RESUMO
OBJECTIVE: In 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current addendum provides further recommendations regarding the use of avacopan in AAV based on a review of newly available evidence. METHODS: An updated systematic literature review on avacopan (formerly, CCX168) using Medline, Embase, and the Cochrane Library was performed for publications up to September 2022. New recommendations were developed and categorized according to the EULAR grading levels, as done for previous CanVasc recommendations. A modified Delphi procedure and videoconferences were used to reach ≥80% consensus on the inclusion, wording and grading of each recommendation. RESULTS: Three new recommendations were developed. They focus on avacopan therapy indication and duration, as well as timely glucocorticoid tapering. CONCLUSION: These 2022 addended recommendations provide rheumatologists, nephrologists and other specialists caring for patients with AAV with guidance for the use of avacopan, based on current evidence and consensus from Canadian experts.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Consenso , Canadá , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Citoplasma , Anticorpos Anticitoplasma de NeutrófilosRESUMO
OBJECTIVES: To characterize the utilization and discontinuation of medications before, during and after pregnancy among women with RA. METHODS: We used population-based administrative data to identify women with RA who had a singleton pregnancy ending in delivery between 1 January 2002 and 31 December 2012. We assessed the utilization of RA medications, namely, conventional synthetic DMARDs, biologics, glucocorticosteroids and NSAIDs, across six windows spanning 24 and 12 months before the start of pregnancy, each trimester of pregnancy and 12 months post-pregnancy. We defined medication discontinuation as no prescription in a given window following a prescription in the preceding window and evaluated predictors using logistic regression models, calculating adjusted odds ratios (ORs) and 95% CIs. RESULTS: We studied 1730 pregnancies in 1301 women with RA (mean age at delivery 31.4 ± 5.4 years). We observed substantial medication discontinuation, particularly in the first trimester, with discontinuation of antimalarials in 57.3% of patients, azathioprine 59.1%, sulfasalazine 69.5% and biologics 50.8%. Factors inversely associated with discontinuation of antimalarials in the first trimester were maternal age [OR 0.90 (95% CI 0.86, 0.95)] and number of rheumatology visits [OR 0.86 (95% CI 0.75, 0.97)] and for biologics, prior adverse birth outcome [OR 0.22 (95% CI 0.05, 0.95)]. CONCLUSION: Our population-based study shows frequent discontinuation of medications for RA, particularly in the first trimester. Findings indicate a need to educate women with RA who are planning pregnancy on the benefits and risks of medications during pregnancy.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Desprescrições , Glucocorticoides/uso terapêutico , Complicações na Gravidez/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Abatacepte/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Azatioprina/uso terapêutico , Produtos Biológicos , Colúmbia Britânica , Cloroquina/uso terapêutico , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Feminino , Compostos de Ouro/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Leflunomida/uso terapêutico , Modelos Logísticos , Idade Materna , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Razão de Chances , Cuidado Pré-Concepcional , Gravidez , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Reumatologia , Rituximab/uso terapêutico , Sulfassalazina/uso terapêuticoRESUMO
OBJECTIVES: Epidemiologic studies evaluating associations between specific arthritis medications and perinatal outcomes are limited. We evaluated the association between conventional synthetic DMARD (csDMARD) use among women with rheumatic disease (RD) and neonatal outcomes. METHODS: We linked population-based data in British Columbia, Canada from 01/01/2002 to 12/31/2012 on all inpatient/outpatient visits and medications with a perinatal registry. For small-for-gestational-age (SGA) births, we assessed csDMARD exposure 90 days preconception or during pregnancy until date of delivery. For congenital anomalies, we determined csDMARD exposure 90 days preconception or during the first trimester. We used multivariable logistic regression models fitted with generalised estimating equations and calculated post-hoc power. RESULTS: There were 185 pregnancies in 175 women (31.3±5.4 years) and 6,064 pregnancies in 4,387 women (31.1±5.4 years) in the csDMARD exposed and unexposed groups, respectively. Hydroxychloroquine, azathioprine, sulfasalazine, and methotrexate exposure before or during pregnancy were not associated with SGA births. The most sufficiently powered analyses were those for hydroxychloroquine, where exposure during pregnancy resulted in an adjusted odds ratio (aOR) of 1.12 (95% confidence interval [CI], 0.65-1.94) for SGA births. Although post-hoc power calculations indicate less power to detect associations between csDMARDs and congenital anomalies, results indicate methotrexate exposure during the first trimester is associated with elevated odds for congenital anomalies (aOR 6.58, 95% CI 1.15-37.75). CONCLUSIONS: Findings are consistent with current guidelines regarding specific csDMARD use during the perinatal period for women with RD. It is important to report well-designed epidemiologic studies to facilitate future RD/csDMARD-specific meta-analyses.
Assuntos
Antirreumáticos , Doenças Reumáticas , Mulheres , Antirreumáticos/efeitos adversos , Canadá , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologiaRESUMO
OBJECTIVES: Despite the high incidence of rheumatic diseases during the reproductive years, little is known about the impact of disease-modifying anti-rheumatic drug (DMARD) use during pregnancy. Our objective was to systematically review and appraise evidence in women with rheumatic disease on the use of traditional and biologic DMARDs during pregnancy and the risk of congenital malformation outcomes. METHODS: We conducted a systematic search of MEDLINE, EMBASE, and INTERNATIONAL PHARMACEUTICAL ABSTRACTS databases. Inclusion criteria were: 1) study sample including women with rheumatic disease; 2) use of traditional and/or biologic DMARDs during pregnancy; and 3) congenital malformation outcome(s) reported. We extracted information on study design, data source, number of exposed pregnancies, type of DMARD, number of live births, and number of congenital malformations. RESULTS: Altogether, we included 79 studies; the majority were based on designs that did not involve a comparison group, including 26 case reports, 17 case series, 20 cross-sectional studies, and 4 surveys. Studies that had a comparator group included 1 case control, 10 cohort studies, and 1 controlled trial. Hydroxychloroquine and azathioprine represent the most studied traditional DMARD exposures and, among biologics, most of the reports were on infliximab and etanercept. CONCLUSIONS: This is the first systematic review on the use of both traditional and biologic DMARDs during pregnancy among women with rheumatic diseases and congenital malformation outcomes, with a focus on study design and quality. Findings confirm the limited number of studies, as well as the need to improve study designs.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Antirreumáticos/efeitos adversos , Complicações na Gravidez/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Feminino , Humanos , Gravidez , RiscoRESUMO
OBJECTIVE: To examine how female patients with RA form decisions about having children, pregnancy, and medication use. METHODS: We employed a constructivist grounded theory design and recruited female participants who are 18 years or older, have a rheumatologist-confirmed RA diagnosis, live in Canada, and are able to communicate in English or French. We collected data through semi-structured individual and focus group interviews using telephone or video conferencing technology. Data collection and analysis were iterative, employed theoretical sampling, reflexive journaling, and peer debriefing, and culminated in a theoretical model. RESULTS: We recruited 21 participants with a mean age of 34 years and median 10 years since RA diagnosis. Overall, 33% had never been pregnant, 57% had previously been pregnant, and 10% were pregnant at the time of interview. Of those who had experienced pregnancy, 64% had at least one pregnancy while diagnosed with RA and of those, 56% used DMARD(s) during a pregnancy. We constructed a patient-centred framework depicting the dynamic relationships between 4 decision-making processes-(1) using medications, (2) having children, (3) planning pregnancy, and (4) parenting-and the substantial impact of healthcare providers on patients' experiences making these decisions. These processes were further influenced by participants' intersecting identities and contextual factors, particularly attitudes towards health and medications, disease onset and severity, familial support system, and experiences interacting with the healthcare system. CONCLUSION: Our framework provides insight into how patients make reproductive decisions in the context of managing RA and the opportunities for providers to support them at each decision-making process. A patient-centred care approach is suggested to support female patients with RA in making reproductive and medication choices aligning with their individual desires, needs, and values.
Assuntos
Antirreumáticos , Artrite Reumatoide , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Criança , Tomada de Decisões , Feminino , Teoria Fundamentada , Humanos , Grupo Associado , GravidezRESUMO
Calcific uremic arteriolopathy (calciphylaxis) is a devastating but rare complication seen predominantly in dialysis patients that often is fatal. Because of the rarity of the disease and the multifactorial nature of its cause, no clinical trials have been conducted to date to determine the best therapy for the condition. We report a case series of 7 patients at a single institution in whom a systematic multi-interventional treatment strategy was implemented, consisting of trigger-agent cessation (calcium-based phosphate binders, alphacalcidol, and warfarin), wound management, and antibiotic therapy, supplemented by intensified hemodialysis (4 hours daily for 7 days followed by 5-6 times weekly), intravenous sodium thiosulfate (12.5-25 g intravenously 3 times a week), and attempted oxygen therapy (given through a face mask or hyperbaric chamber as tolerated by patient circumstance). Treatments selected were based on literature review, consensus discussion, and attempts to address the physiologic disturbances that underlie the condition. All 7 patients identified with biopsy-proven calcific uremic arteriolopathy were treated with this regimen in 2007-2010, with 6 of 7 showing complete recovery. We suggest that consistent implementation of a multi-interventional approach may alter the course of this devastating disease. Further studies are needed to confirm and extend these findings.
Assuntos
Calciofilaxia/terapia , Rim/irrigação sanguínea , Adulto , Idoso , Idoso de 80 Anos ou mais , Arteríolas/patologia , Quelantes/administração & dosagem , Cinacalcete , Terapia Combinada , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Naftalenos/uso terapêutico , Oxigenoterapia , Poliaminas/uso terapêutico , Diálise Renal , Sevelamer , Tiossulfatos/administração & dosagemRESUMO
OBJECTIVE: Partners of patients with RA often take on supportive roles given the debilitating nature of RA. Our objective was to explore the perspectives, attitudes and experiences of partners of female patients with RA regarding reproductive experiences and decision-making. METHODS: We conducted a qualitative study involving semi-structured interviews with partners of female patients with RA. We defined a partner as an individual within a romantic relationship. Constructivist grounded theory was applied to interview transcripts to identify and conceptualize themes. RESULTS: We interviewed 10 partners of female patients with RA (10 males; mean age, 35 [23-56] years), of whom 40% had at least one child with a female patient with RA and did not desire additional children. We identified four themes representing stages of reproductive decision-making: (1) developing an understanding of RA, (2) contemplating future family decision-making, (3) initiating reproductive decision-making with partner, and (4) reflecting on past reproductive experiences. Participants contemplated their attitudes and perspectives regarding pregnancy and used available information to support their partner's medication decisions. When reflecting on their reproductive experiences, participants shared the impacts of past reproductive decisions on their romantic relationship and their mental health and wellbeing. CONCLUSION: Our study highlights the need for comprehensive support for both female patients with RA and their partners at all stages of reproductive decision-making. Health-care providers can identify opportunities for intervention that involves female patients with RA and their partners to minimize stress and its negative impacts on the family.
RESUMO
OBJECTIVE: In 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aims to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence. METHODS: A needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014 to September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a 2-step modified Delphi procedure to reach > 80% consensus on the inclusion, wording, and grading of each new and revised recommendation. RESULTS: Eleven new and 16 revised recommendations were created and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary material for practical use was revised to reflect the updated recommendations. CONCLUSION: The 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos , Canadá , Consenso , Citoplasma , HumanosRESUMO
PURPOSE: Optical coherence tomography (OCT) is an optical imaging method that can visualize cellular and extracellular structures at and below tissue surface. The objective of the study was to determine if OCT could characterize preneoplastic changes in the bronchial epithelium identified by autofluorescence bronchoscopy. EXPERIMENTAL DESIGN: A 1.5-mm fiberoptic probe was inserted via a bronchoscope into the airways of 138 volunteer heavy smokers participating in a chemoprevention trial and 10 patients with lung cancer to evaluate areas that were found to be normal or abnormal on autofluorescence bronchoscopy. Radial scanning of the airways was done to generate OCT images in real time. Following OCT imaging, the same sites were biopsied for pathologic correlation. RESULTS: A total of 281 OCT images and the corresponding bronchial biopsies were obtained. The histopathology of these areas includes 145 normal/hyperplasia, 61 metaplasia, 39 mild dysplasia, 10 moderate dysplasia, 6 severe dysplasia, 7 carcinoma in situ, and 13 invasive carcinomas. Quantitative measurement of the epithelial thickness showed that invasive carcinoma was significantly different than carcinoma in situ (P=0.004) and dysplasia was significantly different than metaplasia or hyperplasia (P=0.002). In addition, nuclei of the cells corresponding to histologic results became more discernible in lesions that were moderate dysplasia or worse compared with lower-grade lesions. CONCLUSION: Preliminary data suggest that autofluorescence bronchoscopy-guided OCT imaging of bronchial lesions is technically feasible. OCT may be a promising nonbiopsy tool for in vivo imaging of preneoplastic bronchial lesions to study their natural history and the effect of chemopreventive intervention.
Assuntos
Carcinoma in Situ/patologia , Neoplasias Pulmonares/patologia , Lesões Pré-Cancerosas/patologia , Tomografia de Coerência Óptica , Idoso , Brônquios/patologia , Broncoscopia , Quimioprevenção , Ensaios Clínicos como Assunto , Epitélio/patologia , Feminino , Humanos , Hiperplasia/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Rheumatoid arthritis (RA) disproportionately affects more women than men, often striking during childbearing years. Because the Internet, particularly social media, is increasingly used by patients with chronic conditions seeking and sharing information, our objective was to conduct a qualitative descriptive study of threads on the social news website, Reddit, to understand the information needs and concerns of women with RA regarding pregnancy and parenting. METHODS: We searched threads (original posts and responses) on three subreddit sites, "r/Thritis," "r/Rheumatoid," and "r/BabyBumps," over a 10-year period between October 27, 2008, and October 27, 2018. All threads were reviewed, and those that specifically mentioned having RA and fertility/family planning, pregnancy/reproduction, and/or parenting/having children were included. We applied a thematic analysis to the threads, which involved initial line-by-line coding, clustering of codes into subcategories and categories, and abstraction into final themes. RESULTS: We identified 87 threads and included 59 for qualitative analysis. The thematic analysis led to the identification of five themes. Theme one (finding a community) captures motivations for seeking information online. Themes two (making decisions about pregnancy and having children) and three (worrying about the impacts of arthritis on pregnancy and parenting) capture women's concerns and thought processes. Themes four (information needs for managing arthritis throughout the perinatal period) and five (pregnancy information and resources for women with arthritis) describe the community's specific informational needs. CONCLUSION: A qualitative analysis of publicly available threads about the relationship between RA and issues of pregnancy and parenting identified areas of concern and further information need. These forums also provided an online community where women with RA sought social support and encouragement. Altogether, findings speak to the importance of supporting the information and care needs of women with RA who are pregnant or considering pregnancy.
RESUMO
BACKGROUND: With improved therapies and management, more women with inflammatory arthritides (IA) are considering pregnancy. Our objective was to survey rheumatologists across Canada about their IA management in pregnancy to identify practice patterns and knowledge gaps. METHODS: We administered an online survey with questions regarding medications for IA treatment including conventional synthetic disease modifying antirheumatic drugs (csDMARDs) and biologics/small molecules in planned and unplanned pregnancies. Email invitations were sent to members of the Canadian Rheumatology Association. We calculated responses frequencies and a priori set a cut-off of ≥75% to define consensus. RESULTS: Ninety rheumatologists participated in the survey (20% participation rate); 57% have been practicing for > 10 years, 32% for ≤10 years, and 11% in training. There was consensus on discontinuation of 4 csDMARDs - cyclophosphamide (100%), leflunomide (98%), methotrexate (96%), and mycophenolate mofetil (89%) - in planned pregnancies but varied responses on when to discontinue them or what to do in unplanned pregnancies. Respondents agreed that 3 csDMARDs - azathioprine (84%), hydroxychloroquine (95%), and sulfasalazine (77%) - were safe to continue in planned and unplanned pregnancies. There was consensus with use of 4 biologics - adalimumab (81%), certolizumab (80%), etanercept (83%), and infliximab (76%) - in planned pregnancies but uncertainty on when they should be discontinued and their use in unplanned pregnancies. CONCLUSIONS: This national survey shows consensus among rheumatologists on the use of some csDMARDs and biologics/small molecules in IA patients planning pregnancy but varied knowledge on when to discontinue and what to do in unplanned pregnancies.
RESUMO
OBJECTIVE: To describe the long-term outcomes of patients with Takayasu arteritis (TAK) and renal artery involvement (RAI). METHODS: A retrospective review of 122 patients with TAK at three tertiary centres in Canada, Sweden and the UK. Data on demographics, laboratory and clinical parameters, medications and angiography findings were collected. Non-renal and renal parameters were compared at baseline and follow-up. RESULTS: A total of 37 patients (30%) with RAI were identified: 18 (49%) with unilateral and 19 (51%) with bilateral RAI. Patients were predominantly female (89%). The median age at diagnosis was 27 years [interquartile range (IQR) 16-38]. The median follow-up time was 7 years (IQR 2-12). Hypertension was seen in 27 patients (73%) at presentation and 25 (68%) at follow-up. The median estimated glomerular filtration (eGFR) at presentation was 94 and 98 ml/min/1.73 m2 in those with unilateral and bilateral RAI, respectively. The corresponding median eGFR at follow-up was 101.5 and 104 ml/min/1.73 m2, respectively. Three patients at presentation and two at follow-up had an eGFR of <60 ml/min/1.73 m2. Five underwent endovascular intervention and three required surgical interventions. Among the 33 patients with radiologic follow-up, 23 (69%) had persistent RAI and 10 (30%) had resolution of RAI. One (6%) patient with unilateral RAI developed bilateral RAI and three (19%) with bilateral RAI regressed to unilateral RAI. Over time, 23 (62%) patients had stable renal function, 7 (19%) had improvement and 4 had a decline in renal function; no patient developed end-stage renal disease (ESRD). CONCLUSION: In this series of TAK patients with RAI, long-term non-renal and renal outcomes were favourable. No patient experienced ESRD or died.
RESUMO
The development of array comparative genomic hybridization (array CGH) at tiling-path resolution has enabled the detection of gene-sized segmental DNA copy number gains and losses. Here, we present the first application of whole genome tiling-path array CGH to archival clinical specimens for the detailed analysis of oral squamous cell carcinomas (OSCC). We describe the genomes of 20 OSCCs as well as a selection of matched normal DNA in unprecedented detail. Examination of their whole genome profiles enabled the identification of alterations ranging in size from whole-arm, segmental, to gene size alterations. Tiling-path resolution enabled the detection of many more alterations within each tumor than previously reported, many of which include narrow alterations found to be frequent events among the 20 OSCCs. We report the presence of several novel frequent submegabase alterations, such as the 0.58 Mb gain at 5p15.2 containing triple functional domain (TRIO), detected in 45% of cases. We also report the first coamplification of two gene clusters, by fine-mapping the precise base pair boundaries of the high-level amplification at 11q22.2-22.3 containing both matrix metalloproteinase and baculoviral IAP repeat-containing protein 2 (BIRC) gene clusters. These results show the large improvement in detection sensitivity and resolution compared with genome interval marker arrays and the utility of tiling resolution array CGH for the detection of both submegabase and single copy gains and losses in cancer gene discovery.
Assuntos
Carcinoma de Células Escamosas/genética , Aberrações Cromossômicas , Neoplasias Bucais/genética , Hibridização de Ácido Nucleico/métodos , Quinase 6 Dependente de Ciclina , Quinases Ciclina-Dependentes/biossíntese , Quinases Ciclina-Dependentes/genética , Feminino , Amplificação de Genes , Dosagem de Genes , Genoma Humano , Fatores de Troca do Nucleotídeo Guanina/biossíntese , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Masculino , Microdissecção , Neoplasias Bucais/enzimologia , Inclusão em Parafina , Fosfoproteínas/biossíntese , Fosfoproteínas/genética , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/genéticaRESUMO
Loss of 3p has been associated with oral cancer progression and is common in many cancers. However, regions of alteration on 3p are poorly defined. We have constructed a high-resolution chromosomal array using a tiling set of 535 human bacterial artificial chromosomes that provides near complete coverage of 3p. Array comparative genomic hybridization analysis of 20 microdissected oral squamous cell carcinomas showed multiple and recurrent segments of copy number changes. These include a deletion containing the FHIT gene; novel segments of copy decrease at 3p22, 3p24, and 3p26; and an unexpected approximately 0.7 Mbp segmental increase at 3p21. These data strongly support the value of using chromosomal array comparative genomic hybridization for detailed profiling of oral squamous cell carcinomas.
Assuntos
Hidrolases Anidrido Ácido , Carcinoma de Células Escamosas/genética , Cromossomos Humanos Par 3/genética , Neoplasias Bucais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Dosagem de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Hibridização de Ácido Nucleico/métodosRESUMO
Vasculitides are classified by the size, type and location of the predominantly involved vessels and by their primary or secondary nature. Their treatment depends on the type of vasculitis, its etiology (when known), and its severity and must be further adjusted by the individual characteristics and comorbidities of patients. In this paper, we review how the classification and definition of vasculitides have evolved over the past years and how it has affected therapeutic changes. As new genetic markers are being discovered and the pathogenesis of vasculitides continues to be elucidated, further modifications in classification and treatment can be expected.