Socioeconomic status and wait times for pediatric surgery in Canada.

OBJECTIVES: Even in a publicly funded health care system, access to care may be related to socioeconomic status (SES). For children, delays in surgical procedures can have profound functional, social, and psychological effects with lifelong impact. The purpose of this study was to determine whether SES was related to meeting surgical wait time access targets for children. We also assessed the effects of gender, age, and distance to hospital on meeting access targets. METHODS: Patient addresses, referral wait times, and surgical wait times were obtained for 39,287 surgical procedures between 2005 and 2011 at the Hospital for Sick Children. Using census data, we derived household income quintile, distance to hospital, and indices of social and material deprivation. These indices were correlated with the percentage of children meeting clinic referral wait time targets and receiving surgery within the Pediatric Canadian Access Targets for Surgery. RESULTS: Across all SES quintiles, 33% of children exceeded their referral wait time targets, and 28% of children exceeded their surgical wait time targets. Indices of material or social deprivation and age did not correlate with the time from referral to clinic consultation (P = .54, .40, and .58, respectively). Gender was statistically significant (P < .001), but the difference was small (odds ratio = 0.87 for girls). Distance was also statistically significant (P = .005), and these differences translate into clinically meaningful differences in meeting wait time targets. Regarding completion of surgical procedures, material deprivation, distance, and gender did not correlate with longer wait times for surgery (P = .44, .09, .59, respectively). Social deprivation was statistically significant (P = .02) but not clinically significant. Increasing patient age was significantly associated with increased proportion of out-of-window wait times (P < .001). SES did not affect the timeliness of completion of surgery even when the urgency of the surgery (priority level based on diagnosis) was considered. CONCLUSIONS: SES does not predict the timeliness of delivery for pediatric surgical services.

Bupropion and Escitalopram During Lactation.

OBJECTIVE: To report a case of seizure-like symptoms in an infant exposed to bupropion and escitalopram through breastfeeding. CASE SUMMARY: A 6.5-month-old female infant, breastfed by a mother treated with bupropion XL 150 mg/d and escitalopram 10 mg/d for depression, presented to our hospital with severe emesis and tonic seizure-like symptoms. The symptoms resolved with supportive therapy. Urine toxicology screen in the infant revealed bupropion and escitalopram. Bupropion, and its active metabolite, hydroxybupropion, were analyzed and quantified both in the infant's serum and in the breast milk. Diagnostic workup for seizure etiologies was otherwise negative. After being asymptomatic for 48 hours, her discharge diagnosis was adverse events associated with bupropion and escitalopram in lactation. An objective causality assessment (Naranjo assessment) revealed that this adverse effect was probable. DISCUSSION: The adverse events in our case were associated with serum concentrations of bupropion and hydroxybupropion that are lower than the reported therapeutic range, perhaps suggesting that infants, compared with adults, may have a higher susceptibility to the epileptogenic effects of bupropion and/or hydroxybupropion. Furthermore, although we do not have escitalopram serum concentrations, this drug interaction may have had a contributing role in this case, possibly because of cytochrome P4502D6 inhibition by bupropion and metabolites. CONCLUSION: As the number of reproductive-aged women requiring polytherapy to control their depression is increasing, further research is needed to establish the safety of combined antidepressants, such as selective serotonin reuptake inhibitors and bupropion, during lactation.

Rat-derived processed nerve allografts support more axon regeneration in rat than human-derived processed nerve xenografts.

Processed nerve allografts are increasingly used as "off the shelf" nerve replacements for surgically bridging nerve gaps. Benchmarking the regenerative capacity of a commercially available human-derived nerve or xenograft in a rat nerve injury model would provide a convenient platform for future studies seeking to modify the processed nerve graft. Human and rat processed nerve grafts were used to bridge a 14 mm defect in a Sprague-Dawley rat sciatic nerve. Reversed autografts served as a positive control group. Twelve weeks following surgery, the distal nerve stumps were retrograde labeled and harvested for histology and histomorphometry. The cross-sectional areas of the human- and rat-derived processed nerve grafts were similar. Neuron counts and myelinated axon counts following use of the human-derived processed xenografts were decreased compared with those obtained from both the rat-derived processed nerve allografts and the autografts; the rat-derived processed nerve allografts were statistically equivalent to autografts. Measures of nerve fiber diameter and myelination revealed inferior axon regeneration maturity in both processed nerve grafts compared with autografts. Processed xenografts showed significantly reduced regeneration compared with autografts or processed allografts indicating that cross-species immunological reactions are important considerations in this rat model.

Fibrin gels containing GDNF microspheres increase axonal regeneration after delayed peripheral nerve repair.

AIM: Recovery following nerve transection declines when target reconnection is delayed for prolonged periods. GDNF has previously been shown to promote motor axon regeneration following delayed nerve repair. MATERIALS & METHODS: We constructed delivery systems using fibrin gels containing free GDNF or poly(lactide-co-glycolide) microspheres with GDNF. The delivery systems were implanted with fluorescent fibrinogen surrounding the common fibular (CF; peroneal) nerve in transgenic Thy-1 GFP rats (whose axons express GFP) to track degradation of the system. A delayed nerve repair model was designed by transecting the rat CF nerve, where nerve regeneration was prevented by ligating the two stumps to surrounding muscle for 2 months prior to resuture. At resuture, either a delivery system with GDNF or an additional group consisting of fibrin gels with empty microspheres were implanted surrounding the repair site. In an additional positive control, the CF was transected and repaired immediately without delay. RESULTS: ELISA assays demonstrated GDNF release in vitro for 2 weeks from fibrin gels with GDNF microspheres. Implanted delivery systems, including GDNF microspheres, remained surrounding the nerve for at least 10 days compared with 3 days for free GDNF. Four weeks after repair, histomorphometry of distal nerve cross-sections taken 20 mm from the repair site demonstrated increased fiber diameter and myelin thickness due to release of GDNF from microspheres compared with empty microspheres. Additionally, the number of motoneurons that regenerated their axons to the same site increased to comparable levels as immediate repair due to the extended delivery of GDNF from microspheres. CONCLUSION: These findings demonstrate that early measures of nerve regeneration after delayed nerve repair is improved by GDNF microspheres implanted at the coaptation site.

Experimental and clinical evidence for use of decellularized nerve allografts in peripheral nerve gap reconstruction.

Despite the inherent capability for axonal regeneration, recovery following severe peripheral nerve injury remains unpredictable and often very poor. Surgeons typically use autologous nerve grafts taken from the patient's own body to bridge long nerve gaps. However, the amount of suitable nerve available from a given patient is limited, and using autologous grafts leaves the patient with scars, numbness, and other forms of donor-site morbidity. Therefore, surgeons and engineers have sought off-the-shelf alternatives to the current practice of autologous nerve grafting. Decellularized nerve allografts have recently become available as an alternative to traditional nerve autografting. In this review, we provide a critical analysis comparing the advantages and limitations of the three major experimental models of decellularized nerve allografts: cold preserved, freeze-thawed, and chemical detergent based. Current tissue engineering-based techniques to optimize decellularized nerve allografts are discussed. We also evaluate studies that supplement decellularized nerve grafts with exogenous factors such as Schwann cells, stem cells, and growth factors to both support and enhance axonal regeneration through the decellularized allografts. In examining the advantages and disadvantages of the studies of decellularized allografts, we suggest that experimental methods, including the animal model, graft length, follow-up time, and outcome measures of regenerative progress and success be consolidated. Finally, all clinical studies in which decellularized nerve allografts have been used to bridge nerve gaps in patients are reviewed.

Validation of spontaneous assessment of baroreceptor reflex sensitivity and its relation to heart rate variability in the ovine fetus pre- and near-term.

Assessment of baroreceptor reflex sensitivity (BRS) in the ovine fetus provides insight into autonomic cardiovascular regulation. Currently, assessment of BRS relies on vasoactive drugs, but this approach is limited by feasibility issues and by the nonphysiologic nature of the stimulus. Thus we aimed to validate the method of spontaneous BRS assessment against the reference method of using vasoactive drugs in preterm (0.76 gestation, n = 16) and near-term (0.86 gestation, n = 16) chronically instrumented ovine fetuses. The BRS measures derived from the spontaneous and reference methods correlated at both gestational ages (R = 0.67 +/- 0.03). The sequence method of spontaneous BRS measures also correlated both to the root mean square of standard deviations (RMSSD), which is a measure of fetal heart rate variability reflecting vagal modulation (R = 0.69 +/- 0.03), and to fetal body weight (R = 0.65 +/- 0.03), which is a surrogate for growth trajectory of each fetus. The methodology presented may aid in developing new models to study BRS and cardiovascular control in ovine fetus in the last trimester of pregnancy.