Faculty Bibliography

BACKGROUND:Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. METHODS:This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. FINDINGS:Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. INTERPRETATION:In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran. FUNDING:Alnylam Pharmaceuticals.

OBJECTIVE:To review the contemporary issues of healthcare disparities in Headache Medicine with regard to race/ethnicity, socioeconomic status and geography and propose solutions for addressing these disparities. METHODS:An internet and PubMed search was performed and literature was reviewed for key concepts underpinning disparities in Headache Medicine. Content was refined to areas most salient to our goal of informing the provision of equitable care in headache treatment through discussions with this group of 16 experts from a range of headache subspecialties. RESULTS:Taken together, a multitude of factors including racism, socioeconomic status and insurance status and geographical disparities contribute to the inequities that exist within the healthcare system when treating headache disorders. Interventions such as improving public education, advocacy, optimizing telemedicine, engaging in community outreach to educate primary care providers, training providers in cultural sensitivity and competence and implicit bias, addressing health literacy and developing recruitment strategies to increase representation of underserved groups within headache research are proposed as solutions to ameliorate disparities. CONCLUSION/CONCLUSIONS:Neurologists have a responsibility to provide and deliver equitable care to all. It is important that disparities in the management of headache disorders are identified and addressed.

Over the last decade, internet gaming has been a fast-growing recreational activity. Gamers risk their leisure activity becoming an addiction. In the present study, we aimed to measure the prevalence of Internet Gaming Disorder (IGD) in an adult population of video game players and to investigate the association between demographic variables, Autism Spectrum Disorder (ASD) traits, Attention-Deficit Hyperactivity Disorder (ADHD) severity, and IGD in adults. Through an online survey, we recruited 4260 individuals aged between 18 and 55 years old, who were members of online communities of video gamers. We collected demographic data and administered three questionnaires: the Internet Gaming Disorder Scale-Short Form (IGD9-SF), the Autism Spectrum Quotient (AQ), and the Adult ADHD Self-Report Scale (ASRS). Of the overall sample, 29.67% scored above the cut-off of 21 points for the IGD9-SF. Multiple linear regression models showed that daily spare time, autistic traits, and ADHD symptoms were positively associated with the severity of IGD in adults, after controlling for demographic variables. Future studies are required in order to explore factors linked to IGD in adults.

Undiagnosed and untreated obstructive sleep apnea (OSA) is associated with health comorbidities and negatively affects quality of life. Alternative treatments should be considered in patients who are unable to tolerate or benefit from positive airway pressure treatment. When properly indicated, positional devices, oral appliances, airway surgery, and hypoglossal nerve stimulation have been shown to be effective in treating OSA. Hypoglossal nerve stimulation is a successful second-line treatment with low associated morbidity and complication rate.

INTRODUCTION/BACKGROUND:The recurrent laryngeal nerves(RLN) run immediately posterior to the thyroid capsule and could be injured during thyroid radiofrequency ablation(RFA). This study assesses whether RLN functional integrity is altered during RFA using continuous intraoperative neuromonitoring(CIONM). METHODS:Prospective case series of twenty nodules treated with RFA under general anesthesia utilizing the laryngeal adductor reflex(LAR) for CIONM. RESULTS:Thirteen nodules abutted the posterior thyroid capsule and 'danger triangle' for RLN injury. The ablative field did not breach the posterior capsule; 40 W was the maximal power used adjacent to the capsule. No patient experienced significant LAR amplitude alterations. Pre and postoperative laryngoscopy and voice assessments were comparable. At 12 months' median follow-up, no patient displayed posterior nodule regrowth. CONCLUSIONS:This prospective case series supports the premise that benign nodule RFA is safe with regards to RLN functional integrity provided the posterior capsule is not breached by the ablation zone and posterior power is ≤ 40 W.

OBJECTIVE:To identify priorities for administrative, epidemiologic and diagnostic research in sepsis. DESIGN/METHODS:As a follow-up to a previous consensus statement about sepsis research, members of the Surviving Sepsis Campaign Research Committee, representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine addressed six questions regarding care delivery, epidemiology, organ dysfunction, screening, identification of septic shock, and information that can predict outcomes in sepsis. METHODS:Six questions from the Scoring/Identification and Administration sections of the original Research Priorities publication were explored in greater detail to better examine the knowledge gaps and rationales for questions that were previously identified through a consensus process. RESULTS:The document provides a framework for priorities in research to address the following questions: (1) What is the optimal model of delivering sepsis care?; (2) What is the epidemiology of sepsis susceptibility and response to treatment?; (3) What information identifies organ dysfunction?; (4) How can we screen for sepsis in various settings?; (5) How do we identify septic shock?; and (6) What in-hospital clinical information is associated with important outcomes in patients with sepsis? CONCLUSIONS:There is substantial knowledge of sepsis epidemiology and ways to identify and treat sepsis patients, but many gaps remain. Areas of uncertainty identified in this manuscript can help prioritize initiatives to improve an understanding of individual patient and demographic heterogeneity with sepsis and septic shock, biomarkers and accurate patient identification, organ dysfunction, and ways to improve sepsis care.

Delivering healthcare to people living with Parkinson's disease (PD) may be challenging in face of differentiated care needs during a PD journey and a growing complexity. In this regard, integrative care models may foster flexible solutions on patients' care needs whereas Parkinson Nurses (PN) may be pivotal facilitators. However, at present hardly any training opportunities tailored to the care priorities of PD-patients are to be found for nurses. Following a conceptual approach, this article aims at setting a framework for training PN by reviewing existing literature on care priorities for PD. As a result, six prerequisites were formulated concerning a framework for training PN. The proposed training framework consist of three modules covering topics of PD: (i) comprehensive care, (ii) self-management support and (iii) health coaching. A fourth module on telemedicine may be added if applicable. The framework streamlines important theoretical concepts of professional PD management and may enable the development of novel, personalized care approaches.

OBJECTIVES/OBJECTIVE:Opioids are frequently used for analgesia in patients with acute subarachnoid hemorrhage (SAH) due to a high prevalence of headache and neck pain. However, it is unclear if this practice may pose a risk for opioid dependence, as long-term opioid use in this population remains unknown. We sought to determine the prevalence of opioid use in SAH survivors, and to identify potential risk factors for opioid utilization. METHODS:We analyzed a cohort of consecutive patients admitted with non-traumatic and suspected aneurysmal SAH to an academic referral center. We included patients who survived hospitalization and excluded those who were not opioid-naïve. Potential risk factors for opioid prescription at discharge, 3 and 12 months post-discharge were assessed. RESULTS:Of 240 SAH patients who met our inclusion criteria (mean age 58.4 years [SD 14.8], 58% women), 233 (97%) received opioids during hospitalization and 152 (63%) received opioid prescription at discharge. Twenty-eight patients (12%) still continued to use opioids at 3 months post-discharge, and 13 patients (6%) at 12-month follow up. Although patients with poor Hunt and Hess grades (odds ratio 0.19, 95% CI 0.06-0.57) and those with intraventricular hemorrhage (odds ratio 0.38, 95% CI 0.18-0.87) were less likely to receive opioid prescriptions at discharge, we did not find significant differences between patients who had long-term opioid use and those who did not. CONCLUSION/CONCLUSIONS:Opioids are regularly used in both the acute SAH setting and immediately after discharge. A considerable number of patients also continue to use opioids in the long-term. Opioid-sparing pain control strategies should be explored in the future.

CASE:A 68-year-old woman who underwent a C5 to C6 anterior cervical discectomy and fusion (ACDF) surgery presented with new-onset postoperative quadriplegia. During discectomy, intraoperative neurophysiological monitoring alerted of a spinal cord (SC) dysfunction. The surgery was halted, and measures to ensure adequate SC perfusion were initiated. In the next 2-week follow-up, patient's motor deficit progressively improved. CONCLUSIONS:We report an unusual and devastating outcome of new-onset quadriplegia after an elective ACDF and highlight the relevance of intraoperative monitoring during cervical spine surgery to early recognize and treat SC impending injury.