Dose escalation randomised study of efmarodocokin alfa in healthy volunteers and patients with ulcerative colitis.

BACKGROUND: The interleukin-22 cytokine (IL-22) has demonstrated efficacy in preclinical colitis models with non-immunosuppressive mechanism of action. Efmarodocokin alfa (UTTR1147A) is a fusion protein agonist that links IL-22 to the crystallisable fragment (Fc) of human IgG4 for improved pharmacokinetic characteristics, but with a mutation to minimise Fc effector functions. METHODS: This randomised, phase 1b study evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of repeat intravenous dosing of efmarodocokin alfa in healthy volunteers (HVs; n=32) and patients with ulcerative colitis (n=24) at 30-90 µg/kg doses given once every 2 weeks or monthly (every 4 weeks) for 12 weeks (6:2 active:placebo per cohort). RESULTS: The most common adverse events (AEs) were on-target, reversible, dermatological effects (dry skin, erythema and pruritus). Dose-limiting non-serious dermatological AEs (severe dry skin, erythema, exfoliation and discomfort) were seen at 90 µg/kg once every 2 weeks (HVs, n=2; patients, n=1). Pharmacokinetics were generally dose-proportional across the dose levels, but patients demonstrated lower drug exposures relative to HVs at the same dose. IL-22 serum biomarkers and IL-22-responsive genes in colon biopsies were induced with active treatment, and microbiota composition changed consistent with a reversal in baseline dysbiosis. As a phase 1b study, efficacy endpoints were exploratory only. Clinical response was observed in 7/18 active-treated and 1/6 placebo-treated patients; clinical remission was observed in 5/18 active-treated and 0/6 placebo-treated patients. CONCLUSION: Efmarodocokin alfa had an adequate safety and pharmacokinetic profile in HVs and patients. Biomarker data confirmed IL-22R pathway activation in the colonic epithelium. Results support further investigation of this non-immunosuppressive potential inflammatory bowel disease therapeutic. TRIAL REGISTRATION NUMBER: NCT02749630.

Racial disparities in pedestrian-related injury hospitalizations in the United States.

BACKGROUND: Racial/ethnic disparity has been documented in a wide variety of health outcomes, and environmental components are contributors. For example, food deserts have been tied to obesity rates. Pedestrian injuries are strongly tied to environmental factors, yet no studies have examined racial disparity in pedestrian injury rates. We examine a nationally-representative sample of pedestrian-related hospitalizations in the United States to identify differences in incidence, severity, and cost by race/ethnicity. METHODS: Patients with ICD diagnosis E-codes for pedestrian injuries were drawn from the United States Nationwide Inpatient Sample (2009-2016). Rates were calculated using the United States Census. Descriptive statistics and generalized linear regression were used to examine characteristics (age, sex, severity of illness, mortality rates, hospital admissions, length of stay, total costs) associated with hospitalizations for pedestrian injuries. RESULTS: The annual average of pedestrian-related deaths exceeded 5000 per year and hospitalizations exceeded 47,000 admissions per year. The burden of injury from pedestrian-related hospitalizations was higher among Black, Hispanic, and Multiracial/Other groups in terms of admission rates, costs per capita, proportion of children injured, and length of stay compared to Whites and Asian or Pacific Islander race/ethnicities. Compared to Whites, hospital admission rates were 1.92 (95% CI: 1.89-1.94) and 1.20 (95% CI: 1.19-1.21) times higher for Multiracial/Other and Blacks, respectively. Costs per capita ($USD) were $6.30, $4.14, and $3.22 for Multiracial/Others, Blacks, and Hispanics, compared to $2.88 and $2.32 for Whites and Asian or Pacific Islanders. Proportion of lengths of stay exceeding one week were larger for Blacks (26.4%), Hispanics (22.6%), Asian or Pacific Islanders (23.1%), and Multiracial/Other (24.1%), compared to Whites (18.6%). Extreme and major loss of function proportions were also highest among Black (34.5%) and lowest among Whites (30.2%). CONCLUSIONS: Results from this study show racial disparities in pedestrian injury hospitalization rates and outcomes, particularly among Black, Hispanic, and Multiracial/Other race/ethnicity groups and support population and system-level approaches to prevention. Access to transportation is an indicator for health disparity, and these results indicate that access to safe transportation also shows inequity by race/ethnicity.

Solid phase synthesis and spectroscopic characterization of the active and inactive forms of bacteriophage S21 pinholin protein.

The mechanism for the lysis pathway of double-stranded DNA bacteriophages involves a small hole-forming class of membrane proteins, the holins. This study focuses on a poorly characterized class of holins, the pinholin, of which the S21 protein of phage ϕ21 is the prototype. Here we report the first in vitro synthesis of the wildtype form of the S21 pinholin, S2168, and negative-dominant mutant form, S21IRS, both prepared using solid phase peptide synthesis and studied using biophysical techniques. Both forms of the pinholin were labeled with a nitroxide spin label and successfully incorporated into both bicelles and multilamellar vesicles which are membrane mimetic systems. Circular dichroism revealed the two forms were both >80% alpha helical, in agreement with the predictions based on the literature. The molar ellipticity ratio [θ]222/[θ]208 for both forms of the pinholin was 1.4, suggesting a coiled-coil tertiary structure in the bilayer consistent with the proposed oligomerization step in models for the mechanism of hole formation. 31P solid-state NMR spectroscopic data on pinholin indicate a strong interaction of both forms of the pinholin with the membrane headgroups. The 31P NMR data has an axially symmetric line shape which is consistent with lamellar phase proteoliposomes lipid mimetics.

Vascular mortality in participants of a bipolar genomics study.

BACKGROUND: In prior work, we identified a relationship between symptom burden and vascular outcomes in bipolar disorder. OBJECTIVE: We sought to replicate these findings using a readily accessible measure of mood disorder chronicity and vascular mortality. METHODS: We conducted a mortality assessment using the National Death Index for 1716 participants with bipolar I disorder from the National Institute of Mental Health Genetics Initiative Bipolar Disorder Consortium. We assessed the relationship between the duration of the most severe depressive and manic episodes and time to vascular mortality (cardiovascular or cerebrovascular) using Cox proportional hazards models, adjusting for potentially confounding variables. RESULTS: Mortality was assessed a mean for 7 years following study intake, at which time 58 participants died, 18 of vascular causes. These participants had depression for much longer than their counterparts did (Wilcoxon rank sum Z = 2.30, p = 0.02) and the duration of the longest depressive episode in years was significantly associated with time to vascular mortality in models (hazard ratio = 1.16, 95% confidence interval: 1.02-1.33, p = 0.02), which controlled for age, gender, vascular disease equivalents, and vascular disease risk factors. The duration of longest mania was not related to vascular mortality. CONCLUSION: The duration of the most severe depression is independently predictive of vascular mortality, lending further support to the idea that mood disorders hasten vascular mortality in a dose-dependent fashion. Further study of the relevant mechanisms by which mood disorders may hasten vascular disease and of integrated treatments for mood and cardiovascular risk factors is warranted.

Accessory Extensor Pollicis Longus Tendon Incidentally Discovered During Dorsal Distal Radius Plating.

Anatomical variations of the extensor pollicis longus (EPL) tendon are rare. Variations are typically asymptomatic, yet knowledge of these variations poses significance in the setting of dorsal approaches to wrist surgery. We present a case of an accessory EPL tendon that was discovered intraoperatively in the fourth dorsal compartment during open repair of a distal radius fracture with a dorsal spanning plate. If not correctly identified, the accessory EPL could have been entrapped beneath the plate, resulting in limited thumb extension and potentially tendon rupture.

Cross-sectional and longitudinal assessments of function in prodromal-to-mild Alzheimer's disease: A comparison of the ADCS-ADL and A-IADL-Q scales.

Introduction: Prior observational work in a heterogeneous cohort of participants with mild cognitive impairment suggests the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q) may have greater sensitivity for functional decline than the more established Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. However, the relative utility of the A-IADL-Q versus the ADCS-ADL for clinical trials in early Alzheimer's disease (AD) remains uncertain. Methods: We compared baseline and longitudinal performance of the A-IADL-Q and ADCS-ADL in participants with biomarker-confirmed prodromal (pAD; n = 158) or mild (mAD; n = 283) AD enrolled in the 18-month Tauriel study of semorinemab (NCT03289143). Results: The A-IADL-Q exhibited numerically stronger discrimination between pAD and mAD participants at baseline per Cohen's d analyses and similar sensitivity to longitudinal decline across cohorts over 18 months relative to the ADCS-ADL. Discussion: The comparable performance of the ADCS-ADL and A-IADL-Q supports the utility of the A-IADL-Q in early AD clinical trials. Highlights: The Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q) may be more sensitive than the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL) for distinguishing prodromal and mild Alzheimer's disease (AD).A-IADL-Q and ADCS-ADL are similarly sensitive to decline in early AD over 18 months.Comparable performance of these indices supports A-IADL-Q use in future AD trials.Additional AD clinical trial data could extend findings across more diverse cohorts.

Oral Therapy for Aerococcus urinae Bacteremia and Thoracic Spondylodiscitis of Presumed Urinary Origin.

Background: Aerococcus urinae (A urinae), considered a rare pathogen, has been identified with increasing frequency in urine cultures. Only 8 cases of spondylodiscitis due to A urinae have been reported. Optimal treatment for invasive A urinae infection is undefined. However, the reported cases were treated successfully with diverse antibiotic regimen combinations, all including a ß-lactam and beginning with at least 2 weeks of IV antibiotics. Case Presentation: A 74-year-old man presented to the emergency department after 2 weeks of midthoracic back pain, lower extremity weakness, gait imbalance, fatigue, anorexia, rigors, and subjective fevers. The patient was presumed to have discitis secondary to a urinary tract infection with possible pyelonephritis and was given empiric vancomycin and ceftriaxone. Spinal magnetic resonance imaging with contrast supported spondylodiscitis. Preliminary results from the admission blood and urine cultures showed gram-positive cocci in clusters. Conclusions: A urinae urinary tract infection in the absence of obvious predisposing factors should prompt evaluation for urinary outflow obstruction. We suspect a review of a US Department of Veterans Affairs population might uncover a higher incidence of A urinae infection than previously suspected.

Trends in shaken baby syndrome diagnosis codes among young children hospitalized for abuse.

OBJECTIVE: To investigate national trends of SBS diagnosis codes and how trends varied among patient and hospital characteristics. METHODS: We examined possible SBS, confirmed SBS, and non-SBS abuse diagnosis codes among children age three and younger who were hospitalized for abuse between 1998 and 2014 using a secondary analysis of the National Inpatient Sample, the largest US all-payer inpatient care database (N = 66,854). A baseline category logit model was used based on a quasi-likelihood approach (QIC) with an independent working correlation structure. RESULTS: The rate (per 100,000 census population of children age 3 and younger) of confirmed and possible SBS diagnosis codes was 5.4 (± 0.3) between 1998 and 2014, whereas the rate of non-SBS abuse was 19.6 (± 1.0). The rate of confirmed SBS diagnosis codes increased from 3.8 (± 0.3) in 1998 to 5.1 (± 0.9) in 2005, and decreased to 1.3 (± 0.2) in 2014. Possible SBS diagnosis codes were 0.6 (± 0.2) in 1998, increasing to 2.4 (± 0.4) in 2014. Confirmed SBS diagnosis codes have declined since 2002, while possible SBS diagnosis codes have increased. All abuse types were more frequent among infants, males, children from low-income homes, and urban teaching hospitals. CONCLUSIONS: We investigated seventeen-year trends of SBS diagnosis codes among young children hospitalized for abuse. The discrepancy between trends in possible and confirmed SBS diagnosis codes suggests differences in norms for utilizing SBS diagnosis codes, which has implications for which hospital admissions are coded as AHT. Future research should investigate processes for using SBS diagnosis codes and whether all codes associated with abusive head injuries in young children are classified as AHT. Our findings also highlight the relativity defining and applying SBS diagnosis codes to children admitted to the hospital for shaking injuries. Medical professionals find utility in using SBS diagnosis codes, though may be more apt to apply codes related to possible SBS diagnosis codes in children presenting with abusive head injuries. Clarifying norms for SBS diagnosis codes and refining definitions for AHT diagnosis will ensure that young children presenting with, and coded for, abusive head injuries are included in overall counts of AHT based on secondary data of diagnosis codes. This baseline data, an essential component of child abuse surveillance, will enable ongoing efforts to track, prevent, and reduce child abuse.

Medical referral and license disposition for drivers in Iowa.

INTRODUCTION: Driver retirement and determination of fitness-to-drive are important aspects of reducing the risk of motor-vehicle collision for an older driver. A lack of information about the review process may lead to poor evaluation of drivers or an increased testing burden to referred drivers. METHODS: This paper evaluates the license review process for the state of Iowa. We evaluated data from January 2014 to January 2018 and described the source of referral, testing process, and ultimate license disposition. Cox proportional hazards for competing risk were used to determine the risk of having a change in restrictions on the license and the risk of license denial. RESULTS: 20,742 individuals were followed through the medical referral process. The most common source of referrals was licensing officials (39.7%). Drivers referred by licensing officials were less likely to be denied their license when compared to drivers from other sources (HR = 0.92 95%CI: 0.87-0.98); however, licensing official referrals were more likely to result in license restrictions compared to other sources (HR = 1.91, 95%CI: 1.82-2.00). Drivers referred by either law enforcement or a physician were more likely to ultimately have their license denied. CONCLUSIONS: Physician and law enforcement referred the drivers most likely to have their license denied. A smaller proportion of drivers were referred by physicians and law enforcement compared to licensing officials. Practical Applications: Licensing agencies should work with physicians and law enforcement to identify drivers who may need a review of their license. Comprehensive tracking of all medical referrals for a driver's license review is important for individual states to understand the burden of their driver referral process and for identifying referral sources with a high proportion of referrals with no licensing change for targeted outreach and education.

Trends, Diagnoses, and Hospitalization Costs of Child Abuse and Neglect in the United States of America.

We conducted a secondary analysis of the National Inpatient Sample (NIS) to examine child abuse and neglect hospitalization from 1998-2016. The NIS is the largest all-payer, inpatient care database in the United States and is maintained by the Health Care Utilization Project. Participants were youth 18 years and younger with discharged diagnoses of child abuse and neglect from hospitals. The rate of child abuse or neglect hospitalizations did not vary significantly over the study period (1998-2016), which on average was 6.9 per 100,000 children annually. Males (53.0%), infants (age < 1; 47.3%), and young children (age 1-3; 24.2%) comprised most of the child maltreatment cases. Physical abuse was the most frequent type of maltreatment leading to hospitalization. Government insurance was the most common payer source, accounting for 77.3% of all child maltreatment hospitalizations and costing 1.4 billion dollars from 2001-2016. Hospitalizations due to child abuse and neglect remain steady and are costly, averaging over $116 million per year. The burden on government sources suggests a high potential for return on investment in effective child abuse prevention strategies.

The Medical Referral Process and Motor-Vehicle Crash Risk for Drivers with Dementia.

Cognitive and physical impairment can occur with dementia and reduce driving ability. In the United States, individual states have procedures to refer and evaluate drivers who may no longer be fit to drive. The license review process is not well understood for drivers with dementia. This study uses comprehensive data from the Iowa Department of Transportation to compare the referral process for drivers with and without dementia from January 2014 through November 2019. The likelihood of failing an evaluation test was compared between drivers with and without dementia using logistic regression. The risk of motor-vehicle crash after referral for review of driving ability was compared using a Cox proportional hazard model. Analysis controlled for the age and sex of the referred driver. Drivers with dementia performed worse on all tests evaluated except the visual screening test. After the referral process, the risk of crash was similar between those with and without dementia. Drivers with dementia were denied their license more frequently than referred drivers without dementia. However, drivers with dementia who successfully kept their license as a result of the license review process were not at an increased risk of crash compared to other referred drivers.

Active S2168 and inactive S21IRS pinholin interact differently with the lipid bilayer: A 31P and 2H solid state NMR study.

Pinholins are a family of lytic membrane proteins responsible for the lysis of the cytosolic membrane in host cells of double stranded DNA bacteriophages. Protein-lipid interactions have been shown to influence membrane protein topology as well as its function. This work investigated the interactions of pinholin with the phospholipid bilayer while in active and inactive confirmations to elucidate the different interactions the two forms have with the bilayer. Pinholin incorporated into deuterated DMPC-d54 lipid bilayers, along with 31P and 2H solid state NMR (SS-NMR) spectroscopy were used to probe the protein-lipid interactions with the phosphorus head group at the surface of the bilayer while interactions with the 2H nuclei were used to study the hydrophobic core. A comparison of the 31P chemical shift anisotropy (CSA) values of the active S2168 pinholin and inactive S21IRS pinholin indicated stronger head group interactions for the pinholin in its active form when compared to that of the inactive form supporting the model of a partially externalized peripheral transmembrane domain (TMD) of the active S2168 instead of complete externalized TMD1 as suggested by Ahammad et al. JPC B 2019. The 2H quadrupolar splitting analysis showed a decrease in spectral width for both forms of the pinholin when compared to the empty bilayers at all temperatures. In this case the decrease in the spectral width of the inactive S21IRS form of the pinholin showed stronger interactions with the acyl chains of the bilayer. The presence of the inactive form's additional TMD within the membrane was supported by the loss of peak resolution observed in the 2H NMR spectra.

Conformational Differences Are Observed for the Active and Inactive Forms of Pinholin S21 Using DEER Spectroscopy.

Bacteriophages have evolved with an efficient host cell lysis mechanism to terminate the infection cycle and release the new progeny virions at the optimum time, allowing adaptation with the changing host and environment. Among the lytic proteins, holin controls the first and rate-limiting step of host cell lysis by permeabilizing the inner membrane at an allele-specific time known as "holin triggering". Pinholin S21 is a prototype holin of phage Φ21 which makes many nanoscale holes and destroys the proton motive force, which in turn activates the signal anchor release (SAR) endolysin system to degrade the peptidoglycan layer of the host cell and destruction of the outer membrane by the spanin complex. Like many others, phage Φ21 has two holin proteins: active pinholin and antipinholin. The antipinholin form differs only by three extra amino acids at the N-terminus; however, it has a different structural topology and conformation with respect to the membrane. Predefined combinations of active pinholin and antipinholin fine-tune the lysis timing through structural dynamics and conformational changes. Previously, the dynamics and topology of active pinholin and antipinholin were investigated (Ahammad et al. JPCB 2019, 2020) using continuous wave electron paramagnetic resonance (CW-EPR) spectroscopy. However, detailed structural studies and direct comparison of these two forms of pinholin S21 are absent in the literature. In this study, the structural topology and conformations of active pinholin (S2168) and inactive antipinholin (S2168IRS) in DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) proteoliposomes were investigated using the four-pulse double electron-electron resonance (DEER) EPR spectroscopic technique to measure distances between transmembrane domains 1 and 2 (TMD1 and TMD2). Five sets of interlabel distances were measured via DEER spectroscopy for both the active and inactive forms of pinholin S21. Structural models of the active pinholin and inactive antipinholin forms in DMPC proteoliposomes were obtained using the experimental DEER distances coupled with the simulated annealing software package Xplor-NIH. TMD2 of S2168 remains in the lipid bilayer, and TMD1 is partially externalized from the bilayer with some residues located on the surface. However, both TMDs remain incorporated in the lipid bilayer for the inactive S2168IRS form. This study demonstrates, for the first time, clear structural topology and conformational differences between the two forms of pinholin S21. This work will pave the way for further studies of other holin systems using the DEER spectroscopic technique and will give structural insight into these biological clocks in molecular detail.

Family Communication Patterns and Teen Driving Intervention Effectiveness.

Objectives: Teen drivers are at increased crash risk, largely due to lack of experience. Parents play a key role in influencing teen behaviors and attitudes around driving safety. Parent-involved interventions may improve teen driving safety but tend to be resource intensive and have limited scalability. In this study, we examined how family communication patterns (FCPs) impact teen risky driving and the effectiveness of a parent-focused teen driving intervention. Methods: Our data came from a large randomized controlled teen driving intervention trial. We randomized parent-teen dyads into one of 3 groups: parent communication intervention plus in-vehicle event recorder feedback; in-vehicle event recorder feedback only ; or control. The primary outcome variable was teen risky driving (self-reports and triggered events); the primary exposure variables were FCPs and intervention group. We used generalized linear models to calculate effect estimates. Results: Teens' baseline risky driving did not vary by family communication pattern. The impact of the parent-focused intervention was stronger in families with a laissez-faire FCP. The laissez-faire FCP focuses little on child conformity and downplays communication. Conclusions: These results provide a framework for targeting high-resource teen driving interventions (event recorder feedback and parent-communication training) to families with laissez-faire communication patterns to attain the greatest risk reductions.

A randomized trial to test the impact of parent communication on improving in-vehicle feedback systems.

This randomized controlled trial evaluated the impact of integrating Steering Teens Safe, a parent communication intervention, with feedback from an in-vehicle video recording system. In-vehicle video systems that trigger a recording when the vehicle exceeds a g-force threshold have been used to provide feedback to young drivers. Few of these programs have involved parental engagement. Parent-teen dyads were randomized to three groups and 150 dyads completed the study. All groups received an in-vehicle video system that recorded driving events. The control group received no feedback or intervention. In the first intervention group, teens received real-time feedback, and parent-teen dyads received summary feedback, based on information recorded by the in-vehicle system. The second intervention group received the same feedback, plus parents were taught strategies to improve communication with their teen about safe driving. The primary outcome variable was unsafe driving event rates per 1000 miles driven and the primary independent variable was group assignment. Generalized linear models were used to calculate effect estimates. Compared with the control group, the Event Recorder Feedback group had a rate ratio of 0.35 (95% CI = 0.24 - 0.50) and the combined intervention group (Event Recorder Feedback and parent communication) had a rate ratio of 0.21 (95% CI = 0.15 - 0.30). Furthermore, the combined intervention group had a significantly lower event rate than the Event Recorder Feedback only group (rate ratio = 0.60, 95% CI = 0.41 - 0.87). While in-vehicle feedback systems can help reduce unsafe driving events in early independent driving, teaching parents strategies for effective communication with their young driver may further improve impact.

The Impact of Legislation on Gas Can- and Mattress-Related Burn Injuries.

Burn prevention program success requires thorough evaluation of intervention outcomes. The impact of 2 engineering-specific burn prevention regulations, the Children's Gasoline Burn Prevention Act and the Standard for the Flammability of Mattress Sets, will be assessed. Records from 1997 to 2015 within the Consumer Product Safety Commission's (CPSC) National Electronic Injury Surveillance System (NEISS) were reviewed. After identifying gas can- and mattress-involved burn injuries, injury incidence was estimated by utilizing survey sampling weights associated with each record. Logistic regression, incorporating estimated injury incidence and adjusting for gender and age, was performed to test for change in injury risk following these regulations. Within NEISS, there were 493 burns involving gas cans, yielding an estimated 19,339 injuries (95% confidence interval [CI], 15,781-22,896) during the 19-year study period. The odds of a gas can burn injury after legislation decreased by 67% for children younger than 5 years (odds ratio [OR], 0.33; 95% CI, 0.16-0.66; P = 0.0018). There was no significant change in risk for persons 5 years and older (OR, 1.07; 95% CI, 0.80-1.41; P = 0.66). During the same time, there were 219 NEISS burns involving mattresses, yielding an estimated 6864 injuries (95% CI, 5071-8658). The odds of a mattress burn injury following legislation enactment decreased by 31% for all ages (OR, 0.69; 95% CI, 0.51-0.94; P = 0.02). Both regulations decreased the odds of injury in their target populations. This study demonstrates that passive interventions involving engineering standards remain a powerful tool for burn prevention and should be the focus of future efforts to improve burn care.

Cost of hospitalization for firearm injuries by firearm type, intent, and payer in the United States.

BACKGROUND: Firearm injuries disproportionately affect young, male, non-White populations, causing substantial individual and societal burden. Annual costs for hospitalized firearm injuries have not been widely described, as most previous cost studies have focused on lifetime costs. We examined a nationally-representative database of hospitalizations in the US to estimate per-hospital and overall hospital costs for firearm injuries by intent, type of weapon, and payer source. METHODS: We conducted a retrospective cohort study of all firearm injury hospitalizations in the National Inpatient Sample from 2003 through 2013. The National Inpatient Sample, maintained by the Healthcare Utilization Project, is a stratified and weighted national sample of more than 20% of all hospitals. All admissions for firearm injuries were identified through Ecodes, yielding a weighted total of 336,785 for the study period. Average annual per-patient and overall hospital costs were estimated using generalized linear modelling, controlling for patient and hospital variables. Costs by intent, firearm type, and payer sources were estimated. RESULTS: Annually from 2003 through 2013, 30,617 hospital admissions were for firearm injuries, for an annual rate of 10.1 admissions per 100,000 US population. More than 80% of hospitalizations were among individuals aged 15-44, and rates were nine times higher for males than females and nearly ten times higher for the Black than the White population. More than 60% of admissions were for assaults, and 70% of the injuries that had a known firearm type were from handguns. The average annual admission cost was $622 million. The highest per-admission costs were for injuries from assault weapons ($32,237 per admission) and for legal intervention ($33,462 per admission), but the highest total costs were for unspecific firearm type ($373 million) and assaults ($389 million). A quarter of firearm injury hospitalizations were among the uninsured, yielding average annual total costs of $155 million. CONCLUSION: Hospitals can project that government insurance will be the highest source for firearm injury reimbursement, and depending on healthcare access laws, that many of their firearm injury admissions will not be covered by insurance.

Risk factors for suicide in bipolar I disorder in two prospectively studied cohorts.

BACKGROUND: These analyses were undertaken to determine whether similar risk factors for suicide emerged across two prospectively studied cohorts of individuals with bipolar I disorder. METHODS: The NIMH Collaborative Study of Depression (CDS) recruited 288 patients with bipolar I disorder from 1978-1981 as they sought treatment. Subjects were followed semiannually and then annually for up to 30 years. The Bipolar Genomics studies identified individuals through clinical referrals and advertisement. Clinical follow-up did not occur but personal identifiers of 1748 were matched with National Death Index (NDI) records. Kaplan-Meier survival analyses tested ten potential risk factors. RESULTS: The CDS and Genomic follow-ups encompassed 12,667 and 4529 person-years, respectively. Suicides/100 person-years were 0.26 and 0.055. The demographic or clinical variables that predicted suicide differed considerably in the two cohorts. The odds ratio for suicide for those with any history of suicide attempt was 2.3 and 2.8, respectively, and was the third highest odds ratio of the tested risk factors in both studies. CONCLUSIONS: Differences in the sources of participants in studies of suicide risk may result in marked differences across studies in both rates of suicide and in risk factors. A history of suicide attempt is a relatively robust risk factor across samples.

Sexual Functioning in Adolescents With Major Depressive Disorder.

OBJECTIVE: To examine sexual functioning in adolescents with depression. METHODS: Between September 2010 and March 2014, 235 participants who were between 15 and 20 years old and were unmedicated or within 1 month of beginning antidepressant treatment completed the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Changes in Sexual Functioning Questionnaire (CSFQ). They were also assessed to establish the presence of a DSM-IV-TR major depressive episode (MDE). The Student t test and χ² test were used to compare continuous and categorical variables, respectively, across participants with versus without MDE. Multivariable linear regression analysis examined the association between depression and sexual functioning. RESULTS: After the investigators controlled for age, female sex, antidepressant use, and the presence of generalized anxiety disorder, the presence of MDE was associated with a lower score on the CSFQ overall (P < .0007) and on its desire (P < .09), arousal (P < .001), and orgasm (P < .007) subscales. Antidepressants were not associated with sexual functioning either in the sample overall or in those with MDE. Beck Depression Inventory items related to affective symptoms (P < .03), rather than those tapping into neurovegetative or cognitive functioning, accounted for the association between depression and lower sexual functioning. Furthermore, with higher BDI scores, males exhibited a steeper decline than females in both the CSFQ total score and the desire subscale (sex × BDI score interaction effect: P < .03). Anxiety was not significantly associated with sexual functioning. CONCLUSIONS: Major depressive disorder in older adolescents is associated with lower sexual functioning, particularly in males. This appears most related to affective symptoms. The potential impact of such impairment on future sexual functioning deserves further examination. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02147184.

Toxoplasmosis Titers and past Suicide Attempts Among Older Adolescents Initiating SSRI Treatment.

Latent infection with toxoplasmosis is a prevalent condition that has been linked in animal studies to high-risk behaviors, and in humans, to suicide and suicide attempts. This analysis investigated a relationship between suicide attempt history and toxoplasmosis titers in a group of older adolescents who had recently begun treatment with an SSRI. Of 108 participants, 17 (15.7 %) had a lifetime history of at least one suicide attempt. All were given structured and unstructured diagnostic interviews and provided blood samples. Two individuals (11.9%) with a past suicide attempt, and two (2.1%) without this history, had toxoplasmosis titers ≥ 10 IU/ml (p = 0.166). Those with a past suicide attempt had mean toxoplasmosis titers that were significantly different (p = 0.018) from those of patients who lacked this history. An ROC analysis suggested a lower optimal threshold for distinguishing patients with and without suicide attempts (3.6 IU/ml) than that customarily used to identify seropositivity. Toxoplasmosis titers may quantify a proneness to suicidal behavior in younger individuals being treated with antidepressants.