Surgical versus nonsurgical management for type II odontoid fractures in the elderly population: a systematic review.

BACKGROUND: Odontoid process fractures, of which type II constitute the majority, are an increasingly important cause of morbidity and mortality in the elderly population. The incidence of geriatric type II fractures is steadily increasing in line with the aging population. However, the decision between surgical and non-surgical intervention for type II fractures in the elderly remains controversial. PURPOSE: The present study aims to synthesize the current published literature comparing outcomes following surgical and non-surgical interventions for type II odontoid fractures in the elderly population (≥65 years old). STUDY DESIGN/SETTING: Systematic review and meta-analysis were performed. METHODS: A systematic search of MEDLINE, MEDLINE In-Progress & Other Non-Indexed Citations, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) was performed to identify available evidence in English language. Studies with extractable data for all type II odontoid fractures in participants aged 65 years or older and which compared surgical and non-surgical intervention were included. Methodological quality was assessed using the Downs & Black checklist. Primary outcomes were mortality at short-term follow-up (≤3 months), mortality at long-term follow-up (predetermined study endpoint or mean follow-up length), and radiological union rate. Funding was provided by The University of Edinburgh for travel expenses to present this paper at the Society of British Neurological Sciences 2016 Conference ($170). RESULTS: Twelve studies (n=1,098), all non-randomized, met eligibility criteria. Methodological quality was particularly poor in the confounding, bias, and power domains of assessment. Substantial methodological and statistical heterogeneity allowed only a narrative synthesis of the primary outcomes. Overall, data on mortality at short-term follow-up appeared to favor neither surgical nor non-surgical intervention. A small favorable outcome in surgically managed patients over non-surgically managed patients in terms of mortality at long-term follow-up was not proven conclusive because of considerable heterogeneity in study methodologies. Inadequate reporting of the time point of union assessment introduced the potential for significant intra- and interstudy heterogeneity and precluded assessment of union rates. CONCLUSIONS: Evidence on this controversial topic is sparse, markedly heterogeneous, and of poor quality. Well-designed prospective trials adhering to guidance published by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative are required to inform clinical practice on this contentious but growing issue. Future randomized controlled trials should include an assessment of frailty and medical comorbidities with suitable patients subsequently randomized to surgical or non-surgical treatment.

Psychiatric symptomatology after delirium: a systematic review.

Delirium is an acute and usually transient severe neuropsychiatric syndrome associated with significant long-term physical morbidity. However, its chronic psychiatric sequelae remain poorly characterized. To investigate the prevalence of psychiatric symptoms, namely anxiety, depressive, and post-traumatic stress disorder (PTSD) symptoms after delirium, a systematic literature search of MEDLINE, EMBASE and PsycINFO databases was performed independently by two authors in March 2016. Bibliographies were hand-searched, and a forward- and backward-citation search using Web of Science was performed for all included studies. Of 6411 titles, we included eight prospective cohort studies, including 370 patients with delirium and 1073 without delirium. Studies were heterogeneous and mostly included older people from a range of clinical groups. Consideration of confounders was variable. The prevalence of depressive symptoms was almost three times higher in patients with delirium than in patients without delirium (22.2% vs 8.0%, risk ratio = 2.79; 95% confidence interval = 1.36-5.73). There was no statistically significant difference between the prevalence of anxiety symptoms between patients with and without delirium. The prevalence of PTSD symptoms after delirium was inconclusive: only one study investigated this and no association between PTSD symptoms after delirium was reported. There is limited published evidence of the prevalence of psychiatric symptoms after non-ICU delirium and the strongest evidence is for depressive symptoms. Further longitudinal studies are warranted to investigate the prevalence of anxiety and PTSD symptoms.

The prion protein protease sensitivity, stability and seeding activity in variably protease sensitive prionopathy brain tissue suggests molecular overlaps with sporadic Creutzfeldt-Jakob disease.

INTRODUCTION: Variably protease sensitive prionopathy (VPSPr) is a recently described, sporadic human prion disease that is pathologically and biochemically distinct from the currently recognised sporadic Creutzfeldt-Jakob disease (sCJD) subtypes. The defining biochemical features of the abnormal form of the prion protein (PrPSc) in VPSPr are increased sensitivity to proteolysis and the presence of an N- and C-terminally cleaved ~8 kDa protease resistant PrPSc (PrPres) fragment. The biochemical and neuropathological profile of VPSPr has been proposed to resemble either Gerstmann-Sträussler-Scheinker syndrome (GSS) or familial CJD with the PRNP-V180I mutation. However, in some cases of VPSPr two protease resistant bands have been observed in Western blots that co-migrate with those of type 2 PrPres, suggesting that a proportion of the PrPSc present in VPSPr has properties similar to those of sCJD. RESULTS: Here, we have used conformation dependent immunoassay to confirm the presence of PrPSc in VPSPr that is more protease sensitive compared with sCJD. However, CDI also shows that a proportion of PrPSc in VPSPr resists PK digestion of its C-terminus, distinguishing it from GSS associated with ~8 kDa PrPres, and showing similarity to sCJD. Intensive investigation of a single VPSPr case with frozen tissue from multiple brain regions shows a broad, region-specific spectrum of protease sensitivity and differential stability of PrPSc in the absence of PK treatment. Finally, using protein misfolding cyclic amplification and real-time quaking induced conversion, we show that VPSPr PrPSc has the potential to seed conversion in vitro and that seeding activity is dispersed through a broad range of aggregate sizes. We further propose that seeding activity is associated with the ~19 and ~23 kDa PrPres rather than the ~8 kDa fragment. CONCLUSIONS: Therefore, PrPSc in VPSPr is heterogeneous in terms of protease sensitivity and stability to denaturation with the chaotrope GdnHCl and includes a proportion with similar properties to that found in sCJD.