Are pediatric interns prepared to perform infant lumbar punctures? A multi-institutional descriptive study.

BACKGROUND: There are few data describing pediatric interns' experiences, knowledge, attitudes, and skills related to common procedures. This information would help guide supervisors' decisions about interns' preparedness and training needs. OBJECTIVES: This study aimed to describe pediatric interns' medical school experiences, knowledge, attitudes, and skills with regard to infant lumbar punctures (LPs) and to describe the impact of these factors on interns' infant LP skills. METHODS: This prospective cross-sectional descriptive study was conducted at 21 academic medical centers participating during 2010. Participants answered 8 knowledge questions, 3 attitude questions, and 6 experience questions online. Skills were assessed on an infant LP simulator using a 15-item subcomponent checklist and a 4-point global assessment. RESULTS: Eligible interns numbered 493, with 422 (86%) completing surveys and 362 (73%) completing skills assessments. The majority 287/422 (68%) had never performed an infant LP; however, 306 (73%) had observed an infant LP during school. The mean (SD) knowledge score was 63% (±21%). The mean (SD) subcomponent skills checklist score was 73% (±21%). On the global skills assessment, 225 (62%) interns were rated as beginner, and 137 (38%) were rated as competent, proficient, or expert. Independent predictors of an above-beginner simulator performance included infant LP experience on a patient (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.4-3.5), a knowledge score greater than 65% (OR, 2.4; 95% CI, 1.5-3.7), or self-reported confidence (OR, 3.5; 95% CI, 1.9-6.4). CONCLUSIONS: At the start of residency, the majority of pediatric interns have little experience, poor knowledge, and low confidence and are not prepared to perform infant LPs.

Intellectual Property of Psychedelics for Addiction Treatment: Enabling Access and Protecting Innovation Opportunities Through Preserving the Public Domain.

OBJECTIVE: Recent research has shown potential for psychedelic therapeutics as addiction treatments; however, some academic institutions, commercial entities and individuals are attempting to monopolize psychedelic compounds through exploiting the patent process. METHODS: This Perspective article describes efforts that have been devised to mitigate exclusionary patent practices pertinent to psychedelic therapeutics for addiction. RESULTS: The non-profit Porta Sophia has identified 170 patent documents focused on treating addiction through psychedelics, and many of these patents could threaten to privatize public domain knowledge and severely limit or increase the cost of research if granted. Patent examiners who determine if a patent application should be granted must negate false claims to innovation. Yet, given the unique history of psychedelics, prior knowledge can be difficult to find. As a result, overreaching patents may be granted, causing dramatic shifts in access to addiction-focused psychedelic research, treatments, and funding. CONCLUSIONS: As the field of psychedelics approaches this critical inflection point of FDA decisions, it is imperative for all stakeholders - including university investigators, academic and commercial patent seekers, and policy makers - to utilize available tools for determining prior knowledge. Maintaining an informed awareness of legal patent eligibility and limitations is crucial for establishing an ethical patent landscape and ensuring subsequent access to these potential life-altering psychedelic therapeutics for addiction.

Genome-wide association mapping of loci for antipsychotic-induced extrapyramidal symptoms in mice.

Tardive dyskinesia (TD) is a debilitating, unpredictable, and often irreversible side effect resulting from chronic treatment with typical antipsychotic agents such as haloperidol. TD is characterized by repetitive, involuntary, purposeless movements primarily of the orofacial region. In order to investigate genetic susceptibility to TD, we used a validated mouse model for a systems genetics analysis geared toward detecting genetic predictors of TD in human patients. Phenotypic data from 27 inbred strains chronically treated with haloperidol and phenotyped for vacuous chewing movements were subject to a comprehensive genomic analysis involving 426,493 SNPs, 4,047 CNVs, brain gene expression, along with gene network and bioinformatic analysis. Our results identified ~50 genes that we expect to have high prior probabilities for association with haloperidol-induced TD, most of which have never been tested for association with human TD. Among our top candidates were genes regulating the development of brain motor control regions (Zic4 and Nkx6-1), glutamate receptors (Grin1 and Grin2a), and an indirect target of haloperidol (Drd1a) that has not been studied as well as the direct target, Drd2.

Immediate Hypersensitivity to Polyethylene Glycols and Polysorbates: More Common Than We Have Recognized.

BACKGROUND: The most common immediate hypersensitivity to macrogols is associated with polyethylene glycol (PEG) 3350; however, the epidemiology, mechanisms, and cross-reactivity are poorly understood. Thousands of medications contain either PEGs or structurally similar polysorbates. OBJECTIVE: Our objective was to better understand the mechanism, cross-reactivity, and scope of PEG hypersensitivity. METHODS: Two cases with a past history of immediate hypersensitivity to PEG-containing medications were used to study potential mechanisms and cross-reactivity of immediate reactions to PEG 3350. Skin testing and oral challenges with PEG and polysorbate-containing agents were employed to determine clinical reactivity and cross-reactivity between the 2 allergens. Enzyme-linked immunosorbent assay and electrochemiluminescent immunoassay were used to detect anti-PEG specific IgG and IgE, respectively, using PEGylated protein or PEG alone as antigens in 2 cases and 6 PEG 3350 tolerant controls. We searched US Food and Drug Administration (FDA) adverse event reports for immediate reactions to PEG 3350 to determine the potential scope of this problem in the United States. RESULTS: Skin and provocation testing demonstrated symptomatic reactivity in both cases to PEG 3350 and polysorbate 80. Plasma samples were positive for anti-PEG specific IgE and IgG antibodies only in cases and binding increased directly proportional to the molecular weight of PEG tested. FDA adverse event reports revealed 53 additional cases of possible PEG 3350 anaphylaxis. CONCLUSIONS: Immediate hypersensitivity to PEG 3350 with cross-reactive polysorbate 80 hypersensitivity may be underrecognized in clinical practice and can be detected with clinical skin testing. Our studies raise the possibility of an IgE-mediated type I hypersensitivity mechanism in some cases.

Family member presence for procedures: the resident's perspective.

OBJECTIVE: To describe resident acceptance of and comfort with family member presence (FMP) during pediatric invasive procedures and resuscitation in a large, multicenter pediatric residency program. To determine if increased level of training impacts on opinion toward FMP for procedures. DESIGN AND METHODS: Seventy-six residents of postgraduate levels 1-4 were administered a survey about FMP for procedures. The survey consisted of 4 Likert-scale questions and 1 multiple-choice question of resident acceptance of and comfort with FMP during procedures and cardiopulmonary resuscitation (CPR). Statistical analysis was performed using the Mann-Whitney U test and one-way analysis of variance (ANOVA). RESULTS: Fifty-three residents (70%) responded. Residents were accepting of FMP during procedures, with a mean score of 3.9/5. However, residents were less accepting of FMP presence during CPR, with a mean score of 2.84/5. There was a trend toward increased comfort and acceptance of FMP with increased level of training; however, this was not statistically significant. In our study, nearly one half of residents (45%) reported that their major reservation toward FMP was that resident anxiety could result in procedure or resuscitation failure. CONCLUSION: The residents in our pediatric training program generally accept FMP for procedures. Residents were less accepting of FMP for CPR than for procedures. Residents most commonly oppose FMP for procedures because they believe this will make them anxious and lead to failure. This information provides insight into the implementation of FMP for procedures in a medical education setting.

Duration of fever and markers of serious bacterial infection in young febrile children.

BACKGROUND: Despite the drastic change in the evaluation of the febrile young child due to the decreased incidence of serious bacterial infections (SBI) effected by Haemophilus influenza type B and pneumococcal vaccine, there remains a small role for blood work in the evaluation of these patients. Bacterial markers including white blood cell (WBC) count, absolute neutrophil count (ANC) and C-reactive protein (CRP) have been studied and are widely used as predictors of SBI in febrile children. It has been suggested that CRP values should be interpreted cautiously when fever has been present <12 h based on the kinetics of this biological marker. This limitation has not been previously addressed with CRP, nor was it described with other markers, specifically WBC and ANC, therefore the purpose of the present paper was to assess WBC, ANC and CRP values as predictors of SBI in relation to duration of fever. METHODS: Patients who presented to a pediatric emergency department between the ages of 1 and 36 months, with fever > or =39 degrees C and no source of infection had a complete blood count (CBC) blood culture, and CRP level drawn. A urinalysis and/or urine culture was obtained when age and gender appropriate. A chest X-ray was performed at the discretion of the treating physician. The study subjects were enrolled prospectively and then divided into two groups based on duration of fever of < or = or >12 h, and compared. RESULTS: One hundred and twenty-eight patients were originally enrolled. Nine patients were excluded. Seventeen patients (14%) had SBI. One patient (<1%) had bacteremia, three (3%) had pneumonia, and 13 (10%) had urinary tract infections. Forty-five patients presented with fever < or =12 h and 74 patients presented with fever >12 h. Area under the curve (AUC) for WBC, ANC and CRP was significantly larger in patients with SBI presenting with fever >12 h (0.85, 0.83, 0.92 respectively) compared to patients with SBI who presented with fever for <12 h (0.37, 0.42, 0.68 respectively). CONCLUSIONS: Bacterial markers studied were more predictive of SBI if the duration of fever was >12 h as shown by the AUC. CRP performed better than WBC and ANC in both scenarios.