Use of alpha-adrenergic antagonists for lower urinary tract symptoms is not associated with worsening cognitive function.

INTRODUCTION: Alpha-adrenergic antagonists are widely prescribed for lower urinary tract symptoms (LUTS), however there has been a report that their use is associated with dementia. Our objective was to investigate if new users of alpha-adrenergic antagonists with varying levels of cognitive impairment had an increased risk of cognitive decline compared to non-users. METHODS: This was a retrospective cohort study, utilizing data from the National Alzheimer's Coordinating Center (NACC) data set. After applying relevant exclusion criteria, 916 people who were newly using alpha-antagonist medications were matched with a propensity score to 916 who were not using these medications. The primary outcome was a clinically relevant cognitive decline measured by the Clinical Dementia Rating (CDR) Dementia Staging Instrument or the mini mental state examination (MMSE). Secondary outcomes included scores from other cognitive assessment tools. RESULTS: The matched cohorts did not differ significantly in baseline characteristics. There were no statistically significant differences in baseline or follow-up cognitive scores between those exposed and nonexposed to alpha-adrenergic antagonists. Clinically significant cognitive decline (as defined by the CDR) occurred in 9.72% of the exposed group and 8.19% of the nonexposed group. There was no observed effect of alpha-adrenergic antagonists on cognitive decline, as measured with the CDR (odds ratio [OR] 1.34, p = 0.14) or the MMSE (OR 0.98, p = 0.92). Stratified analyses by cognitive status and apolipoprotein E genotype interaction assessment also demonstrated no significant associations. CONCLUSION: Alpha-adrenergic antagonists for LUTS do not appear to increase the risk of cognitive decline, offering reassurance to clinicians and patients.

ß-arrestin-biased Allosteric Modulator of Neurotensin Receptor 1 Reduces Ethanol Drinking and Responses to Ethanol Administration in Rodents.

Alcohol use disorders (AUDs) impose an enormous societal and financial burden, and world-wide, alcohol misuse is the 7th leading cause of premature death1. Despite this, there are currently only 3 FDA approved pharmacological treatments for the treatment of AUDs in the United States. The neurotensin (Nts) system has long been implicated in modulating behaviors associated with alcohol misuse. Recently, a novel compound, SBI-553, that biases the action of Nts receptor 1 (NTSR1) activation, has shown promise in preclinical models of psychostimulant misuse. Here we investigate the efficacy of this compound to alter ethanol-mediated behaviors in a comprehensive battery of experiments assessing ethanol consumption, behavioral responses to ethanol, sensitivity to ethanol, and ethanol metabolism. Additionally, we investigated behavior in avoidance and cognitive assays to monitor potential side effects of SBI-553. We find that SBI-553 reduces binge-like ethanol consumption in mice without altering avoidance behavior or novel object recognition. We also observe sex-dependent differences in physiological responses to sequential ethanol injections in mice. In rats, we show that SBI-553 attenuates sensitivity to the interoceptive effects of ethanol (using a Pavlovian drug discrimination task). Our data suggest that targeting NTSR1 signaling may be promising to attenuate alcohol misuse, and adds to a body of literature that suggests NTSR1 may be a common downstream target involved in the psychoactive effects of multiple reinforcing substances.

Ceftaroline for Central Nervous System Infections: Case Report of a Young Infant, and Scoping Review.

BACKGROUND: Managing health care acquired and device-associated intracranial infections in young children can be challenging given adverse antibiotic side effects and difficulties in achieving adequate central nervous system (CNS) antibiotic concentrations. Ceftaroline is a cephalosporin with a favorable safety profile and activity against methicillin-resistant Staphylococci and several Gram-negative organisms. Published data on the use of ceftaroline for CNS infections in children and adults are limited. METHODS: We describe a 2-month-old infant with ventriculo-subgaleal shunt-associated methicillin-resistant Staphylococcus epidermidis ventriculitis, which was successfully treated with ceftaroline, in addition to vancomycin and rifampin. We conducted a scoping review of English-language literature retrieved from PubMed, EMBASE and Web of Science that assessed the use of ceftaroline for CNS infections. RESULTS: We identified 22 articles for inclusion in our review, which described 92 unique patients, of whom 2 were <21 years old. Ceftaroline was commonly used in conjunction with other antibiotics to treat infections caused by Staphylococcus aureus, coagulase-negative Staphylococci and Streptococcus pneumoniae. Most case reports described clinical success with ceftaroline, though small case series and cohort studies yielded mixed efficacy assessments. Adverse effects attributed to ceftaroline were rare and included reversible myelosuppression, eosinophilia, hepatotoxicity and nephrotoxicity. Pharmacokinetic/pharmacodynamic studies suggested similar CNS penetration through inflamed meninges as other beta lactam antibiotics. CONCLUSIONS: We identified a growing body of published evidence supporting the use of ceftaroline in combination with other agents for the treatment of CNS infections. In absence of clinical trials, additional real-world data are needed to define the efficacy and safety of ceftaroline for children and adults with CNS infections.

Pediatric Tuberculosis Infection Care Facilitators and Barriers: A Qualitative Study.

BACKGROUND: A total of 700 000 US children and adolescents are estimated to have latent tuberculosis (TB) infection. Identifying facilitators and barriers to engaging in TB infection care is critical to preventing pediatric TB disease. We explored families' and clinicians' perspectives on pediatric TB infection diagnosis and care. METHODS: We conducted individual interviews and small group discussions with primary care and subspecialty clinicians, and individual interviews with caregivers of children diagnosed with TB infection. We sought to elicit facilitators and barriers to TB infection care engagement. We used applied thematic analysis to elucidate themes relating to care engagement, and organized themes using a cascade-grounded pediatric TB infection care engagement framework. RESULTS: We enrolled 19 caregivers and 24 clinicians. Key themes pertaining to facilitators and barriers to care emerged that variably affected engagement at different steps of care. Clinic and health system themes included the application of risk identification strategies and communication of risk; care ecosystem accessibility; programs to reduce cost-related barriers; and medication adherence support. Patient- and family-level themes included TB knowledge and beliefs; trust in clinicians, tests, and medical institutions; behavioral skills; child development and parenting; and family resources. CONCLUSIONS: Risk identification, education techniques, trust, family resources, TB stigma, and care ecosystem accessibility enabled or impeded care cascade engagement. Our results delineate an integrated pediatric TB infection care engagement framework that can inform multilevel interventions to improve retention in the pediatric TB infection care cascade.

Implementation and Perceived Effectiveness of Prospective Audit and Feedback and Preauthorization by US Pediatric Antimicrobial Stewardship Programs.

BACKGROUND: Antimicrobial stewardship programs (ASPs) promote optimal antimicrobial use to prevent resistance, improve outcomes, and reduce costs. We explored how pediatric ASPs enact prospective audit and feedback (PAF) and preauthorization and characterized programs' perceptions of how these choices affected attainment of stewardship goals. METHODS: We conducted focus groups with US pediatric ASP practitioners, organized by predominant strategy: PAF, preauthorization, or a hybrid. We asked open-ended questions about organization, staffing, and operation of these strategies, as well as rationales for and perceived advantages and disadvantages of these choices. We used applied thematic analysis to analyze transcripts, organizing coded text into themes and categories. We formulated a conceptual model for how the design and performance of PAF and preauthorization affect stewardship goals and stewards' work experiences. RESULTS: Eighteen physicians and 14 pharmacists from 24 hospitals participated in five focus groups. Stewards described myriad advantages and limitations of PAF and preauthorization that support or detract from stewardship goals. For example, PAF uncovered institutional trends in antibiotic use and fostered relationship building but was time-consuming. Preauthorization efficiently reduced broad-spectrum antimicrobial use, yet offered limited educational opportunities. How these strategies facilitated or impeded appropriate antimicrobial use in turn affected stewards' professional satisfaction, creating a feedback loop that could reinforced positive or negative outcomes. CONCLUSIONS: ASPs reported differing emphasis on and implementation of PAF and preauthorization. Each strategy entailed contrasting benefits and trade-offs for steward satisfaction and perceived efficacy, suggesting that a hybrid approach could enable ASPs to maximize strengths of each to mitigate drawbacks of the other.

Clinical factors associated with need for neurosurgical care in young children with imaging for macrocephaly: a case control study.

BACKGROUND: Macrocephaly is present in 2.3% of children with important neurosurgical conditions in the differential diagnosis. The objective of this study was to identify clinical associations with actionable imaging findings among children with head imaging for macrocephaly. METHODS: We conducted a case-control study of head imaging studies ordered for macrocephaly among children 24 months and younger in a multistate children's health system. Four neurosurgeons reviewed the images, determining cases to be a 'concern' if neurosurgical follow-up or intervention was indicated. Electronic health records were reviewed to collect patient-level data and to determine if surgery was performed. Controls were matched 3:1 to cases of 'concern' in a multivariate model using conditional logistic regression. RESULTS: In the study sample (n = 1293), 46 (4%) were concern cases, with 15 (1%) requiring surgery. Significant clinical factors associated with neurosurgical concern were bulging fontanel [aOR 7.47, (95% CI: 2.28-24.44), P < 0.001], prematurity [aOR 21.26, (95% CI: 3.76-120.21), P < 0.001], any delay [aOR 2.67, (95% CI: 1.13-6.27), P = 0.03], and head-weight Z-score difference (W_diff, defined as the difference between the Z-scores of head circumference and weight) [aOR 1.70, (95% CI: 1.22-2.37), P = 0.002]. CONCLUSIONS: Head imaging for macrocephaly identified few patients with findings of concern and fewer requiring surgery. A greater head-weight Z-score difference appears to represent a novel risk factor for neurosurgical follow-up or intervention.

Prospective evaluation of postoperative pain and opioid use after minor urologic surgery.

INTRODUCTION: Filling an opioid prescription after a minor urologic procedure increases patient risk of overdose and misuse. Strategies to reduce the number of opioids reaching the community are critical. This study evaluates opioid use after minor urologic procedures at a Canadian academic center and guides future prescribing recommendations. METHODS: We prospectively evaluated patients over 18 years old undergoing minor urologic procedures (penile, scrotal, urethral, etc.) from September 2020 to May 2022. Consenting participants were given a pain diary and postoperative pain questionnaire. Patients on chronic pain medications or those who had major surgery within six months were excluded. Response rate, pain on visual analog scale, pain control satisfaction, quantity of opioids prescribed, and consumption of opioid and non-opioid medication were collected and analyzed. RESULTS: Ninety-five patients met the inclusion criteria. The mean age was 61.7 years (range 20- 87) and 96% of patients identified as male. The response rate for the opioid diary and pain questionnaire was 57%. Forty-two patients (78%) were offered an opioid prescription following their surgery, but only 12 of those patients (22%) filled and consumed any opioids analgesics. Forty-two patients (78%) used no postoperative opioids, and the mean oral morphine equivalents (OME) consumed was 5.87 (standard deviation 16.7). There was a total of 259 OME unused from post-procedure prescriptions. The mean overall pain score for patients who did and did not fill opioid prescriptions were 3.18/10 and 1.79/10 (p<0.01), respectively, with mean overall pain management satisfaction score of 8.63/10 and 8.58/10 (p=0.94), respectively. CONCLUSIONS: Most patients undergoing minor urologic procedures do not require opioids to manage postoperative pain. Based on our data, we suggest that a prescription for 39 OME would adequately treat postoperative pain in 95% of patients undergoing minor urologic procedures. Education around pain management with non-narcotic modalities is imperative, and practice changes are warranted to address the opioid crisis within our specialty.

Achondroplasia Natural History Study (CLARITY): 60-year experience with hydrocephalus in achondroplasia from four skeletal dysplasia centers.

OBJECTIVE: The objective of this study was to describe the incidence and management of hydrocephalus in patients with achondroplasia over a 60-year period at four skeletal dysplasia centers. METHODS: The Achondroplasia Natural History Study (CLARITY) is a registry for clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the US from 1957 to 2017. Data were entered and stored in a REDCap database and included surgeries with indications and complications, medical diagnoses, and radiographic information. RESULTS: A total of 1374 patients with achondroplasia were included in this study. Of these, 123 (9%) patients underwent treatment of hydrocephalus at a median age of 14.4 months. There was considerable variation in the percentage of patients treated for hydrocephalus by center and decade of birth, ranging from 0% to 28%, although in the most recent decade, all centers treated less than 6% of their patients, with an average of 2.9% across all centers. Undergoing a cervicomedullary decompression (CMD) was a strong predictor for treatment of hydrocephalus (OR 5.8, 95% CI 3.9-8.4), although that association has disappeared in those born since 2010 (OR 1.1, 95% CI 0.2-5.7). In patients born since 1990, treatment of hydrocephalus with endoscopic third ventriculostomy (ETV) has become more common; it was used as the first line of treatment in 38% of patients in the most recent decade. Kaplan-Meier analysis suggests that a single ETV will treat hydrocephalus in roughly half of these patients. CONCLUSIONS: While many children with achondroplasia have features of hydrocephalus with enlarged intracranial CSF spaces and relative macrocephaly, treatment of hydrocephalus in achondroplasia patients has become relatively uncommon in the last 20 years. Historically, there was a significant association between symptomatic foramen magnum stenosis and treatment of hydrocephalus, although concurrent treatment of both has fallen out of favor with the recognition that CMD alone will treat hydrocephalus in some patients. Despite good experimental data demonstrating that hydrocephalus in achondroplasia is best understood as communicating in nature, ETV appears to be reasonably successful in certain patients and should be considered an option in selected patients.

Tracheal Narrowing and Its Impact on Anesthesia Care in Patients With Morquio A (Mucopolysaccharidosis Type IVA): An Observational Study.

BACKGROUND: Recently, tracheal narrowing has been recognized as a significant comorbid condition in patients with Morquio A, also known as mucopolysaccharidosis IVA. We studied a large cohort of patients with Morquio A to describe the extent of their tracheal narrowing and its relationship to airway management during anesthesia care. METHODS: This is an observational study, collecting data retrospectively, of a cohort of patients with Morquio A. Ninety-two patients with Morquio A syndrome were enrolled, among whom 44 patients had their airway evaluated by computed tomography angiography and had undergone an anesthetic within a year of the evaluation. Our hypothesis was that the tracheal narrowing as evaluated by computed tomography angiography increases with age in patients with Morquio A. The primary aim of the study was to examine the degree of tracheal narrowing in patients with Morquio A and describe the difficulties encountered during airway management, thus increasing awareness of both the tracheal narrowing and airway management difficulties in this patient population. In addition, the degree of tracheal narrowing was evaluated for its association with age or spirometry parameters using Spearman's rank correlation. Analysis of variance followed by the Bonferroni test was used to further examine the age-based differences in tracheal narrowing for the 3 age groups: 1 to 10 years, 11 to 20 years, and >21 years. RESULTS: Patient age showed a positive correlation with tracheal narrowing ( rs= 0.415; 95% confidence interval [95% CI], 0.138-0.691; P = .005) with older patients having greater narrowing of the trachea. Among spirometry parameters, FEF25%-75% showed an inverse correlation with tracheal narrowing as follows: FEF25%-75% versus tracheal narrowing: ( rs = -0.467; 95% CI, -0.877 to -0.057; P = .007). During anesthetic care, significant airway management difficulties were encountered, including cancelation of surgical procedures, awake intubation using flexible bronchoscope, and failed video laryngoscopy attempts. CONCLUSIONS: Clinically significant tracheal narrowing was present in patients with Morquio A, and the degree of such narrowing likely contributed to the difficulty with airway management during their anesthetic care. Tracheal narrowing worsens with age, but the progression appears to slow down after 20 years of age. In addition to tracheal narrowing, spirometry values of FEF25%-75% may be helpful in the overall evaluation of the airway in patients with Morquio A.

Area-Based Sociodemographic Factors Associated with Latent Tuberculosis Infection in a Low-Prevalence Setting.

Area-based sociodemographic markers, such as census tract foreign-born population, have been used to identify individuals and communities with a high risk for tuberculosis (TB) infection in the United States. However, these markers have not been evaluated as independent risk factors for TB infection in children. We evaluated associations between census tract poverty, crowding, foreign-born population, and the CDC's Social Vulnerability Index (CDC-SVI) ranking and TB infection in a population of children tested for TB infection in Boston, Massachusetts. After adjustment for age, crowding, and foreign-born percentage, increasing census tract poverty was associated with increased odds of TB infection (adjusted odds ratio [aOR] per 10% increase in population proportion living in poverty: 1.20 [95% CI, 1.04-1.40]; P = 0.01), although this association was attenuated after further adjustment for preferred language. In separate models, increasing CDC-SVI ranking was associated with increased odds of TB infection, including after adjustment for age and language preference (aOR per 10-point increase in CDC-SVI rank: 1.08 [95% CI, 1.02-1.15]; P = 0.01). Our findings suggest area-based sociodemographic factors may be valuable for characterizing TB infection risk and defining the social ecology of pediatric TB infection in low-burden settings.

Behavioral Predictors of Intention to Use a Text Messaging Reminder System Among People Living With HIV in Rural Uganda: Survey Study.

BACKGROUND: The expansion of cellular phones in sub-Saharan Africa spurred the development of SMS text message-based mobile health (mHealth) technology. Numerous SMS text message-based interventions have attempted to increase retention in care for people living with HIV in sub-Saharan Africa. Many of these interventions have failed to scale. Understanding theory-grounded factors leading to mHealth acceptability is needed to create scalable, contextually appropriate, and user-focused interventions to improve longitudinal HIV care for people living with HIV in sub-Saharan Africa. OBJECTIVE: In this study, we aimed to understand the relationship between constructs from the Unified Theory of Acceptance and Use of Technology (UTAUT), constructs identified in previous qualitative research, and behavioral intention to use a novel SMS text message-based mHealth intervention designed to improve care retention among people living with HIV initiating treatment in rural Uganda. METHODS: We conducted a survey of people living with HIV who were newly initiating HIV care in Mbarara, Uganda, and had agreed to use a novel SMS text message-based system that notified them of abnormal laboratory results and reminded them to return to the clinic. Survey items assessed behavioral intention to use the SMS text messaging system; constructs from UTAUT; and demographics, literacy, SMS text messaging experience, HIV status disclosure, and social support. We used factor analysis and logistic regression to estimate the relationships between UTAUT constructs and the behavioral intention to use the SMS text messaging system. RESULTS: A total of 249 participants completed the surveys, of whom 115 (46.2%) expressed high behavioral intention to use the SMS text messaging intervention. In a multivariable analysis, we found that performance expectancy (adjusted odds ratio [aOR] of the scaled factor score 5.69, 95% CI 2.64-12.25; P<.001), effort expectancy (aOR of the scaled factor score 4.87, 95% CI 1.75-13.51; P=.002), and social influence (measured as a 1-unit Likert score increase in the perception that clinical staff have been helpful in the use of the SMS text messaging program; aOR 3.03, 95% CI 1.21-7.54; P=.02) were significantly associated with high behavioral intention to use the SMS text messaging program. SMS text messaging experience (aOR/1-unit increase 1.48, 95% CI 1.11-1.96; P=.008) and age (aOR/1-year increase 1.07, 95% CI 1.03-1.13; P=.003) were also significantly associated with increased odds of high intention to use the system. CONCLUSIONS: Performance expectancy, effort expectancy, and social influence, as well as age and SMS experience, were drivers of high behavioral intention to use an SMS text messaging reminder system among people living with HIV initiating treatment in rural Uganda. These findings highlight salient factors associated with SMS intervention acceptability in this population and indicate attributes that are likely to be key to the successful development and scaling of novel mHealth interventions.

Racial and Ethnic Differences in Length of Stay for US Children Hospitalized for Acute Osteomyelitis.

OBJECTIVE: To examine the associations between race and ethnicity and length of stay (LOS) for US children with acute osteomyelitis. STUDY DESIGN: Using the Kids' Inpatient Database, we conducted a cross-sectional study of children <21 years old hospitalized in 2016 or 2019 with acute osteomyelitis. Using survey-weighted negative binomial regression, we modeled LOS by race and ethnicity, adjusting for clinical and hospital characteristics and socioeconomic status. Secondary outcomes included prolonged LOS, defined as LOS of >7 days (equivalent to LOS in the highest quartile). RESULTS: We identified 2388 children discharged with acute osteomyelitis. The median LOS was 5 days (IQR, 3-7). Compared with White children, children of Black race (adjusted incidence rate ratio [aIRR] 1.15; 95% CI, 1.05-1.27), Hispanic ethnicity (aIRR 1.11; 95% CI, 1.02-1.21), and other race and ethnicity (aIRR 1.12; 95% CI, 1.01-1.23) had a significantly longer LOS. The odds of Black children experiencing prolonged LOS was 46% higher compared with White children (aOR, 1.46; 95% CI, 1.01-2.11). CONCLUSIONS: Children of Black race, Hispanic ethnicity, and other race and ethnicity with acute osteomyelitis experienced longer LOS than White children. Elucidating the mechanisms underlying these race- and ethnicity-based differences, including social drivers such as access to care, structural racism, and bias in provision of inpatient care, may improve management and outcomes for children with acute osteomyelitis.

Interferon Gamma Release Assay Results and Testing Trends Among Patients Younger Than 2 Years Old at Two US Health Centers.

BACKGROUND: Interferon-gamma release assays (IGRAs) are approved for children ≥2 years old to aid in diagnosis of Mycobacterium tuberculosis (TB) infection and disease. Tuberculin skin tests (TSTs) continue to be the recommended method for diagnosis of TB infection in children <2 years, in part due to limited data and concern for high rates of uninterpretable results. METHODS: We performed a retrospective cohort study of IGRA use in patients <2 years old in 2 large Boston healthcare systems. The primary outcome was the proportion of valid versus invalid/indeterminate IGRA results. Secondary outcomes included concordance of IGRAs with paired TSTs and trends in IGRA usage over time. RESULTS: A total of 321 IGRA results were analyzed; 308 tests (96%) were valid and 13 (4%) were invalid/indeterminate. Thirty-seven IGRAs were obtained in immunocompromised patients; the proportion of invalid/indeterminate results was significantly higher among immunocompromised (27%) compared with immunocompetent (1%) patients ( P < 0.001). Paired IGRAs and TSTs had a concordance rate of 64%, with most discordant results in bacille Calmette-Guérin-vaccinated patients. The proportion of total TB tests that were IGRAs increased over the study period (Pearson correlation coefficient 0.85, P < 0.001). CONCLUSIONS: The high proportion of valid IGRA test results in patients <2 years of age in a low TB prevalence setting in combination with the known logistical and interpretation challenges associated with TSTs support the adoption of IGRAs for this age group in certain clinical scenarios. Interpretation of IGRAs, particularly in immunocompromised patients, should involve consideration of the broader clinical context.

5α-reductase inhibitors and the risk of bladder cancer in a large, population-based cohort.

PURPOSE: The ability of 5α-reductase inhibitors (5ARI) to reduce the risk of new onset bladder cancer (BC) has been studied with variable results. Our objective was to conduct a retrospective cohort population-based study to evaluate the association between 5ARI use, BC diagnosis, and BC mortality. PATIENTS AND METHODS: We used routinely collected health care data from Ontario, Canada. Men ≥66 years of age with a prescription for a 5ARI were matched to non-5ARI users. Matching was done using a propensity score of selected covariates to make 96 different covariates comparable. We measured 5 additional baseline variables which may have impacted the risk of future BC diagnosis: prior cystoscopy, urine cytology, urinalysis, gross hematuria episodes, and transurethral resection of a bladder lesion. Only the first period of continuous usage of 5ARIs was considered. The prespecified at-risk period for outcomes started 1 year after initiating therapy and ended at the last date of 5ARI exposure + 1 year. RESULTS: We identified 93,197 men who initiated 5ARI therapy (52% dutasteride, and 48% finasteride) between 2003 and 2013 and matched them 1:1 to men who did not start a 5ARI. The median at-risk period for the 5ARI group was 1.68 years (interquartile range 1.00, 4.27). With adjustment for the variables related to prior BC investigations there was no significant difference in BC diagnosis (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.82-1.32) during the period of 0 to <2 years of 5ARI use; however, after ≥2 years of 5ARI use, the risk of BC diagnosis was significantly lower among the 5ARI group (HR 0.82, 95% CI 0.79-0.94). In a similarly adjusted model, BC mortality was lower among 5ARI users, but no longer statistically significant (HR 0.82, 95% CI 0.65, 1.02). When stratified by type of 5ARI, finasteride significantly reduced the risk of BC diagnosis after ≥2 years of continuous use (HR 0.86, 95% CI 0.76, 0.96); however, dutasteride did not (HR 0.92, 95% CI 0.83, 1.03). CONCLUSIONS: In a large cohort of men, the use of a 5ARI was associated with a significantly decreased the risk of BC diagnosis after more than 2 years of continuous therapy.

Multicenter Analysis of Attrition from the Pediatric Tuberculosis Infection Care Cascade in Boston.

OBJECTIVE: To characterize losses from the pediatric tuberculosis (TB) infection care cascade to identify ways to improve TB infection care delivery. STUDY DESIGN: We conducted a retrospective cohort study of children (age <18 years) screened for TB within 2 Boston-area health systems between January 2017 and May 2019. Patients who received a tuberculin skin test (TST) and/or an interferon gamma release assay (IGRA) were included. RESULTS: We included 13 353 tests among 11 622 patients; 93.9% of the tests were completed. Of 199 patients with positive tests for whom TB infection evaluation was clinically appropriate, 59.3% completed treatment or were recommended to not start treatment. Age 12-17 years (vs < 5 years; aOR 1.59; 95% CI, 1.32-1.92), non-English/non-Spanish language preference (vs English; aOR, 1.34; 95% CI, 1.02-1.76), and receipt of an IGRA (vs TST, aOR, 30.82; 95% CI, 21.92-43.34) were associated with increased odds of testing completion. Odds of testing completion decreased as census tract social vulnerability index quartile increased (ie, social vulnerability worsened; most vulnerable quartile vs least vulnerable quartile, aOR, 0.77; 95% CI, 0.60-0.99). Odds of completing treatment after starting treatment were higher in females (vs males; aOR, 2.35; 95% CI, 1.14-4.85) and were lower in patients starting treatment in a primary care clinic (vs TB/infectious diseases clinic; aOR, 0.44; 95% CI, 0.27-0.71). CONCLUSIONS: Among children with a high proportion of negative TB infection tests, completion of testing was high, but completion of evaluation and treatment was moderate. Transitions toward IGRA testing will improve testing completion; interventions addressing social determinants of health are important to improve treatment completion.

A multicomponent ethanol response battery across a cumulative dose ethanol challenge reveals diminished adolescent rat ethanol responsivity relative to adults.

Adolescence is a conserved developmental period associated with low alcohol responsivity, which can contribute to heavy drinking and development of an alcohol use disorder (AUD) later in life. To investigate ethanol responsivity between adolescent and adult rats, we developed an ethanol response battery (ERB) to assess acute ethanol responses across cumulative doses of ethanol during the rising phase of the blood ethanol curve. We tested the hypothesis that adolescent male and female rats would exhibit lower ethanol responsivity to a cumulative ethanol challenge relative to adults. Male and female adolescent (postnatal day [P]40) and adult (P85) Wistar rats underwent ERB assessment following consecutive doses of ethanol (i.e., 1.0, 1.0, and 1.0 g/kg) to produce cumulative ethanol doses of 0.0, 1.0, 2.0, and 3.0 g/kg. The ERB consisted of (1) the 6-point behavioral intoxication rating scale, (2) body temperature assessment, (3) tail blood collection, (4) accelerating rotarod assessment, (5) tilting plane assessment, and (6) loss of righting reflex (LORR) assessment. Across cumulative ethanol doses, adolescent and adult rats evidenced progressive changes in ERB measures. On the ERB, adolescent rats of both sexes evidenced (1) lower intoxication rating, (2) blunted hypothermic responses, particularly in females, (3) longer latencies to fall from the accelerating rotarod, and (4) less tilting plane impairment relative to adults despite comparable BECs. All adult rats, regardless of sex, displayed a LORR at the 3.0 g/kg cumulative ethanol dose while among the adolescent rats, only one male rat and no females showed the LORR. These data reveal decreased adolescent ethanol responsivity across body temperature, intoxication, balance, and coordination responses to a cumulative ethanol challenge as assessed using the novel ERB relative to adults. The results of this study suggest that adolescent-specific low ethanol responsivity may contribute to adolescent binge drinking and increased risk for development of an AUD.

Increasing Use Of Interferon Gamma Release Assays Among Children ≥2 Years of Age in a Setting With Low Tuberculosis Prevalence.

US guidelines recommend interferon gamma release assays (IGRAs) for diagnosis of tuberculosis infection in children. In this retrospective cohort study, IGRA use in children 2-17 years of age increased substantially between 2015 and 2021. Testing in inpatient/subspecialty settings (vs. primary care), public (vs. private) insurance, lower age and non-English preferred language were associated with increased odds of receiving an IGRA.

Tangential cranial gunshot wound in an infant in historical context: illustrative case.

BACKGROUND: Military neurosurgeons have long known that tangential cranial gunshot wounds can be associated with intracranial complications out of proportion to the external appearance of the injury. This phenomenon seems not to have been described in infancy. OBSERVATIONS: An infant suffered a massive, acute subdural hemorrhage from a contralateral tangential gunshot wound that did not facture the skull. LESSONS: Similar to adults, infants are subject to catastrophic intracranial injury from gunshots that do not penetrate the skull. The nature of the injury in this case reflected distinctive aspects of the tissue characteristics and proportions of the infant head.

Testing and Scaling Interventions to Improve the Tuberculosis Infection Care Cascade.

Tuberculosis (TB) preventive therapy (TPT) is increasingly recognized as the key to eliminating tuberculosis globally and is particularly critical for children with TB infection or who are in close contact with individuals with infectious TB. But many barriers currently impede successful scale-up to provide TPT to those at high risk of TB disease. The cascade of care in TB infection (and the related contact management cascade) is a conceptual framework to evaluate and improve the care of persons who are potential candidates for TPT. This review summarizes recent literature on barriers and solutions in the TB infection care cascade, focusing on children in both high- and low-burden settings, and drawing from studies on children and adults. Identifying and closing gaps in the care cascade will require the implementation of tools that are new (e.g. computer-assisted radiography) and old (e.g. efficient contact tracing), and will be aided by innovative implementation study designs, quality improvement methods, and shared clinical practice with primary care providers.