36 for IPL (P < .001) in GS eyes. In the EG group, 23 of 36 superpixels had significant negative IPL RoC compared with 13 of 36 superpixels for GCL (P = .006). CONCLUSIONS: GCL thickness is more likely to demonstrate change over time compared with IPL in glaucoma suspects. There is no evidence of preferential IPL thinning in eyes with suspected early glaucoma damage.

Utilizing Soccer for Delivery of HIV and Substance Use Prevention for Young South African Men: 6-Month Outcomes of a Cluster Randomized Controlled Trial.

Young men in South Africa face the intersecting epidemics of HIV, substance use and endemic poverty. We tested the effectiveness of a behavioral intervention using soccer training to reduce the cluster of risks associated with HIV and substance use. This cluster randomized controlled trial was conducted with men aged 18-29 years old in 27 neighborhoods in the townships of Cape Town, South Africa. Neighborhoods were randomized to receive for 6 months either: (1) Soccer League (SL; n = 18 neighborhoods, n = 778 men) who attended soccer three times weekly (72 sessions; 94% uptake, 45.5% weekly attendance rate), combined with an HIV/substance use, cognitive-behavioral intervention; or (2) a Control Condition (CC; n = 9; 415 men) who received educational materials and referrals at 3 month intervals. The primary outcome was the number of significant changes in a cluster of outcomes including HIV-related risks, substance abuse, employment/income, mental health, violence, and community engagement. There was only one significant difference on the rapid diagnostic tests for mandrax at 6 months, an insufficient number of changes to indicate a successful intervention. A group-based behavioral intervention was ineffective in addressing multiple risk behaviors among at-risk young men, similar to the findings of several recent soccer-related interventions. Early adulthood may be too late to alter well-established patterns of risk behaviors.Clinical Trial Registration This trial was prospectively registered on 24 November 2014 with ClinicalTrials.gov NCT02358226.

Multivariate Longitudinal Modeling of Macular Ganglion Cell Complex: Spatiotemporal Correlations and Patterns of Longitudinal Change.

Purpose: To investigate spatiotemporal correlations among ganglion cell complex (GCC) superpixel thickness measurements and explore underlying patterns of longitudinal change across the macular region. Design: Longitudinal cohort study. Subjects: One hundred eleven eyes from 111 subjects from the Advanced Glaucoma Progression Study with ≥ 4 visits and ≥ 2 years of follow-up. Methods: We further developed our proposed Bayesian hierarchical model for studying longitudinal GCC thickness changes across macular superpixels in a cohort of glaucoma patients. Global priors were introduced for macular superpixel parameters to combine data across superpixels and better estimate population slopes and intercepts. Main Outcome Measures: Bayesian residual analysis to inspect cross-superpixel correlations for subject random effects and residuals. Principal component analysis (PCA) to explore underlying patterns of longitudinal macular change. Results: Average (standard deviation [SD]) follow-up and baseline 10-2 visual field mean deviation were 3.6 (0.4) years and -8.9 (5.9) dB, respectively. Superpixel-level random effects and residuals had the greatest correlations with nearest neighbors; correlations were higher in the superior than in the inferior region and strongest among random intercepts, followed by random slopes, residuals, and residual SDs. PCA of random intercepts showed a first large principal component (PC) across superpixels that approximated a global intercept, a second PC that contrasted the superior and inferior macula, and a third PC, contrasting inner and nasal superpixels with temporal and peripheral superpixels. PCs for slopes, residual SDs, and residuals were remarkably similar to those of random intercepts. Conclusions: Introduction of cross-superpixel random intercepts and slopes is expected to improve estimation of population and subject parameters. Further model enhancement may be possible by including cross-superpixel random effects and correlations to address spatiotemporal relationships in longitudinal data sets.

Performance of the American Heart Association/American College of Cardiology/Heart Rhythm Society versus European Society of Cardiology guideline criteria for hospital admission of patients with syncope.

BACKGROUND: Current American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) and European Society of Cardiology (ESC) guidelines recommend different strategies to avoid low-yield admissions in patients with syncope. OBJECTIVE: The purpose of this study was to directly compare the safety and efficacy of applying admission criteria of both guidelines to patients presenting with syncope to the emergency department in 2 multicenter studies. METHODS: The international BASEL IX (BAsel Syncope EvaLuation) study (median age 71 years) and the U.S. SRS (Improving Syncope Risk Stratification in Older Adults) study (median age 72 years) were investigated. Primary endpoints were sensitivity/specificity for the adjudicated diagnosis of cardiac syncope (BASEL IX only) and 30-day major adverse cardiovascular events (30d-MACE). RESULTS: Among 2560 patients in the BASEL IX and 2085 in SRS studies, ACC/AHA/HRS and ESC criteria recommended admission for a comparable number of patients in BASEL IX (27% vs 28%), but ACC/AHA/HRS criteria less often in SRS (19% vs 32%; P <.01). Recommendations were discordant in ∼25% of patients. In BASEL IX, sensitivity for cardiac syncope and 30d-MACE among patients without admission criteria was comparable for ACC/AHA/HRS and ESC criteria (64% vs 65%, P = .86; and 67% vs 71%, P = .15, respectively). In SRS, sensitivity for 30d-MACE was lower with ACC/AHA/HRS (54%) vs ESC criteria (88%; P <.001). Similarly, specificity for cardiac syncope and 30d-MACE in BASEL IX was comparable for both guidelines, but in SRS the ACC/AHA/HRS guidelines showed a higher specificity for 30d-MACE than the ESC guidelines. CONCLUSION: ACC/AHA/HRS and ESC guidelines showed disagreement regarding admission for 1 in 4 patients and had only modest sensitivity, all indicating possible opportunities for improvements.

Association of early migration with child growth, cognition and behaviour in South Africa.

OBJECTIVE: The main objective of the study was to examine the association of migration with child growth, cognition and behaviour in South Africa. METHODS: Secondary analysis assessing effects of migration on child outcomes among a population cohort of women and children (n = 1238) recruited in Cape Town, South African townships and repeatedly assessed from birth to age eight. Logistic regression models analysed sociodemographic predictors of migration and longitudinal models assessed the association of child migration, with or without their mother, on child growth, cognition and behavioural outcomes. RESULTS: By 8 years post-birth, 41% of children born in the townships in Cape Town had migrated to the rural Eastern Cape. Staying in Cape Town, or not migrating, was associated with having an older mother. Children who migrated with their mothers were shorter and weighed less than those who did not migrate. Children who migrated had larger vocabularies and those who migrated with their mothers had fewer behavioural problems than children who stayed in Cape Town. CONCLUSION: Migration in South Africa between peri-urban Cape Town and rural Eastern Cape areas during a child's early years is common and is associated with both positive and negative child outcomes.

Angiosarcoma of the Uterus: A Systematic Review.

Primary uterine angiosarcoma is an extremely rare neoplasm. Due to its rarity, knowledge regarding this malignancy is limited to a few scattered case reports. To better understand the prognostic factors and optimal management of these neoplasms, we have performed a systematic analysis of the disease. A systematic literature search of this entity yielded 25 reported cases of this entity. In addition, we searched the National Cancer Institute Surveillance, Epidemiology, and End Results database to find 4 additional cases and added a case diagnosed in our institution. We analyzed the patients' demographic characteristics and the different treatment protocols utilized to treat this malignancy. Patients were primarily treated by surgery with or without adjuvant chemotherapy and radiotherapy. Survival analysis was performed to examine the role of various factors in the outcome for the patients. There was no correlation with age of diagnosis, or treatment modality used, however, better outcomes were seen in patients presenting with smaller sized tumors. Our study is the first attempt to systematically study this rare malignancy in hopes of leading to a more standardized, evidence-based, and improved treatment protocol.

Ganglion Cell Complex: The Optimal Measure for Detection of Structural Progression in the Macula.

PURPOSE: To test the hypothesis that macular ganglion cell complex (GCC) thickness from optical coherence tomography (OCT) provides a stronger change signal regardless of glaucoma severity compared with other macular measures. DESIGN: Prospective cohort study. METHODS: Eyes were from 112 patients with moderate to severe glaucoma at baseline from a tertiary glaucoma center. In each 3° × 3° macular superpixel, a hierarchical Bayesian random intercept and slope model with random residual variance was fit to longitudinal full macular thickness (FMT), outer retina layers, GCC, ganglion cell-inner plexiform layer (GCIPL), and ganglion cell layer (GCL) measurements. We estimated population- and individual-level slopes and intercepts. Proportions of substantial worsening and improving superpixel slopes were compared between layers and in superpixels with mild to moderate vs severe damage (total deviation of corresponding visual field location ≥ -8 vs < -8 dB). RESULTS: Mean (SD) follow-up time and baseline 10-2 visual field mean deviation were 3.6 (0.4) years and -8.9 (5.9) dB, respectively. FMT displayed the highest proportion of significant negative slopes (1932/3519 [54.9%]), followed by GCC (1286/3519 [36.5%]), outer retina layers (1254/3519 [35.6%]), (GCIPL) (1075/3518 [30.6%]), and (GCL) (698/3518 [19.8%]). Inner macular measures detected less worsening in the severe glaucoma group; yet GCC (223/985 [22.6%]) identified the highest proportion (GCIPL: 183/985 [18.6%]; GCL: 106/985 [10.8%]). Proportions of positive rates were small and comparable among all measures. CONCLUSIONS: GCC is the optimal macular measure for detection of structural change in eyes with moderate to severe glaucoma. Although a higher proportion of worsening superpixels was observed for FMT, a large portion of FMT change could be attributed to changes in outer retina layers.

Characteristics and Longitudinal Patterns of Erectile Dysfunction Drug Use Among Men Who Have Sex with Men in the U.S.

We investigated the longitudinal relationship between erectile dysfunction (ED) drug use with behavioral factors, including substance use and sexual activities in men who have sex with men from the Multicenter AIDS Cohort Study during 1998-2016 (n = 1636). We used a bivariate random-intercept model to evaluate ED drug use along with other behavioral factors to assess relationships between the two outcomes over time on a population level and also at the individual level. Average ED drug use among men who have sex with men (MSM) with HIV was positively correlated with average use of marijuana (r = .19), poppers (r = .27), and stimulants (r = .25). In this group, testosterone use (r = .32), multiple partners (r = .41), insertive anal intercourse with condom (r = .40), and insertive anal intercourse without condom (r = .43) all showed moderate correlations over time with average ED use (p < .001). Associations among MSM without HIV were similar, with average marijuana use (r = .19) and stimulant use (r = .22) being positively correlated with average ED drug use, and were also correlated with having multiple partners (r = .36), insertive anal intercourse with condom (r = .22), and insertive anal intercourse without condom (r = .18) over time. Positive within-individual associations between ED drug use and multiple partners and insertive anal intercourse with and without condom were observed regardless of HIV serostatus. This study showed that MSM who reported use of ED drugs were also, on average, more likely to use recreational drugs and engage in sexual activities, such as having multiple partners and insertive anal intercourse. Within individuals, average ED drug use was also positively correlated with sexual behaviors.

Association of Attention-Deficit/Hyperactivity Disorder Diagnoses With Pediatric Traumatic Brain Injury: A Meta-analysis.

Importance: There are conflicting accounts about the risk for attention-deficit/hyperactivity disorder (ADHD) following traumatic brain injury (TBI), possibly owing to variations between studies in acute TBI severity or when ADHD was assessed postinjury. Analysis of these variations may aid in identifying the risk. Objective: To conduct a meta-analysis of studies assessing ADHD diagnoses in children between ages 4 and 18 years following concussions and mild, moderate, or severe TBI. Data Sources: PubMed, PsycInfo, and Cochrane Central Register of Controlled Trials (1981-December 19, 2019) were searched including the terms traumatic brain injury, brain injuries, closed head injury, blunt head trauma, concussion, attention deficit disorders, ADHD, and ADD in combination with childhood, adolescence, pediatric, infant, child, young adult, or teen. Study Selection: Limited to English-language publications in peer-reviewed journals and patient age (4-18 years). Differences about inclusion were resolved through consensus of 3 authors. Data Extraction and Synthesis: MOOSE guidelines for abstracting and assessing data quality and validity were used. Odds ratios with 95% credible intervals (CrIs) are reported. Main Outcomes and Measures: The planned study outcome was rate of ADHD diagnoses. Results: A total of 12 374 unique patients with TBI of all severity levels and 43 491 unique controls were included in the 24 studies in this review (predominantly male: TBI, 61.8%; noninjury control, 60.9%; other injury control, 66.1%). The rate of pre-TBI ADHD diagnoses was 16.0% (95% CrI, 11.3%-21.7%), which was significantly greater than the 10.8% (95% CrI, 10.2%-11.4%) incidence of ADHD in the general pediatric population. Compared with children without injuries, the odds for ADHD were not significantly increased following concussion (≤1 year: OR, 0.32; 95% CrI, 0.05-1.13), mild TBI (≤1 year: OR, 0.56; 0.16-1.43; >1 year: OR, 1.07; 95% CrI, 0.35-2.48), and moderate TBI (≤1 year: OR, 1.28; 95% CrI, 0.35-3.34; >1 year: OR, 3.67; 95% CrI, 0.83-10.56). The odds for ADHD also were not significantly increased compared with children with other injuries following mild TBI (≤1 year: OR, 1.07; 95% CrI, 0.33-2.47; >1 year: OR, 1.18; 95% CrI, 0.32-3.12) and moderate TBI (≤1 year: OR, 2.34; 95% CrI, 0.78-5.47; >1 year: OR, 3.78; 95% CrI, 0.93-10.33). In contrast, the odds for ADHD following severe TBI were increased at both time points following TBI compared with children with other injuries (≤1 year: OR, 4.81; 95% CrI, 1.66-11.03; >1 year: OR, 6.70; 95% CrI, 2.02-16.82) and noninjured controls (≤1 year: OR, 2.62; 95% CrI, 0.76-6.64; >1 year: OR, 6.25; 95% CrI, 2.06-15.06), as well as those with mild TBI (≤1 year OR, 5.69; 1.46-15.67: >1 year OR, 6.65; 2.14-16.44). Of 5920 children with severe TBI, 35.5% (95% CrI, 20.6%-53.2%) had ADHD more than 1 year postinjury. Conclusions and Relevance: This study noted a significant association between TBI severity and ADHD diagnosis. In children with severe but not mild and moderate TBI, there was an association with an increase in risk for ADHD. The high rate of preinjury ADHD in children with TBI suggests that clinicians should carefully review functioning before a TBI before initiating treatment.