Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.

BACKGROUND: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. METHODS: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants. FINDINGS: Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group. INTERPRETATION: Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone. FUNDING: National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).

Firearm exposure and safety training of rural Iowa youth.

PURPOSE: Our objective was to investigate rural adolescents' use of firearms and whether they had received firearm training. METHODS: 2019 Iowa FFA Leadership Conference attendees were surveyed. Descriptive and comparative analyses were performed. RESULTS: One thousand three hundred and eighty-two FFA members aged 13-18 years participated. The vast majority (85%) had fired a rifle/shotgun; 58% reported firing them >20 times. Of those who had fired rifles/shotguns, 32% had done so before 9 years old; 79% before 13 years. Most had also fired a handgun (62%), with 30% having fired handguns >20 times. Of those who had fired handguns, 34% had done so before 11 years old. The average age for first firing rifles/shotguns was 10.1 (SD 2.9) years, and 11.9 (SD 2.8) years for handguns. Males, older teenagers, and those living on farms or in the country had significantly greater percentages that had fired a rifle/shotgun or a handgun. Greater proportions of males had used firearms >20 times and started firing them at younger ages. Over half (55%) reported having gone hunting. Of those, 24% first hunted before 9 years old; 48% before 11 years. Of those who had used a firearm, 61% had completed a firearm safety training course. For hunters, 80% had taken a course. CONCLUSIONS: Most participants had used firearms, and many did so at very young ages. Substantial numbers had not received formal training. The authors believe that families should be counseled when it is developmentally appropriate to introduce youth to firearms, and all should take firearm safety training before using them.

Right dorsal colitis in horses: A multicenter retrospective study of 35 cases.

BACKGROUND: Right dorsal colitis (RDC) is a nonsteroidal anti-inflammatory drug (NSAID) induced, protein losing enteropathy in horses associated with a high case fatality rate. OBJECTIVES: To describe signalment, NSAID usage, clinical presentations, clinical pathology, ultrasonographic findings, treatments, outcomes, and factors associated with survival in horses diagnosed with RDC. ANIMALS: Thirty-five horses from 7 Australian equine hospitals diagnosed with RDC. METHODS: Retrospective case series. Clinical records of cases were accepted if definitively or presumptively diagnosed by an internist with RDC and had ≥3 of: hypoproteinemia or hypoalbuminemia; diarrhea with negative test results for infectious diseases; colic for which other diseases were excluded or right dorsal colon thickening on ultrasound. Descriptive data analysis was performed for categorical and continuous variables. Univariate binominal logistic regressions were used to assess factors associated with survival. RESULTS: An overdose of NSAIDs occurred in 84% (21/25) cases where dose was known. Common clinical presentations included diarrhea (69%; 22/32), colic (61%; 20/33), and tachycardia (53%, 17/32). Common clinicopathological findings included hypoalbuminemia (83%; 26/31), hypocalcaemia (79%, 23/29), and hyperlactatemia (77%, 14/18). The right dorsal colon wall appeared subjectively thickened in 77% (24/31) cases using ultrasonography. Case fatality rate was 43% (15/35). Odds of survival significantly decreased with increasing heart rate (odds 0.84, 95% CI = 0.71-0.92, P = .01), packed cell volume (odds 0.91, 95% CI 0.82-0.98, P = .05) and abnormal appearance of mucous membranes (odds 0.05, 95% CI 0.005-0.28, P = .001) on hospital presentation. CONCLUSIONS AND CLINICAL IMPORTANCE: An overdose of NSAIDs is common in horses diagnosed with RDC. Serum albumin concentrations should be monitored in horses receiving a prolonged course of NSAIDs. Overall prognosis for RDC remains fair.

Impact of a switch to immediate release on the patient viewing of diagnostic test results in an online portal at an academic medical center.

Patient portals allow patients to access their personal health information. The 21st Century Cures Act in the United States sought to eliminate 'information blocking', requiring timely release upon request of electronic health information including diagnostic test results. Some health systems, including the one in the present study, chose a systematic switch to immediate release of all or nearly all diagnostic test results to patient portals as part of compliance with the Cures Act. Our primary objective was to study changes in the time to view test results by patients before and after implementation of Cures Act-related changes. This retrospective pre-post study included data from two 10-month time periods before and after implementation of Cures Act-related changes at an academic medical center. The study included all patients (adult and pediatric) with diagnostic testing (laboratory and imaging) performed in the outpatient, inpatient, or emergency department settings. Between February 9, 2020 and December 9, 2021, there was a total of 3 809 397 diagnostic tests from 204 605 unique patients (3 320 423 tests for adult patients; 488 974 for pediatric patients). Overall, 56.5% (115 627) of patients were female, 84.1% (172 048) white, and 96.5% (197 517) preferred English as primary language. The odds of viewing test results within 1 and 30 days after portal release increased monthly throughout both time periods before and after the Cures Act for all patients. The rate of increase was significantly higher after implementation only in the subgroup of tests belonging to adult patients with active MyChart accounts. Immediate release shifted a higher proportion of result/report release to weekends (3.2% pre-Cures vs 15.3% post-Cures), although patient viewing patterns by day of week and time of day were similar before and after immediate release changes. The switch to immediate release of diagnostic test results to the patient portal resulted in a higher fraction of results viewed within 1 day across outpatient, inpatient, and emergency department settings.

Improving the Quality of Written Discharge Instructions: A Multisite Collaborative Project.

BACKGROUND AND OBJECTIVES: Written discharge instructions help to bridge hospital-to-home transitions for patients and families, though substantial variation in discharge instruction quality exists. We aimed to assess the association between participation in an Institute for Healthcare Improvement Virtual Breakthrough Series collaborative and the quality of pediatric written discharge instructions across 8 US hospitals. METHODS: We conducted a multicenter, interrupted time-series analysis of a medical records-based quality measure focused on written discharge instruction content (0-100 scale, higher scores reflect better quality). Data were from random samples of pediatric patients (N = 5739) discharged from participating hospitals between September 2015 and August 2016, and between December 2017 and January 2020. These periods consisted of 3 phases: 1. a 14-month precollaborative phase; 2. a 12-month quality improvement collaborative phase when hospitals implemented multiple rapid cycle tests of change and shared improvement strategies; and 3. a 12-month postcollaborative phase. Interrupted time-series models assessed the association between study phase and measure performance over time, stratified by baseline hospital performance, adjusting for seasonality and hospital fixed effects. RESULTS: Among hospitals with high baseline performance, measure scores increased during the quality improvement collaborative phase beyond the expected precollaborative trend (+0.7 points/month; 95% confidence interval, 0.4-1.0; P < .001). Among hospitals with low baseline performance, measure scores increased but at a lower rate than the expected precollaborative trend (-0.5 points/month; 95% confidence interval, -0.8 to -0.2; P < .01). CONCLUSIONS: Participation in this 8-hospital Institute for Healthcare Improvement Virtual Breakthrough Series collaborative was associated with improvement in the quality of written discharge instructions beyond precollaborative trends only for hospitals with high baseline performance.

Striving towards access to essential medicines for human and animal health; a situational analysis of access to and use of antifungal medications for histoplasmosis in Ethiopia.

Antifungal medications are vital in combatting fungal diseases that affect over a billion people annually. Antifungal medications for people and equids are scarce in Ethiopia, where lack of resources to treat fungal infection, in particular histoplasmosis, is a major health challenge. Histoplasmosis is endemic within the equine population in Ethiopia, where it is estimated that one in five horses are infected. This disease has far reaching impacts on equine welfare and the socio-economic wellbeing of families. The burden of histoplasmosis in people in Ethiopia is currently unknown, representing a blind spot in public health surveillance. Previous research has identified contact with wildlife, and domestic animal species as possible transmission pathways for histoplasmosis however, questions remain about the role of equids in human histoplasmosis. Given the close proximity of people and animals in this setting, the high level of endemic disease among equids, and the common sources of anti-fungals in Ethiopia, our study adopted a One-Health approach to examine how systemic issues affect access to, and use of antifungals to treat histoplasmosis among people and equids. A qualitative study was conducted in 6 urban regions of Oromia, Ethiopia in December 2018, incorporating semi-structured face-to-face interviews and focus group discussions. Twenty-seven individual interviews were held with doctors (n = 7), pharmacists (n = 12), veterinarians (n = 5), para-veterinarians (n = 2) and an equid owner (n = 1). Eleven focus groups were conducted with equid owners (n = 42), 3 with veterinarians (n = 6), 1 with para-veterinarians (n = 2) and 1 with pharmacists (n = 2). Transcripts were analysed using thematic analysis, and dimensions of key themes conceptualised and compared. Two overarching themes namely, 'Structural', and 'Human factors', summarised the main limitations to access to antifungal medications. 'Structural factors' included the national reliance on importation of medicines or pharmaceutical ingredients, inaccurate demand forecasting due to poor recording of the shortfall within the pharmaceutical supply chain, deficiencies in diagnostic capacity for fungal disease and, a healthcare system funded with a significant component of out-of-pocket expenditure. 'Human factors' that influenced access to antifungals included the perception of the expense of antifungals compared with competing needs such as food and education, the social stigma attached to histoplasmosis that could lead to delays in treatment seeking and, readily available home remedies or alternative treatment options. Furthermore, it was reported that trust in healthcare and veterinary provisions was undermined by a perceived lack of efficacious medications. Access to antifungals remains an urgent public health and animal welfare concern in Ethiopia. Key points within the supply and distribution chain that affect access to anti-fungals are identified, and policies that facilitate anti-fungal procurement and distribution should be reviewed. This paper highlights the structural, socio-economic and cultural factors influencing the management of infection with histoplasmosis, including how it is understood, identified and treated. This study identifies areas where further cross-sectorial work is needed to address these factors to improve disease control and clinical outcomes observed in human and animal histoplasmosis within Ethiopia.

Collaborative to Increase Lethal Means Counseling for Caregivers of Youth With Suicidality.

BACKGROUND: The number of youth presenting to hospitals with suicidality and/or self-harm has increased substantially in recent years. We implemented a multihospital quality improvement (QI) collaborative from February 1, 2018 to January 31, 2019, aiming for an absolute increase in hospitals' mean rate of caregiver lethal means counseling (LMC) of 10 percentage points (from a baseline mean performance of 68% to 78%) by the end of the collaborative, and to evaluate the effectiveness of the collaborative on LMC, adjusting for secular trends. METHODS: This 8 hospital collaborative used a structured process of alternating learning sessions and action periods to improve LMC across hospitals. Electronic medical record documentation of caregiver LMC was evaluated during 3 phases: precollaborative, active QI collaborative, and postcollaborative. We used statistical process control to evaluate changes in LMC monthly. Following collaborative completion, interrupted time series analyses were used to evaluate changes in the level and trend and slope of LMC, adjusting for covariates. RESULTS: In the study, 4208 children and adolescents were included-1314 (31.2%) precollaborative, 1335 (31.7%) during the active QI collaborative, and 1559 (37.0%) postcollaborative. Statistical process control analyses demonstrated that LMC increased from a hospital-level mean of 68% precollaborative to 75% (February 2018) and then 86% (October 2018) during the collaborative. In interrupted time series analyses, there were no significant differences in LMC during and following the collaborative beyond those expected based on pre-collaborative trends. CONCLUSIONS: LMC increased during the collaborative, but the increase did not exceed expected trends. Interventions developed by participating hospitals may be beneficial to others aiming to improve LMC for caregivers of hospitalized youth with suicidality.

Novel variant Hendra virus genotype 2 infection in a horse in the greater Newcastle region, New South Wales, Australia.

In October 2021, the first contemporary detection of Hendra virus genotype 2 (HeV-g2) was made by veterinary priority disease investigation in a horse near Newcastle, New South Wales, Australia, as part of routine veterinary priority disease surveillance. This discovery followed an update of Hendra virus diagnostic assays following retrospective identification of this variant from 2015 via sentinel emerging infectious disease research, enabling timely detection of this case. The sole infected horse was euthanized in moribund condition. As the southernmost recognised HeV spill-over detection to date, it extends the southern limit of known cases by approximately 95 km. The event occurred near a large urban centre, characterised by equine populations of diverse type, husbandry, and purpose, with low HeV vaccination rates. Urgent multi-agency outbreak response involved risk assessment and monitoring of 11 exposed people and biosecurity management of at-risk animals. No human or additional animal cases were recognised. This One Health investigation highlights need for research on risk perception and strategic engagement to support owners confronted with the death of companion animals and potential human exposure to a high consequence virus. The location and timing of this spill-over event diverging from that established for prototype HeV (HeV-g1), highlight benefit in proactive One Health surveillance and research activities that improve understanding of dynamic transmission and spill-over risks of both HeV genotypic lineages and related but divergent emerging pathogens.

Thromboprophylaxis for children hospitalized with COVID-19 and MIS-C.

Background: Limited data exist about effective regimens for pharmacological thromboprophylaxis in children with acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C). Objectives: Study the outcomes of institutional thromboprophylaxis protocol for primary venous thromboembolism (VTE) prevention in children hospitalized with acute COVID-19/MIS-C. Methods: This single-center retrospective cohort study included consecutive children (aged less than 21 years) with COVID-19/MIS-C who received tailored intensity thromboprophylaxis, primarily with low-molecular-weight heparin, from April 2020 through October 2021. Thromboprophylaxis was given to those with moderate to severe disease based on the World Health Organization scale and exposure to two or more VTE risk factors. Therapeutic intensity was considered for severe illness. Clinical recovery along with D-dimer improvement determined thromboprophylaxis duration. Outcomes were incident VTEs, bleeding, and mortality. Results: Among 211 hospitalizations, 45 (21.3%) received thromboprophylaxis (COVID-19, 16; MIS-C, 29). Median age was 14.8 years (interquartile range [IQR], 8.9-16.1). Among 35 (77.8%) with severe illness, 27 (60.0%) required respiratory support, and 19 (42.2%) required an intensive care unit stay. Median hospitalization was 6 days (IQR, 5.0-10.5). Median thromboprophylaxis duration was 19 days (IQR, 6.0-31.0) with therapeutic intensity in 24 (53.3%) and prophylactic in 21 (46.7%). Outcomes were as follows: VTE, 1 (2.2%); death, 1 (2.2%, unrelated to bleeding/thrombosis); major/clinically relevant nonmajor bleeding, 0; and minor bleeding, 7 (15.5%). D-dimer was elevated in a majority at diagnosis (median, 2.3; IQR, 1.2-3.3 mg/ml fibrinogen-equivalent units) and was noninformative in assessing disease severity. D-dimer normalized at thromboprophylaxis discontinuation. Conclusions: Our experience of using clinically directed thromboprophylaxis with tailored intensity approach for children hospitalized with COVID-19 and MIS-C favors its inclusion in current standard of care. The role of D-dimer in directing thromboprophylaxis management deserves further evaluation.

Midwives' Perspectives about Vitamin K Prophylaxis Against Vitamin K Deficiency Bleeding of the Newborn.

BACKGROUND: The American Academy of Pediatrics recommends one intramuscular (IM) vitamin K injection at birth to prevent Vitamin K Deficiency Bleeding of the Newborn (VKDB). Among factors associated with IM vitamin K refusal, investigators have reported an increased frequency of IM vitamin K refusal among parents who select midwife-assisted deliveries. Reasons behind this association are unclear. METHODS: To understand the perspectives of midwives on IM vitamin K prophylaxis and approach to counseling parents using qualitative methodology, we conducted in-depth semi-structured interviews of midwives associated with 3 tertiary academic medical centers and surrounding communities in Connecticut, Iowa and Michigan. We used the grounded theory approach and the constant comparative method until saturation was reached. RESULTS: We interviewed 19 white female midwives from different training pathways. Participants who were Certified Nurse Midwives (CNMs) routinely recommended IM vitamin K prophylaxis and Certified Professional Midwives (CPMs) took a more neutral approach. The following 4 themes emerged: (1) Emphasis on an educational approach to counseling that supports parents' decision-making authority; (2) Low-intervention philosophy in the midwifery model of care attracts certain parents; (3) Need for relationship building between midwives and pediatricians and (4) Opportunities for the future. CONCLUSIONS: Midwives in our study perceived that the midwifery model of care, the focus on physiologic birth and prioritizing parents' decision-making autonomy appears to attract a sub-set of expectant parents with certain belief systems who question interventions such as IM vitamin K prophylaxis. There are opportunities for better collaboration between midwives and pediatricians.

Respiratory Distress: Three Patient Cases.

As mentioned in the January 2022 Pediatrics in Review Commentary, we now present three patients who have a common chief complaint followed by 5 questions for CME credit. All three cases have discussions on presentation, the differential diagnosis, and management that collectively serve as a Review article. The common theme here is that all three patients have difficulty breathing. We hope you will enjoy this review format.

NT-proBNP Levels Following IVIG Treatment of Multisystem Inflammatory Syndrome in Children.

BACKGROUND AND OBJECTIVES: N-terminal of probrain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) levels are often elevated in multisystem inflammatory syndrome in children (MIS-C) secondary to inflammation, myocardial dysfunction, or increased wall tension. Intravenous immunoglobulin (IVIG), accepted treatment of MIS-C, may transiently increase myocardial tension and contribute to an increase in NT-proBNP. We sought to study the association between pre- and post-IVIG levels of NT-proBNP and CRP and their clinical significance. METHODS: This single-center, retrospective, cohort study included consecutive children, aged ≤21 years, with diagnosis of MIS-C who received IVIG from April 2020 to October 2021. Data collection included clinical characteristics, laboratory tests, management, and outcomes. Study cohort consisted of patients who received IVIG and had NT-proBNP levels available pre- and post-IVIG. RESULTS: Among 35 patients with MIS-C, 30 met inclusion criteria. Twenty-four, 80%, showed elevation in NT-proBNP post-IVIG. The median NT-proBNP level pre-IVIG was 1921 pg/mL (interquartile range 548-3956), significantly lower than the post-IVIG median of 3756 pg/mL (interquartile range 1342-7634)) (P = .0010). The median pre-IVIG CRP level was significantly higher than the post-IVIG level (12 mg/dL vs 8 mg/dL, P = .0006). All but 1 recovered before discharge, and none had signs of worsening cardiac function post-IVIG. In those who recovered, NT-proBNP had normalized by discharge or 1-week follow-up. CONCLUSIONS: Our study shows that NT-proBNP levels often transiently increase immediately after IVIG therapy without signs of worsening myocardial function. These values should be interpreted in the context of CRP levels and clinical recovery.

Intravenous Immunoglobulin Nonresponse in Pediatric Patients Treated for Kawasaki Disease at a US Hospital.

OBJECTIVE: Kawasaki disease (KD) is an acute febrile childhood vasculitis with a predilection for the coronary arteries treated with IVIG. In the United States, scoring systems to identify children at high-risk of persistent fever after initial IVIG treatment are lacking. Our study attempts to identify variables associated with IVIG non-response. METHODS: Retrospective review of patients ages 0 to 18 admitted to an US academic children's hospital between August 1, 2010, and August 31, 2019, with the diagnosis of acute KD who received IVIG during hospitalization. RESULTS: A total of 64 patients were included, 73% male and 66% Caucasian with a mean age of 3.67 ± 3.35 years. Forty-eight patients (75%) received 1 dose of IVIG, and 16 (25%) received 2 doses of IVIG. The groups did not differ significantly at baseline. None had coronary artery aneurysms detected during hospitalization. Older age, female sex, Caucasian compared with African American race, leukocytosis, and hyponatremia were associated with a higher likelihood of IVIG non-response but none reached statistical significance. Patients who received ibuprofen (n = 26) were more likely to be IVIG non-responsive (p < 0.05). Aspirin dosing varied but was not predictive of IVIG non-response. CONCLUSIONS: In this study, risk factors to predict IVIG non-response in patients treated for KD were not identified. IVIG non-response was significantly more common in those receiving ibuprofen during the acute treatment phase. Larger studies are needed to validate the association of ibuprofen administration and IVIG non-response in patients with KD.

Concordance of Umbilical Cord Drug Screening in Multiple Births: Experience from a Reference Laboratory and Academic Medical Center.

The objective of this study was to review the results of umbilical cord drug screening in twins and triplets (multiples) to compare the detected drug(s) and/or drug metabolite(s). Results that did not agree between multiples were considered mismatched and investigated. A retrospective analysis was conducted using de-identified data from a national reference laboratory, and results were compared with data from an academic medical center, where detailed medical chart review was performed. Umbilical cord was analyzed for stimulants, sedatives, opioids and other drugs and metabolites. For the reference laboratory dataset, 23.3% (n = 844) of 3,616 umbilical cords from twins (n = 3,550) or triplets (n = 66) were positive for one or more drugs and/or metabolites. Of these, mismatched results were identified for 37 sets of twins (2.1%) and no sets of triplets. The most frequent mismatches were found in opioids (n = 24), with morphine (n = 5) being the most mismatched of any single analyte in the panel. Mismatches for the marijuana metabolite 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (9-COOH-THC) in the reference laboratory dataset occurred in 6 of 737 sets of twins (0.8%) and no triplets. For the academic medical center dataset, 21.9% (n = 57) of 260 umbilical cords tested positive for one or more drugs and/or metabolite(s). Of these, four mismatches (3.2%) were identified, including 9-COOH-THC (n = 2), phentermine (n = 1) and oxycodone (n = 1), all involving twins. All involved cases where the discrepant analyte was likely present in the negative twin but either slightly below the reporting cutoff threshold or failed analytical quality criteria. Mismatched results of umbilical cord drug screening occur in less than 4% of twins and most often occur when the analyte is slightly above the reporting cutoff in just one infant.

Distinguishing Features Common to Dual Fatal Herpes Simplex Virus Infections That Occur in Both a Pregnant Woman and Her Newborn Infant.

Deaths from herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are rare. A major exception is perinatally acquired HSV-1 or HSV-2 infection where the neonatal death rate is substantial. Fatal HSV infection also occurs occasionally in pregnant women. The goal of this review is to enumerate the reports that describe dual deaths of both a pregnant woman and her newborn from a herpesvirus infection. A total of 15 reports were found in the medical literature, of which five described pregnant women with HSV encephalitis and 10 described women with disseminated HSV infection. When the virus was typed, most cases of dual mother/newborn deaths were caused by HSV-2. Of interest, in two situations caused by HSV-1, the pregnant woman probably acquired her primary HSV-1 infection from one of her children and not by sexual transmission. Complete genomic sequencing was performed on one set of HSV-1 isolates collected from mother (blood) and newborn (blood and skin). The mother's strain and the newborn's skin strain were 98.9% identical. When the newborn's two strains were compared, they were 97.4% identical. Only one mother was tested by the HerpeSelect IgG antibody kit. During the nine days of her undiagnosed disseminated infection preceding her death, her serology was negative. In summary, although dual mother/newborn deaths from HSV infection are rare, they continue to be reported as recently as 2017.

Data on the relationship between lamotrigine and levetiracetam serum/plasma levels and toxicity: Experience at an academic medical center.

Lamotrigine and levetiracetam are second-generation anti-epileptic drugs used for the management of seizure disorders and some other medical conditions. In the related research article using retrospective data from an academic medical center, we analyzed 5046 samples originating from 1930 unique patients that had lamotrigine drug levels performed on serum/plasma and 4359 samples from 2451 patients that had levetiracetam drug levels performed. The data in this article provides the patient demographic, clinical location at time of drug level, and specific lamotrigine or levetiracetam serum/plasma drug level for all patients. For those instances with lamotrigine drug level greater than 14.0 mg/L or levetiracetam drug level of 80 mg/L or higher, additional data from chart review includes: indication for ordering the drug level, two main presenting signs or symptoms at time of drug level, timing of drug level (random, trough, peak, or unknown), changes in drug dosing following the drug level, concomitant therapy with valproic acid (lamotrigine only), and details related to drug overdose (if applicable). The analyzed data is provided in the supplementary tables included in this article. Volumes of test ordering by year is included in a figure. The dataset reported is related to the research article entitled "Correlation of Elevated Lamotrigine and Levetiracetam Serum/Plasma Levels with Toxicity: A Long-Term Retrospective Review at an Academic Medical Center" [K. E. Wood, K. L. Palmer, M.D. Krasowski, Correlation of elevated lamotrigine and levetiracetam serum/plasma levels with toxicity: A long-term retrospective review at an academic medical center, Toxicol. Rep. (2021) 8:1592-1598].

Rural youth's exposure to firearm violence and their attitudes regarding firearm safety measures.

BACKGROUND: In the wake of an epidemic in firearm-related deaths and injuries, youth have become leading voices of concern. This study's objective was to investigate rural youth's personal experiences with firearm-related violence, and their attitudes towards firearms and gun violence prevention strategies. METHODS: Attendees of the 2019 Iowa FFA Leadership Conference were surveyed about personal experiences with firearm-associated deaths and injuries, and their attitudes regarding firearm-related issues. Descriptive (frequencies), bivariate (chi square, Fisher's exact test) and multivariable logistic regression analyses were performed utilizing Stata 15.1 (StataCorp, College Station, Texas). RESULTS: Responses from 1382 FFA members 13-18 years of age were analyzed. About 5% had personally seen someone threatened with a firearm. Over one-third (36%) stated they knew someone who had been killed or injured by gunfire. Of these, over two-thirds knew of someone who had died or was injured unintentionally and 30% knew of someone killed or injured intentionally (e.g. suicide). Nearly all agreed or strongly agreed that the right to use firearms for hunting and shooting sports should be legal (94%), that a firearm safety course should be required to get a hunting license (89%), and that there should be a required background check before purchasing a firearm (89%). Over three-fifths (61%) agreed or strongly agreed that there should be laws requiring safe storage of firearms in homes. Although still high, lesser support for firearm safety policies was seen among males, older youth, participants living on farms or in the country, and youth who hunted, had firearms in their homes, and/or were in homes with unsafe firearm storage. CONCLUSIONS: The majority of youth in this study supported firearm safety measures including required training, background checks, and safe firearm storage in homes. These findings are consistent with the national youth-led call for firearm safety. Additionally, over one-third of respondents personally knew someone who was killed or injured by a firearm and 5% had seen someone or been personally threatened with firearm violence. Our study did not investigate the effects of firearm violence on participants' mental health and wellbeing, but future studies addressing this question seem highly justified.

Correlation of elevated lamotrigine and levetiracetam serum/plasma levels with toxicity: A long-term retrospective review at an academic medical center.

Lamotrigine and levetiracetam are widely used second-generation anti-epileptic drugs. Existing literature indicates that overdose of either drug is typically benign, but neurologic and cardiac toxicity can occur in some cases. In this retrospective study, we analyzed a large dataset of serum/plasma drug levels for lamotrigine and levetiracetam. The data covered 1,930 unique patients (5,046 levels) for lamotrigine and 2,451 patients (4,359 levels) for levetiracetam. We performed detailed chart review on all patients with one or more lamotrigine levels greater than 14.0 mg/L (293 unique patients) and all patients with one or more levetiracetam levels of 80 mg/L or higher (106 unique patients). No deaths directly attributable to lamotrigine or levetiracetam toxicity were reported. For cases with lamotrigine levels greater than 14.0 mg/L, the majority of patients were asymptomatic (55.3 %, n = 162). The most common presenting symptoms were ataxia (14.3 %, n = 42), seizures (14.0 %, n = 41), dizziness (11.9 %, n = 35), and altered mental status (11.6 %, n = 34). There were 12 overdoses (11 intentional) involving lamotrigine, all of which presented with either altered mental status (n = 8) or seizures (n = 4). The highest estimated dose reportedly ingested was 20 g. Cardiac toxicity was observed in two cases involving intentional overdose of lamotrigine. For patients with levetiracetam serum/plasma levels of 80 mg/L or higher, 48 patients (45.3 %) were asymptomatic. Symptomatic patients most commonly presented with seizures (31.1 %, n = 33) and altered mental status (15.1 %, n = 16), and none showed cardiac symptoms. There were only two cases involving intentional levetiracetam overdose, one of which presented with altered mental status after ingestion of 45 g and the other asymptomatic after ingestion of 6 g. Overall, our data is consistent with previous investigations that lamotrigine and levetiracetam toxicity most typically presents with neurologic symptoms and rarely cardiac arrhythmias. Approximately half of the patients with elevated lamotrigine or levetiracetam drug levels are asymptomatic.