Do Substances Used in Adolescence Predict the Persistence of Substance Use Disorders in Adulthood? A 15-Year Study of Youth After Detention.

PURPOSE: Investigate if the type of substance use disorder (SUD) in adolescence predicts SUDs in adulthood and examine sex and racial/ethnic differences in the persistence of SUDs. METHODS: Data are from the Northwestern Juvenile Project, a 15-year longitudinal study of 1829 youth randomly sampled from detention in Chicago, IL (1995-1998). Interviewers assessed SUDs using structured diagnostic interviews. RESULTS: Compared with females without an SUD at detention, females with cannabis alone, comorbid alcohol and cannabis, or SUDs other than alcohol and cannabis at detention had higher odds of having an SUD 5 years later (25%, 32%, and 36% vs. 15%, adjusted odds ratio [AOR] = 1.94, 95% confidence interval [CI] 1.11-3.40; AOR = 2.76, 95% CI 1.58-4.83; AOR = 3.46, 95% CI 1.56-7.66, respectively). Males and females with SUDs other than alcohol and cannabis at detention had greater odds of having an SUD 15 years later, compared with those without an SUD at detention (males: 36% vs. 14%, AOR = 2.98, 95% CI 1.14-7.83; females: 29% vs. 8%, AOR = 4.77, 95% CI 1.85-12.30). Among youth with an SUD at detention, males were more likely than females to have an SUD 15 years later (AOR = 1.84, 95% CI 1.03-3.29); non-Hispanic White and Hispanic males were more likely to persist than Black males (AOR = 3.32, 95% CI 1.50-7.35; AOR = 2.32, 95% CI 1.04-5.18, respectively). DISCUSSION: The type of SUD during adolescence matters. Youth with SUDs such as cocaine and opioids fared the worst. Healthcare providers must collaborate with correctional officials to increase service provision.

Inequities in Mental Health Services: A 16-Year Longitudinal Study of Youth in the Justice System.

OBJECTIVE: To examine: (1) if youth who have mental health disorders receive needed services after they leave detention-and as they age; and (2) inequities in service use, focusing on demographic characteristics and type of disorder. METHOD: We used data from the Northwestern Juvenile Project, a longitudinal study of 1,829 youth randomly sampled from detention in Chicago, Illinois in 1995. Participants were re-interviewed up to 13 times through 2015. Interviewers assessed disorders using structured diagnostic interviews and assessed service use using the Child and Adolescent Service Assessment and the Services Assessment for Children and Adolescents. RESULTS: Less than 20% of youth who needed services received them, up to median age 32 years. Female participants with any disorder had nearly twice the odds of receiving services compared with male participants (OR: 1.82; 95% CI: 1.41, 2.35). Compared with Black participants with any disorder, non-Hispanic White and Hispanic participants had 2.14 (95% CI: 1.57, 2.90) and 1.50 (95% CI: 1.04, 2.15) times the odds of receiving services. People with a disorder were more likely to receive services during childhood (< age 18) than during adulthood (OR: 2.29; 95% CI: 1.32, 3.95). Disorder mattered: participants with an internalizing disorder had 2.26 times and 2.43 times the odds of receiving services compared with those with a substance use disorder (respectively, 95% CI: 1.26, 4.04; 95% CI: 1.49, 3.97). CONCLUSION: Few youth who need services receive them as they age; inequities persist over time. We must implement evidence-based strategies to reduce barriers to services.

Substance Use Disorders and HIV/AIDS Risk Behaviors in Youth After Juvenile Detention: A 16-Year Longitudinal Study.

PURPOSE: To examine the association between substance use disorders (SUDs) and HIV/AIDS risk behaviors in detained youth as they age. METHODS: Prospective longitudinal study of a stratified random sample of 1,829 youth aged 10 to 18 years at baseline, sampled between November 1995 and June 1998 from the Cook County Juvenile Temporary Detention Center, Chicago, Illinois, and reinterviewed up to 13 times (to median age 32); 17,766 interviews overall. RESULTS: Youth had greater odds of engaging in every risk behavior when they had an SUD compared with when they did not have an SUD. For example, SUD was associated with condomless vaginal sex with a high-risk partner (OR: 2.28, 95% CI: 1.84-2.82). SUD was also associated with multiple partners, although the strength varied by time and sex (e.g., 16 years after baseline, OR: 3.58, 95% CI: 2.46-5.23 females; OR: 2.07, 95% CI: 1.48-2.88 males). Types of SUD-alcohol, comorbid alcohol and marijuana, drugs other than marijuana-were also associated with HIV/AIDS risk behaviors. DISCUSSION: SUDs and HIV/AIDS risk behaviors are linked among youth in the juvenile justice system and as they age. There is a longstanding need for targeted and integrated HIV and SUD services, but this need remains unmet.

Nonfatal Firearm Injury and Firearm Mortality in High-risk Youths and Young Adults 25 Years After Detention.

Importance: Youths, especially Black and Hispanic males, are disproportionately affected by firearm violence. Yet, no epidemiologic studies have examined the incidence rates of nonfatal firearm injury and firearm mortality in those who may be at greatest risk-youths who have been involved with the juvenile justice system. Objectives: To examine nonfatal firearm injury and firearm mortality in youths involved with the juvenile justice system and to compare incidence rates of firearm mortality with the general population. Design, Setting, and Participants: The Northwestern Juvenile Project is a 25-year prospective longitudinal cohort study of 1829 youths after juvenile detention in Chicago, Illinois. Youths were randomly sampled by strata (sex, race and ethnicity, age, and legal status [juvenile or adult court]) at intake from the Cook County Juvenile Temporary Detention Center. Participants were interviewed at baseline (November 1995 to June 1998) and reinterviewed as many as 13 times over 16 years, through February 2015. Official records on mortality were collected through December 2020. Data analysis was conducted from November 2018 to August 2022. Main Outcomes and Measures: Participants self-reported nonfatal firearm injuries. Firearm deaths were identified from county and state records and collateral reports. Data on firearm deaths in the general population were obtained from the Illinois Department of Public Health. Population counts were obtained from the US census. Results: The baseline sample of 1829 participants included 1172 (64.1%) males and 657 (35.9%) females; 1005 (54.9%) Black, 524 (28.6%) Hispanic, 296 (16.2%) non-Hispanic White, and 4 (0.2%) from other racial and ethnic groups (mean [SD] age, 14.9 [1.4] years). Sixteen years after detention, more than one-quarter of Black (156 of 575 [27.1%]) and Hispanic (103 of 387 [26.6%]) males had been injured or killed by firearms. Males had 13.6 (95% CI, 8.6-21.6) times the rate of firearm injury or mortality than females. Twenty-five years after the study began, 88 participants (4.8%) had been killed by a firearm. Compared with the Cook County general population, most demographic groups in the sample had significantly higher rates of firearm mortality (eg, rate ratio for males, 2.8; 95% CI, 2.0-3.9; for females: 6.5; 95% CI, 3.0-14.1; for Black males, 2.5; 95% CI, 1.7-3.7; for Hispanic males, 9.6; 95% CI, 6.2-15.0; for non-Hispanic White males, 23.0; 95% CI, 11.7-45.5). Conclusions and Relevance: This is the first study to examine the incidence of nonfatal firearm injury and firearm mortality in youths who have been involved with the juvenile justice system. Reducing firearm injury and mortality in high-risk youths and young adults requires a multidisciplinary approach involving legal professionals, health care professionals, educators, street outreach workers, and public health researchers.

Relationship Between Socioeconomic Status and the Outcome of Lumbar Epidural Steroid Injections for Lumbar Radiculopathy.

OBJECTIVE: The aim of the study was to investigate the relationship between socioeconomic status and pain reduction from epidural steroid injections for lumbar radiculopathy. METHODS: The retrospective cohort consisted of patients undergoing epidural steroid injection for lumbar radiculopathy ( n = 544). Numeric Pain Rating Scale was measured at baseline and 2 wks after epidural steroid injection. Socioeconomic status was estimated using median family income in patients' ZIP code. Linear and mixed models examined demographic and clinical differences in pain before and after injection and whether family income moderated the effect. RESULTS: Majority of patients were White (72.4%), female (56.4%), engaged in physical activity (68.2%), and underwent unilateral, transforaminal epidural steroid injection (86.0% and 92.1%, respectively). Non-White patients and those who did not engage in physical activity had higher baseline pain ( P < 0.05). Lower socioeconomic status was associated with higher baseline pain (ß = 0.06 per $10,000, P = 0.01). Patients with lower socioeconomic status experienced larger improvement in pain after epidural steroid injection: -1.56 units for patients in the 10th percentile of family income versus -0.81 for 90th percentile. Being a current smoker was associated with higher pain (ß = 0.76, P = 0.03) and engaging in structured physical activity with less pain (ß = -0.07 P < 0.01). CONCLUSIONS: Lower socioeconomic status was independently associated with higher pain alleviation after controlling for other potentially influential demographics. Modifiable lifestyle factors may be a target of potential intervention.

Quality Improvement Initiative for Aspirin Screening and Prescription Rates for Preeclampsia Prevention in an Outpatient Obstetric Clinic.

OBJECTIVE: Hypertensive disorders of pregnancy (HDP) impact 10% of pregnancies in the United States and cause adverse maternal and neonatal outcomes such as prematurity and low birth weight. Aspirin administration to at-risk individuals during pregnancy can reduce risk of HDP. STUDY DESIGN: Define-Measure-Assess-Improve-Control methodology was utilized to improve aspirin screening in an outpatient obstetric clinic. Retrospective cohort analysis compared outcome metrics pre- and postimplementation by using logistic regression models, adjusting for race and insurance. Key informant interviews and process mapping identified barriers to aspirin screening. A multidisciplinary team implemented low-cost strategies such as provider education, additional screening by ancillary staff, automated electronic reminders, and standardized patient counseling. RESULTS: Over 6 months, the screening rate improved from 62.5 to 92.0% (adjusted odds ratio [aOR] = 6.89, 95% confidence interval [CI]: 3.30-14.43). The prescription rate for patients correctly identified to be eligible for aspirin improved from 66.7 to 82.4% (aOR = 1.96, 95% CI: 0.88-4.35). CONCLUSION: Comprehensive, tailored quality improvement efforts can significantly increase aspirin screening and prescription, which may decrease maternal and neonatal morbidity due to HDP. KEY POINTS: · Initiative improved overall and correct screening rates.. · Initiative increased provider knowledge of eligibility.. · Low-cost interventions can have high impact over short time interval..

Natural history of 10-meter walk/run test performance in spinal muscular atrophy: A longitudinal analysis.

As trials and treatments for spinal muscular atrophy (SMA) rapidly evolve, understanding the natural history and potential utility of the 10-meter walk/run test (10MWRT) in ambulant individuals is critical. Study aims were to: 1) establish change over time and across age for 10MWRT time in an untreated natural history cohort of young, ambulatory participants with SMA and 2) identify relations between 10MWRT time and age, SMA type, SMN2 copy number and anthropometrics. Untreated individuals (n = 56) age 2 to 21 years who were enrolled in a long-term natural history study between 2005 and 2014 and met inclusion criteria were included. Linear mixed effects models were used to assess changes in 10MWRT time with age and associations with SMA type, SMN2 copy number, and body mass. SMA type 3b (versus 3a), SMN2 copy number 4 (versus 3) and lower body mass were associated with faster 10MWRT. 10MWRT performance improved between 3 and 8 years of age, was stable between 9 and 10, and gradually declined from 11 to 18. Findings provide the first longitudinal natural history report of 10MWRT time in young individuals with SMA and offer a critical foundation for interpreting childhood change in short distance walking speed with pharmacologic treatment.

A comprehensive survey of collaborative biostatistics units in academic health centers.

The organizational structures of collaborative biostatistics units in academic health centers (AHCs) in the United States and their important contributions to research are an evolving and active area of discussion and inquiry. Collaborative biostatistics units may serve as a centralized resource to investigators across various disciplines or as shared infrastructure for investigators within a discipline (e.g., cancer), or a combination of both. The characteristics of such units vary greatly, and there has been no comprehensive review of their organizational structures described in the literature to date. This manuscript summarizes the current infrastructure of such units using responses from 129 leaders. Most leaders were over 45 years old, held doctoral degrees, and were on a 12-month appointment. Over half were tenured or on a tenure track and held primary appointments in a school of medicine. Career advancement metrics most important included being funded as co-investigator on NIH grants and being either first or second author on peer-reviewed publications. Team composition was diverse in terms of expertise and training, and funding sources were typically hybrid. These results provide a benchmark for collaboration models and evaluation and may be used by institutional administrators as they build, evaluate, or restructure current collaborative quantitative support infrastructure.

Functional evaluation of human ion channel variants using automated electrophysiology.

Patch clamp recording enabled a revolution in cellular electrophysiology, and is useful for evaluating the functional consequences of ion channel gene mutations or variants associated with human disorders called channelopathies. However, due to massive growth of genetic testing in medical practice and research, the number of known ion channel variants has exploded into the thousands. Fortunately, automated methods for performing patch clamp recording have emerged as important tools to address the explosion in ion channel variants. In this chapter, we present our approach to harnessing automated electrophysiology to study a human voltage-gated potassium channel gene (KCNQ1), which harbors hundreds of mutations associated with genetic disorders of heart rhythm including the congenital long-QT syndrome. We include protocols for performing high efficiency electroporation of heterologous cells with recombinant KCNQ1 plasmid DNA and for automated planar patch recording including data analysis. These methods can be adapted for studying other voltage-gated ion channels.

Echocardiographic parameters associated with in-hospital adverse outcomes in patients with Takotsubo syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is an acute heart failure syndrome that leads to significant morbidity and mortality. We sought to evaluate the association of cardiac mechanics on presentation with in-hospital adverse outcomes in patients with apical TTS. METHODS: We retrospectively identified 468 patients with TTS based on ICD-9/10 codes between 2006 and 2017. The association of echocardiographic parameters with a composite outcome of heart failure and all-cause mortality during the index hospitalization was analyzed. RESULTS: One hundred and forty one patients with the apical subtype and adequate imaging were included. 113 (80.1%) were female, left ventricular ejection fraction (LVEF) was 41.7% ± 12.4%, and global longitudinal strain was -10.1% ± 3.2%. The composite outcome occurred in 58 patients (41%), with heart failure occurring in 55 patients and death occurring in nine patients. Global longitudinal strain, global circumferential strain, global radial strain, right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular free wall strain were significantly worse in patients who experienced the composite outcome in univariate analyses. However, only LVEF was independently associated with the composite outcome in multivariable-adjusted analysis. CONCLUSIONS: In patients with apical TTS, the strain has limited prognostic utility in the acute setting compared to LVEF, which was the only echocardiographic parameter associated with in-hospital heart failure and all-cause mortality.

Prevalence, Comorbidity, and Continuity of Psychiatric Disorders in a 15-Year Longitudinal Study of Youths Involved in the Juvenile Justice System.

Importance: Previous studies have found that one-half to three-quarters of youths detained in juvenile justice facilities have 1 or more psychiatric disorders. Little is known about the course of their disorders as they age. Objective: To examine the prevalence, comorbidity, and continuity of 13 psychiatric disorders among youths detained in a juvenile justice facility during the 15 years after detention up to a median age of 31 years, with a focus on sex and racial/ethnic differences. Design, Setting, and Participants: The Northwestern Juvenile Project is a longitudinal cohort study of health needs and outcomes of 1829 randomly selected youths in a temporary juvenile detention center in Cook County, Illinois. Youths aged 10 to 18 years were interviewed in detention from November 20, 1995, through June 14, 1998. Participants were reinterviewed up to 12 times during the 15-year study period through February 2015, for a total of 16 372 interviews. The sample was stratified by sex, race/ethnicity (Black, Hispanic, and non-Hispanic White), age (10-13 years or 14-18 years), and legal status (processed in juvenile or adult court). Data analysis was conducted from February 2014, when data preparation began, to March 2020. Exposures: Detention in a juvenile justice facility. Main Outcomes and Measures: Psychiatric disorders, assessed by the Diagnostic Interview Schedule for Children, version 2.3 at the baseline interviews. Follow-up interviews were conducted using the Diagnostic Interview Schedule for Children, version IV; the Diagnostic Interview Schedule, version IV; and the World Mental Health Composite International Diagnostic Interview (beginning at the 6-year follow-up interview). Results: The study included 1829 youths sampled at baseline (1172 males and 657 females; mean [SD] age, 14.9 [1.4] years). Although prevalence and comorbidity of psychiatric disorders decreased as the 1829 participants aged, 52.3% of males and 30.9% of females had at least 1 or more psychiatric disorders 15 years postdetention. Among participants with a disorder at baseline, 64.3% of males and 34.8% of females had a disorder 15 years later. Compared with females, males had 3.37 times the odds of persisting with a psychiatric disorder 15 years after baseline (95% CI, 1.79-6.35). Compared with Black participants and Hispanic participants, non-Hispanic White participants had 1.6 times the odds of behavioral disorders (odds ratio, 1.56; 95% CI, 1.27-1.91 and odds ratio, 1.59; 95% CI, 1.23-2.05, respectively) and greater than 1.3 times the odds of substance use disorders (odds ratio, 1.90; 95% CI, 1.55-2.33 and odds ratio, 1.39; 95% CI, 1.11-1.73, respectively) throughout the follow-up period. Behavioral disorders and substance use disorders were the most prevalent 15 years after detention. Conclusions and Relevance: This study's findings suggest that persistent psychiatric disorders may complicate the transition from adolescence to adulthood, which is already challenging for youths involved in the juvenile justice system, many of whom are from racial/ethnic minority groups and low-income backgrounds. The pediatric health community should advocate for early identification and treatment of disorders among youths in the justice system.

Association of Firearm Access, Use, and Victimization During Adolescence With Firearm Perpetration During Adulthood in a 16-Year Longitudinal Study of Youth Involved in the Juvenile Justice System.

Importance: Preventing firearm violence requires understanding its antecedents. Yet no comprehensive longitudinal study has examined how involvement with firearms during adolescence-use, access, and victimization (defined as threatened with a weapon or gunshot injury)-is associated with the perpetration of firearm violence in adulthood. Objective: To examine the association between firearm involvement during adolescence and subsequent firearm perpetration and ownership in adulthood among youth involved in the juvenile justice system. Design, Setting, and Participants: This cohort study analyzed interview responses of 1829 randomly selected participants as part of the Northwestern Juvenile Project, a longitudinal study of health needs and outcomes of youth sampled from a temporary juvenile detention center in a large US city. Youth aged 10 to 18 years were interviewed in detention from November 1995 through June 1998. Participants were reinterviewed up to 13 times over 16 years through February 2015, for a total of 17 776 interviews. The sample was stratified by sex, race/ethnicity, age, and legal status (juvenile or adult court). Data were analyzed from April 2017, when data preparation began, through November 2020. Exposures: Firearm involvement during adolescence: use (ie, threaten, shoot), access (ownership, ease of access, firearm in household, membership in gang that carries firearms), and victimization (gunshot injury, threatened with a weapon). Main Outcomes and Measures: Firearm involvement during adulthood: perpetration of firearm violence (ie, threatening with or using a firearm) and firearm ownership. Results: Among the 1829 participants, 1388 had a 16-year follow-up interview: 860 males, 528 females; 809 were African American, 203 were non-Hispanic White; 374 were Hispanic; and 2 were other race/ethnicity; median (interquartile range) age of 32 (30-32) years. Eighty-five percent of males and 63.2% of females were involved with firearms as adolescents. Compared with females, males had significantly higher odds of every type of involvement except having a firearm in the home. In adulthood, 41.3% of males and 10.5% of females perpetrated firearm violence. Adolescents who had been threatened with a weapon or injured by firearms had 3.1 (95% CI, 2.0-4.9) and 2.4 (95% CI, 1.2-4.9) times the odds of perpetrating violence during adulthood. Similar associations were found for firearm ownership. Conclusions and Relevance: Involvement with firearms during adolescence-including victimization-is a significant risk factor for firearm perpetration and ownership during adulthood.

Facilitating reproducible research through direct connection of data analysis with manuscript preparation: StatTag for connecting statistical software to Microsoft Word.

OBJECTIVES: To enhance reproducible research by creating a broadly accessible, free, open-source software tool for connecting Microsoft Word to statistical programs (R/R Markdown, Python, SAS, Stata) so that results may be automatically updated in a manuscript. MATERIALS AND METHODS: We developed StatTag for Windows as a Microsoft Word plug-in using C# and for macOS as a native application using Objective-C. Source code is available under the MIT license at https://github.com/stattag. RESULTS: StatTag links analysis file(s) (R/R Markdown, SAS, Stata, or Python) and a Word document, invokes the statistical program(s) to obtain results, and embeds selected output in the document. StatTag can accommodate multiple statistical programs with a single document and features an interface to view, edit, and rerun statistical code directly from Word. DISCUSSION AND CONCLUSION: StatTag may facilitate reproducibility within increasingly multidisciplinary research teams, improve research transparency through review and publication, and complement data-sharing initiatives.

Left Atrial Dilation and Risk of One-Year Readmission after Embolic Stroke of Undetermined Source.

BACKGROUND: Structural left atrial and ventricular abnormalities on the electrocardiogram (ECG) and transthoracic echocardiogram (TTE) at the time of ischemic stroke have been associated with morbidity and mortality. Yet, the prognostic impact of the same in embolic stroke of undetermined source (ESUS), a relevant subtype of ischemic stroke with a unique pathophysiology, has not been well studied to date. Our aim was to assess the predictive impact of left atrio-ventricular ECG and TTE abnormalities on one-year hospital readmission after ESUS from an ongoing single center prospective stroke registry in the U.S. METHODS: We identified 369 ESUS patients who had at least 1 year of complete follow-up between 2013 and 2018. We examined the association of abnormal left atrio-ventricular findings on ECG and TTE, as well as basic demographic and clinical characteristics, measured at index admission with time to 1-year hospital readmission using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards regression. RESULTS: Recurrent ischemic stroke and cardiovascular causes constituted 60% of all readmissions. Patients with left atrial dilation on TTE were more likely to readmitted within 1 year (HR 1.51; 95% CI, 1.04-2.21). Bundle branch block, pathologic Q-wave, and troponin elevation curves diverged, but were not significantly associated with readmission (log-rank p=0.34, p=0.08, p=0.42, respectively). CONCLUSIONS: Following ESUS, left atrial dilation on TTE was associated with 1-year overall hospital readmission, of which cardiovascular and cerebrovascular ischemic events, and heart failure were a notable proportion. Our data support ongoing studies of atrial cardiopathy in ESUS patients.

National Characteristics of Surgeons Performing Vasectomy: Increasing Specialization and a Persistent Gender Gap.

OBJECTIVE: To describe trends in the characteristics of urologic surgeons performing vasectomy over time. METHODS: We performed a retrospective, cross-sectional study examining surgeon characteristics for case logs from the American Board of Urology between 2004 and 2013. We used generalized estimating equations with a log link and negative binomial distribution to examine demographic differences (gender, rural location, and surgeon volume) in the number of vasectomies surgeons performed over time. RESULTS: Between 2004 and 2013, 5316 urologists had case logs collected within the 7-month certification window. The majority of these surgeons self-identified as general urologists (82.8%), and a small proportion identified as andrology and infertility specialists (1.7%). Across all years, the median number of vasectomies performed per certifying surgeon during the study period was 14 (interquartile range 6-26). The majority of vasectomies were performed by high-volume surgeons (≥ 26 vasectomies) ranging from 49.2% to 66.9% annually, whereas the proportion performed by low-volume (≤ 5 vasectomies) surgeons ranged from 3.3% to 6.6% annually. Male surgeons performed vasectomies 2.20 times more frequently than female surgeons (95% confidence interval 1.93-2.49; P <.0001) across the study period with no evidence to suggest this gap changed over time (gender-year interaction 1.01 [95% confidence interval: 0.97-1.06; p = .576]). CONCLUSION: While the majority of urologists performing vasectomy identify as general urologists, there appears to be a focus on vasectomy practice among a small number of high-volume surgeons. Furthermore, while the number of female surgeons performing vasectomies increased, a gender gap persists in the proportion of vasectomies performed by females.

The intrinsic cell type-specific excitatory connectivity of the developing mouse subiculum is sufficient to generate synchronous epileptiform activity.

KEY POINTS: The activity of local excitatory circuits of the subiculum has been suggested to be involved in the initiation of pathological activity in epileptic patients and experimental animal models of temporal lobe epilepsy. We have taken advantage of multimodal techniques to classify subicular cells in distinct subclasses and have investigated their morphofunctional properties and connectivity in vitro. Our results indicate that local subicular excitatory circuits are connected in a cell type-specific fashion and that synapses are preferentially established on basal vs. apical dendrites. We show that local excitatory circuits, isolated from extrasubicular inputs and pharmacologically disinhibited, are sufficient to initiate synchronous epileptiform activity in vitro. In conclusion, this work provides a high-resolution description of local excitatory circuits of the subiculum and highlights their mechanistic involvement in the generation of pathological activity. ABSTRACT: The subiculum has been suggested to be involved in the initiation of pathological discharges in human patients and animal models of temporal lobe epilepsy. Although converging evidence has revealed the existence of functional diversity within its principal neurons, much less attention has been devoted to its intrinsic connectivity and whether its local excitatory circuits are sufficient to generate epileptiform activity. Here, we have directly addressed these two key points in mouse subicular slices. First, using multivariate techniques, we have distinguished two groups of principal cells, which we have termed type 1 and type 2. These subgroups roughly overlap with what were classically indicated as regular and bursting cells, and showed differences in the extension and complexity of their apical dendrites. Functional connectivity was found both between similar (homotypic) and different (heterotypic) types of cells, with a marked asymmetry within heterotypic pairs. Unitary excitatory postsynaptic potentials (uEPSPs) revealed a high degree of variability both in amplitude, failure rate, rise time and half-width. Post hoc analysis of functionally connected pairs suggested that the observed uEPSPs were mediated by few contact sites, predominantly located on the basal dendrites. When surgically isolated from extrasubicular excitatory afferents, pharmacologically disinhibited subicular slices generated hyper-synchronous discharges. Thus, we conclude that local subicular excitatory circuits, connected according to cell type-specific rules, are sufficient to promote epileptiform activity. This conclusion fits well with a previous suggestion that local subicular events, purely mediated by excitatory connections, may underlie the pre-ictal discharges that govern interictal-ictal transitions.

The relationship between the number of available therapeutic options and government payer (medicare part D) spending on topical drug products.

The cost of prescription drugs has increased at rates far exceeding general inflation in recent history, with topical drugs increasing at a disproportionate rate compared to other routes of administration. We assessed the relationship between net changes in the number of therapeutic options, defined as any approved drug or therapeutic equivalent on the market, and prescription topical drug spending. Drugs were divided based on the category of use through pairing of Medicare Part D Prescriber Public Use and Food and Drug Administration (FDA) approved drug products databases. Across drug classes, we modeled the log of the ratio of total spending per unit in 2015 to total spending per unit in 2011 as a linear function of net number of topical therapeutic options over this time period. Primary outcomes include total Medicaid Part D spending on topical drugs and net change in the number of available therapeutic options within each category of use. Total spending on topical drugs increased by 61%, while the number of units dispensed increased by only 18% from 2011-2015. The greatest total spending increases were in categories with few new therapeutic options, such as topical corticosteroid and antifungal medications. Each net additional therapeutic option during 2011-2015 was associated with an reduction in how much relative spending per unit increased (95% CI 2.5%-14.4%, p = 0.013). Stimulating greater competition through increasing the net number of therapeutic options within each major topical category of use may place downward pressure on topical prescription drug spending under medicare Part D.

Antibiotic prophylaxis after urethroplasty may offer no benefit.

PURPOSE: Patients often receive antibiotic prophylaxis after urethroplasty to minimize the risk of urinary tract infection (UTI). The aim of this study was to determine the frequency of UTIs after urethroplasty and its impact on urethral and incisional healing. METHODS: Patients undergoing urethroplasty by a single surgeon from 2000 to 2012 were retrospectively reviewed. All patients received preoperative antibiotic prophylaxis and postoperative prophylaxis for 30 days or until catheter removal. We reviewed urine cultures obtained within 30 days after urethroplasty in symptomatic patients, and rates of stricture recurrence and wound complications. A positive culture was defined as > 1000 cfu/mL of an organism. RESULTS: 398 patients were included with a mean age of 43.5 years at time of surgery. We identified 102 positive urine cultures (25.6%) within 30 days of urethroplasty. 78 stricture recurrences (19.6%) occurred at an average of 3 years after surgery and 18 (4.5%) experienced a wound complication, with a 52 month mean follow-up. There were no significant differences in stricture recurrence (p = 0.36) or wound complications (p = 0.42) between patients who had a positive and negative urine culture. On multivariate analysis, positive urine cultures (HR 1.0, 95% CI 0.6-1.8, p = 0.88) were not associated with stricture recurrence, while lichen sclerosis (HR 3.2, 95% CI 1.1-9.2, p = 0.03) and previous urethroplasty (HR 2.3, 95% CI 1.1-4.6, p = 0.03) were. CONCLUSION: Bacterial colonization and UTIs despite antimicrobial prophylaxis are common in urethroplasty patients. This, however, does not appear to impair urethral healing or influence wound healing, suggesting that postoperative prophylaxis may in fact offer no benefit.