Nathalie Carrier

Anti-Sa antibodies and antibodies against cyclic citrullinated peptide are not equivalent as predictors of severe outcomes in patients with recent-onset polyarthritis

The prognostic value of two antibodies targeting citrullinated antigens, anti-Sa and anti-cyclic citrullinated peptide (CCP), present at inclusion, was evaluated prospectively in a cohort of 165 consecutive patients with recent-onset or early polyarthritis (EPA) followed for up to 30 months. Patients were treated according to current Good Clinical Practice standards. Predefined outcomes were severe arthritis and persistent arthritis. At inclusion, a median of 3 months after disease onset, 133 (81%) patients fulfilled at least four American College of Rheumatology criteria for rheumatoid arthritis and 30 (18%) had erosive changes on radiographs of hands and feet. Disease-modifying anti-rheumatic drugs were used in close to 80% of the patients at 30 months. Joint damage increased linearly over time, whereas disease activity declined markedly and remained low at each follow-up. Autoantibodies were identified in 76 (46%) patients: rheumatoid factor (RF) in 68 (41%), anti-CCP in 53 (33%), and anti-Sa in 46 (28%). All three antibodies were correlated, but anti-Sa antibodies best predicted severity at 18 and 30 months. RF and anti-CCP performed less well. For both outcomes, anti-Sa alone performed better than any combination of antibodies. The presence of any autoantibody identified about 50 to 60% of the patients with poor outcomes. In multivariate analysis, anti-Sa (odds ratio (OR) 8.83), the presence of erosions at inclusion (OR 3.47) and increasing age (OR 1.06/year) were significantly associated with severity, whereas RF and anti-CCP were not significant predictors. Persistent arthritis was present in up to 84% of patients; autoantibodies were specific but poorly sensitive predictors of this outcome. We conclude that assays for antibodies against citrullinated antigens differ in their ability to predict poorer outcomes in patients with EPA. In our EPA cohort treated in accordance with current standards, detection of anti-Sa but not of RF or anti-CCP antibodies, in combination with clinical and radiological variables present at the first encounter, allowed the identification of a subgroup of EPA patients suffering more rapid and more severe joint damage over 30 months.

Campylobacteriosis in urban versus rural areas: a case-case study integrated with molecular typing to validate risk factors and to attribute sources of infection.

Campylobacter infection is a leading cause of bacterial gastroenteritis worldwide, and most clinical cases appear as isolated, sporadic infections for which the source is rarely apparent. From July 2005 to December 2007 we conducted a prospective case-case study of sporadic, domestically-acquired Campylobacter enteritis in rural versus urban areas and a prevalence study of Campylobacter in animal and environmental sources in the Eastern Townships, Quebec. Isolates were typed using Multilocus Sequence Typing (MLST) to reinforce the case-case findings and to assign a source probability estimate for each human isolate. The risk of human campylobacteriosis was 1.89-fold higher in rural than urban areas. Unconditional multivariate logistic regression analysis identified two independent risk factors associated with human Campylobacter infections acquired in rural area: occupational exposure to animals (OR = 10.6, 95% CI: 1.2–91, p = 0.032), and household water coming from a private well (OR = 8.3, 95% CI: 3.4–20.4, p<0.0001). A total of 851 C. jejuni isolates (178 human, 257 chicken, 87 bovine, 266 water, 63 wild bird) were typed using MLST. Among human isolates, the incidence rates of clonal complexes (CC) CC-21, CC-45, and CC-61 were higher in rural than urban areas. MLST-based source attribution analysis indicated that 64.5% of human C. jejuni isolates were attributable to chicken, followed by cattle (25.8%), water (7.4%), and wild birds (2.3%). Chicken was the attributable source for the majority of cases, independent of residential area, sex and age. The increased incidence in rural compared to urban areas was associated with occupational exposure to animals, particularly cattle among those aged 15–34 years, and with consumption of private well water. Both bovine and water exposure appeared to contribute to the seasonal variation in campylobacteriosis. These results provide a basis for developing public education and preventive programs targeting the risk factors identified.

The Complex Vaginal Flora of West African Women with Bacterial Vaginosis

Background The spectrum of bacteria associated with bacterial vaginosis (BV) has recently expanded through taxonomic changes and the use of molecular methods. These methods have yet to be used in large-scale epidemiological studies in Africa where BV is highly prevalent. Methods An analysis of samples obtained during a clinical trial of the management of vaginal discharge in four West African countries. Samples were available from 1555 participants; 843 (54%) had BV. Nucleic acids of 13 bacterial genera or species potentially associated with BV were detected through the polymerase chain reaction. Results The associations between various components of the vaginal flora were complex. Excluding Lactobacillus, the other 12 micro-organisms were all associated with each other at the p≤0.001 level. The prevalence of various bacterial genera or species varied according to age, sexual activity and HIV status. In multivariate analysis, the presence of Gardnerella vaginalis, Bifidobacterium, Megasphaera elsdenii, Dialister, Mycoplasma hominis, Leptotrichia, and Prevotella were independently associated with BV as was the absence of Lactobacillus and Peptoniphilus. However, Mobiluncus, Atopobium vaginae, Anaerococcus, and Eggerthella were not independently associated with BV. Unexpectedly, after treatment with a regimen that included either metronidazole or tinidazole, the proportion of patients with a complete resolution of symptoms by day 14 increased with the number of bacterial genera or species present at enrolment. Conclusions Numerous bacterial genera or species were strongly associated with each other in a pattern that suggested a symbiotic relationship. BV cases with a simpler flora were less likely to respond to treatment. Overall, the vaginal flora of West African women with BV was reminiscent of that of their counterparts in industrialized countries.

Thermotolerant Coliforms Are Not a Good Surrogate for Campylobacter spp. in Environmental Water

ABSTRACT This study aimed to assess the importance of quantitatively detecting Campylobacter spp. in environmental surface water. The prevalence and the quantity of Campylobacter spp., thermotolerant coliforms, and Escherichia coli in 2,471 samples collected weekly, over a 2-year period, from 13 rivers and 12 streams in the Eastern Townships, Québec, Canada, were determined. Overall, 1,071 (43%), 1,481 (60%), and 1,463 (59%) samples were positive for Campylobacter spp., thermotolerant coliforms, and E. coli, respectively. There were weak correlations between the weekly distributions of Campylobacter spp. and thermotolerant coliforms (Spearmans ρ coefficient = 0.27; P = 0.008) and between the quantitative levels of the two classes of organisms (Kendall tau-b correlation coefficient = 0.233; P < 0.0001). Well water samples from the Eastern Townships were also tested. Five (10%) of 53 samples from private surface wells were positive for Campylobacter jejuni, of which only 2 were positive for thermotolerant coliforms. These findings suggest that microbial monitoring of raw water by using only fecal indicator organisms is not sufficient for assessing the occurrence or the load of thermophilic Campylobacter spp. Insights into the role of environmental water as sources for sporadic Campylobacter infection will require genus-specific monitoring techniques.

The DERAA HLA-DR alleles in patients with early polyarthritis: protection against severe disease and lack of association with rheumatoid arthritis autoantibodies.

OBJECTIVE To define the association of alleles encoding the HLA-DR rheumatoid arthritis (RA) protective epitope (DERAA) with the presence of RA-associated antibodies at study inclusion and with severe outcome in patients with early polyarthritis (EPA). METHODS Consecutive EPA patients (n = 210) were evaluated early (mean of 4.8 months after diagnosis) and prospectively (for 30 months). HLA class II typing was performed by polymerase chain reaction using sequence-specific primers, and HLA-DR alleles DERAA, RA-associated shared epitope (SE), and non-SE/non-DERAA (neither SE nor DERAA) were identified. RA-associated antibodies identified were anti-Sa/citrullinated vimentin, anti-cyclic citrullinated peptide 2, and IgM rheumatoid factor. Severe disease was defined according to a preset threshold of joint destruction and/or functional limitation. RESULTS DERAA and SE alleles were present in 62 and 110 of the 210 EPA patients, respectively. At 30 months, severe disease was present in 78 patients (37%). In contrast to SE alleles, DERAA alleles were not associated with the production of RA-associated antibodies, but were strongly protective against severe disease at 30 months (odds ratio 0.30, P < 0.001). DERAA alleles emerged as a strong, independent protective marker on multivariate analysis. The protective effect of DERAA was seen only in patients who did not already have erosions at study inclusion, was independent of the presence of antibodies, but was not associated with spontaneous remission. CONCLUSION In our EPA cohort, the presence of a DERAA sequence was a strong independent predictor of a better prognosis, but only in the absence of erosive disease that was already present at inclusion. Identification of DERAA alleles may help in managing the large subgroup of EPA patients who do not have erosions at baseline.

Impact of methicillin resistant Staphylococcus aureus contact isolation units on medical care.

Background Patient isolation using contact precautions has gained widespread use to halt MRSA transmission, however supportive data is scarce and concerns regarding patient safety and satisfaction have been raised. At our institution, MRSA patients are isolated on a dedicated ward (cohort isolation), rather than in separate rooms. Our objectives were (1) to determine the proportion of bedside medical visits to patients on an isolation ward, (2) to quantify complications in those patients and (3) to determine if those complications are related to isolation and if they can be prevented. Methods This retrospective case-control study was performed on the two sites of a tertiary teaching hospital in Sherbrooke, QC, Canada. We matched MRSA patients with an admission diagnosis of heart failure or chronic obstructive pulmonary disease to similar non-isolated controls. The proportion of bedside visits was ascertained through the number of progress notes with subjective elements or with a physical examination. Complications were sought through an extensive file review, and events were analysed according to Baker’s CAES causality and preventability scales. Results Overall, 111 patient pairs were analysed (35 with heart failure and 76 with COPD). Isolated patients received less bedside visits (subjective notes/1,000 patient-days: 849.6 vs. 983.3, p = 0,001). Attending physicians (454.5 vs. 451.4, p = 0,02) and residents (347.0 vs. 416.9, p = 0.01) are responsible for this discrepancy, while medical students appear to visit isolated and non-isolated patients equally (116.5 vs. 114.9, p = 0.90). Isolated patients showed a tendency towards longer stay and more preventable complications, although no difference in the total number of complications was observed. Conclusion Isolated patients have less documented care that suggests less bedside visits from the medical staff, which could hamper the therapeutical relationship. Further studies are needed to explain this finding.

Outcomes in recent‐onset inflammatory polyarthritis differ according to initial titers, persistence over time, and specificity of the autoantibodies

To prospectively evaluate the predictive value of initial titers and subsequent variations of 3 rheumatoid arthritis–associated antibodies for outcomes at 30 months in patients with recent‐onset polyarthritis.

Evaluation of Bleeding Risk in Patients Exposed to Therapeutic Unfractionated or Low-Molecular Weight Heparin: A Cohort Study in the Context of a Quality Improvement Initiative

Background: Bleeding associated with the use of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) can be a serious complication of health-care management and should be the focus of quality improvement initiatives by institutions. Objective: To measure the incidence of bleeding with UFH and LMWH and evaluate associated risk factors, Methods: An observational cohort study was conducted at a secondary and tertiary care hospital in Canada. All adults receiving therapeutic doses of UFH or LMWH between April 2006 and March 2007, with the exception of cardiac surgery patients, were included. Bleeding episodes were classified per the GUSTO scale. Results: Of 3066 hospitalizations, the incidence of moderate or severe bleeding was 3.5%. Advanced age (OR 1.02. 95% CI 1.01 to 1.04; p< 0.001), female sex (OR 1.80, 95% CI 1.21 to 2.66; p = 0.003), UFH instead of LMWH (OR 4.72, 95% CI 2.17 to 10.30; p< 0.001), creatinine clearance (CrCI) (OR 0.89, 95% CI 0.84 to 0.95; p < 0.001, for a difference of 10 mL/min in CrCI), and supratherapeutic activated partial thromboplastin time (aPTT) (OR 3.88.95% CI 2.25 to 6.69; p < 0.001 for >180 vs <90 seconds) were associated with a higher risk of bleeding in univariate analysis. In a multivariate model without aPTT, CrCI (OR 0.90, 95% CI 0.85 to 0.96; p< 0.001, for a difference of 10 mL/min in CrCI) and UFH (OR 2.35,95% CI 1.11 to 4.98; p = 0.005) were significant predictors of bleeding. Among the bleeding episodes, 31% were in a postoperative context and 15% were following a puncture. Conclusions: Our findings show that CrCI and aPTT values, as well as the type of heparin used, are significant predictors of bleeding in patients receiving UFH or LMWH and that dosages should be adjusted to patient weight. The reason for all supratherapeutic aPTT levels should be sought and corrective measures taken immediately.

The World Health Organization Fracture Risk Assessment Tool (FRAX) Underestimates Incident and Recurrent Fractures in Consecutive Patients With Fragility Fractures

CONTEXT The World Health Organization Fracture Risk Assessment tool (FRAX) was developed to identify patients at risk of sustaining a fragility fracture (FF). OBJECTIVE The objective of the study was to evaluate estimated FRAX probabilities of FF at the time of a FF and to compare them with the observed incidence of recurrent FF. METHODS A prospective cohort included men and women older than 50 years at the time of a FF. FRAX scores without bone mineral density [FRAX-body mass index (BMI)] were calculated prior to and after the inclusion FF. Recurrent FFs were recorded over a 4-year follow-up. Determinants associated with recurrent FF were determined by univariate and multivariate analyses. RESULTS FRAX-BMI scores were available in 1399 of the 1409 recruited patients. A high-risk FRAX-BMI score was present in only 42.7% patients before and 56.4% after the incident FF. Most FF patients at low or moderate risk before their initial FF were men, younger than 65 years, or without previous FF. Over a median follow-up of 3 years, recurrent FF occurred in 108 patients (2.69 per 100 patient-years). The overall sensitivity of post-FF FRAX to predict a recurrent FF was 71.3% and was specifically lower in patients younger than 65 years (13%) and without previous FF (63%) at inclusion. CONCLUSIONS The FRAX-BMI scores were below the Canadian threshold for treatment in more than half the patients at the time of a FF and in close to a third of patients with recurrent FF. FRAX-BMI severely underestimates the FF risk in patients younger than 65 years old and after a single FF.

Statins may increase intracerebral hemorrhage volume.

BACKGROUND Some studies have suggested an association between hypocholesterolemia and intracerebral hemorrhage (ICH). In the SPARCL trial, statin use increased ICH risk. We tested the hypothesis that use of statins affects the volume of spontaneous ICH and contributes to the progression of ICH volume between baseline and follow-up CT scans. METHODS Consecutive cases of spontaneous ICH were reviewed. Secondary causes were excluded. We measured ICH volume on the baseline and follow-up CT scans using the AxBxC/2 method. Multivariate analysis and logistic regression modeling were used. The primary outcome was the ICH volume on the baseline CT scan. Secondary outcomes included volume variation between the baseline and the first follow up CT scans and death. RESULTS Of 303 subjects, 71 were taking a statin at the time of the ICH (23%). Statin users were significantly more likely to be younger, to have co-morbidities and take anticoagulant or anti-platelet medication. They also had a higher baseline ICH volume than non-statin users (median 31.2 [10, 82.1] ml vs 16 [4, 43.8] ml; p=0.006). Adjusting for possible confounders, statins remained associated with an increased ICH volume (p=0.007). There was a significant mean ICH volume progression between the first and second CT scans in statin users (+10.8 vs +0.9 ml; p=0.03; 95% CI: [-1, +22.6] [-2.5, +4.3]). No difference in mortality was seen between the two groups. CONCLUSION Treatment with HMG-CoA reductase inhibitors may be a risk factor for increased ICH volume in spontaneous brain hemorrhages and could contribute to hemorrhages volume progression.