Needs assessment for enhancing pediatric clerkship readiness.

BACKGROUND: Many students report feeling inadequately prepared for their clinical experiences in pediatrics. There is striking variability on how pediatric clinical skills are taught in pre-clerkship curricula. METHODS: We asked students who completed their clerkships in pediatrics, family medicine, surgery, obstetrics-gynecology and internal medicine to rate their pre-clinical training in preparing them for each clerkship, specifically asking about medical knowledge, communication, and physical exam skills. Based on these results, we surveyed pediatric clerkship and clinical skills course directors at North American medical schools to describe the competence students should have in the pediatric physical exam prior to their pediatric clerkship. RESULTS: Close to 1/3 of students reported not feeling adequately prepared for their pediatrics, obstetrics-gynecology, or surgery clerkship. Students felt less prepared to perform pediatric physical exam skills compared to physical exam skills in all other clerkships. Pediatric clerkship directors and clinical skills course directors felt students should have knowledge of and some ability to perform a wide spectrum of physical exam skills on children. There were no differences between the two groups except that clinical skills educators identified a slightly higher expected competence for development assessment skills compared to pediatric clerkship directors. CONCLUSIONS: As medical schools undergo cycles of curricular reform, it may be beneficial to integrate more pre-clerkship exposure to pediatric topics and skills. Further exploration and collaboration establishing how and when to incorporate this learning could serve as a starting point for curricular improvements, with evaluation of effects on student experience and performance. A challenge is identifying infants and children for physical exam skills practice.

A translational study: Involvement of miR-21-5p in development and maintenance of neuropathic pain via immune-related targets CCL5 and YWHAE.

Neuropathic pain occurs in more than half of the patients suffering from peripheral neuropathies. We investigated the role of microRNA (miR)-21 in neuropathic pain using a murine-human translational approach. We applied the spared nerve injury (SNI) model at the sciatic nerve of mice and assessed the potential analgesic effect of perineurial miR-21-5p inhibitor application. Immune-related targets of miR-21-5p were determined by a qRT-PCR based cytokine and chemokine array. Bioinformatical analysis identified potential miR-21-5p targets interacting with CC-chemokine ligand (CCL)5. We validated CCL5 and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein (YWHAE), an interaction partner of miR-21-5p and CCL5, by qRT-PCR in murine common peroneal and tibial nerves. Validated candidates were then investigated in white blood cell and sural nerve biopsy samples of patients with focal to generalized pain syndromes, i.e. small fiber neuropathy (SFN), polyneuropathy (PNP), and nerve lesion (NL). We showed that perineurial miR-21-5p inhibition reverses SNI-induced mechanical and heat hypersensitivity in mice and found a reduction of the SNI-induced increase of the pro-inflammatory mediators CCL5 (p < 0.01), CCL17 (p < 0.05), and IL-12ß (p < 0.05) in miR-21-5p inhibitor-treated mice. In silico analysis revealed several predicted and validated targets for miR-21-5p with CCL5 interaction. Among these, we found lower YWHAE gene expression in mice after SNI and perineurial injections of a scrambled oligonucleotide compared to naïve mice (p < 0.05), but this was not changed by miR-21-5p inhibition. Furthermore, miR-21-5p inhibition led to a further increase of the SNI-induced increase in TGFß (p < 0.01). Patient biomaterial revealed different systemic expression patterns of miR-21-5p, with higher expression in SFN and lower expression in NL. Further, we showed higher systemic expression of pro-inflammatory mediators in white blood cells of SFN patients compared to healthy controls. We have conducted a translational study comparing results from animal models to human patients with three different neuropathic pain syndromes. We identified CCL5 as a miR-21 dependent common player in the mouse SNI model and the human painful disease SFN.

Reduced gene expression of netrin family members in skin and sural nerve specimens of patients with painful peripheral neuropathies.

OBJECTIVE: To investigate the expression of axon guidance cues in skin and sural nerve biopsies of patients with polyneuropathies (PNP) as potential markers of nerve de- and regeneration and inflammation. METHODS: We prospectively recruited 88 patients with PNP and compared data between patient subgroups and healthy controls. All patients underwent skin punch and/or sural nerve biopsy at the lower leg and proximal thigh. We characterized gene expression profiles of netrin family members as target genes involved in neuronal de- and regeneration [netrin 1, deleted in colorectal cancer (DCC), uncoordinated5H2, neogenin 1 (NEO1), netrin G1, netrin G2] using quantitative real-time PCR. RESULTS: Gene expression of netrin 1 (p < 0.05 in proximal skin), DCC (p < 0.001 in distal skin), NEO1 (p < 0.05 in distal skin), netrin G1 (p < 0.05 in proximal and p < 0.01 in distal skin), and netrin G2 (p < 0.001 in distal skin) was lower in skin biopsies of patients with neuropathy compared to healthy controls. Gene expression of NEO1 (p < 0.05 in distal skin), netrin G2 (p < 0.05 in distal skin), and DCC (p < 0.05 in sural nerve) was lower in samples of patients with painful compared to painless PNP and also correlated positively with intraepidermal nerve fiber density. Skin and sural nerve gene expression of the investigated target genes did not differ between neuropathies of different etiologies. CONCLUSION: We show reduced cutaneous and neural axon guide expression, which may contribute to a dysregulation of nerve fiber de- and regeneration.

Tumor necrosis factor-α links heat and inflammation with Fabry pain.

Fabry disease (FD) is an X-linked lysosomal storage disorder associated with pain triggered by heat or febrile infections. We modelled this condition by measuring the cytokine expression of peripheral blood mononuclear cells (PBMC) from FD patients in vitro upon stimulation with heat and lipopolysaccharide (LPS). We enrolled 67 FD patients and 37 healthy controls. We isolated PBMC, assessed their gene expression of selected pro- and anti-inflammatory cytokines, incubated them with heat, LPS, globotriaosylceramide (Gb3), and tumor necrosis factor-α (TNF), and measured TNF secretion in the supernatant and intracellular Gb3 accumulation, respectively. We found increased TNF, interleukin (IL-)1ß, and toll-like receptor 4 (TLR4) gene expression in FD men (p < .05 to p < .01). TNF and IL-10 were higher, and IL-4 was lower in the subgroup of FD men with pain compared to controls (p < .05 to p < .01). Hereby, TNF was only increased in FD men with pain and classical mutations (p < .05) compared to those without pain. PBMC from FD patients secreted more TNF upon stimulation with LPS (p < .01) than control PBMC. Incubation with Gb3 and an additional α-galactosidase A inhibitor did not further increase TNF secretion, but incubation with TNF greatly increased the Gb3 load in FD PBMC compared to controls (p < .01). Also, LPS incubation and heat challenge (40 °C) increased Gb3 accumulation in PBMC of patients compared to baseline (p < .05 each), while no alterations were observed in control PBMC. Our data show that TNF holds a crucial role in the pathophysiology of FD associated pain, which may open a novel perspective for analgesic treatment in FD pain.

Sensory profiles and immune-related expression patterns of patients with and without neuropathic pain after peripheral nerve lesion.

In this multicenter cross-sectional study, we determined sensory profiles of patients with (NL-1) and without neuropathic pain (NL-0) after nerve lesion and assessed immune-related systemic gene expression. Patients and matched healthy controls filled in questionnaires and underwent neurological examination, neurophysiological studies, quantitative sensory testing, and blood withdrawal. Neuropathic pain was present in 67/95 (71%) patients (NL-1). Tactile hyperalgesia was the most prominent clinical sign in NL-1 patients (P < 0.05). Questionnaires showed an association between neuropathic pain and the presence of depression, anxiety, and catastrophizing (P < 0.05 to P < 0.01). Neuropathic pain was frequently accompanied by other chronic pain (P < 0.05). Quantitative sensory testing showed ipsilateral signs of small and large fiber impairment compared to the respective contralateral side, with elevated thermal and mechanical detection thresholds (P < 0.001 to P < 0.05) and lowered pressure pain threshold (P < 0.05). Also, more loss of function was found in patients with NL-1 compared to NL-0. Pain intensity was associated with mechanical hyperalgesia (P < 0.05 to P < 0.01). However, quantitative sensory testing did not detect or predict neuropathic pain. Gene expression of peptidylglycine α-amidating monooxygenase was higher in NL patients compared with healthy controls (NL-1, P < 0.01; NL-0, P < 0.001). Also, gene expression of tumor necrosis factor-α was higher in NL-1 patients compared with NL-0 (P < 0.05), and interleukin-1ß was higher, but IL-10 was lower in NL-1 patients compared with healthy controls (P < 0.05 each). Our study reveals that nerve lesion presents with small and large nerve fiber dysfunction, which may contribute to the presence and intensity of neuropathic pain and which is associated with a systemic proinflammatory pattern.

Lemierre's Syndrome Presenting as Multifocal Pyomyositis in a Young Child.

Lemierre's syndrome is more common in young adults and the majority of patients present with pharyngitis. Multifocal pyomyositis is very rare in this setting and in young children. We present here a case of multifocal pyomyositis caused by Fusobacterium spp. in a young child. Fusobacterium should be considered in the differential diagnosis of multifocal pyomyositis of unclear etiology.

Pediatric residency program handover: before and after the ACGME requirement.

OBJECTIVE: To determine what changes occurred in pediatric residency programs with regards to handover education and assessment before and after the Accreditation Council for Graduate Medical Education (ACGME) requirement mandating monitoring safe handover practices in July 2011. METHODS: We sent surveys at 2 time periods to all pediatric program directors in the United States, as identified from a list provided by the Association of Pediatric Program Directors. Respondents were asked about their program demographics, whether they had handover curricula, how trainees were taught to perform handovers, and perceived barriers to effective handover. RESULTS: Response rates were 58% in both survey years. After the ACGME requirement, only 1 of 3 of programs reported a handover curriculum with goals, objectives, and assessment tools. There was a statistically significant increase in the percentage of those responding that resident handover education primarily occurred by role modeling (66% vs 82%; P < .05). Other learners (visiting residents, medical students) also continued to learn handover skills by role modeling (55% vs 56%; P = NS). Lack of feedback and interruptions were recognized as barriers to successful handover by program directors in both survey years. CONCLUSIONS: There is a continued need for handover curricula with didactic and practical components as well as assessment pieces within pediatric residency programs. Barriers to effective handover such as lack of feedback and interruptions continue to be major problems. There is a lack of faculty ownership and interest in learner handover that may affect long-term successes. Because role modeling continues to be the main way in which trainees learn handover, specific attention should be given to teach role-modeling techniques.

Effectiveness of monovalent and pentavalent rotavirus vaccine.

OBJECTIVE: Previous US evaluations have not assessed monovalent rotavirus vaccine (RV1, a G1P[8] human rotavirus strain) effectiveness, because of its later introduction (2008). Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose RV1 and 3-dose pentavalent vaccine (RV5) series against rotavirus disease resulting in hospital emergency department or inpatient care. METHODS: Children were eligible for enrollment if they presented to 1 of 5 hospitals (3 in Georgia, 2 in Connecticut) with diarrhea of ≤10 days' duration during January through June 2010 or 2011, and were born after RV1 introduction. Stools were collected; immunization records were obtained from providers and state electronic immunization information system (IIS). Case-subjects (children testing rotavirus antigen-positive) were compared with 2 control groups: children testing rotavirus negative and children selected from IIS. RESULTS: Overall, 165 rotavirus-case subjects and 428 rotavirus-negative controls were enrolled. Using the rotavirus-negative controls, RV1 VE was 91% (95% confidence interval [CI] 80 to 95) and RV5 VE was 92% (CI 75 to 97) among children aged ≥8 months. The RV1 VE against G2P[4] disease was high (94%, CI 78 to 98), as was that against G1P[8] disease (89%, CI 70 to 96). RV1 effectiveness was sustained among children aged 12 through 23 months (VE 91%; CI 75 to 96). VE point estimates using IIS controls were similar to those using rotavirus-negative controls. CONCLUSIONS: RV1 and RV5 were both highly effective against severe rotavirus disease. RV1 conferred sustained protection during the first 2 years of life and demonstrated high effectiveness against G2P[4] (heterotypic) disease.

Parent understanding of the role of doctors and doctors in training on an inpatient pediatric ward.

BACKGROUND: Many physician trainees care for patients in an academic hospital. We studied parent understanding of the roles of medical students, interns, residents, and attending physicians in the inpatient setting of a children's hospital. DESCRIPTION: Surveys were given to parents during a hospital stay on a medical service asking about the responsibilities and education of physicians and trainees. EVALUATION: The majority of respondents knew that medical students were not doctors, could not write prescriptions, or supervise residents or attendings. Most respondents did not know that an intern had completed medical school, was a doctor, or could write prescriptions. Most respondents knew that attendings had graduated from medical school, were doctors, and supervise interns and students. Factors affecting understanding of these roles included the parent's level of education and race. CONCLUSION: Confusion exists about the different roles of physicians and trainees, particularly in parents without a college education, and who self-identify as non-White.

Life-threatening sepsis caused by Burkholderia cepacia from contaminated intravenous flush solutions prepared by a compounding pharmacy in another state.

We report 2 life-threatening cases of Burkholderia cepacia sepsis caused by infusate contamination during compounding. Bacterial isolates from the patients' blood cultures and the infusate were indistinguishable by pulsed-field gel electrophoresis. Proper quality controls at a local and national level are important for ensuring safe delivery of compounded medications to patients in all settings, including those outside health care facilities.

Dietary iron content mediates hookworm pathogenesis in vivo.

Hookworm infection is associated with growth delay and iron deficiency anemia in developing countries. A series of experiments were designed in order to test the hypothesis that host dietary iron restriction mediates susceptibility to hookworm infection using the hamster model of Ancylostoma ceylanicum. Animals were maintained on diets containing either 10 ppm iron (iron restricted) or 200 ppm iron (standard/high iron), followed by infection with A. ceylanicum third-stage larvae. Infected animals fed the standard diet exhibited statistically significant growth delay and reduced blood hemoglobin levels compared to uninfected controls on day 20 postinfection. In contrast, no statistically significant differences in weight or hemoglobin concentration were observed between infected and uninfected animals fed the iron-restricted diet. Moreover, iron-restricted animals were observed to have reduced intestinal worm burdens on day 10 and day 20 postinfection compared to those of animals maintained on the standard/high-iron diet. In a subsequent study, animals equilibrated on diets containing a range of iron levels (10 ppm, 40 ppm, 100 ppm, or 200 ppm) were infected with A. ceylanicum and followed for evidence of hookworm disease. Infected animals from the intermediate-dietary iron (40- and 100-ppm) groups exhibited greater weight loss and anemia than those in the low (10-ppm)- or high (200-ppm)-iron diet groups. Mortality was also significantly higher in the intermediate-dietary-iron groups. These data suggest that severe dietary iron restriction impairs hookworm development in vivo but that moderate iron restriction enhances host susceptibility to severe disease.