Alström Syndrome: Mutation Spectrum of ALMS1

Alström Syndrome (ALMS), a recessive, monogenic ciliopathy caused by mutations in ALMS1, is typically characterized by multisystem involvement including early cone‐rod retinal dystrophy and blindness, hearing loss, childhood obesity, type 2 diabetes mellitus, cardiomyopathy, fibrosis, and multiple organ failure. The precise function of ALMS1 remains elusive, but roles in endosomal and ciliary transport and cell cycle regulation have been shown. The aim of our study was to further define the spectrum of ALMS1 mutations in patients with clinical features of ALMS. Mutational analysis in a world‐wide cohort of 204 families identified 109 novel mutations, extending the number of known ALMS1 mutations to 239 and highlighting the allelic heterogeneity of this disorder. This study represents the most comprehensive mutation analysis in patients with ALMS, identifying the largest number of novel mutations in a single study worldwide. Here, we also provide an overview of all ALMS1 mutations identified to date.     

Paramedic-Initiated Home Care Referrals and Use of Home Care and Emergency Medical Services

Objective: We examined the association between paramedic-initiated home care referrals and utilization of home care, 9-1-1, and Emergency Department (ED) services. Methods: This was a retrospective cohort study of individuals who received a paramedic-initiated home care referral after a 9-1-1 call between January 1, 2011 and December 31, 2012 in Toronto, Ontario, Canada. Home care, 9-1-1, and ED utilization were compared in the 6 months before and after home care referral. Nonparametric longitudinal regression was performed to assess changes in hours of home care service use and zero-inflated Poisson regression was performed to assess changes in the number of 9-1-1 calls and ambulance transports to ED. Results: During the 24-month study period, 2,382 individuals received a paramedic-initiated home care referral. After excluding individuals who died, were hospitalized, or were admitted to a nursing home, the final study cohort was 1,851. The proportion of the study population receiving home care services increased from 18.2% to 42.5% after referral, representing 450 additional people receiving services. In longitudinal regression analysis, there was an increase of 17.4 hours in total services per person in the six months after referral (95% CI: 1.7–33.1, p = 0.03). The mean number of 9-1-1 calls per person was 1.44 (SD 9.58) before home care referral and 1.20 (SD 7.04) after home care referral in the overall study cohort. This represented a 10% reduction in 9-1-1 calls (95% CI: 7–13%, p < 0.001) in Poisson regression analysis. The mean number of ambulance transports to ED per person was 0.91 (SD 8.90) before home care referral and 0.79 (SD 6.27) after home care referral, representing a 7% reduction (95% CI: 3–11%, p < 0.001) in Poisson regression analysis. When only the participants with complete paramedic and home care records were included in the analysis, the reductions in 9-1-1 calls and ambulance transports to ED were attenuated but remained statistically significant. Conclusions: Paramedic-initiated home care referrals in Toronto were associated with improved access to and use of home care services and may have been associated with reduced 9-1-1 calls and ambulance transports to ED.     

Views from the field: Medical student experiences and perceptions of interprofessional learning and collaboration in rural settings

Exploring the perceived environment where students are educated, as well as where they practice, is particularly important for educators and practitioners working in situations of interprofessional rural and remote health. In this study, we explored the perceptions of undergraduate medical students regarding interprofessionalism across their four-year undergraduate program which focuses on rural health. A thematic content analysis of the text-data was conducted on a convenience sample of 47 student responses to essay questions across four cohorts of a four-year undergraduate medical program. The medical program has an explicit social accountability mandate for responsiveness to the needs of a rural population and thus students have multiple opportunities to experience interprofessional education and collaboration in rural contexts. Participants reported (a) blurring and flexibility of roles in a primarily positive manner, (b) participating in unstructured interprofessional learning and collaboration, (c) experiencing the importance of social connections to interprofessional collaboration and learning, and (d) realisations that interprofessional collaboration is a means of overcoming barriers in rural areas. We discuss our findings using the socio-material perspective of complexity theory. These findings may be used to inform undergraduate programs in re-defining, re-creating, developing, and fostering interprofessional learning opportunities for medical students in rural communities as well as to support clinical faculty through ongoing professional development.     

Brominated Flame Retardants and Other Persistent Organohalogenated Compounds in Relation to Timing of Puberty in a Longitudinal Study of Girls

Background

Exposure to hormonally active chemicals could plausibly affect pubertal timing, so we are investigating this in the Breast Cancer and the Environment Research Program.

Objectives

Our goal was to examine persistent organic pollutants (POPs) in relation to pubertal onset.

Methods

Ethnically diverse cohorts of 6- to 8-year-old girls (n = 645) provided serum for measure of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and lipids. Tanner stages [breast (B) and pubic hair (PH)], and body mass index (BMI) were measured at up to seven annual clinic visits. Using accelerated failure time models, we calculated time ratios (TRs) for age at Tanner stages 2 or higher (2+) and POPs quartiles (Q1–4), adjusting for confounders (race/ethnicity, site, caregiver education, and income). We also calculated prevalence ratios (PRs) of Tanner stages 2+ at time of blood sampling.

Results

Cross-sectionally, the prevalence of B2+ and PH2+ was inversely related to chemical serum concentrations; but after adjustment for confounders, only the associations with B2+, not PH2+, were statistically significant. Longitudinally, the age at pubertal transition was consistently older with greater chemical concentrations; for example: adjusted TR for B2+ and Q4 for ΣPBDE = 1.05; 95% CI: 1.02, 1.08, for ΣPCB = 1.05; 95% CI: 1.01, 1.08, and for ΣOCP = 1.10; 95% CI: 1.06, 1.14, indicating median ages of about 6 and 11 months older than least exposed, and with similar effect estimates for PH2+. Adjusting for BMI attenuated associations for PCBs and OCPs but not for PBDEs.

Conclusions

This first longitudinal study of puberty in girls with serum POPs measurements (to our knowledge) reveals a delay in onset with higher concentrations.

Citation

Windham GC, Pinney SM, Voss RW, SjÖdin A, Biro FM, Greenspan LC, Stewart S, Hiatt RA, Kushi LH. 2015. Brominated flame retardants and other persistent organohalogenated compounds in relation to timing of puberty in a longitudinal study of girls. Environ Health Perspect 123:1046–1052; http://dx.doi.org/10.1289/ehp.1408778     

Epibulbar schwannoma in a 12-year-old boy: A case report and review of literature

Schwannomas are benign, encapsulated, primary neurilemmal tumors composed of proliferating Schwann cells. Schwannomas are commonly seen in the orbit, but are rare on the epibulbar surface. Herein, we report a case of a 12-year-old boy who presented to us with a slow-growing painless subconjunctival mass in the left eye. There was no intraocular extension of the mass and intra-operatively, the mass could be clearly delineated and was excised off the underlying sclera. Histopathological examination of the mass showed typical features of schwannoma and immunohistochemistry helped to confirm the diagnosis. There was no recurrence of the lesion observed at follow-up 26 months after surgery. Here, we describe this uncommon tumor and review the available literature. Although rare, an epibulbar schwannoma should be considered in the differential diagnosis of an amelanotic, painless subconjunctival nodular mass. Excision of the lesion is the recommended treatment.     

Multiphasic changes in systemic VEGF following intravitreal injections of ranibizumab in a child

Purpose

To investigate whether intravitreal ranibizumab injections administered to a child alter systemic plasma levels of total and free VEGF 165.

Methods

A 9-year-old child sustained a choroidal rupture from blunt trauma. He subsequently developed a secondary choroidal neovascular membrane, which was treated with five ranibizumab injections over a period of 8 months. Peripheral venous blood samples were taken at each visit over a period of 12 months and plasma was extracted. Plasma VEGF 165 levels were determined using enzyme-linked immunosorbent assay and were assayed both pre- and post-immunodepletion to remove complexed VEGF.

Results

Plasma VEGF 165 levels proved labile following intravitreal injection of ranibizumab. Levels increased by 30% above baseline following the first intravitreal ranibizumab injection, but then returned to baseline despite two subsequent injections. There was then a rebound increase of 67% in total plasma VEGF levels following a further injection, which remained above baseline for 12 weeks despite two further intravitreal ranibizumab injections. Baseline levels were re-attained 26 weeks after the final injection.

Conclusions

These results suggest intravitreal ranibizumab injections can cause significant, multiphasic changes in systemic VEGF levels. This may be of particular clinical significance in children as VEGF is known to be vital in the development of major organs, in addition to its role in the maintenance of normal organ function in adults.