Background: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease of unknown etiology. Although known to be rare, precise information on the frequency of ALS is essential to anticipate future demands on health resources and as baseline information for epidemiological studies. As part of a new ALS epidemiological initiative in Canada, we conducted a systematic review of published incidence and prevalence research in Canada. Methods: Electronic searches and bibliographic reviews of pertinent publications were conducted. Results: We identified 6 published studies from 4 Canadian provinces conducted between 1974 and 2004; 2 were available only as abstracts. Reported annual incidence rates were similar and study quality was generally good, but there was insufficient detail to adequately assess the methodological quality of 3 of the studies. The most recent studies reported an annual ALS age-adjusted incidence of 2.13 per 100,000 in Nova Scotia (2003–2004) and a crude mean annual incidence of 2.4 per 100,000 in Newfoundland and Labrador (2000–2004). Conclusions: There are limited data on the frequency of ALS in Canada. We found no studies from 6 of the Canadian provinces or from the territories. Future research is needed to estimate the frequency of occurrence of ALS in Canada.
BackgroundBiomarkers are of much interest in rheumatoid arthritis (RA). Valid, reliable and convenient biomarkers, to detect early disease, predict severity and monitor treatment response are essential to achieving optimal outcomes. Several biomarkers have been suggested but are largely not validated. Validated measures of rheumatoid factor(RF), citrullination antibodies(ACPA), C-reactive protein(CRP) and erythrocyte sedimentation rate(ESR) do not provide a complete picture. 14–3–3η, a protein from a family of highly conserved regulatory molecules, has promising data as a novel RA biomarker and is the focus of this review.ObjectivesThis review aimed to identify the literature characterising 14–3–3η and its utility in RA.MethodsSearch terms 14–3–3η, biomarker and rheumatoid arthritis were used in Pubmed, Web of Science and Embase databases and reference lists of relevant papers were scanned. Inclusion criteria were confirmed RA, 14–3–3η and English language.ResultsSeven key papers were identified on 14–3–3η proteins1-6 and one on 14–3–3η antibodies (14–3–3η-Ab)7. Detecting RA: 14–3–3η was elevated in patients with RA compared to healthy controls2,4 and patients with other diseases (p<0.001)4. Being positive for 14–3–3η (>0.19 ng/mL) showed sensitivity and specificity of 63.3% and 92.6%4 to detect RA, increasing to 91.7% and 99.6%, respectively when an ROC-determined optimal cut-off of 0.879 ng/mL was used2. When combined with current markers RF ±ACPA the detection capacity for early RA increased to 78% and for established RA to 96%, compared to 72% and 88%4, respectively for RF ±ACPA alone. Including the 14–3–3η-Ab further increased detection7. The 14–3–3η-Ab appeared at higher levels in early, treatment naïve RA, while no difference was seen in established RA compared to controls7. The 14–3–3η-Ab was not associated with inflammatory markers ESR or CRP7. Although higher levels of the 14–3–3η protein were detected in early RA (p<0.05), rate of detection was higher in established RA2. Predicting disease severity: Baseline 14–3–3η status was associated with increased disease severity1,2,3,4,5, higher median DAS (6.3 vs 5.7, p=0.026) and HAQ scores (1.9 vs 1.0, p=0.001)4. Significant associations with baseline DAS28-ESR, CDAI and SDAI (p<0.045 – p<0.001) were also reported3. Physical symptoms are closely related to 14–3–3η levels2; patients achieving DAS28-ESR-defined remission had significantly lower levels than non-remitters3. Radiographic progression was significantly associated with higher 14–3–3η1 5, OR=6.2 (95%CI 1.3 to 30.2) in early RA and 2.5 (95%CI 1.0 to 1.4) in established RA5. Conflicting results on associations with existing markers ESR, CRP, RF, and ACPA have been reported1,2,3,4,5,6. Treatment response: 14–3–3η levels are dynamic with changing disease activity1,3. Also, pre-treatment 14–3–3η levels were an independent predictor of response to some therapies3.Conclusions14–3–3η protein and Ab are promising biomarkers in RA diagnosis, disease severity and response to treatment. Future research characteris...
Rheumatoid arthritis (RA) is a chronic multisystem inflammatory disorder with significant morbidity and mortality. Making an early diagnosis and providing appropriate treatment decisions based on clinical and other parameter results in good disease control. Biomarkers, such as C reactive protein (CRP), anti-cyclic citrullinated peptides (anti-CCP), and erythrocyte sedimentation rate (ESR), have been traditionally used. Recently novel biomarkers are described. This article reviews the evidence behind a novel biomarker 14-3-3 η that has been found to provide additional diagnostic and prognostic information as well as predicting response to treatment. A systematic literature review is presented showing the evidence behind this molecule.
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