Natural Autoantibodies in Biologic-Treated Rheumatoid Arthritis and Ankylosing Spondylitis Patients: Associations with Vascular Pathophysiology.

Cardiovascular (CV) morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Natural autoantibodies (nAAb) are involved in innate immunity, as well as autoimmunity, inflammation, and atherosclerosis. There have not been any studies assessing the effects of biologics on nAAbs in RA and AS, also in relation to vascular pathophysiology. Fifty-three anti-TNF-treated RA and AS patients were included in a 12-month follow-up study. Anti-citrate synthase (CS) and anti-topoisomerase I fragment 4 (TOPO-F4) IgM and IgG levels were determined by ELISA. Ultrasonography was performed to assess brachial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV). Other variables were also evaluated at baseline and 6 and 12 months after treatment initiation. Anti-TNF therapy improved FMD in RA and PWV in AS and stabilized ccIMT. TNF inhibition increased anti-CS IgM and IgG, and possibly also anti-TOPO-F4 IgG levels. Various correlation analyses revealed that nAAbs might be independently involved in autoimmunity as well as changes in inflammation and vascular pathology over time in biologic-treated patients (p < 0.05). We also found associations between anti-TOPO-F4 IgG and anti-Hsp60 IgG (p < 0.05). Baseline nAAb levels or nAAb level changes might determine changes in CRP, disease activity, FMD, PWV, and ccIMT over time (p < 0.05). The interplay between arthritis and inflammatory atherosclerosis, as well as the effects of anti-TNF biologics on these pathologies, might independently involve nAAbs.

Six-Month Follow-Up of Periodontal Condition in Rheumatoid Arthritis and Ankylosing Spondylitis Arthritis Patients Undergoing Anti-Tumour Necrosis Factor-α Therapy.

In our present study, we aimed to assess the effects of anti-TNF therapy on periodontal condition in a mixed cohort of patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Moreover, we wished to determine whether the baseline dental condition of these patients would affect response to biological therapy. A cohort of 24 arthritis patients was consecutively recruited before starting anti-TNFα therapy. After the dropout of six patients, we evaluated the dental status of 18 subjects at baseline and after 6 months of biological therapy. Clinical responder (R) and non-responder (NR) status was determined after 6 months of anti-TNF treatment. Plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD), PPDmax, clinical attachment loss (CAL), and CALmax were determined. During the 6-month treatment period, six patients (3 RA and 3 AS) terminated the study prematurely as they did not respond to treatment (NR). Therefore, 18 patients were included in the full analysis. There were no major differences in PI, BOP, PPD, PPD max, CAL, and CALmax, among R and NR patients. TNF inhibition resulted in increased GI (0.65 ± 0.34 vs. 0.88 ± 0.30; p < 0.05), as well as decreased PPDmax (4 ± 1.94 vs. 2.72 ± 1.36; p < 0.05) and CALmax (5.22 ± 2.56 vs. 2.72 ± 1.36; p < 0.05) after 6 months. Eight patients had incomplete canal fillings or dead pulps and/or apical periodontitis; six in the R and two in the NR group. In our present study, anti-TNF therapy seemed to worsen the extent of gingival inflammation (GI); however our results also do not support the reduction of mean CPD and CAL as reported by others.

Using machine learning to standardize medication records in a pan-Canadian electronic medical record database: a data-driven algorithm study focused on antibiotics prescribed in primary care.

BACKGROUND: Most antibiotics dispensed by community pharmacies in Canada are prescribed by family physicians, but using the prescribing information contained within primary care electronic medical records (EMRs) for secondary purposes can be challenging owing to variable data quality. We used antibiotic medications as an exemplar to validate a machine-learning approach for cleaning and coding medication data in a pan-Canadian primary care EMR database. METHODS: The Canadian Primary Care Sentinel Surveillance Network database contained an estimated 42 million medication records, which we mapped to an Anatomic Therapeutic Chemical (ATC) code by applying a semisupervised classification model developed using reference standard labels derived from the Health Canada Drug Product Database. We validated the resulting ATC codes in a subset of antibiotic records (16 119 unique strings) to determine whether the algorithm correctly classified the medication according to manual review of the original medication record. RESULTS: In the antibiotic subset, the algorithm showed high validity (sensitivity 99.5%, specificity 92.4%, positive predictive value 98.6%, negative predictive value 97.0%) in classifying whether the medication was an antibiotic. INTERPRETATION: Our machine-learning algorithm classified unstructured antibiotic medication data from primary care with a high degree of accuracy. Access to cleaned EMR data can support important secondary uses, including community-based antibiotic prescribing surveillance and practice improvement.

Effect of tofacitinib therapy on angiotensin converting enzyme activity in rheumatoid arthritis.

Introduction: The Renin-Angiotensin-Aldosterone system (RAAS) has been implicated in the regulation of the cardiovascular system and linked to rheumatoid arthritis (RA). Little information has become available on the effects of Janus kinase (JAK) inhibition on RAAS. Here we studied the effects of 12-month tofacitinib treatment on angiotensin converting enzyme (ACE), ACE2 production and ACE/ACE2 ratios in RA along with numerous other biomarkers. Patients and methods: Thirty RA patients were treated with tofacitinib in this prospective study. Serum ACE concentrations were assessed by ELISA. ACE2 activity was determined by a specific quenched fluorescent substrate. ACE/ACE2 ratios were calculated. We also determined common carotid intima-media thickness (ccIMT), brachial artery flow-mediated vasodilation (FMD) and carotid-femoral pulse-wave velocity (cfPWV) by ultrasound. C-reactive protein (CRP), rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) were also determined. All measurements were performed at baseline, as well as after 6 and 12 months of tofacitinib treatment. Results: After the dropout of 4 patients, 26 completed the study. Tofacitinib treatment increased ACE levels after 6 and 12 months, while ACE2 activity only transiently increased at 6 months. The ACE/ACE2 ratio increased after 1 year of therapy (p < 0.05). Logistic regression analyses identified correlations between ACE, ACE2 or ACE/ACE2 ratios and RF at various time points. Baseline disease duration also correlated with erythrocyte sedimentation rate (ESR) (p < 0.05). One-year changes of ACE or ACE2 were determined by tofacitinib treatment plus ACPA or RF, respectively (p < 0.05). Conclusion: JAK inhibition increases serum ACE and ACE/ACE2 ratio in RA. Baseline inflammation (ESR), disease duration and ACPA, as well as RF levels at various time points can be coupled to the regulation of ACE/ACE2 ratio. The effect of tofacitinib on RAAS provides a plausible explanation for the cardiovascular effects of JAK inhibition in RA.

Effects of 1-year tofacitinib therapy on angiogenic biomarkers in rheumatoid arthritis.

OBJECTIVES: Cardiovascular (CV) morbidity and mortality, and perpetuated synovial angiogenesis have been associated with RA. In our study we evaluated angiogenic factors in relation to vascular inflammation and function, and clinical markers in RA patients undergoing 1-year tofacitinib therapy. METHODS: Thirty RA patients treated with either 5 mg or 10 mg twice daily tofacitinib were included in a 12-month follow-up study. Eventually, 26 patients completed the study and were included in data analysis. Levels of various angiogenic cytokines (TNF-α, IL-6), growth factors [VEGF, basic fibroblast (bFGF), epidermal (EGF), placental (PlGF)], cathepsin K (CathK), CXC chemokine ligand 8 (CXCL8), galectin-3 (Gal-3) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) were determined at baseline, and at 6 and 12 months after initiating tofacitinib treatment. In order to assess flow-mediated vasodilation, common carotid intima-media thickness (ccIMT) and carotid-femoral pulse-wave velocity, ultrasonography was performed. Synovial and aortic inflammation was also assessed by 18F-fluorodeoxyglucose-PET/CT. RESULTS: One-year tofacitinib therapy significantly decreased IL-6, VEGF, bFGF, EGF, PlGF and CathK, while it increased Gal-3 production (P < 0.05). bFGF, PlGF and NT-proBNP levels were higher, while platelet-endothelial cell adhesion molecule 1 (PECAM-1) levels were lower in RF-seropositive patients (P < 0.05). TNF-α, bFGF and PlGF correlated with post-treatment synovial inflammation, while aortic inflammation was rather dependent on IL-6 and PECAM-1 as determined by PET/CT (P < 0.05). In the correlation analyses, NT-proBNP, CXCL8 and Cath variables correlated with ccIMT (P < 0.05). CONCLUSIONS: Decreasing production of bFGF, PlGF or IL-6 by 1-year tofacitinib therapy potentially inhibits synovial and aortic inflammation. Although NT-proBNP, CXCL8 and CathK were associated with ccIMT, their role in RA-associated atherosclerosis needs to be further evaluated.

Documenting cannabis use in primary care: a descriptive cross-sectional study using electronic medical record data in Alberta, Canada.

OBJECTIVE: Documenting cannabis use is important for patient care, but no formal requirements for consistent reporting exist in primary care. The objective of this study was to understand how cannabis use is documented in primary care electronic medical record (EMR) data. RESULTS: This was a cross-sectional study using de-identified EMR data from over 398,000 patients and 333 primary care providers in Alberta, Canada. An automated pattern-matching algorithm was developed to identify text and ICD-9 diagnostic codes indicating cannabis use in the EMR. There was a total of 11,724 records indicating cannabis use from 4652 patients, representing approximately 1.2% of the patient sample. Commonly used terms and ICD-9 codes included cannabis, marijuana/marihuana, THC, 304.3 and 305.2. Nabilone was the most frequently prescribed cannabinoid medication. Slightly more males and those with a chronic condition had cannabis use recorded more often. Overall, very few patients have cannabis use recorded in primary care EMR data and this is not captured in a systematic way. We propose several strategies to improve the documentation of cannabis use to facilitate more effective clinical care, research, and surveillance.

Older persons living with dementia and their use of acute care services over 2 years in Alberta.

OBJECTIVE: To characterize transitions to acute and residential care and identify variables associated with specific transitions among community-based persons living with dementia (PLWD). DESIGN: Retrospective cohort study using primary care electronic medical record data linked with health administrative data. SETTING: Alberta. PARTICIPANTS: Adults aged 65 years or older living in the community who had been diagnosed with dementia and who saw a Canadian Primary Care Sentinel Surveillance Network contributor between January 1, 2013, and February 28, 2015. MAIN OUTCOME MEASURES: All emergency department visits, hospitalizations, residential care (supportive living and long-term care) admissions, and deaths within a 2-year follow-up period. RESULTS: In total, 576 PLWD were identified who had a mean (SD) age of 80.4 (7.7) years; 55% were female. In 2 years, 423 (73.4%) had at least 1 transition and, of these, 111 (26.2%) had 6 or more. Emergency department visits, including multiple visits, were common (71.4% had ≥1, 12.1% had ≥4). Of those hospitalized (43.8%), nearly all were admitted from the emergency department; the average (SD) length of stay was 23.6 (35.8) days, and 32.9% had at least 1 alternate level of care day. In total, 19.3% entered residential care, most admitted from hospital. Those admitted to hospital and those admitted to residential care were older and had greater historical health system use, including home care. One-quarter of the sample did not have any transitions (or die) during follow-up; they were typically younger and had limited historical health system use. CONCLUSION: Older PLWD experienced frequent, and frequently compound, transitions that have implications for them, their family members, and the health system. There was also a large proportion without transitions suggesting that appropriate supports enable PLWD to do well in their own communities. The identification of PLWD who are at risk of or who make frequent transitions may allow for more proactive implementation of community-based supports and smoother transitions to residential care.

Effects of tofacitinib therapy on arginine and methionine metabolites in association with vascular pathophysiology in rheumatoid arthritis: A metabolomic approach.

Introduction: Rheumatoid arthritis (RA) has been associated with changes in lipid, arginine and NO metabolism with increased cardiovascular (CV) risk. The aim of this study is to evaluate the effect of tofacitinib, a Janus kinase (JAK) inhibitor, on arginine and methionine metabolism in correlation with inflammation, functional and pathological vascular changes during one-year treatment of patients with RA. Materials and methods: Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) levels. We assessed brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) by ultrasound at baseline and after 6 and 12 months. We also determined plasma L-arginine, L-citrulline, L-ornithine, inducible nitric oxide synthase (iNOS), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-N-monomethyl-arginine (L-NMMA), cysteine, homocysteine, and methionine levels at these time points. Results: Twenty-six patients (13 on each arm) completed the study. CRP, ESR and DAS28 decreased significantly during one-year treatment with tofacitinib. Arginine and ADMA showed a negative univariate correlation with CRP but not with FMD, PWV or IMT. Tofacitinib at 10 mg bid significantly increased L-arginine, L-ornithine, iNOS and methionine levels after 12 months. ADMA and SDMA levels did not change in our study. Methionine showed negative correlation with FMD at baseline and positive correlation with PWV after 12 months. No change was observed in FMD and PWV but a significant increase was measured in IMT at 6 and 12 months. Multivariate analysis indicated variable correlations of L-arginine, L-citrulline, ADMA, L-NMMA, homocysteine and methionine with DAS28, CRP, ESR and RF but not with anti-CCP after one-year treatment. With respect to vascular pathophysiology, only PWV and methionine correlated with each other. Conclusion: One-year tofacitinib treatment suppressed systemic inflammation and improved functional status in RA. FMD, PWV have not been affected by one-year tofacitinib treatment., while IMT increased further despite treatment. Increased arginine and methionine might contribute to the anti-inflammatory effects of tofacitinib. Increased arginine availability with no changing ADMA may protect FMD and PWV from deterioration. The increase of IMT in the anti-inflammatory environment cannot be explained by arginine or methionine metabolism in this study.

Effects of One-Year Tofacitinib Therapy on Lipids and Adipokines in Association with Vascular Pathophysiology in Rheumatoid Arthritis.

Background: Cardiovascular (CV) morbidity, mortality and metabolic syndrome are associated with rheumatoid arthritis (RA). A recent trial has suggested increased risk of major CV events (MACE) upon the Janus kinase (JAK) inhibitor tofacitinib compared with anti-tumor necrosis factor α (TNF-α) therapy. In our study, we evaluated lipids and other metabolic markers in relation to vascular function and clinical markers in RA patients undergoing one-year tofacitinib therapy. Patients and methods: Thirty RA patients treated with either 5 mg or 10 mg bid tofacitinib were included in a 12-month follow-up study. Various lipids, paraoxonase (PON1), myeloperoxidase (MPO), thrombospondin-1 (TSP-1) and adipokine levels, such as adiponectin, leptin, resistin, adipsin and chemerin were determined. In order to assess flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and arterial pulse-wave velocity (PWV) ultrasonography were performed. Assessments were carried out at baseline, and 6 and 12 months after initiating treatment. Results: One-year tofacitinib therapy significantly increased TC, HDL, LDL, APOA, APOB, leptin, adipsin and TSP-1, while significantly decreasing Lp(a), chemerin, PON1 and MPO levels. TG, lipid indices (TC/HDL and LDL/HDL), adiponectin and resistin showed no significant changes. Numerous associations were found between lipids, adipokines, clinical markers and IMT, FMD and PWV (p < 0.05). Regression analysis suggested, among others, association of BMI with CRP and PWV (p < 0.05). Adipokines variably correlated with age, BMI, CRP, CCP, FMD, IMT and PWV, while MPO, PON1 and TSP-1 variably correlated with age, disease duration, BMI, RF and PWV (p < 0.05). Conclusions: JAK inhibition by tofacitinib exerts balanced effects on lipids and other metabolic markers in RA. Various correlations may exist between metabolic, clinical parameters and vascular pathophysiology during tofacitinib treatment. Complex assessment of lipids, metabolic factors together with clinical parameters and vascular pathophysiology may be utilized in clinical practice to determine and monitor the CV status of patients in relation with clinical response to JAK inhibition.

A cross-sectional study evaluating cardiovascular risk and statin prescribing in the Canadian Primary Care Sentinel Surveillance Network database.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in Canada. Assessment and management of CVD risk is essential in reducing disease burden. This includes both clinical risk factors and socioeconomic factors, though few studies report on socioeconomic status in relation to CVD risk and treatment. The primary objective of this study was to estimate the cardiovascular risk of patients attending primary care practices across Canada; secondly, to evaluate concordance with care indicators suggested by current clinical practice guidelines for statin prescribing according to patients' cardiovascular risk and socioeconomic status. METHODS: This cross-sectional observational study used the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) database, which is comprised of clinical data from primary care electronic medical records. Patients aged 35-75y with at least one visit to their primary care provider between 2012 and 2016 were included. Patients were assigned to a CVD risk category (high, medium, low) and a deprivation quintile was calculated for those with full postal code available. Descriptive analyses were used to determine the proportion of patients in each risk category. Logistic regression was used to evaluate the consistency of statin prescribing according to national clinical guidelines by risk category and deprivation quintile. RESULTS: A total of 324,526 patients were included. Of those, 116,947 (36%) of patients were assigned to a high CVD risk category, primarily older adults, males, and those with co-morbidities. There were statistically significant differences between least (quintile 1) and most (quintile 5) deprived socioeconomic quintiles, with those at high CVD risk disproportionately in Q5 (odds ratio 1.4). Overall, 48% of high-risk patients had at least one statin prescription in their record. Patients in the lower socioeconomic groups had a higher risk of statin treatment which deviated from clinical guidelines. CONCLUSIONS: Primary care patients who are at high CVD risk are more often male, older, have more co-morbidities and be assigned to more deprived SES quintiles, compared to those at low CVD risk. Additionally, patients who experience more challenging socioeconomic situations may be less likely to receive CVD treatment that is consistent with care guidelines.

Effects of targeted therapies on bone in rheumatic and musculoskeletal diseases.

Generalized bone loss (osteoporosis) and fragility fractures can occur in rheumatic and musculoskeletal diseases including rheumatoid arthritis and spondyloarthritis (SpA; including ankylosing spondylitis and psoriatic arthritis). In addition, rheumatoid arthritis can involve localized, periarticular bone erosion and, in SpA, local (pathological) bone formation can occur. The RANK-RANKL-osteoprotegerin axis and the Wnt-ß-catenin signalling pathway (along with its inhibitors sclerostin and Dickkopf 1) have been implicated in inflammatory bone loss and formation, respectively. Targeted therapies including biologic DMARDs and Janus kinase (JAK) inhibitors can stabilize bone turnover and inhibit radiographic joint damage, and potentially also prevent generalized bone loss. Targeted therapies interfere at various points in the mechanisms of local and generalized bone changes in systemic rheumatic diseases, and they effect biomarkers of bone resorption and formation, bone mass and risk of fragility fractures. Studies on the effects of targeted therapies on rates of fragility fracture are scarce. The efficacy of biologic DMARDs for arresting bone formation in axial SpA is debated. Improved understanding of the most relevant therapeutic targets and identification of important targeted therapies could lead to the preservation of bone in inflammatory rheumatic and musculoskeletal diseases.

Development of a case definition for hearing loss in community-based older adults: a cross-sectional validation study.

BACKGROUND: Research based in primary care suggests that hearing loss may be underreported as well as inconsistently recorded in patient histories. In this study, we aimed to develop and validate a case definition for hearing loss among older adults in primary care, using electronic medical records. METHODS: We used data from adult patients aged 55 years and older from 13 practices in the Southern Alberta Primary Care Research Network database, part of the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), from Dec. 1, 2014, to Dec. 31, 2016. We developed a hearing loss case definition that was translated into an electronic algorithm. A record review was undertaken as the reference standard, followed by application of the algorithm to the sample. Validation metrics included sensitivity, specificity, positive predictive value and negative predictive value, as well as prevalence. We assessed risk factors using the Fisher exact test and odds ratios. RESULTS: The sample included 1000 patients; 496 (49.6%) were female and the mean age was 67.5 (standard deviation 9.6) years. Sensitivity of the case definition algorithm was determined to be 87.3% (95% confidence interval [CI] 76.5%-94.4%) with specificity valued at 94.8% (95% CI 93.1%-96.1%). Positive and negative predictive values were 52.9% (95% CI 42.8%-62.8%) and 99.1% (95% CI 98.2%-99.6%), respectively. The prevalence of hearing loss within the sample was 6.3% (95% CI 4.9%-7.9%). Older age was a significant risk factor for hearing loss (t = 4.98, 95% CI 3.76-8.65). Men had greater odds of hearing loss than women (odds ratio 1.65, 95% CI 0.98-2.79). INTERPRETATION: The validated case definition for hearing loss in community-based older adults had high sensitivity and specificity. It may be applied to surveillance and future epidemiologic research within the CPCSSN database.

Prevalence of polypharmacy and associated adverse health outcomes in adult patients with chronic kidney disease: protocol for a systematic review and meta-analysis.

BACKGROUND: Polypharmacy, often defined as the concomitant use of ≥ 5 medications, has been identified as a significant global public health threat. Aging and multimorbidity are key drivers of polypharmacy and have been linked to a broad range of adverse health outcomes and mortality. Patients with chronic kidney disease (CKD) are particularly at high risk of polypharmacy and use of potentially inappropriate medications given the numerous risk factors and complications associated with CKD. The aim of this systematic review will be to assess the prevalence of polypharmacy among adult patients with CKD, and the potential association between polypharmacy and adverse health outcomes within this population. METHODS/DESIGN: We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and PsycINFO and grey literature from inception onwards (with no language restrictions) for observational studies (e.g., cross-sectional or cohort studies) reporting the prevalence of polypharmacy in adult patients with CKD (all stages including dialysis). Two reviewers will independently screen all citations, full-text articles, and extract data. Potential conflicts will be resolved through discussion. The study methodological quality will be appraised using an appropriate tool. The primary outcome will be the prevalence of polypharmacy. Secondary outcomes will include any adverse health outcomes (e.g., worsening kidney function) in association with polypharmacy. If appropriate, we will conduct random effects meta-analysis of observational data to summarize the pooled prevalence of polypharmacy and the associations between polypharmacy and adverse outcomes. Statistical heterogeneity will be estimated using Cochran's Q and I2 index. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., sex, kidney replacement therapy, multimorbidity). DISCUSSION: Given that polypharmacy is a major and a growing public health issue, our findings will highlight the prevalence of polypharmacy, hazards associated with it, and medication thresholds associated with adverse outcomes in patients with CKD. Our study will also draw attention to the prognostic importance of improving medication practices as a key priority area to help minimize the use of inappropriate medications in patients with CKD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: [ CRD42020206514 ].

Salivary citrullinated proteins in rheumatoid arthritis and associated periodontal disease.

Periodontal disease (PD) can be an important precipitating factor in the production of citrullinated proteins. Its importance is emphasized, but it is not the only way to produce citrullinated proteins. The aim of the current study was to determine the periodontal conditions and the salivary citrullinated protein content in patients with rheumatoid arthritis (RA) compared to healthy controls. We also wished to correlate citrullinated protein levels in the saliva and serum biomarkers with the periodontal status and temporomandibular joint (TMJ) involvement of patients with RA. Twenty-three patients with RA and 17 healthy controls participated the study. Saliva samples were taken: citrulline content of saliva was measured. Blood test results for patients with RA were collected. TMJ disorders were described. Cariological and periodontal indices were registered. Periodontal conditions and periodontal staging were also registered. Comparison of measured values between groups was performed. Intragroup correlation of patients' values was counted. The prevalence of TMJ complaints was significantly higher in the RA group (8/23) versus controls (1/17). The patients with RA had worse periodontal condition because more patients with RA had gingivitis with a significantly higher bleeding on probing (BOP) (RA: 22.4 ± 25.0%; controls: 6.36 ± 11.6%; p = 0.018). Gingival index (GI) was also significantly higher in the patients than in controls (RA: 0.68 ± 0.58; controls: 0.19 ± 0.38; p = 0.010). The citrullinated protein (relative) content of saliva did not differ significantly (p = 0.147) between patients with RA (1102.2 ± 530.8) and healthy controls (1873.1 ± 1594.9). In RA, the salivary anti-CCP levels positively correlated with PD staging (R = 0.464, p = 0.039) . Control subjects more commonly had healthy gingiva than RA patients. Moreover, in the control group more individuals had intact and reduced height periodontium than periodontitis compared to the RA group. There was no significant difference in the levels of salivary citrulline between patients with RA and controls, despite the significant differences in their periodontal status. Thus, salivary citrulline levels are not associated with RA disease severity.

Chronic obstructive pulmonary disease as a risk factor in primary care: a Canadian retrospective cohort study.

Chronic obstructive pulmonary disease (COPD) is a complex disease that is predicted to be the third most common cause of death by 2030. In Canada, the care and management of chronic conditions is largely provided by primary care providers. Although there is emerging research and initiatives that describe the prevalence of COPD in Canadian primary care settings, to our knowledge, there have been no efforts to use a large pan-Canadian database to analyze COPD as a risk factor for other common chronic conditions managed in primary care. We report the risk of developing comorbidities after the onset of COPD, that is, the extent to which COPD is a risk factor for developing common chronic conditions (heart failure, depression, anxiety, coronary artery disease, diabetes, anemia, hypertension, ischemic heart disease, underweight, and osteoporosis). After adjusting for age, sex, urban vs rural residence, and smoking status, the relative risks for patients with COPD at baseline were significantly higher for subsequent incidence of anemia, anxiety, diabetes, depression, heart failure, ischemic heart disease, lung cancer, osteoporosis, sleep apnea, underweight, and hypertension than patients without COPD. Using a cut-point of a 200% increase in relative risk as indicative of particular clinical relevance, COPD has a statistically and clinically significant association with developing lung cancer, becoming underweight, and developing heart failure.

Angiotensin Converting Enzyme Activity in Anti-TNF-Treated Rheumatoid Arthritis and Ankylosing Spondylitis Patients.

INTRODUCTION: Angiotensin-converting enzyme (ACE) and ACE2 have been implicated in the regulation of vascular physiology. Elevated synovial and decreased or normal ACE or ACE2 levels have been found in rheumatoid arthritis (RA). Very little is known about the effects of tumor necrosis factor α (TNF-α) inhibition on ACE or ACE2 homeostasis. In this study, we assessed the effects of one-year anti-TNF therapy on ACE and ACE2 production in RA and ankylosing spondylitis (AS) in association with other biomarkers. PATIENTS AND METHODS: Forty patients including 24 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 16 AS patients treated with ETN were included in a 12-month follow-up study. Serum ACE levels were determined by commercial ELISA, while serum ACE2 activity was assessed using a specific quenched fluorescent substrate. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV) in all patients. In addition, CRP, rheumatoid factor (RF) and ACPA were also measured. All assessments were performed at baseline and 6 and 12 months after treatment initiation. RESULTS: Anti-TNF therapy increased ACE levels in the full cohort, as well as in the RA and AS subsets. ACE2 activity increased in the full cohort, while the ACE/ACE2 ratio increased in the full cohort and in the RA subset (p < 0.05). Uni- and multivariable regression analyses determined associations between ACE or ACE/ACE2 ratios at different time points and disease duration, CRP, RF, FMD and IMT (p < 0.05). ACE2 activity correlated with CRP. The changes of ACE or ACE2 over 12 months were determined by treatment together with either RF or FMD (p < 0.05). CONCLUSIONS: Anti-TNF treatment may increase ACE and ACE2 in the sera of RA and AS patients. ACE and ACE2 may be associated with disease duration, markers of inflammation and vascular pathophysiology. The effects of TNF inhibition on ACE and ACE2 may reflect, in part, the effects of these biologics on the cardiovascular system.

Eight pillars of oncorheumatology: Crossroads between malignancies and musculoskeletal diseases.

ONCORHEUMATOLOGY: RELATIONSHIP BETWEEN MALIGNANCIES AND MUSCULOSKELETAL DISEASES: Oncorheumatology is the meeting point of tumor formation and rheumatic musculoskeletal diseases (RMD). Multiple interactions exist between these two medical specialties. One major field is the topic of malignancies associated with rheumatic diseases, while the other topic covers the development of musculoskeletal disease in cancer patients. Within the first group, secondary malignancies may be associated with rheumatic diseases. Mostly sustained inflammation is responsible for transition into cancer. Tumor-associated antigens (TAA) with adhesive properties are present on tumor cells. These molecules may also be expressed by inflammatory leukocytes and soluble TAA levels may be elevated in RMDs. There has been continuous debate with respect to the possible carcinogenicity of conventional and targeted antirheumatic drugs. Very recent data from registries suggest that neither biologics, nor JAK inhibitors increase cancer risk in arthritis patients. The issue of physiotherapy in rheumatic patients with recent or current cancer has also been controversial. Some modalities, primarily exercise, may be safely applied to patients with RMD and cancer. The second large topic includes paraneoplastic syndromes. Musculoskeletal paraneoplasias are triggered by tumor-derived mediators. These syndromes are sometimes slightly different from the classical RMDs. Various chemotherapies may also be associated with autoimmune side effects. Recently, these immune-related complications have also been observed in cancer patients treated with immune-checkpoint inhibitors. Sex hormone-deprivation therapies, such as aromatase inhibitors and anti-androgens are widely used for the treatment of breast and prostate cancer, respectively. These compounds may induce bone loss and lead to osteoporosis. Finally, primary and secondary malignancies of the musculoskeletal system may also interest rheumatologists. In this review, the clinical, practical aspects of these eight pillars of oncorheumatology will be discussed.

Primary care EMR and administrative data linkage in Alberta, Canada: describing the suitability for hypertension surveillance.

OBJECTIVE: To describe the process for linking electronic medical record (EMR) and administrative data in Alberta and examine the advantages and limitations of utilising linked data for hypertension surveillance. METHODS: De-identified EMR data from 323 primary care providers contributing to the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) in Alberta were used. Mapping files from each contributing provider were generated from their EMR to facilitate linkage to administrative data within the provincial health data warehouse. Deterministic linkage was conducted using valid personal healthcare number (PHN) with age and/or sex. Characteristics of patients and providers in the linked cohort were compared with population-level sources. Criteria used to define hypertension in both sources were examined. RESULTS: Data were successfully linked for 6307 hypertensive patients (96.2% of eligible patients) from 49 contributing providers. Non-linkages from invalid PHN (n=246) occurred more for deceased patients and those with fewer primary care encounters, with differences due to type of EMR and patient EMR status. The linked cohort had more patients who were female, >60 years and residing in rural areas compared to the provincial healthcare registry. Family physicians were more often female and medically trained in Canada compared to all physicians in Alberta. Most patients (>97%) had ≥1 record in the registry, pharmacy, emergency/ambulatory care and claims databases; 44.3% had ≥1 record in the hospital discharge database. CONCLUSION: EMR-administrative data linkage has the potential to enhance hypertension surveillance. The current linkage process in Alberta is limited and subject to selection bias. Processes to address these deficiencies are under way.

Oncorheumatology: relationship between malignancies and musculoskeletal diseases / Onkoreumatológia: a daganatos és mozgásszervi kórképek összefüggései

Oncorheumatology is the meeting point of tumour formation and rheumatic diseases. Multiple interactions exist between these two medical specialties. One major field is the topic of malignancies associated with rheumatic diseases, while the other topic covers the development of musculoskeletal disease in cancer patients. In the first group, secondary malignancies associated with rheumatic diseases, role of tumour-associated antigens in rheumatology, the possible carcinogenicity of conventional and targeted antirheumatic drugs and physical therapy of rheumatic patients with recent or current cancer will be discussed. The second large topic includes paraneoplastic syndromes, autoimmune-rheumatic side effects of oncotherapies (chemotherapy and immunotherapy), effects of hormone-deprivation therapies on bone and primary and secondary malignancies of the musculoskeletal system. Orv Hetil. 2020; 161(28): 1151-1165.