Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 245
Filtrar
1.
Ann Rheum Dis ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915121

RESUMO

OBJECTIVES: Using a reversible multistate model, we prospectively examined neuropsychiatric (NP) events for attribution, outcome and association with health-related quality of life (HRQoL), in an international, inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: Annual assessments for 19 NP events attributed to SLE and non-SLE causes, physician determination of outcome and patient HRQoL (short-form (SF)-36 scores) were measured. Time-to-event analysis and multistate modelling examined the onset, recurrence and transition between NP states. RESULTS: NP events occurred in 955/1827 (52.3%) patients and 592/1910 (31.0%) unique events were attributed to SLE. In the first 2 years of follow-up the relative risk (95% CI) for SLE NP events was 6.16 (4.96, 7.66) and non-SLE events was 4.66 (4.01, 5.43) compared with thereafter. Patients without SLE NP events at initial assessment had a 74% probability of being event free at 10 years. For non-SLE NP events the estimate was 48%. The majority of NP events resolved over 10 years but mortality was higher in patients with NP events attributed to SLE (16%) versus patients with no NPSLE events (6%) while the rate was comparable in patients with non-SLE NP events (7%) compared with patients with no non-SLE events (6%). Patients with NP events had lower SF-36 summary scores compared with those without NP events and resolved NP states (p<0.001). CONCLUSIONS: NP events occur most frequently around the diagnosis of SLE. Although the majority of events resolve they are associated with reduced HRQoL and excess mortality. Multistate modelling is well suited for the assessment of NP events in SLE.

2.
J Am Heart Assoc ; 9(1): e012940, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31902326

RESUMO

Background Randomized controlled trials showed that newer glucose-lowering agents are cardioprotective, but most participants were men. It is unknown whether benefits are similar in women. Methods and Results Among adults with type 2 diabetes mellitus not controlled with metformin with no prior use of insulin, we assessed for sex differences in the cardiovascular effectiveness and safety of sodium-glucose-like transport-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors, initiated as second-line agents relative to sulfonylureas (reference-group). We studied type 2 diabetes mellitus American adults with newly dispensed sulfonylureas, SGLT-2i, GLP-1RA, or dipeptidyl peptidase-4 inhibitors (Marketscan-Database: 2011-2017). We used multivariable Cox proportional hazards models with time-varying exposure to compare time to first nonfatal cardiovascular event (myocardial infarction/unstable angina, stroke, and heart failure), and safety outcomes between drugs users, and tested for sex-drug interactions. Among 167 254 type 2 diabetes mellitus metformin users (46% women, median age 59 years, at low cardiovascular risk), during a median 4.5-year follow-up, cardiovascular events incidence was lower in women than men (14.7 versus 16.7 per 1000-person-year). Compared with sulfonylureas, hazard ratios (HRs) for cardiovascular events were lower with GLP-1RA (adjusted HR-women: 0.57, 95% CI: 0.48-0.68; aHR-men: 0.82, 0.71-0.95), dipeptidyl peptidase-4 inhibitors (aHR-women: 0.83, 0.77-0.89; aHR-men: 0.85, 0.79-0.91) and SGLT-2i (aHR-women: 0.58, 0.46-0.74; aHR-men: 0.69, 0.57-0.83). A sex-by-drug interaction was statistically significant only for GLP-1RA (P=0.002), suggesting greater cardiovascular effectiveness in women. Compared with sulfonylureas, risks of adverse events were similarly lower in both sexes for GLP-1RA (aHR-women: 0.81, 0.73-0.89; aHR-men: 0.80, 0.71-0.89), dipeptidyl peptidase-4 inhibitors (aHR-women: 0.82, 0.78-0.87; aHR-men: 0.83, 0.78-0.87) and SGLT-2i (aHR-women: 0.68, 0.59-0.78; aHR-men: 0.67, 0.59-0.78) (all sex-drug interactions for adverse events P>0.05). Conclusions Newer glucose-lowering drugs were associated with lower risk of cardiovascular events than sulfonylureas, with greater effectiveness of GLP-1RA in women than men. Overall, they appeared safe, with a better safety profile for SGLT-2i than for GLP-1RA regardless of sex.

3.
J Autoimmun ; : 102340, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31629628

RESUMO

OBJECTIVE: The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE. METHODS: Included were 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who met the 1997 American College of Rheumatology classification criteria with 5-years of follow-up data available. Baseline sera from patients and age- and sex-matched controls were assayed for suPAR. Organ damage was assessed annually using the SLICC/ACR damage index (SDI). RESULTS: The levels of suPAR were higher in patients who accrued damage, particularly those with SDI≥2 at 5 years (N = 32, 46.8% increase, p = 0.004), as compared to patients without damage. Logistic regression analysis revealed a significant impact of suPAR on SDI outcome (SDI≥2; OR = 1.14; 95% CI 1.03-1.26), also after adjustment for confounding factors. In an optimized logistic regression to predict damage, suPAR persisted as a predictor, together with baseline disease activity (SLEDAI-2K), age, and non-Caucasian ethnicity (model AUC = 0.77). Dissecting SDI into organ systems revealed higher suPAR levels in patients who developed musculoskeletal damage (SDI≥1; p = 0.007). CONCLUSION: Prognostic biomarkers identify patients who are at risk of acquiring early damage and therefore need careful observation and targeted treatment strategies. Overall, suPAR constitutes an interesting biomarker for patient stratification and for identifying SLE patients who are at risk of acquiring organ damage during the first 5 years of disease.

4.
Arthritis Rheumatol ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31631584

RESUMO

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC-FI values with damage accrual in the SLICC inception cohort. METHODS: The baseline visit was defined as the first at which both organ damage (SLICC/ACR Damage Index [SDI]) and health-related quality of life (Short-Form 36 [SF-36]) were assessed. Baseline SLICC-FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression estimated the association between baseline SLICC-FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics. RESULTS: The 1549 SLE patients eligible for this analysis were mostly female (88.7%) with mean (standard deviation, SD) age 35.7 (13.3) years and median (interquartile range) disease duration 1.2 (0.9-1.5) years at baseline. Mean (SD) baseline SLICC-FI was 0.17 (0.08) with a range of 0-0.51. Over a mean (SD) follow-up of 7.2 (3.7) years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC-FI values (per 0.05 increment) were associated with higher rates of increase in the SDI during follow-up (Incidence Rate Ratio [IRR] 1.19; 95% CI 1.13-1.25), after adjusting for age, sex, ethnicity/region, education, baseline SLEDAI-2K, baseline SDI, and baseline use of corticosteroids, antimalarials, and immunosuppressives. CONCLUSION: The SLICC-FI predicts damage accrual in incident SLE, which further supports the SLICC-FI as a valid health measure in SLE.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31609532

RESUMO

OBJECTIVES: There is a paucity of data regarding healthcare costs associated with damage accrual in systemic lupus erythematosus (SLE). We describe costs associated with damage states across the disease course using multi-state modeling. METHODS: Patients from 33 centres in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology (ACR) Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten-year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multi-state model. RESULTS: 1687 patients participated, 88.7% female, 49.0% of Caucasian race/ethnicity, mean age at diagnosis 34.6 years (SD 13.3), and mean follow up 8.9 years (range 0.6-18.5). Annual costs were higher in those with higher SDIs (SDI ≥ 5: $22 006 2019 CDN, 95% CI $16 662, $27 350 versus SDI=0: $1833, 95% CI $1134, $2532). Similarly, 10-year cumulative costs were higher in those with higher SDIs at the beginning of the 10-year interval (SDI ≥ 5: $189 073, 95% CI $142 318, $235 827 versus SDI=0: $21 713, 95% CI $13 639, $29 788). CONCLUSION: Patients with the highest SDIs incur 10-year cumulative costs that are almost 9-fold higher than those with the lowest SDIs. By estimating the damage trajectory and incorporating annual costs, damage can be used to estimate future costs, critical knowledge for evaluating the cost-effectiveness of novel therapies.

6.
J Rheumatol ; 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31474597

RESUMO

OBJECTIVE: Hydroxychloroquine (HCQ) and chloroquine (CQ) are key drugs in systemic lupus (SLE) and related diseases. Retinal toxicity remains the most concerning complication. We studied factors potentially associated with retinal toxicity, using case-control analyses. METHODS: Within our lupus clinic cohort, we identified patients with retinal changes using the SLICC Damage Index. We confirmed HCQ/CQ retinopathy with chart review, and selected up to three SLE controls for each case, matched on age at SLE diagnosis and SLE duration. RESULTS: Over an average 12.8 years of follow-up, within 326 patients exposed to antimalarial drugs, 18(5.5%) developed retinal toxicity. The minimum number of years of HCQ/CQ exposure before retinopathy developed was 8 years (maximum 33 years). Mean HCQ/CQ duration was similar in cases (18.5 years, 95% CI 15.2, 21.7) and controls (16.7 years, 95% CI 14.3, 19.0) likely due to our matching on SLE duration. Versus controls, cases tended to have more renal disease (cases 22.2%, controls 14.8%) and were slightly less likely to be Caucasian (cases 61.1%, controls 74.1%), but neither variables reached statistical significance. Among patients with retinal toxicity, the number previously exposed to CQ was more than three times that in controls. CONCLUSION: Just over 5% of patients developed anti-malarial retinal complications, over an average of 12.8 years. No cases were detected in the first 5 years of therapy. Past CQ use was more common in cases versus controls. Future studies using larger cohorts are underway to better define the roles of therapy duration, race/ethnicity, and other factors.

7.
J Pain Res ; 12: 2379-2390, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534361

RESUMO

Objectives: Access to multidisciplinary pain treatment facilities (MPTF) in Canada is limited by long waiting lists. However, little is known about the factors associated with access to MPTF specifically for persons with rheumatic conditions. This study aimed to 1) determine the waiting time for services in publicly funded MPTF for persons with rheumatic conditions in the province of Quebec, Canada, as well as 2) identify the factors associated with waiting time. Methods: This study was conducted using the Quebec Pain Registry, a large database of patients who received pain management services in MPTF. Sociodemographic and clinical variables were assessed for potential associations with waiting time. Descriptive, bivariate analyses and multiple linear regression analyses were conducted. Results: A total of 3,665 patients with rheumatic conditions were identified within the registry. Patients had a mean age of 55±14 years and the majority were women (65.7%). The average waiting time was 241.2±308.9 days (median=126), with 34.2% of the patients waiting longer than 6 months before having a first appointment. Results indicate that longer pain duration, lower household income, pain onset following a motor vehicle accident, having fibromyalgia, being on permanent disability or unemployed and being referred by a family physician (versus specialist) were significantly associated with longer waiting times. Conclusions: Many patients with rheumatic conditions (especially fibromyalgia) face long delays before receiving services in Quebec's MPTF. This study identified several factors associated with waiting time and emphasizes the need to improve access to pain management services.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31535689

RESUMO

OBJECTIVE: Interstitial lung disease (ILD) is a leading cause of mortality in SSc. Little is known about the benefits of immunosuppressive drugs in mild ILD. Our aim was to determine whether use of CYC or MMF was associated with an improved ILD course in patients with normal or mildly impaired lung function. METHODS: A retrospective cohort of SSc subjects with ILD, disease duration below seven years and no exposure to CYC or MMF prior to the baseline visit was constructed from the Canadian Scleroderma Research Group registry. Subjects were categorized as having mild ILD if baseline forced vital capacity (FVC % predicted) was >85%. The primary exposure was any use of CYC or MMF at the baseline visit. FVC at one year was compared between exposed and unexposed subjects, using multivariate linear regression. RESULTS: Out of 294 eligible SSc-ILD subjects, 116 met criteria for mild ILD. In this subgroup, mean (s.d.) disease duration was 3.7 (2.0) years. Thirteen (11.2%) subjects were exposed to CYC or MMF at baseline. The one-year FVC was higher in exposed subjects compared with unexposed subjects, by a difference of 8.49% (95% CI: 0.01-16.98%). None of the exposed subjects experienced clinically meaningful progression over two years, whereas 24.6% of unexposed subjects did. CONCLUSION: In this real-world setting, CYC/MMF exposure at baseline was associated with higher FVC values and a lower risk of progression among subjects with mild ILD. These data suggest a window of opportunity to preserve lung function in SSc-ILD.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31560453

RESUMO

OBJECTIVES: 1) To investigate whether physical therapists (PTs) can correctly identify new-onset inflammatory arthritis; 2) To assess whether PTs are aware that new-onset inflammatory arthritis cases should be referred to a rheumatologist; 3) To explore the comfort level of PTs to refer to medical specialists; 4) To determine factors associated with correctly identifying inflammatory arthritis and referring to a rheumatologist. METHODS: We sent a questionnaire to PTs in two Canadian provinces describing four case scenarios (new-onset rheumatoid arthritis - RA; knee osteoarthritis - OA; new-onset ankylosing spondylitis - AS; and low back pain- LBP). Participants were asked to identify probable medical diagnoses and indicate their plan of action. We describe the frequencies of our outcomes and use logistic regression to explore associated factors. RESULTS: 352 PTs responded. The proportions who correctly identified each of the four cases were: 90, 83, 77, 100% respectively for RA, OA, AS, and LBP. Among those, 77%, 30%, 73% and 3% respectively indicated that it was 'very' or 'extremely' important to refer to a rheumatologist. About two-thirds felt 'extremely' or 'quite' comfortable to refer to a specialist. PTs working in rural areas were less likely to refer. CONCLUSION: Most PTs correctly identified the clinical cases and were aware of the importance of prompt referral to rheumatology for inflammatory disease. Most indicated that it was not very important to refer those with OA and LBP. This implies that many PTs can distinguish between inflammatory and non-inflammatory conditions and appropriately refer suspected inflammatory arthritis to rheumatology.

10.
Lupus Sci Med ; 6(1): e000325, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31448125

RESUMO

Objectives: Chronic rheumatic diseases can challenge social and family relationships. We compared marital status in patients with systemic lupus erythematous (SLE) with their general population counterparts, stratified by sex and age of SLE onset. Methods: We performed a cross-sectional analysis of a cohort of 382 patients with SLE at our centre (349 females, 33 males). We determined how many were married or living common-law at the time of last study visit. Patients were then divided into: SLE diagnosis before 18, between 18 and 30, between 31 and 44 and after 45 years of age. We then compared marital status among male and female patients with SLE, to Quebec age-specific marital statistics. Results: Of 382 patients with SLE, 202 (52.9%) were married or living common-law, which was 9% lower than general population rates (95% CI 2% to 16%). One-third of women with paediatric-onset SLE were married or living common-law, which was 28% lower than their general population counterparts (95% CI 6% to 46%). Half of women diagnosed between age 18 and 30 were married or living common law, which was 14% less than general population rates (95% CI 4% to 25%). We could not establish significant differences for women diagnosed after age 30, or for males, versus their general population counterparts. Conclusions: Women diagnosed with SLE before age 30 were less likely to be married/living common-law, versus general population rates. This was not apparent for those diagnosed later in life. We did not clearly establish this effect in males, possibly due to power issues (vs a true effect of sex/gender). Additional studies (eg, focus groups) could elucidate reasons for our findings.

11.
Arthritis Rheumatol ; 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31390162

RESUMO

OBJECTIVE: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. RESULTS: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy. CONCLUSION: PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.

12.
Clin Epigenetics ; 11(1): 110, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366403

RESUMO

OBJECTIVE: To compare DNA methylation in subjects positive vs negative for anti-citrullinated protein antibodies (ACPA), a key serological marker of rheumatoid arthritis (RA) risk. METHODS: With banked serum from a random subset (N = 3600) of a large general population cohort, we identified ACPA-positive samples and compared them to age- and sex-matched ACPA-negative controls. We used a custom-designed methylome panel to conduct targeted bisulfite sequencing of 5 million CpGs located in regulatory or hypomethylated regions of DNA from whole blood (red blood cell lysed). Using binomial regression models, we investigated the differentially methylated regions (DMRs) between ACPA-positive vs ACPA-negative subjects. An independent set of T cells from RA patients was used to "validate" the differentially methylated sites. RESULTS: We measured DNA methylation in 137 subjects, of whom 63 were ACPA-positive, 66 were ACPA-negative, and 8 had self-reported RA. We identified 1303 DMRs of relevance, of which one third (402) had underlying genetic effects. These DMRs were enriched in intergenic CpG islands (CGI) and CGI shore regions. Furthermore, the genes associated with these DMRs were enriched in pathways related to Epstein-Barr virus infection and immune response. In addition, 80 (38%) of 208 RA-specific DMRs were replicated in T cells from RA samples. CONCLUSIONS: Sequencing-based high-resolution methylome mapping revealed biologically relevant DNA methylation changes in asymptomatic individuals positive for ACPA that overlap with those seen in RA. Pathway analyses suggested roles for viral infections, which may represent the effect of environmental triggers upstream of disease onset.

13.
Curr Opin Rheumatol ; 31(6): 678-681, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31403485

RESUMO

PURPOSE OF REVIEW: Patients with systemic lupus erythematosus (SLE) have altered incidences of certain malignancies as compared with the general population. This review summarizes the recent literature on risk of malignancy in SLE and proposed mechanisms for these altered susceptibilities. RECENT FINDINGS: Recent studies have confirmed previous data showing an increased risk of hematological, lung, thyroid, liver, cervical and vulvovaginal cancers, while demonstrating a decreased risk of breast and prostate cancer. Lymphomagenesis in SLE has been linked to increased activity of multiple inflammatory cytokines as well as possible viral causes. The decreased rates of hormone-sensitive cancers, such as breast and prostate is speculated to be related to the presence of lupus autoantibodies and downregulation of certain proteins in SLE. This knowledge has been utilized to investigate new therapeutic modalities for these malignancies. SUMMARY: Recent data confirm previously reported altered malignancy rates in SLE. There has been some elucidation of mechanisms underlying cancer development in SLE, although additional work is yet to be done.

14.
Genet Epidemiol ; 43(7): 844-863, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31407831

RESUMO

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.


Assuntos
Doenças Autoimunes/genética , Predisposição Genética para Doença , Linfoma não Hodgkin/genética , Alelos , Feminino , Antígenos HLA/genética , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
15.
J Clin Epidemiol ; 116: 39-48, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31352006

RESUMO

OBJECTIVES: The aim of the study was to quantify the risk of major congenital malformations (MCM) associated with first-trimester exposure to antiemetics. STUDY DESIGN AND SETTING: Using the Quebec Pregnancy Cohort (1998-2015), first-trimester doxylamine-pyridoxine, metoclopramide, and ondansetron exposures were assessed for their association with MCM. Generalized estimating equations were used to estimate odds ratios (OR), adjusting for potential confounders (aOR). RESULTS: Within 17 years of follow-up, the prevalence of antiemetic use during pregnancy increased by 76%. Within our cohort, 45,623 pregnancies were exposed to doxylamine-pyridoxine, 958 to metoclopramide, and 31 to ondansetron. Doxylamine-pyridoxine and metoclopramide use were associated with an increased risk of overall MCM (aOR 1.07, 95% confidence interval [CI]: 1.03-1.11; 3,945 exposed cases) and (aOR 1.27, 95% CI: 1.03-1.57; 105 exposed cases), respectively. Doxylamine-pyridoxine exposure was associated with increased risks of spina bifida (aOR 1.87, 95% CI: 1.11-3.14; 23 exposed cases), nervous system (aOR 1.25, 95% CI: 1.06-1.47; 225 exposed cases), and musculoskeletal system defects (aOR 1.08, 95% CI: 1.02-1.14; 1,735 exposed cases). Metoclopramide exposure was associated with an increased risk of genital organ defects (aOR 2.26, 95% CI: 1.14-4.48; 10 exposed cases). No statistically significant association was found between ondansetron exposure and the risk of overall MCM. CONCLUSION: First-trimester doxylamine-pyridoxine and metoclopramide exposure was associated with a significantly increased risk of overall and specific MCM.

16.
J Rheumatol ; 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31203224

RESUMO

OBJECTIVE: To quantify population-level and practice-level encounters with rheumatologists over time. METHODS: We conducted a population-based study from 2000 to 2015 in Ontario, Canada, where all residents are covered by a single-payer healthcare system. Annual total number of unique patients seen by rheumatologists, the number of new patients seen, and total number of encounters with rheumatologists were identified. RESULTS: From 2000 to 2015, the percentage of the population seen by rheumatologists was constant over time (2.7%). During this time, Ontario had a stable supply of rheumatologists (0.8 full-time equivalents/75,000). From 2000 to 2015, the number of annual rheumatology encounters increased from 561,452 to 786,061, but the adjusted encounter rates remained stable over time (at 62 encounters per 1000 population). New patient assessment rates declined over time from 10 new outpatient assessments per 1000 in 2000 to 6 per 1000 in 2015. The crude volume of new patients seen annually decreased and an increasing proportion of rheumatology encounters were with established patients. We observed a shift in patient case mix over time, with more assessments for systemic inflammatory conditions. Rheumatologists' practice volumes, practice sizes, and the annual number of days providing clinical care decreased over time. CONCLUSION: Over a 15-year period, the annual percentage of the population seen by a rheumatologist remained constant and the volume of new patients decreased, while followup patient encounters increased. Patient encounters per rheumatologist decreased over time. Our findings provide novel information for rheumatology workforce planning. Factors affecting clinical activity warrant further research.

17.
Lupus Sci Med ; 6(1): e000324, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205728

RESUMO

Background: SLE is associated with increased risk of diffuse large B-cell lymphoma (DLBCL). DLBCL is routinely classified by cell of origin (COO), with germinal centre B-cell (GCB) being more common and indicating better prognosis in the general population. We studied COO subtyping in patients with SLE diagnosed with DLBCL and their survival. Patients and methods: We evaluated 20 cases of SLE with DLBCL. Immunohistochemistry analysis was performed (BCL2, MYC, BCL6, CD10, CD20, FOXP1, GCET1, MUM1) in tissue microarrays. We examined associations between molecular and clinical features, including overall survival. Results: Of the 20 DLBCL SLE cases, 12/20 cases (60%) were classified as non-GCB using Hans or Choi algorithms. MYC and BCL2 protein expression was positive in 6/20 (30%) and 8/20 (40%) SLE cases, respectively, with 2/20 (10%) co-expressing both markers. Seven (7/20) had only extranodal involvement at DLBCL diagnosis. As expected, non-GCB cases had worse survival. Cases presenting exclusively with extranodal disease were associated with shorter SLE duration and better survival despite higher BCL2 protein expression. Conclusions: We present novel data characterising DLBCL in SLE. Sixty per cent of the DLBCL in patients with SLE were non-GCB. The nodal and extranodal distribution in SLE was similar to what is known in the general population, but extranodal disease occurred more often with short SLE duration and was associated with longer overall survival. More research on cancer in SLE is the key to further understanding the complex interplay between cancer and the immune system.

18.
BMC Rheumatol ; 3: 1, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31149655

RESUMO

Background: Good communication is central to a high-quality consultation process. We assessed the quality of referral information from primary care physicians (PCPs) to rheumatologists and the quality and timeliness of consultation letters from rheumatologists back to PCPs. Methods: We sampled referral letters between 2000 and 2013 from 168 PCPs and performed a retrospective chart review of 2430 patients referred to 146 rheumatologists. We assessed the completeness and timeliness of referral and consultation letters. Results: Osteoarthritis (n = 787, 32%) and systemic inflammatory rheumatic diseases (n = 745, 31%) comprised the top reasons for referral. Only 55% of referral letters summarized the patients' medical history. Referral letters provided some details of diagnostic tests (51% labs, 34% imaging) but there was underreporting of this information on referral letters. Almost all referral letters (92%) contained details of at least one patient symptom, with the most common complaint being joint pain (54%). Only half of all referral letters provided symptom duration. The PCP only stressed an urgent consultation among 211 patients (9%). Overall, 69% of consultation letters were returned to PCPs within 30 days of consultation visit. Conclusion: We found that basic items necessary for appropriate triage, including a description of symptoms or other relevant history and results of investigations were often lacking in referral letters. The delay of receipt of consultation letters may further represent a lost opportunity for coordination and continuity of care, and may affect the quality of care patients receive.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31112011

RESUMO

OBJECTIVE: To assess "real-word" practice patterns surrounding treatment initiation and treatment adjustments over time for methotrexate (MTX) and non-MTX-based treatments strategies in early rheumatoid arthritis (ERA). METHODS: We studied an incident multicenter ERA cohort (enrolled 2007-2017 within one year of symptoms) fulfilling ACR/EULAR criteria. Adult RA patients were eligible if they initiated MTX (+/-other DMARDs) within 90 days of cohort entry. We compared time until treatment change for four initial MTX-based therapy and time to second treatment change after the first change. Treatment change definition included: change of route for MTX monotherapy, adding or stopping a DMARD/biologic, and changing dose/frequency of a DMARD or biologic. RESULTS: There was great variability of treatment at initiation and during therapy adjustment. In 1,484 ERA patients, the majority initiated MTX monotherapy (oral or subcutaneous, SC). Patients on SC MTX mono changed less (45% vs 79%) and remained longer (hazard ratio, HR: 0.52, 95% CI: 0.41-0.67) on therapy than those on oral MTX. Most therapy adjustments involved adding a DMARD or changing to a non-MTX DMARD. Those on biologics and on triple therapy had a longer time without treatment change (HR: 0.26, 95% CI: 0.16-0.42 and HR: 0.57, 95% CI: 0.38-0.85). CONCLUSIONS: We found large variability in the way MTX-based therapies are prescribed in clinical practice. Our findings support use of subcutaneous MTX monotherapy or MTX combination as initial therapy. For subsequent treatment after initial MTX-based therapy, those initiating either biologics or triple therapy had a longer time to treatment change than oral MTX monotherapy. This article is protected by copyright. All rights reserved.

20.
J Manag Care Spec Pharm ; 25(6): 697-704, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31134863

RESUMO

BACKGROUND: The treatment for hepatitis C virus (HCV) infection has evolved over time, and direct-acting antivirals (DAA) have revolutionized HCV therapy. OBJECTIVES: To (a) assess early treatment discontinuation and (b) identify predictors of early discontinuation in a cohort of patients receiving second-generation DAAs. METHODS: We identified HCV patients newly prescribed simeprevir/sofosbuvir (SIM/SOF), ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir (OPrD), sofosbuvir/velpatasvir (SOF/VEL), elbasvir/grazoprevir (EBR/GZR), and glecaprevir/pibrentasvir (GLE/PIB) between 2014 and 2017. Early discontinuation was defined as duration of therapy less than 8 weeks. Multivariable logistic regression was performed to evaluate the association of drug regimens and potential predictive factors to early discontinuation. RESULTS: We identified 26,098 DAA-treated patients: 67.8% with LDV/SOF, 9.9% with OPrD, 8.5% with SIM/SOF, 7.8% with SOF/VEL, 5.2% with EBR/GZR, and 0.8% with GLE/PIB. With approval of new therapies in 2016 and 2017, use of OPrD, LDV/SOF, and SIM/SOF declined substantially. At baseline, there was some heterogeneity of past HCV drug use and comorbidity across groups; patients on SIM/SOF had the highest frequency of previous interferon, cirrhosis, and decompensated cirrhosis. Most HCV patients received therapy for 8-12 weeks; fewer patients went through 16-week and 24-week therapy courses. Early discontinuation rates (95% CI) were 7.1% (6.0-8.2) for SIM/SOF, 3.2% (2.9-3.5) for LDV/SOF, 9.6% (8.5-10.7) for OPrD, 3.1% (2.3-3.8) for SOF/VEL, 4.2% (3.1-5.3) for EBR/GZR, and 2.5% (0.3-4.7) for GLE/PIB. In multivariable analyses, versus OPrD, patients starting other drug regimens were less likely to discontinue therapy early. Early discontinuation was more common in women, patients with baseline anemia, and Medicare and Medicaid patients. CONCLUSIONS: These real-world data confirm low rates of early discontinuation in users of second-generation DAAs. Future research focusing on socio-economic and sex/gender issues may help further optimize care for patients with HCV. DISCLOSURES: This study was funded by the Canadian Institutes of Health Research. Klein has received grants for investigator-initiated trials from ViiV Healthcare, Janssen, Gilead, and Merck, as well as consulting fees from ViiV Healthcare, Merck, and AbbVie. Feld has received research support and/or scientific consulting fees from AbbVie, Contravir, Enanta, Gilead, Janssen, Merck, and Wako. All other authors have no conflicts of interest to declare. Results from this study were presented as a poster at the 34th International Conference of Phamacoepidemiology and Therapeutic Risk Management; August 22-26, 2018; Prague, Czech Republic.


Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Antivirais/farmacologia , Canadá , Combinação de Medicamentos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resposta Viral Sustentada
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA