Examination of the Accuracy of Existing Overdose Surveillance Systems.

Importance: Health departments have used a variety of methods for overdose surveillance, and the Centers for Disease Control and Prevention (CDC) is implementing a standardized case definition to improve overdose surveillance nationally. The comparative accuracy of the CDC opioid overdose case definition vs existing state opioid overdose surveillance systems is unknown. Objective: To evaluate the accuracy of the CDC opioid overdose case definition and existing Rhode Island Department of Health (RIDOH) state opioid overdose surveillance system. Design, Setting, and Participants: This cross-sectional study of ED opioid overdose visits was conducted at 2 EDs in Providence, Rhode Island, at the state's largest health system from January to May 2021. Electronic health records (EHRs) were reviewed for opioid overdoses identified by the CDC case definition and opioid overdoses reported to the RIDOH state surveillance system. Included patients were those at study EDs whose visit met the CDC case definition, was reported to the state surveillance system, or both. True overdose cases were confirmed by EHR review using a standard case definition; 61 of 460 EHRs (13.3%) were double reviewed to estimate classification accuracy. Data were analyzed from January through May 2021. Main Outcome and Measure: Accurate identification of an opioid overdose was assessed by estimating the positive predictive value of the CDC case definition and state surveillance system using results from the EHR review. Results: Among 460 ED visits that met the CDC opioid overdose case definition, were reported to the RIDOH opioid overdose surveillance system, or both (mean [SD] age, 39.7 [13.5] years; 313 males [68.0%]; 61 Black [13.3%], 308 White [67.0%], and 91 other race [19.8%]; and 97 Hispanic or Latinx [21.1%] among each patient visit), 359 visits (78.0%) were true opioid overdoses. For these visits, the CDC case definition and RIDOH surveillance system agreed that 169 visits (36.7%) were opioid overdoses. Of 318 visits meeting the CDC opioid overdose case definition, 289 visits (90.8%; 95% CI, 87.2%-93.8%) were true opioid overdoses. Of 311 visits reported to the RIDOH surveillance system, 235 visits (75.6%; 95% CI, 70.4%-80.2%) were true opioid overdoses. Conclusions and Relevance: This cross-sectional study found that the CDC opioid overdose case definition more often identified true opioid overdoses compared with the Rhode Island overdose surveillance system. This finding suggests that using the CDC case definition for opioid overdose surveillance may be associated with improved data efficiency and uniformity.

To Treat or Not to Treat: Ethics of Management of Refractory Status Myoclonus Following Pediatric Anoxic Brain Injury.

The development of status myoclonus (SM) in a postcardiac arrest patient has historically been thought of as indicative of not only a poor neurologic outcome but of neurologic devastation. In many instances, this may lead clinicians to initiate conversations about withdrawal of life sustaining therapies (WLST) regardless of the time from return of spontaneous circulation (ROSC). Recent studies showing a percentage of patients may make a good recovery has called into question whether a self-fulfilling prophecy has developed where the concern for a poor neurologic outcome leads clinicians to prematurely discuss WLST. The issue is only further complicated by changing terminology, lack of neuro-axis localization, and limited data regarding association with electroencephalogram (EEG) characteristics, all of which could aid in the understanding of the severity of neurologic injury associated with SM. Here we review the initial literature reporting SM as indicative of poor neurologic outcome, the studies that call this into question, the various definitions of SM and related terms as well as data regarding association with EEG backgrounds. We propose that improved prognostication on outcomes results from combining the presence of SM with other clinical variables (eg EEG patterns, MRI findings, and clinical exam). We discuss the ethical implications of using SM as a prognostic tool and its impact on decisions about life-sustaining care in children following cardiac arrest. We advocate for prognostication efforts to be delayed for at least 72 hours following ROSC and thus to treat SM in those early hours and days.

Statewide Policy to Increase Provision of Take-Home Naloxone at Emergency Department Visits for Opioid Overdose, Rhode Island, 2018‒2019.

In 2017, Rhode Island responded to rising overdose deaths by establishing statewide emergency department (ED) treatment standards for opioid overdose and opioid use disorder. One requirement of the policy is that providers prescribe or provide take-home naloxone to anyone presenting to EDs with opioid overdose. Among adults presenting to EDs with opioid overdose from 2018 to 2019, approximately half received take-home naloxone. Receipt of naloxone was associated with administration of naloxone before ED presentation, ED policy certification level, and regional overdose frequency. (Am J Public Health. 2023;113(4):372-377. https://doi.org/10.2105/AJPH.2022.307213).

Peroral Endoscopic Myotomy; Novice Surgeon Learning Curve.

INTRODUCTION: Peroral endoscopic myotomy (POEM) is a novel endoscopic procedure used to treat achalasia and other spastic esophageal disorders that is an alternative to Heller myotomy. We seek to define the learning curve of POEM for a foregut surgeon with no formal endoscopic or POEM training by analyzing different intraoperative factors in a single series. METHODS AND PROCEDURES: The first 38 consecutive patients undergoing POEM by a single foregut surgeon were included in this retrospective study. Inverse curve regression models were used to analyze total operative time (TOT) and total operative time per centimeter of myotomy (TOT-CM), in addition to other intraoperative variables. Clinical outcomes were reported as pre- and post-operative Eckardt Scores. RESULTS: All patients had type II achalasia with no post-operative complications observed. Eckardt scores improved postoperatively (median (range): 1 (0-4)) compared with the preoperative scores (10 (8-12)) (P < .001). The total operative time (median 76 minutes, range 51-129) decreased significantly over the course of the series (R2 = .38, P < .001), with a learning plateau at 70 minutes and a learning rate of 12 cases. Total operative time per centimeter of myotomy (median 7.08 min/cm, range 4.25 to 15.38) decreased over time (R2 = .45, P < .001), with a learning plateau at 7 minutes/cm and a learning rate of 12 cases. CONCLUSION: The number of cases for a foregut surgeon to become proficient in a POEM procedure was found to be 12-14 cases. The learning curve for a POEM in a formally trained foregut surgeon may be comparable to an endoscopically trained interventionist.

Bi-allelic CAMSAP1 variants cause a clinically recognizable neuronal migration disorder.

Non-centrosomal microtubules are essential cytoskeletal filaments that are important for neurite formation, axonal transport, and neuronal migration. They require stabilization by microtubule minus-end-targeting proteins including the CAMSAP family of molecules. Using exome sequencing on samples from five unrelated families, we show that bi-allelic CAMSAP1 loss-of-function variants cause a clinically recognizable, syndromic neuronal migration disorder. The cardinal clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, severe neurodevelopmental delay, cortical visual impairment, and seizures. The neuroradiological phenotype comprises a highly recognizable combination of classic lissencephaly with a posterior more severe than anterior gradient similar to PAFAH1B1(LIS1)-related lissencephaly and severe hypoplasia or absence of the corpus callosum; dysplasia of the basal ganglia, hippocampus, and midbrain; and cerebellar hypodysplasia, similar to the tubulinopathies, a group of monogenic tubulin-associated disorders of cortical dysgenesis. Neural cell rosette lineages derived from affected individuals displayed findings consistent with these phenotypes, including abnormal morphology, decreased cell proliferation, and neuronal differentiation. Camsap1-null mice displayed increased perinatal mortality, and RNAScope studies identified high expression levels in the brain throughout neurogenesis and in facial structures, consistent with the mouse and human neurodevelopmental and craniofacial phenotypes. Together our findings confirm a fundamental role of CAMSAP1 in neuronal migration and brain development and define bi-allelic variants as a cause of a clinically distinct neurodevelopmental disorder in humans and mice.

A Virtual Community of Practice: An International Educational Series in Pediatric Neurocritical Care.

Pediatric neurocritical care (PNCC) is a rapidly growing field. Challenges posed by the COVID-19 pandemic on trainee exposure to educational opportunities involving direct patient care led to the creative solutions for virtual education supported by guiding organizations such as the Pediatric Neurocritical Care Research Group (PNCRG). Our objective is to describe the creation of an international, peer-reviewed, online PNCC educational series targeting medical trainees and faculty. More than 1600 members of departments such as pediatrics, pediatric critical care, and child neurology hailing from 75 countries across six continents have participated in this series over a 10-month period. We created an online educational channel in PNCC with over 2500 views to date and over 130 followers. This framework could serve as a roadmap for other institutions and specialties seeking to address the ongoing problems of textbook obsolescence relating to the rapid acceleration in knowledge acquisition, as well as those seeking to create new educational content that offers opportunities for an interactive, global audience. Through the creation of a virtual community of practice, we have created an international forum for pediatric healthcare providers to share and learn specialized expertise and best practices to advance global pediatric health.

Leader sensemaking style in response to crisis: Consequences and insights from the COVID-19 pandemic.

The international scope of the 2020 COVID-19 crisis compelled a response from world leaders across the globe. However, the nature of these responses was far from universal. These circumstances present a unique opportunity to study how leader style influences, and is influenced by, a common crisis. To explore these relationships, the present effort used a content analysis of weekly COVID-19 statements from world leaders spanning the first 19 weeks of the crisis. Results suggest that leaders shifted toward increasingly pragmatic sensemaking approaches as COVID-19 infections increased and that sustained use of pragmatic leadership styles was associated with fewer infections in the long term. In contrast, sustained use of the charismatic sensemaking style was associated with higher observed infection rates.

Macroperiodic Oscillations Are Associated With Seizures Following Acquired Brain Injury in Young Children.

PURPOSE: Seizures occur in 10% to 40% of critically ill children. We describe a phenomenon seen on color density spectral array but not raw EEG associated with seizures and acquired brain injury in pediatric patients. METHODS: We reviewed EEGs of 541 children admitted to an intensive care unit between October 2015 and August 2018. We identified 38 children (7%) with a periodic pattern on color density spectral array that oscillates every 2 to 5 minutes and was not apparent on the raw EEG tracing, termed macroperiodic oscillations (MOs). Internal validity measures and interrater agreement were assessed. We compared demographic and clinical data between those with and without MOs. RESULTS: Interrater reliability yielded a strong agreement for MOs identification (kappa: 0.778 [0.542-1.000]; P < 0.0001). There was a 76% overlap in the start and stop times of MOs among reviewers. All patients with MOs had seizures as opposed to 22.5% of the general intensive care unit monitoring population ( P < 0.0001). Macroperiodic oscillations occurred before or in the midst of recurrent seizures. Patients with MOs were younger (median of 8 vs. 208 days; P < 0.001), with indications for EEG monitoring more likely to be clinical seizures (42 vs. 16%; P < 0.001) or traumatic brain injury (16 vs. 5%, P < 0.01) and had fewer premorbid neurologic conditions (10.5 vs. 33%; P < 0.01). CONCLUSIONS: Macroperiodic oscillations are a slow periodic pattern occurring over a longer time scale than periodic discharges in pediatric intensive care unit patients. This pattern is associated with seizures in young patients with acquired brain injuries.

Renal schwannoma: A case report and literature review of a rare and benign entity mimicking an invasive renal neoplasm.

Schwannomas of the kidney are rare with only a handful of cases reported in literature. We present a case of a large Schwannoma of the right kidney causing mass effect with imaging characteristics thought to represent renal cell carcinoma. On imaging, these masses present similarly to solid renal masses and are therefore indistinguishable without tissue diagnosis. Thus, surgical resection is the definitive treatment for renal schwannomas.

Continuous Electroencephalography Monitoring in Critically Ill Infants and Children.

Continuous video electroencephalography (CEEG) monitoring of critically ill infants and children has expanded rapidly in recent years. Indications for CEEG include evaluation of patients with altered mental status, characterization of paroxysmal events, and detection of electrographic seizures, including monitoring of patients with limited neurological examination or conditions that put them at high risk for electrographic seizures (e.g., cardiac arrest or extracorporeal membrane oxygenation cannulation). Depending on the inclusion criteria and clinical characteristics of the population studied, the percentage of pediatric patients with electrographic seizures varies from 7% to 46% and with electrographic status epilepticus from 1% to 23%. There is also evidence that epileptiform and background CEEG patterns may provide important information about prognosis in certain clinical populations. Quantitative EEG techniques are emerging as a tool to enhance the value of CEEG to provide real-time bedside data for management and prognosis. Continued research is needed to understand the clinical value of seizure detection and identification of other CEEG patterns on the outcomes of critically ill infants and children.

Nonoptic pathway tumors in children with neurofibromatosis type 1.

OBJECTIVE: To define the radiologic features and natural history of nonoptic pathway tumors (non-OPTs) in children with neurofibromatosis type 1 (NF1). METHODS: We performed a retrospective cross-sectional analysis of 64 children with NF1 harboring 100 probable non-OPTs. Age at diagnosis, sex, tumor location, number of tumors, symptomology, concurrent OPT, radiographic progression (defined as qualitative and quantitative increases in size), and treatment were assessed. Tumor volumes were measured from initial presentation until treatment or end of disease progression. RESULTS: Sixty-three percent of probable non-OPTs progressed over time, where radiographic progression was concomitantly associated with clinical progression. Fifty-two percent of patients had incidentally identified probable non-OPTs. Twenty-five percent of patients were symptomatic at initial diagnosis, all of whom harbored tumors that grew on subsequent scans and required tumor-directed therapy. There were no clinical differences between probable non-OPTs localized to the brainstem vs other locations with respect to age, sex, concurrent optic pathway glioma, symptomology, and treatment. The average time from diagnosis to stabilization or decrease in tumor size was 2.34 years (SD, 2.15 years). Nineteen biopsied lesions were all histopathologically confirmed as tumor. Six children (9%) had deep extensive tumors, who presented earlier (mean age at diagnosis, 3.88 years), required multiple treatments, and had a shorter mean progression-free survival (48 months). CONCLUSIONS: Over half of children with NF1 in this study developed probable non-OPTs, the majority of which were clinically and radiographically progressive. While brainstem and nonbrainstem gliomas share similar clinical features and natural history, deep extensive tumors comprise a distinct aggressive group of tumors that warrant close attention.

Variation in Treatment and Outcomes of Children With Acute Disseminated Encephalomyelitis.

OBJECTIVES: To characterize variation in treatments and outcomes of pediatric patients admitted to children's hospitals with acute disseminated encephalomyelitis (ADEM). METHODS: In this retrospective cohort study, we used data from the Pediatric Health Information System. Children >30 days old who were hospitalized from 2010 to 2015 with ADEM were included. Variables analyzed were treatments and admission to an ICU. Primary outcomes were discharge disposition and readmissions for relapses (ADEM readmissions) or for continued comorbidities (non-ADEM readmissions). RESULTS: A total of 954 patients with ADEM had 1117 admissions. Treatments included steroids (80%), immunoglobulin (22%), and plasmapheresis (6.6%); 15% of admissions included none of these treatments. Treatments varied by center (P < .001). Thirty-four percent of admissions included ICU admission, which was associated with an increased number and duration of treatments (P < .01). The discharge disposition was home in 85% of admissions; home with health services, rehab facility, or other in 13.6%; and mortality in 1.4%. Twelve percent (117 of 954) of patients had >1 admission for ADEM. Treatment choice and ICU stay were not associated with ADEM readmissions. Sixteen percent (181 of 1101) of ADEM admissions had a non-ADEM readmission within 90 days. Prolonged ICU hospitalization was associated with non-ADEM readmission (adjusted odds ratio 1.9; P = .017) and decreased likelihood of discharge from the hospital to home (adjusted odds ratio 0.1; P < .001). After adjusting for ICU duration, treatment choice and duration were not associated with non-ADEM readmission or hospital disposition. CONCLUSIONS: Significant variation in ADEM treatment exists across centers. Admission to an ICU for ADEM was associated with increased immunotherapy, additional health services at discharge, and readmission for diagnoses other than ADEM.

Adaptive functioning in children with neurofibromatosis type 1: relationship to cognition, behavior, and magnetic resonance imaging.

AIM: To characterize the adaptive behavior profile of children with neurofibromatosis type 1 (NF1) and determine its relationship to neuropsychological functioning and non-neoplastic T2-weighted hyperintense brain lesions on brain magnetic resonance imaging (MRI). METHOD: In this cross-sectional study, we retrospectively reviewed neuropsychological reports from 104 children with NF1 (56 males, 48 females; mean age 10y 4mo; standard deviation [SD] 3y 4mo; range 3y 5mo-17y 6mo), and extracted data from a range of cognitive and behavioral measures, including the Adaptive Behavior Assessment System (ABAS). Brain MRI was retrospectively reviewed in 42 individuals. RESULTS: Adaptive Behavior Assessment System scores were continuously distributed and pathologically shifted by 0.79 to 1.26SD across Conceptual, Social, and Practical domains, and 46.5% of individuals had a composite score in the borderline or impaired range. Impairment in adaptive functioning was correlated with deficits in executive function (r=-9.543, p<0.001), externalizing problems (r=-0.366, p<0.001), and attention (r=-9.467, p=0.001). Cluster analysis revealed three distinct phenotypic subgroups, one of which exhibited normal cognitive ability, but impaired adaptive functioning, with persistent deficits in executive function, behavioral problems, and attention-deficit/hyperactivity disorder symptomatology. There was no relationship between ABAS scores and the number or location of unidentified bright objects. INTERPRETATION: Adaptive functioning deficits are common among children with NF1 and are associated with impairment in other cognitive/behavioral domains, independent of general cognitive ability. WHAT THIS PAPER ADDS: Deficits in adaptive behavior are common in children with neurofibromatosis type 1 (NF1). Poor adaptive functioning is associated with impairments in executive function, externalizing behaviors, and attention, regardless of cognitive ability. The presence or location of unidentified bright objects do not predict adaptive behavior skills in children with NF1.

FUNCIONAMIENTO ADAPTATIVO EN NIÑOS CON NEUROFIBROMATOSIS TIPO 1: RELACIÓN ENTRE COGNICIÓN, COMPORTAMIENTO E IMÁGENES DE RESONANCIA MAGNÉTICA: OBJETIVO: Caracterizar el perfil del comportamiento adaptativo de niños con neurofibromatosis tipo 1 (NF1) y determinar la relación entre el funcionamiento neuropsicológico y las lesiones hiperintensas cerebrales no neoplásicas en T2-pesado de la resonancia magnética cerebral (RM). MÉTODO: En este estudio transversal, revisamos de forma retrospectiva reportes neuropsicológicos de 104 niños con NF1 (56 varones, 48 mujeres, media de edad 10 años 4 meses; desviación estándar (DE) 3 años 4 meses; rango 3 años 5 meses a 17 años 6 meses), y se extrajeron datos de una serie de mediciones cognitivas y conductuales, incluyendo el test sistema de evaluación de la conducta adaptativa (Adaptative Behaivor Assesment System ABAS). Se revisaron 42 RM cerebrales de forma retrospectiva. RESULTADOS: Los resultados ABAS fueron continuamente distribuidos y se cambiaron patológicamente entre 0,79 a 1,26 DE en los dominios de lo conceptual, social y práctico, y 46,5 por ciento de los individuos tuvieron un puntaje limítrofe o sin afectación. La afectación en las funciones adaptativas fue correlacionada con los déficits en funciones ejecutivas (r = -9,543, p < 0,001), externalizar problemas (r = -0,366, p < 0,001), y atención (r = -9,467, p = 0,001). El análisis de grupo revelo tres subgrupos fenotípicos distintos, uno de ellos exhibía una habilidad cognitiva tipica, pero afectación en el funcionamiento adaptativo, con déficits persistentes en función ejecutiva, problemas conductuales, y sintomatología de déficit de atención/hiperactividad. No hubo relación entre el puntaje ABAS y el número o localización de imágenes brillantes no identificadas en la RM cerebral. INTERPRETACIÓN: Los déficits de funcionamiento adaptativo son comunes entre niños con NF1 y son asociados con afectación de otros dominios cognitivo/conductual, independiente de la habilidad cognitiva en general.

FUNCIONAMENTO ADAPTATIVO EM CRIANÇAS COM NEUROFIBROMATOSE TIPO 1: RELAÇÃO COM COGNIÇÃO, COMPORTAMENTO, E IMAGEM DE RESSONÂNCIA MAGNÉTICA: OBJETIVO: Caracterizar o comportamento adaptativo de crianças com neurofibromatose tipo 1 (NF1) e determinar sua relação com funcionamento neuropsicológico e lesões em T2 hiperintensas não neoplásticas ao exame de ressonância magnética (RM). MÉTODO: Neste estudo transversal, revisamos retrospectivamente os relatórios neuropsicológicos de 104 crianças com NF1 (56 do sexo masculino, 48 do sexo feminino; média de idade 10a 4m; desvio padrão [DP] 3a 4m; variação 3a 5m-17a6m), e extraímos dados de uma variedade de medidas cognitivas e comportamentais, incluindo o Sistema de Avaliação do Comportamento Adaptativo (SACA). Imagens de RM cerebral foram retrospectivamente revisadas em 42 indivíduos. RESULTADOS: Os escores SACA foram distribuídos continuamente, e patologicamente deslocados em 0,79 a 1,26 DP nos domínios Conceitual, Social e Prático, e 46,5 por cento dos indivíduos tiveram escore composto na faixa limítrofe ou deficiente. Deficiências no comportamento adaptativo se correlacionaram com déficits na função executiva (r = −9,543, p < 0,001), problemas externalizantes (r = −0,366, p < 0,001), e atenção (r = −9,467, p = 0,001). Análise agrupada revelou três subgrupos genotípicos distintos, um dos quais exibiu capacidade cognitiva normal, mas funcionamento adaptativo deficiente, e sintomatologia de transtorno de deficit de atenção e hiperatividade. Não houve relação entre escores SACA e o número ou localização de objetos luminosos não identificados. INTERPRETAÇÃO: Déficits no funcionamento adaptativo são comuns entre crianças com NF1 e são associados com deficiência em outros domínios cognitivos/comportamentais, independente da capacidade cognitiva geral.

Double-Edged Scalpels: The Trials and Triumphs of Women Surgeons.

The narratives presented in this symposium describe the many ways in which women are harassed from medical school to residency to fellowship and throughout their careers as surgeons. A clear double-edged pattern in the tactics these women used to cope, the challenges they faced, and the responses they encountered emerge, with each being protective or helpful while simultaneously holding them back. Addressing the systemic cultural issues described throughout will be no easy challenge, but the authors of these narratives provide hope that it can be different for future generations of women pursuing surgical careers.

The mTOR pathway in treatment of epilepsy: a clinical update.

Nearly a third of patients with epilepsy have seizures refractory to current medical therapies. In the search for novel drug targets, the mTOR pathway has emerged as key in the regulation of neuronal function, growth and survival, and other cellular processes related to epileptogenesis. Hyperactivation of the mTOR pathway has been implicated in tuberous sclerosis complex and other 'mTORopathies', clinical syndromes associated with cortical developmental malformations and drug-resistant epilepsy. Recently published clinical trials of mTOR inhibitors in tuberous sclerosis complex have shown that these drugs are effective at decreasing seizure frequency. Future studies may establish whether mTOR inhibitors can provide effective treatment for patients with diverse genetic and acquired epilepsies, including preventative, disease-modifying therapies.

Increased prevalence of brain tumors classified as T2 hyperintensities in neurofibromatosis 1.

BACKGROUND: We sought to define the radiologic features that differentiate neoplastic from non-neoplastic T2 hyperintensities (T2Hs) in neurofibromatosis type 1 (NF1) and identify those lesions most likely to require oncologic surveillance. METHODS: We conducted a single-center retrospective review of all available brain MRIs from 68 children with NF1 (n = 190) and 46 healthy pediatric controls (n = 104). All T2Hs identified on MRI were characterized based on location, border, shape, degree of T1 hypointensity, and presence of mass effect or contrast enhancement, and subsequently classified using newly established radiologic criteria as either unidentified bright objects (UBOs) or probable tumors. Lesion classification was pathologically confirmed in 10 NF1 cases. RESULTS: T2Hs were a highly sensitive (94.4%; 95% confidence interval [CI] 86.4%-98.5%) and specific (100.0%; 95% CI 92.3%-100.0%) marker for the diagnosis of NF1. UBOs constituted the majority of T2Hs (82%) and were most frequently located in cerebellar white matter, medial temporal lobe, and thalamus, where they were more likely than probable tumors to be bilateral (p < 0.001) and have nondiscrete borders (p < 0.001). Surprisingly, 57% of children with T2Hs harbored lesions classified as probable tumors, and 28% of children with probable tumors received treatment. In contrast to UBOs, probable tumors were most frequently located within the globus pallidus and medulla, and rarely occurred prior to 3 years of age. CONCLUSIONS: With the implementation of standardized radiologic criteria, a high prevalence of brain tumors was identified in this at-risk population of children, of which nearly one-third required treatment, emphasizing the need for appropriate oncologic surveillance for patients with NF1 harboring nonoptic pathway brain tumors.

Similar Improvements in Patient-Reported Outcomes Among Rheumatoid Arthritis Patients Treated with Two Different Doses of Methotrexate in Combination with Adalimumab: Results From the MUSICA Trial.

INTRODUCTION: In patients with rheumatoid arthritis (RA), combination treatment with methotrexate (MTX) and adalimumab is more effective than MTX monotherapy. From the patients' perspective, the impact of reduced MTX doses upon initiating adalimumab is not known. The objective was to evaluate the effects of low and high MTX doses in combination with adalimumab initiation on patient-reported outcomes (PROs), in MTX-inadequate responders (MTX-IR) with moderate-to-severe RA. METHODS: MUSICA was a randomized, double-blind, controlled trial evaluating the efficacy of 7.5 or 20 mg/week MTX, in combination with adalimumab for 24 weeks in MTX-IR RA patients receiving prior MTX ≥ 15 mg/week for ≥ 12 weeks. PROs were recorded at each visit, including physical function, health-related quality-of-life, work productivity, quality-of-sleep, satisfaction with treatment medication, sexual impairment due to RA, patient global assessment of disease activity (PGA), and patient pain. Last observation carried forward was used to account for missing values. RESULTS: At baseline, patients in both MTX dosage groups had similar demographics, disease characteristics, and PRO scores. Overall, initiation of adalimumab led to significant improvements from baseline in the PROs assessed for both MTX dosage groups. Improvements in presenteeism from baseline were strongly correlated with corresponding improvements in SF-36 (vitality), pain, and physical function. Physical and mental well-being had a good correlation with improvement in sleep. Overall, improvements in disease activity from baseline were correlated with improvements in several PROs. CONCLUSIONS: The addition of adalimumab to MTX in MTX-IR patients with moderate-to-severe RA led to improvements in physical function, quality-of-life, work productivity, quality of sleep, satisfaction with treatment medication, and sexual impairment due to RA, regardless of the concomitant MTX dosage. FUNDING: AbbVie. TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT01185288.

Gender disparities in leadership and scholarly productivity of academic hospitalists.

BACKGROUND: Gender disparities still exist for women in academic medicine but may be less evident in younger cohorts. Hospital medicine is a new field, and the majority of hospitalists are <41 years of age. OBJECTIVE: To determine whether gender disparities exist in leadership and scholarly productivity for academic hospitalists and to compare the findings to academic general internists. DESIGN: Prospective and retrospective observational study. SETTING: University programs in the United States. MEASUREMENTS: Gender distribution of (1) academic hospitalists and general internists, (2) division or section heads for both specialties, (3) speakers at the 2 major national meetings of the 2 specialties, and (4) first and last authors of articles from the specialties' 2 major journals RESULTS: We found equal gender representation of hospitalists and general internists who worked in university hospitals. Divisions or sections of hospital medicine and general internal medicine were led by women at 11/69 (16%) and 28/80 (35%) of university hospitals, respectively (P = 0.008). Women hospitalists and general internists were listed as speakers on 146/557 (26%) and 291/580 (50%) of the presentations at national meetings, respectively (P < 0.0001), first authors on 153/464 (33%) and 423/895 (47%) publications, respectively (P < 0.0001), and senior authors on 63/305 (21%) and 265/769 (34%) articles, respectively (P < 0.0001). CONCLUSIONS: Despite hospital medicine being a newer field, gender disparities exist in leadership and scholarly productivity.