Research Spotlight

Posted January 26th 2016

Consensus Management of Gastrointestinal Events Associated with Delayed-Release Dimethyl Fumarate: A Delphi Study.

J. Theodore Phillips M.D.

J. Theodore Phillips, M.D.

Theodore Phillips, J., A. A. Erwin, S. Agrella, M. Kremenchutzky, J. F. Kramer, M. J. Darkes, J. Kendter, H. Abourjaily, J. Rana and R. J. Fox (2015). “Consensus Management of Gastrointestinal Events Associated with Delayed-Release Dimethyl Fumarate: A Delphi Study.” Neurol Ther 4(2): 137-146.

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INTRODUCTION: Delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF) is indicated for the treatment of patients with relapsing multiple sclerosis. Gastrointestinal (GI) adverse events (AEs) occur with DMF therapy. METHODS: We used a Delphi process to reach consensus among North American clinicians on effective real-world management strategies for GI AEs associated with DMF. Clinicians were asked to complete two rounds of questionnaires developed by a steering committee; consensus in round 2 was attained if >/=70% of respondents agreed on a particular strategy. RESULTS: Consensus was reached on several strategies to manage GI AEs, including administering DMF with food, slow titration, dose reduction, and use of symptomatic therapies. CONCLUSION: These consensus strategies provide clinicians with information on real-world approaches used to address the tolerability of DMF in patients with multiple sclerosis. FUNDING: Biogen.

Posted January 26th 2016

Long stem reverse shoulder arthroplasty and cerclage for treatment of complex long segment proximal humeral fractures with diaphyseal extension in patients more than 65 years old.

Brody Flanagin M.D.E

Brody Flanagin, M.D.

Garofalo, R., B. Flanagin, A. Castagna, E. Y. Lo and S. G. Krishnan (2015). “Long stem reverse shoulder arthroplasty and cerclage for treatment of complex long segment proximal humeral fractures with diaphyseal extension in patients more than 65 years old.” Injury 46(12): 2379-2383.

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INTRODUCTION: Treatment of long segment proximal humeral fractures with extension below the surgical neck into the diaphysis remains a significant challenge for orthopaedic surgeons. The purpose of this paper was to evaluate the clinical and radiological outcomes following primary long-stem RSA with cerclage fixation for complex long segment proximal humeral fractures with diaphyseal extension in patients more than 65 years old. MATERIAL AND METHODS: Between February 2010 and March 2013, 22 patients who suffered a complex proximal humerus fracture with extended diaphyseal involvement underwent surgery with long-stem RSA and cerclages fixation. There were 17 female and 5 male patients, and the mean age was 77.2 years at time of surgery (range 65-84 years). All patients had a 3 or 4-part proximal humerus fracture or a two part fracture with a split of humeral head, with extension to the proximal diaphysis. Clinical and radiographic follow-up was performed on all 22 patients at 6 weeks, at 3, 6, and 12 months postoperatively, and then at 2 years. Clinical evaluation consisted of the shoulder rating Constant scale. X ray evaluation was done to evaluate fracture healing and eventually humeral and glenoid component loosening or other complications. RESULTS: No infections were reported, neither other serious complications. Two patients developed a seroma and one patient developed chronic pain at that was treated with referral to pain management. No patients were lost at follow-up. At final follow-up, average active elevation was 132.5 degrees (range 100 degrees -140 degrees ), external rotation 30 degrees (range 55 degrees -10 degrees ). Average abduction was 120 degrees (range 90 degrees -135 degrees ). The mean adjusted Constant score was 72/100 (range 64-82). All fractures were healed within 3 months after surgery. No loosening of the humeral or glenoid components and no episodes of dislocation/instability were observed in this series. We did not observe scapular notching in any patient on the x-ray at most recent follow-up. CONCLUSION: Long-stem RSA with cerclages wire fixation represents a viable treatment option for complex long-segment displaced proximal humerus fractures with diaphyseal extension in patients older than 65 years. Our results suggest clinical outcomes at two years of follow up are satisfactory with an acceptable complication rate.

Posted January 26th 2016

Pregnancy Outcomes in Subjects Exposed to Certolizumab Pegol.

John Cush M.D.

John Cush, M.D.

Clowse, M. E., D. C. Wolf, F. Forger, J. J. Cush, A. Golembesky, L. Shaughnessy, D. De Cuyper and U. Mahadevan (2015). “Pregnancy Outcomes in Subjects Exposed to Certolizumab Pegol.” Journal of Rheumatology 42(12): 2270-2278.

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OBJECTIVE: To provide information on pregnancy outcomes in women receiving certolizumab pegol (CZP). METHODS: The UCB Pharma safety database was searched for pregnancies through to September 1, 2014. Reports for maternal and paternal CZP exposure were included and outcomes examined, and data on CZP exposure, pregnancy, comorbidities, and infant events were extracted by 2 independent reviewers. Concomitant medications and disease activity were reviewed for clinical trial patients. RESULTS: Of 625 reported pregnancies, 372 (59.5%) had known outcomes. Paternal exposure pregnancies (n = 33) reported 27 live births, 4 miscarriages, 1 induced abortion, and 1 stillbirth. Maternal exposure pregnancies (n = 339) reported 254 live births, 52 miscarriages, 32 induced abortions, and 1 stillbirth. Almost all reported pregnancies had exposure to CZP in the first trimester, when organogenesis takes place, and a third of them continued the drug into the second and/or third trimesters. The most frequent indications for maternal CZP use were Crohn disease (192/339) and rheumatic diseases (118/339). Twelve cases of congenital malformation and a single neonatal death were reported. CONCLUSION: Analysis of pregnancy outcomes after exposure to CZP supports previous reports, suggesting a lack of harmful effect of maternal CZP exposure on pregnancy outcomes. However, additional data from a larger number of outcomes after exposure and studies including an unexposed comparison group are required to fully evaluate CZP safety and tolerability in pregnancy.

Posted January 26th 2016

Functional Recovery From Neuroinvasive West Nile Virus: A Tale of Two Courses.

Kimberly Monden Ph.D.

Kimberly Monden, Ph.D.

Fromm, N. M., D. B. Salisbury, S. J. Driver, M. N. Dahdah and K. R. Monden (2015). “Functional Recovery From Neuroinvasive West Nile Virus: A Tale of Two Courses.” Rehabilitation Psychology 60(4): 383-390.

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Objective: In 2012, the highest numbers of West Nile Virus (WNV) cases were reported by the Center for Disease Control since 2003. This outbreak included over half of the identified patients being classified with one of the more debilitating neuroinvasive subtypes of WNV. Despite improvements in diagnosis and treatment options in symptom management, longitudinal research on WNV neurocognitive and functional outcomes is limited by sample size, retrospective review, and/or reliance on self-report measures for cognitive status and level of independence. This study describes the cases of 2 patients diagnosed with WNV as they complete rehabilitation across the continuum of care. Research Method: Review of two cases that experience different rehabilitation outcomes 4-18 months post diagnosis. Results: The cases presented here demonstrate the potentially differential courses of recovery and outcomes for physical (e.g., balance, ambulation, upper extremity function), cognitive (e.g., attention, executive functions, memory, language, visuospatial), and emotional functioning, as assessed via measures administered by the patient’s physical therapists and neuropsychologists. These patients were evaluated as part of the standard clinical practice to monitor changes, track recovery, and provide recommendations across the continuum of care from admission to discharge from acute inpatient rehabilitation, during outpatient day neurorehabilitation, and while receiving outpatient neuropsychology services. Conclusions: These cases highlight the variability in rehabilitative course for individuals diagnosed with WNV. Consistent follow-up with patients is recommended to ensure management of remitting and chronic symptoms.

Posted January 25th 2016

Adult-onset type 1 diabetes patients display decreased IGRP-specific Tr1 cells in blood.

Hideki Ueno M.D.

Hideki Ueno, M.D.

Chujo, D., T. S. Nguyen, E. Foucat, D. Blankenship, J. Banchereau, G. T. Nepom, D. Chaussabel and H. Ueno (2015). “Adult-onset type 1 diabetes patients display decreased IGRP-specific Tr1 cells in blood.” Clinical Immunology 161(2): 270-277.

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The breakdown of immune tolerance against islet antigens causes type 1 diabetes (T1D). The antigens associated with adult-onset T1D (AT1D) remain largely undefined. It is possible that AT1D patients display a unique type of CD4(+) T cells specific for a certain islet antigen. Here we analyzed the cytokine production profiles of CD4(+) helper T (Th) cells that are specific for three islet antigens; GAD65, preproinsulin, and IGRP in patients with AT1D, juvenile-onset T1D (JT1D), and age-, gender- and human leukocyte antigen (HLA)-matched control adults. While IGRP-specific Th cells in AT1D patients were dominantly Th1 cells, IGRP-specific Th cells in control adults and JT1D patients were dominantly Th2 and T regulatory type 1 (Tr1) cells. Notably, the frequency of IGRP-specific Tr1 cells was significantly lower in AT1D patients than in control adults and JT1D patients. In conclusion, our study suggests that IGRP-specific Th cells play a unique pathogenic role in AT1D.