Extracorporeal photopheresis to attenuate decline in lung function due to refractory obstructive allograft dysfunction.

BACKGROUND: This study was designed to prospectively evaluate the efficacy of extracorporeal photopheresis (ECP) to attenuate the rate of decline of FEV1 in lung transplant recipients with refractory bronchiolitis obliterans. Due to an observed higher than expected early mortality, a preliminary analysis was performed. STUDY DESIGN AND METHODS: Subjects from 10 lung transplant centres were assigned to ECP treatment or to observation based on spirometric criteria, with potential crossover for those under observation. The primary endpoint of this study was to assess response to ECP (i.e., greater than a 50% decrease in the rate of FEV1 decline) before and 6 months after initiation of ECP. Mortality was also evaluated 6 and 12 months after enrolment as a secondary endpoint. RESULTS: Of 44 enrolled subjects, 31 were assigned to ECP treatment while 13 were initially assigned to observation on a non-random basis using specific spirometric inclusion criteria (seven of the observation patients subsequently crossed over to receive ECP). Of evaluable patients, 95% of patients initially assigned to treatment responded to ECP with rates of FEV1 decline that were reduced by 93% in evaluable ECP-treated patients. Mortality rates (percentages) at 6 and 12 months after enrolment was 32% and 41%, respectively. The most common (92%) primary cause of death was respiratory or graft failure. Significantly (p = 0.002) higher rates of FEV1 decline were observed in the non-survivors (-212 ± 177 ml/month) when compared to the survivors (-95 ± 117 ml/month) 12 months after enrolment. In addition, 18 patients with bronchiolitis obliterans syndrome (BOS) diagnosis within 6 months of enrolment had lost 38% of their baseline lung function at BOS diagnosis and 50% of their lung function at enrolment. CONCLUSIONS: These analyses suggest that earlier detection and treatment of BOS should be considered to appreciate improved outcomes with ECP.

The efficacy of extracorporeal photopheresis to arrest bronchiolitis obliterans in lung allograft recipients was compared between two automated photopheresis instruments.

BACKGROUND: The most common instruments used for extracorporeal photopheresis (ECP) treatment in the United States are the UVAR XTS and the CELLEX devices (Therakos, West Chester, PA). When compared to the UVAR XTS instrument, the efficacy of the CELLEX instrument to arrest the decline in lung function in patients with chronic lung allograft dysfunction (CLAD) related to bronchiolitis obliterans (BOS) has not been previously evaluated. METHODS: The relative efficacy of the CELLEX vs UVAR XTS ECP instruments was assessed by comparing the difference in rates of FEV1 decline before and after ECP treatment and survival in two series of lung allograft recipients with BOS who had been treated with these instruments. RESULTS: Similar Slope Difference values for change in rate of decline (6 months Post ECP - Pre ECP) were observed between the two cohorts (UVAR XTS: 85 ± 109 mL/month vs CELLEX: 76 ± 128 mL/month, p=0.72). A similar percentage of patients responded to ECP (UVAR XTS: 77% vs CELLEX: 89%; p=0.36) i.e., as defined as a positive difference in slope between the rate of decline of FEV1 before and 6 months after ECP. Survival at either 6 (p=0.89) or 12 (p=0.8) months after the start of ECP was not associated with instrument used despite a trend in higher early mortality (34% vs 17%, p=0.054) in the patients who were predominately treated with the CELLEX. CONCLUSIONS: Our data support the use of the CELLEX for prospective studies designed to evaluate the merits of ECP in this population.

Pediatric thalamic tumors in the MRI era: a Canadian perspective.

BACKGROUND: Thalamic gliomas are rare. The natural history is unpredictable, and the optimal management of these tumors in children is poorly defined. The aim was to identify outcomes, prognostic factors, and response to various modalities of treatment in a relatively large population of pediatric thalamic tumors from many centers within a fairly homogeneous health care system. METHODS: We performed a Canadian multicenter retrospective review of pediatric thalamic tumors presenting during the MRI era (1989-2012). Radiology and pathology were reviewed by central independent reviewers. Paraffin shavings for RNA extraction were taken and tested for fusion events involving KIAA1549:BRAF. Tumors were classified as unilateral or bithalamic based on their origin on imaging. Univariate and multivariate analyses on factors influencing survival were performed. RESULTS: Seventy-two thalamic tumors were identified from 11 institutions. Females represented 53% of the study population, and the mean age at presentation was 8.9 years. Sixty-two tumors were unilateral and 10 bithalamic. Unilateral tumors had a greater propensity to grow inferiorly towards the brainstem. These tumors were predominantly low grade in comparison to bithalamic tumors which were high-grade astrocytomas. The 5-year overall survival was 61 ± 13% for unithalamic tumors compared to 37 ± 32% for bithalamic tumors (p = 0.097). Multivariate analysis indicated tumor grade as the only significant prognostic factor for unithalamic tumors. Six unilateral tumors, all low grade, were BRAF fusion positive. CONCLUSION: Unilateral and bilateral thalamic tumors behave differently. Surgical resection is an appropriate treatment option in unilateral tumors, most of which are low grade, but outcome is not related to extent of resection (EOR). Bilateral thalamic tumors have a poorer prognosis, but the occasional patient does remarkably well. The efficacy of chemotherapy and radiotherapy has not been clearly demonstrated. Novel therapeutic approaches are required to improve the prognosis for malignant unilateral thalamic tumors and bilateral thalamic tumors.

Trauma association of Canada Pediatric Subcommittee National Pediatric Cervical Spine Evaluation Pathway: consensus guidelines.

BACKGROUND: The Institute of Medicine calls for the use of clinical guidelines and practice parameters to promote "best practices" and improve patient outcomes. In 2006, The Trauma Association of Canada Pediatric Committee set out to create an evidence-based, national pediatric cervical spine (c-spine) clearance guideline based on the literature, existing algorithms from each pediatric trauma center and from expert opinion from across Canada. METHODS: A review of the literature took place in September 2006 using the PubMed database. Search criteria were "cervical spine," "c-spine," "clearance," and "trauma." Limits that were applied were "Languages: English," "Humans," "Type of Article: Meta-Analysis, Practice Guidelines, Randomized Control Trial, Review," and "Ages: all child 0-18 years." These search criteria were repeated in December 2007, April 2009, and October 2009. A total of 248 articles were identified. Existing guidelines were identified and their practices examined as models of care. Two draft guidelines were created for discussion: one for the pediatric patient with a reliable clinical examination and the other for the pediatric patient with an unreliable clinical examination. Via email, telephone, and two national videoconferences, the content of the guidelines was reviewed, discussed, and amended. The final article was prepared and circulated for author input until consensus was reached. RESULTS: A consensus was reached on two pathways to evaluate the pediatric cervical spine: a patient with a reliable clinical examination and a patient with an unreliable examination. CONCLUSION: Presented herein are the consensus Trauma Association of Canada, National Pediatric Cervical Spine Evaluation Pathways for the patient with a reliable clinical examination, and the patient with and unreliable clinical examination.

The law of relocation of children.

The trend in the law of relocation of children following divorce or determination of paternity is to decide cases based on their own facts rather by strong presumptions for or against relocation. Another common approach is to divide the burden between parents. Statutes of many states require the custodial parent to give notice, between 30 and 90 days, of the intent to relocate with the child. Courts consider a variety of factors in relocation cases but differ on the degree to which a benefit to the custodial parent will be presumed to be a benefit to the child. Three national organizations have developed standards for deciding disputes regarding the relocation of children, but none of the standards have been widely adopted. When courts focus on the facts of each case and make careful finding of fact, the best interests of the child are served.

Factors Associated With Mortality and Response to Extracorporeal Photopheresis in Lung Allograft Recipients With Bronchiolitis Obliterans Syndrome.

BACKGROUND: This study was designed to identify factors associated with clinical response to extracorporeal photopheresis (ECP) and mortality after ECP in lung allograft recipients with bronchiolitis obliterans. METHODS: Forced expiratory volume in 1 second (FEV1) values obtained 6 months before (baseline) and 6 months after initiation of ECP were used to plot the linear relationship between FEV1 versus time before and after ECP. Response to ECP was assigned when a positive integer was derived after subtracting the baseline rate of decline from the rate of decline 6 months after ECP. Univariate and multivariate logistic regression analyses were used to identify demographic, treatment-related factors or spirometric parameters that may be associated with response to ECP or mortality at either 6 or 16 months after initiation of ECP. RESULTS: Forced expiratory volume in 1 second just before ECP was associated with mortality (P = 0.007) at 16 months after ECP initiation. An FEV1 of 1.50 L or less had a sensitivity of 87% and specificity of 60% to identify patients who died within 16 months after ECP initiation. Patients whose FEV1 decline exceeded 40 mL/month were 12 times more likely to have a response to ECP (P = 0.0001). Patients whose decline in FEV1 before ECP was statistically significant (P < 0.05) were nearly 10 times (P = 0.008) more likely to respond to ECP. CONCLUSIONS: Forced expiratory volume in 1 second is an important predictor of mortality, and the response to ECP is influenced by both the extent (>40 mL/mo) and statistical significance of the relationship between FEV1 versus time before ECP initiation. Therefore, earlier bronchiolitis obliterans detection and more timely implementation of ECP (ie, when FEV1 values >1.5 L) should be considered especially in patients with a more aggressive rate of decline of lung function.

Identifying the specific needs of adolescents after a mild traumatic brain injury: a service provider perspective.

PRIMARY OBJECTIVE: To identify the specific service needs of adolescents with mild traumatic brain injury (MTBI) and those of their parents through the perspective of expert service providers as well as to compare it to the perspective of adolescents and their parents obtained in a prior study. STUDY DESIGN: Qualitative design including a focus group held with experts in the field of adolescent TBI and a validation survey of other professionals. METHODS AND PROCEDURES: Eight experts from a variety of disciplines participated in a focus group where important needs of adolescents were discussed. Results were then validated through a questionnaire to 33 professionals. MAIN OUTCOMES AND RESULTS: Experts questioned through both methods are generally in agreement and acknowledge that adolescents are unique, but they often find them challenging. Like adolescents themselves, experts identify the need for information as the most important but are wary of offering too much detail and fear that this could encourage malingering of symptoms and problems. Service providers also recognize the importance of supporting adolescents and parents when returning to activities (school and physical activities). CONCLUSIONS: The notion that teens represent a specific group of consumers of healthcare services is supported by findings in this study. These results provide important information to those involved in the structuring of service provision to adolescents following MTBI.