Predictors of adverse outcomes in elders hospitalised for isolated orthopaedic trauma: a multicentre cohort study.

BACKGROUND: Patients >64 years of age now represent more than 51% of injury hospitalisations in Canada. The tools used to identify older patients who could benefit the most from an interdisciplinary approach include complex parameters difficult to collect in the ED, which suggests that better tools with higher accuracy and using items that can be derived from routinely collected data are needed. We aimed to identify variables that are associated with adverse outcomes in older patients admitted to a trauma centre for an isolated orthopaedic injury. METHODS: We conducted a multicentre retrospective cohort study between 1 April 2013 and 31 March 2019 on older patients hospitalised with a primary diagnosis of isolated orthopaedic injury (n=19 928). Data were extracted from the provincial trauma registry (Registre des traumatismes du Québec). We used multilevel logistic regression to estimate the associations between potential predictors and adverse outcomes (extended length of stay, mortality, complications, unplanned readmission and adverse discharge destination). RESULTS: Increasing age, male sex, specific comorbidities, type of orthopaedic injuries, increasing number of comorbidities, severe orthopaedic injury, head injuries and admission in the year before the injury were all significant predictors of adverse outcomes. CONCLUSION: We identified eight predictors of adverse outcomes in patients >64 years of age admitted to a trauma centre for orthopaedic injury. These variables could eventually be used to develop a clinical decision rule to identify elders who may benefit the most from interdisciplinary care.

Identifying Quality Indicators for the Care of Hospitalized Injured Older Adults: A Scoping Review of the Literature.

OBJECTIVES: Older adults represent more than 50% of trauma admissions in many high-income countries. Furthermore, they are at increased risk for complications, resulting in worse health outcomes than younger adults and a significant health care utilization burden. Quality indicators (QIs) are used to assess the quality of care in trauma systems, but few QIs reflect responses to older patients' specific needs. We aimed to (1) identify QIs used to assess acute hospital care for injured older patients, (2) assess support for identified QIs and, (3) identify gaps in existing QIs. DESIGN: Scoping review of the scientific and gray literature. METHODS: Selection and data extraction were performed by 2 independent reviewers. The level of support was assessed by the number of sources reporting QIs and whether they were developed according to scientific evidence, expert consensus, and patients' perspectives. RESULTS: Of 10,855 identified studies, 167 were eligible. Among 257 different QIs identified, 52% were hip fracture specific. Gaps were identified for head injuries, rib, and pelvic ring fractures. Although 61% of QIs assessed care processes, 21% and 18% focused on structures and outcomes, respectively. Although most QIs were based on literature reviews and/or expert consensus, patients' perspective was rarely accounted for. The 15 QIs with the highest level of support included minimum time between emergency department arrival and ward admission, minimum time to surgery for fractures, assessment by a geriatrician, orthogeriatric review for hip fracture patients, delirium screening, prompt and appropriate analgesia, early mobilizations, and physiotherapy. CONCLUSION AND IMPLICATIONS: Multiple QIs were identified, but their level of support was limited, and important gaps were identified. Future work should focus on achieving consensus for a set of QIs to assess the quality of trauma care to older adults. Such QIs could be used for quality improvement and ultimately improve outcomes for injured older adults.

Functional and cognitive decline in older delirious adults after an emergency department visit.

BACKGROUND: the aim of this study was to evaluate the impact of emergency department (ED) stay-associated delirium on older patient's functional and cognitive status at 60 days post ED visit. METHODS: this study was part of the multi-centre prospective cohort INDEED study. This project took place between March 2015 and July 2016 in five participating EDs across the province of Quebec. Independent non-delirious patients aged ≥65, with an ED stay ≥8 hours, were monitored for delirium until 24 hours post ward admission. A 60-day follow-up phone assessment was conducted. Participants were screened for delirium using the Confusion Assessment Method. Functional and cognitive statuses were assessed at baseline and at the 60-day follow-up using OARS and TICS-m. RESULTS: a total of 608 patients were recruited, 393 of which completed the 60-day follow-up. The Confusion Assessment Method was positive in 69 patients (11.8%) during ED stay or within the first 24 hours following ward admission. At 60 days, delirium patients experienced an adjusted loss of -2.9/28 [95%CI: -3.9, -2.0] points on the OARS scale compared to non-delirious patients who lost -1.6 [95%CI: -1.9, -1.3] (P = 0.006). A significant adjusted difference in cognitive function was also noted at 60 days, as TICS-m scores in delirious patients decreased by -1.6 [95%CI: -3.5, 0.2] compared to non-delirious patients, who showed a minor improvement of 0.5 [95%CI: -0.1, 1.1] (P = 0.03). CONCLUSION: seniors who developed ED stay-associated delirium have lower baseline functional and cognitive status than non-delirious patients, and they will experience a more significant decline at 60 days post ED visit.

Is the Drug Burden Index Related to Declining Functional Status at Follow-up in Community-Dwelling Seniors Consulting for Minor Injuries? Results from the Canadian Emergency Team Initiative Cohort Study.

BACKGROUND: The Canadian Emergency Team Initiative (CETI) cohort showed that minor injuries like sprained ankles or small fractures trigger a downward spiral of functional decline in 16% of independent seniors up to 6 months post-injury. Such seniors frequently receive medications with sedative or anticholinergic properties. The Drug Burden Index (DBI), which summarises the drug burden of these specific medications, has been associated with decreased physical and cognitive functioning in previous research. OBJECTIVES: We aimed to assess the contribution of the DBI to functional decline in the CETI cohort. METHODS: CETI participants were assessed physically and cognitively at baseline during their consultations at emergency departments (EDs) for their injuries and up to 6 months thereafter. The medication data were used to calculate baseline DBI and functional status was measured with the Older Americans Resources and Services (OARS) scale. Multivariate linear regression models assessed the association between baseline DBI and functional status at 6 months, adjusting for age, sex, baseline OARS, frailty level, comorbidity count, and mild cognitive impairment. RESULTS: The mean age of the 846 participants was 77 years and their mean DBI at baseline was 0.24. Complete follow-up data at 3 or 6 months was available for 718 participants among whom a higher DBI at the time of injury contributed to a lower functional status at 6 months. Each additional point in the DBI lead to a loss of 0.5 points on the OARS functional scale, p < 0.001. Among those with a DBI ≥ 1, 27.4% were considered 'patients who decline' at 3 or 6 months' follow-up, compared with 16.0% of those with a DBI of 0 (p = 0.06). CONCLUSIONS: ED visits are considered missed opportunities for optimal care interventions in seniors; Identifying their DBI and adjusting treatment accordingly may help limit functional decline in those at risk after minor injury.

Frailty Assessment to Help Predict Patients at Risk of Delirium When Consulting the Emergency Department.

BACKGROUND: Delirium is underdiagnosed in seniors at emergency departments (EDs) even though it is a frequent complication and is associated with functional and cognitive decline. As frailty is an independent predictor of adverse events in seniors, screening for frailty in EDs may help identify those at risk of delirium. OBJECTIVES: To assess if screening older patients for frailty in EDs could help identify those at risk of delirium. METHODOLOGY: This study was part of the multicenter prospective cohort INDEED study. Patients aged ≥ 65 years, initially free of delirium, with an ED stay ≥ 8 h were followed up to 24 h after ward admission. Frailty was assessed at baseline using the Clinical Frailty Scale; seniors with a score ≥ 5/7 were considered frail. Their delirium status was assessed twice daily using the Confusion Assessment Method. RESULTS: Among the 335 included patients, delirium occurred in 20/70 frail (28.6%) patients and in 20/265 (7.6%) robust ones. After adjusting for age and sex, the risk of delirium during ED stay was 3.13 (95% confidence interval 1.60-6.21) times higher in frail than in robust patients. Time between arrival to the ED and the incidence of delirium was also shorter for frail patients than for the robust ones (adjusted hazard ratio 2.44, 95% confidence interval 1.26-4.74). CONCLUSION: Increased frailty is associated with increased delirium during ED stays. Screening for frailty at emergency triage could help ED professionals identify seniors at higher risk of delirium.

Using the Bergman-Paris Question to screen seniors in the emergency department.

OBJECTIVES: In the fast pace of the Emergency Department (ED), clinicians are in need of tailored screening tools to detect seniors who are at risk of adverse outcomes. We aimed to explore the usefulness of the Bergman-Paris Question (BPQ) to expose potential undetected geriatric syndromes in community-living seniors presenting to the ED. METHODS: This is a planned sub-study of the INDEED multicentre prospective cohort study, including independent or semi-independent seniors (≥65 years old) admitted to hospital after an ED stay ≥8 hours and who were not delirious. Patients were assessed using validated screening tests for 3 geriatric syndromes: cognitive and functional impairment, and frailty. The BPQ was asked upon availability of a relative at enrolment. BPQ's sensitivity and specificity analyses were used to ascertain outcomes. RESULTS: A response to the BPQ was available for 171 patients (47% of the main study's cohort). Of this number, 75.4% were positive (suggesting impairment), and 24.6% were negative. To detect one of the three geriatric syndromes, the BPQ had a sensitivity of 85.4% (95% CI [76.3, 92.0]) and a specificity of 35.4% (95% CI [25.1, 46.7]). Similar results were obtained for each separate outcome. Odds ratio demonstrated a higher risk of presence of geriatric syndromes. CONCLUSION: The Bergman-Paris Question could be an ED screening tool for possible geriatric syndrome. A positive BPQ should prompt the need of further investigations and a negative BPQ possibly warrants no further action. More research is needed to validate the usefulness of the BPQ for day-to-day geriatric screening by ED professionals or geriatricians.

Cryptic amyloidogenic elements in mutant NEFH causing Charcot-Marie-Tooth 2 trigger aggresome formation and neuronal death.

Neurofilament heavy chain (NEFH) gene was recently identified to cause autosomal dominant axonal Charcot-Marie-Tooth disease (CMT2cc). However, the clinical spectrum of this condition and the physio-pathological pathway remain to be delineated. We report 12 patients from two French families with axonal dominantly inherited form of CMT caused by two new mutations in the NEFH gene. A remarkable feature was the early involvement of proximal muscles of the lower limbs associated with pyramidal signs in some patients. Nerve conduction velocity studies indicated a predominantly motor axonal neuropathy. Unique deletions of two nucleotides causing frameshifts near the end of the NEFH coding sequence were identified: in family 1, c.3008_3009del (p.Lys1003Argfs*59), and in family 2 c.3043_3044del (p.Lys1015Glyfs*47). Both frameshifts lead to 40 additional amino acids translation encoding a cryptic amyloidogenic element. Consistently, we show that these mutations cause protein aggregation which are recognised by the autophagic pathway in motoneurons and triggered caspase 3 activation leading to apoptosis in neuroblastoma cells. Using electroporation of chick embryo spinal cord, we confirm that NEFH mutants form aggregates in vivo and trigger apoptosis of spinal cord neurons. Thus, our results provide a physiological explanation for the overlap between CMT and amyotrophic lateral sclerosis (ALS) clinical features in affected patients.

JC-virus seroconversion in multiple sclerosis patients receiving natalizumab.

AIM: The objectives of this study were to evaluate the rate of JC virus (JCV) seroconversion/seroreversion in a French cohort of multiple sclerosis (MS) patients receiving natalizumab (NTZ), describe the characteristics of this population, identify risk factors for JCV seropositivity and analyse the additional value of quantitative JCV serology results in this context. METHODS: MS patients from two French MS centres, whose JCV serological status in 2011 while receiving NTZ was known (n=357; first-generation enzyme-linked immunosorbent assay (ELISA) test (Gen1)), were proposed for inclusion in this study. We evaluated the rate of JCV seroconversion over a period of one year with a second-generation ELISA test (Gen2; n=303) and analysed the quantitative results. Multivariate analysis was performed to identify risk factors for JCV seropositivity. RESULTS: Among the patients with Gen2 JCV serology (n=303) that had been JCV-seronegative one year before (n=165), the rate of JCV seroconversion was 26.67% (44/165). We observed a higher proportion of anti-JCV antibody seroconverters (14.5%) than expected (≤3%) but also increasing index values of anti-JCV antibody over time. CONCLUSION: Our data suggest that JCV reactivation occurs during NTZ therapy and leads to an increase in the anti-JCV antibodies titre, thus making them more easily detectable by the second-generation ELISA test.

Extensive myelitis associated with anti-NMDA receptor antibodies.

BACKGROUND: Encephalitis with anti-N-methyl-D-aspartate receptor antibodies (anti-NMDAR-Ab) is a rapid-onset encephalitis including psychosis, seizures, various movement disorders and autonomic system disturbances. CASE PRESENTATION: We report a very unusual case of extensive myelitis associated with anti-NMDAR-Ab. MRI also revealed a hyperintense T2 lesion, non-suggestive of MS, which progressively extended, associated with periventricular gadolinium enhancement visualized on brain MRI. Ophthalmological evaluation showed subclinical right optic neuritis. The absence of anti-AQP4 antibody argued against neuromyelitis optica spectrum disorder. A slight psychomotor slowing prompted us to search for various causes of autoimmune encephalitis. Anti-NMDAR-Ab was found in cerebrospinal fluid. CONCLUSION: In patients with extensive myelitis who are seronegative for anti-AQP4 antibodies, and after other classical causes have been excluded, the hypothesis of atypical anti-NMDAR-Ab encephalitis should also be considered.

Anti-JCV antibody prevalence in a French cohort of MS patients under natalizumab therapy.

To measure the prevalence of JCV-specific antibodies in a French cohort of MS patients treated with natalizumab and to identify risk factor(s) of JCV seropositivity. Progressive multifocal leukoencephalopathy (PML) risk may be stratified by anti-JCV antibody status, duration of natalizumab therapy (≥24 months) and prior exposure to immunosuppressive (IS) drugs. No data are available in France on the prevalence of anti-JCV antibodies and distribution of PML risk factors in patients treated with natalizumab. Sera of 361 patients under natalizumab therapy in two MS centers were analyzed using a previously validated ELISA test. We studied different characteristics: demographic, ethnic, radiological, clinical, prior use of immunomodulatory (IM) or IS drugs and natalizumab exposure duration. The JCV seropositivity rate was 51 % for the whole cohort. Mean natalizumab exposure duration was 27.27 months ± 15.57 (mean ± SD), and prior use of IS drugs was observed in 15.24 % of patients. Twenty-three patients (6.4 %) presented the three PML risk factors. By multivariate analysis, presence of anti-JCV antibodies was significantly linked to age, North African origin and natalizumab exposure duration. Anti-JCV antibody prevalence was similar to previously published data. Anti-JCV antibody status was linked to age. We also suggested that anti-JCV antibody status could be linked to natalizumab exposure duration and ethnic characteristics.