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1.
J Rheumatol ; 51(4): 378-389, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38224992

RESUMO

OBJECTIVE: To evaluate patient-reported outcomes (PROs) after initiation of tumor necrosis factor inhibitor (TNFi) treatment in European real-world patients with psoriatic arthritis (PsA). Further, to investigate PRO remission rates across treatment courses, registries, disease duration, sex, and age at disease onset. METHODS: Visual analog scale or numerical rating scale scores for pain, fatigue, patient global assessment (PtGA), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) from 12,262 patients with PsA initiating a TNFi in 13 registries were pooled. PRO remission rates (pain ≤ 1, fatigue ≤ 2, PtGA ≤ 2, and HAQ-DI ≤ 0.5) were calculated for patients still on the treatment. RESULTS: For the first TNFi, median pain score was reduced by approximately 50%, from 6 to 3, 3, and 2; as were fatigue scores, from 6 to 4, 4, and 3; PtGA scores, from 6 to 3, 3, and 2; and HAQ-DI scores, from 0.9 to 0.5, 0.5, and 0.4 at baseline, 6, 12, and 24 months, respectively. Six-month Lund Efficacy Index (LUNDEX)-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 24%, 31%, 36%, and 43% (first TNFi); 14%, 19%, 23%, and 29% (second TNFi); and 9%, 14%, 17%, and 20% (third TNFi), respectively. For biologic-naïve patients with disease duration < 5 years, 6-month LUNDEX-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 22%, 28%, 33%, and 42%, respectively. Corresponding rates for patients with disease duration > 10 years were 27%, 32%, 41%, and 43%, respectively. Remission rates were 33%, 40%, 45%, and 56% for men and 17%, 23%, 24%, and 32% for women, respectively. For patients aged < 45 years at diagnosis, 6-month LUNDEX-adjusted remission rate for pain was 29% vs 18% for patients ≥ 45 years. CONCLUSION: In 12,262 biologic-naïve patients with PsA, 6 months of treatment with a TNFi reduced pain by approximately 50%. Marked differences in PRO remission rates across treatment courses, registries, disease duration, sex, and age at onset of disease were observed, emphasizing the potential influence of factors other than disease activity on PROs.


Assuntos
Antirreumáticos , Artrite Psoriásica , Produtos Biológicos , Masculino , Humanos , Feminino , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/diagnóstico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Antirreumáticos/uso terapêutico , Resultado do Tratamento , Medidas de Resultados Relatados pelo Paciente , Dor/tratamento farmacológico , Produtos Biológicos/uso terapêutico
2.
Arthritis Rheumatol ; 76(4): 587-598, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37975166

RESUMO

OBJECTIVE: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi. METHODS: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimator. RESULTS: We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80-0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81-0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively). CONCLUSION: Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management.


Assuntos
Antirreumáticos , Artrite Psoriásica , Espondilartrite , Humanos , Feminino , Masculino , Artrite Psoriásica/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Caracteres Sexuais , Fator de Necrose Tumoral alfa , Resultado do Tratamento , Antirreumáticos/uso terapêutico , Espondilartrite/tratamento farmacológico
3.
Commun Med (Lond) ; 3(1): 94, 2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37414856

RESUMO

BACKGROUND: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear. METHODS: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5-18 months after infection. RESULTS: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection. CONCLUSIONS: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.


Persistent symptoms are commonly reported after SARS-CoV-2 infection, and this is often described as long Covid. We compared different symptoms reported following SARS-CoV- 2 infection with the results obtained during various medical evaluations that are often used to assess health, such as blood tests, smell tests, taste tests, hearing tests, etc. We compared symptoms and test results between 1,706 Icelanders who had been infected previously with SARS-CoV-2 infection (cases) and 14,398 individuals who had not been infected (controls). Out of 88 assessed symptoms, 41 were more common in cases than controls. However, relatively few differences were seen in the results obtained from the various medical evaluations (cases had poorer smell and taste test results, slightly less grip strength, and slightly poorer memory recall than controls). The differences seen between symptoms and results of medical evaluations suggests that conventional clinical tests may not be informative in relating symptoms to a past SARS-CoV-2 infection.

5.
Nat Med ; 29(2): 467-472, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36747117

RESUMO

Smoldering multiple myeloma (SMM) is an asymptomatic precursor to multiple myeloma. Here we define the epidemiological characteristics of SMM in the general population in Iceland. The iStopMM study (ClinicalTrials.gov ID: NCT03327597 ) is a nationwide screening study for multiple myeloma precursors where all residents in Iceland 40 years or older were invited to participate. SMM was defined as 10-60% bone marrow plasma cells and/or monoclonal (M) protein concentration ≥3 g dl-1, in the absence of myeloma-defining events. Of the 80,759 who gave informed consent to participate, 75,422 (93%) were screened. The prevalence of SMM in the total population was 0.53% (95% confidence interval (CI) = 0.49-0.57%) in individuals 40 years or older. In men and women, the prevalence of SMM was 0.67% (95% CI = 0.62-0.73%) and 0.39% (95% CI = 0.35-0.43%), respectively; it increased with age in both sexes. For the 193 individuals with SMM, median age was 70 years (range 44-92 years) and 60% were males. The mean M protein concentration of individuals with SMM was 0.62 g dl-1 (range 0.01-3.5 g dl-1) and 73% had 11-20% bone marrow plasma cell infiltration. The high prevalence of SMM has implications for future treatment policies in multiple myeloma as the evidence supporting treatment initiation at the SMM stage is emerging.


Assuntos
Mieloma Múltiplo , Mieloma Múltiplo Latente , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Mieloma Múltiplo/terapia , Prevalência , Fatores de Risco , Progressão da Doença
6.
J Rheumatol ; 49(6 Suppl 1): 57-63, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35365578

RESUMO

At the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Collaborative Research Network (CRN) annual meeting, the GRAPPA-CRN group presented a number of project updates, including a pilot investigator-initiated study to evaluate liquid and tissue biomarkers associated with axial involvement in psoriatic arthritis (PsA). The GRAPPA-CRN session updated progress made with 3 parallel international research initiatives based on 3 previously defined unmet needs in PsA. The Health Initiatives in Psoriasis and PsOriatic arthritis ConsoRTium European States (HIPPOCRATES) is a European research consortium formed to address unmet clinical needs in PsA. The Preventing Arthritis in a multicenter Psoriasis At-Risk Population (PAMPA) is a US-based organization that has defined consensus terminology for preclinical phases of PsA and is interested in the transition process from psoriasis to PsA. An overview of the Accelerating Medicines Partnership Autoimmune and Immune-Mediated Diseases (AMP AIM) program 2.0, a consortium including GRAPPA-CRN members that addressed these 3 unmet needs in PsA, was also presented.


Assuntos
Artrite Psoriásica , Psoríase , Reumatologia , Humanos , Organizações , Projetos Piloto
7.
Clin Infect Dis ; 75(10): 1732-1739, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-35438144

RESUMO

BACKGROUND: The Treatment as Prevention for Hepatitis C program started in 2016 in Iceland, offering treatment with direct-acting antivirals to hepatitis C virus (HCV)-infected individuals. Reinfections through injection drug use (IDU) can hamper elimination efforts. We determined reinfection rates of HCV among patients in the program. METHODS: Clinical data were gathered prospectively. The study cohort consisted of HCV-cured patients with an estimated sustained virologic response between 1 February 2016 and 20 November 2018, with follow-up until 20 November 2019. The observation period and time until reinfection was estimated using a single random point imputation method coupled with Monte Carlo simulation. The reinfection rates were expressed as reinfections per 100 person-years (PY). RESULTS: In total, 640 treatments of 614 patients (417 male; mean age, 44.3 years) resulted in cure, with 52 reinfections subsequently confirmed in 50 patients (37 male). Follow-up was 672.1 PY, with a median time to reinfection of 232 days. History of IDU was reported by 523 patients (84.8%) and recent IDU with 220 treatments (34.4%). Stimulants were the preferred injected drug in 85.5% of patients with a history of IDU. The reinfection rate was 7.7/100 PY. Using multivariate Cox proportional hazards models for interval-censored data, age (hazard ratio, 0.96 [95% confidence interval, .94-.99]) and recent IDU (2.91 [1.48-5.76]) were significantly associated with reinfection risk. CONCLUSIONS: The reinfection rate is high in a setting of widespread stimulant use, particularly in young people with recent IDU. Regular follow-up is important among high-risk populations to diagnose reinfections early and reduce transmission. CLINICAL TRIALS REGISTRATION: NCT02647879.


Assuntos
Usuários de Drogas , Hepatite C Crônica , Hepatite C , Abuso de Substâncias por Via Intravenosa , Humanos , Masculino , Adolescente , Adulto , Hepacivirus , Reinfecção , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Estudos Prospectivos , Recidiva , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C/complicações , Incidência
8.
Front Med (Lausanne) ; 9: 799494, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35155495

RESUMO

OBJECTIVE: Due to a tender process in Iceland, all patients on Humira® were switched nationwide to its biosimilar Imraldi® in March 2019. The study aimed to explore the patient's perspective of the Humira® and Imraldi® injection devices. METHODS: A standard telephone interview was carried out among patients with inflammatory arthritis, inflammatory bowel disease and psoriasis, who underwent this nationwide switching program a few months earlier. RESULTS: The response rate was 84.5% (n = 198). The average age was 50.8 years, and 53.5% were female. The patients self-administered the drugs in 96% of the cases. The majority (90.5%) stated that they received individualized instruction on using the Humira® pen, compared to 18.2% who accepted instruction in the case of the Imraldi® pen. Almost half (46.6%) of the patients found it more difficult to use the Imraldi® pen than the Humira® pen, while only 12.5% found the Imraldi® pen easier to use. Firstly, these differences were due to more painful insertion of the needle (62.2%) and secondly, due to the experience, the injection process was different (63.0%). CONCLUSION: Patients with inflammatory disorders who have been treated regularly with adalimumab preferred the Humira® injection device over the Imraldi® device, according to our results. After all, these injection devices' structure and content are not the same, although both contain the same active ingredient, i.e. adalimumab. Our results highlight the importance of thorough information, not only with an information letter but also with the possibilities for individualized introduction in planning switching to biosimilars.

9.
J Rheumatol ; 49(1): 53-59, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34334358

RESUMO

OBJECTIVE: To compare potential risk factors for the diagnosis of psoriatic arthritis (PsA), psoriasis (PsO), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). METHODS: Four parallel case-control studies were conducted within The Health Improvement Network using data between 1994 and 2015. Patients with PsA, PsO, RA, or AS were identified using validated code lists and matched to controls on age, sex, practice, and year. Risk factors were selected in the time prior to diagnosis. Multivariable logistic regression models were constructed for each disease using automated stepwise regression to test potential risk factors. RESULTS: Patients with incident PsA (n = 7594), PsO (n = 111,375), RA (n = 28,341), and AS (n = 3253) were identified and matched to 75,930, 1,113,345, 283,226, and 32,530 controls, respectively. Median diagnosis age was 48 (IQR 38-59), 43 (IQR 28-60), 60 (IQR 48-71), and 41 (IQR 32-54) years, respectively. In multivariable models, there were some shared and some differing risk factors across all 4 diseases: PsA was associated with obesity, pharyngitis, and skin infections; PsA and PsO were associated with obesity and moderate alcohol intake; PsA and AS were associated with uveitis; and PsA and RA were associated with preceding gout. Both RA and AS were associated with current smoking, former moderate drinking, anemia, osteoporosis, and inflammatory bowel disease. All shared former or current smoking as a risk factor; statin use was inversely associated with all 4 diseases. CONCLUSION: Shared and different risk factors for PsA, PsO, RA, and AS were identified. Statin use was inversely associated with all 4 conditions.


Assuntos
Artrite Psoriásica , Artrite Reumatoide , Psoríase , Espondilite Anquilosante , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/epidemiologia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Estudos de Casos e Controles , Humanos , Fatores de Risco , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/epidemiologia
10.
Arthritis Care Res (Hoboken) ; 74(7): 1205-1218, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-33460531

RESUMO

OBJECTIVE: There is a lack of real-life studies on interleukin-17 (IL-17) inhibition in psoriatic arthritis (PsA). We assessed real-life 6- and 12-month effectiveness (i.e., retention, remission, low disease activity [LDA], and response rates) of the IL-17 inhibitor secukinumab in PsA patients overall and across 1) number of prior biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries. METHODS: Thirteen quality registries in rheumatology participating in the European Spondyloarthritis Research Collaboration Network provided longitudinal, observational data collected as part of routine care for secondary use. Data were pooled and analyzed with Kaplan-Meier plots, log rank tests, Cox regression, and multiple linear and logistic regression analyses. RESULTS: A total of 2,017 PsA patients started treatment with secukinumab between 2015 and 2018. Overall secukinumab retention rates were 86% and 76% after 6 and 12 months, respectively. Crude (LUNDEX adjusted) 6-month remission/LDA (LDA including remission) rates for the 28-joint Disease Activity Index for Psoriatic Arthritis, the Disease Activity Score in 28 joints using the C-reactive protein level, and the Simplified Disease Activity Index (SDAI) were 13%/46% (11%/39%), 36%/55% (30%/46%), and 13%/56% (11%/47%), and 12-month rates were 11%/46% (7%/31%), 39%/56% (26%/38%), and 16%/62% (10%/41%), respectively. Clinical Disease Activity Index remission/LDA rates were similar to the SDAI rates. Six-month American College of Rheumatology 20%/50%/70% improvement criteria responses were 34%/19%/11% (29%/16%/9%); 12-month rates were 37%/21%/11% (24%/14%/7%). Secukinumab effectiveness was significantly better for b/tsDMARD-naive patients, similar across time since diagnosis (<2/2-4/>4 years), and varied significantly across the European registries. CONCLUSION: In this large real-world study on secukinumab treatment in PsA, 6- and 12-month effectiveness was comparable to that in previous observational studies of tumor necrosis factor inhibitors. Retention, remission, LDA, and response rates were significantly better for b/tsDMARD-naive patients, were independent of time since diagnosis, and varied significantly across the European countries.


Assuntos
Anticorpos Monoclonais Humanizados , Antirreumáticos , Artrite Psoriásica , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Europa (Continente) , Humanos , Interleucina-17/antagonistas & inibidores , Resultado do Tratamento
11.
ACR Open Rheumatol ; 4(2): 187-194, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34842362

RESUMO

OBJECTIVE: The objective of this study was to investigate the effect of tumor necrosis factor α inhibitor (TNFi) initiation on the use of antimicrobials among biologic-naïve patients with rheumatoid arthritis (RA). METHODS: Information on all biologic-naïve patients with RA was extracted from ICEBIO, a nationwide registry. Each patient was matched on age, sex, and calendar time to five randomly selected individuals from the general population. All filled antimicrobial and glucocorticoid prescriptions in the 2 years before and after initiation of the first TNFi were extracted from the Prescription Medicines Register. Prescriptions were quantified by using the number of filled prescriptions (NP) and defined daily doses. RESULTS: We extracted information on 359 patients with RA and 1795 comparators. During the 24 months before initiating treatment with TNFi, patients with RA received more prescriptions for antimicrobials than their matched general population comparators (mean ± SD: 2.8 ± 3.4 vs 1.6 ± 2.7; P < 0.001). The 24-month mean NP for patients with RA increased to 3.5 ± 3.9 (P < 0.001) after initiating TNFi: antibiotics, 2.6 ± 3.2 to 3.2 ± 3.5 (P < 0.001); antivirals, 0.06 ± 0.5 to 0.16 ± 0.7 (P = 0.004); and antimycotics, 0.14 ± 0.5 to 0.22 ± 0.9 (P = 0.06). The 12-month mean NP was highest in the second year after TNFi initiation (1.9 ± 2.4). No association was found between NP and glucocorticoids, age, body mass index, or pre-TNFi Disease Activity Score 28-joint count and C-reactive protein. CONCLUSION: Patients with RA on TNFi are more commonly treated for infections in the outpatient settings than previously reported. Patients are prescribed more antimicrobials in the 2 years preceding TNFi initiation than the general population, and this use further increases after initiation of TNFi. In contrast to what is reported for infections requiring hospitalization, outpatient antimicrobial use remained elevated for at least 2 years.

13.
Lancet Gastroenterol Hepatol ; 6(8): 628-637, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34171267

RESUMO

BACKGROUND: WHO has set targets to eliminate hepatitis C virus (HCV) infection as a global health threat by 2030 through a 65% reduction in HCV-related deaths and 80% reduction in HCV incidence. To achieve these goals, WHO set service coverage targets of 90% of the infected population being diagnosed and 80% of eligible patients being treated. In February, 2016, Iceland initiated a nationwide HCV elimination programme known as treatment as prevention for hepatitis C (TraP HepC), which aimed to maximise diagnosis and treatment access. This analysis reports on the HCV cascade of care in the first 3 years of the programme. METHODS: This population-based study was done between Feb 10, 2016, and Feb 10, 2019. Participants aged 18 years or older with permanent residence in Iceland and PCR-confirmed HCV were offered direct-acting antiviral (DAA) therapy. The programme used a multidisciplinary team approach in which people who inject drugs were prioritised. Nationwide awareness campaigns, improved access to testing, and harm reduction services were scaled up simultaneously. The number of infected people in the national HCV registry was used in combination with multiple other data sources, including screening of low-risk groups and high-risk groups, to estimate the total number of HCV infections. The number of people diagnosed, linked to care, initiated on treatment, and cured were recorded during the study. This study is registered with ClinicalTrials.gov, NCT02647879. FINDINGS: In February, 2016, at the onset of the programme, 760 (95% CI 690-851) individuals were estimated to have HCV infection, with 75 (95% CI 6-166) individuals undiagnosed. 682 individuals were confirmed to be HCV PCR positive. Over the next 3 years, 183 new infections (including 42 reinfections) were diagnosed, for a total of 865 infections in 823 individuals. It was estimated that more than 90% of all domestic HCV infections had been diagnosed as early as January, 2017. During the 3 years, 824 (95·3%) of diagnosed infections were linked to care, and treatment was initiated for 795 (96·5%) of infections linked to care. Cure was achieved for 717 (90·2%) of 795 infections. INTERPRETATION: By using a multidisciplinary public health approach, involving tight integration with addiction treatment services, the core service coverage targets for 2030 set by WHO have been reached. These achievements position Iceland to be among the first nations to subsequently achieve the WHO goal of eliminating HCV as a public health threat. FUNDING: The Icelandic Government and Gilead Sciences.


Assuntos
Antivirais/uso terapêutico , Atenção à Saúde/métodos , Hepatite C/prevenção & controle , Vigilância da População/métodos , Saúde Pública , Idoso , DNA Viral/análise , Feminino , Seguimentos , Hepacivirus/genética , Hepatite C/epidemiologia , Humanos , Islândia/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Nature ; 584(7822): 619-623, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32581359

RESUMO

Autoimmune thyroid disease is the most common autoimmune disease and is highly heritable1. Here, by using a genome-wide association study of 30,234 cases and 725,172 controls from Iceland and the UK Biobank, we find 99 sequence variants at 93 loci, of which 84 variants are previously unreported2-7. A low-frequency (1.36%) intronic variant in FLT3 (rs76428106-C) has the largest effect on risk of autoimmune thyroid disease (odds ratio (OR) = 1.46, P = 2.37 × 10-24). rs76428106-C is also associated with systemic lupus erythematosus (OR = 1.90, P = 6.46 × 10-4), rheumatoid factor and/or anti-CCP-positive rheumatoid arthritis (OR = 1.41, P = 4.31 × 10-4) and coeliac disease (OR = 1.62, P = 1.20 × 10-4). FLT3 encodes fms-related tyrosine kinase 3, a receptor that regulates haematopoietic progenitor and dendritic cells. RNA sequencing revealed that rs76428106-C generates a cryptic splice site, which introduces a stop codon in 30% of transcripts that are predicted to encode a truncated protein, which lacks its tyrosine kinase domains. Each copy of rs76428106-C doubles the plasma levels of the FTL3 ligand. Activating somatic mutations in FLT3 are associated with acute myeloid leukaemia8 with a poor prognosis and rs76428106-C also predisposes individuals to acute myeloid leukaemia (OR = 1.90, P = 5.40 × 10-3). Thus, a predicted loss-of-function germline mutation in FLT3 causes a reduction in full-length FLT3, with a compensatory increase in the levels of its ligand and an increased disease risk, similar to that of a gain-of-function mutation.


Assuntos
Códon sem Sentido/genética , Predisposição Genética para Doença/genética , Ligantes , Mutação , Tireoidite Autoimune/genética , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo , Alelos , Doenças Autoimunes/genética , Bases de Dados Factuais , Estudo de Associação Genômica Ampla , Mutação em Linhagem Germinativa , Humanos , Islândia , Íntrons/genética , Leucemia Mieloide Aguda , Mutação com Perda de Função , Sítios de Splice de RNA/genética , Reino Unido
15.
Clin Exp Rheumatol ; 36(6): 1068-1073, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29998835

RESUMO

OBJECTIVES: To identify the proportion of patients with psoriatic arthritis (PsA) who would meet inclusion criteria of the randomised clinical trials that were performed leading up to registration of the tumour necrosis factor inhibitors (TNFi). METHODS: Data from 329 patients with PsA were obtained from an Icelandic database, ICEBIO, medical records at the University Hospital of Iceland, and the private out-patient clinic Laeknasetrid Ltd. The patients were classified according to whether they met the inclusion criteria of the clinical trials that were performed ahead of the registration of each respective TNFi. The reasons for exclusion were also explored. RESULTS: 34% of the patients with complete data available met the inclusion criteria. Clinical data in respect to exclusion and inclusion criteria were incomplete for 13% of the cases. The proportion of patients who met the inclusion criteria was highest among those who received adalimumab and etanercept (53%). Patients who received in iximab had the lowest inclusion rate (23%). The main reason why patients did not meet the inclusion criteria was too few swollen and/or tender joints, or in 45% of excluded cases. CONCLUSIONS: Our results demonstrate that two thirds of patients with PsA in Iceland who are treated with TNFi would not have qualified for the randomised clinical trials performed leading up to the registration of the medications. Further studies with regards to whether outcomes are different between those who met the inclusion criteria and those who did not remain to be performed.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Definição da Elegibilidade/métodos , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Antirreumáticos/efeitos adversos , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/imunologia , Produtos Biológicos/efeitos adversos , Bases de Dados Factuais , Feminino , Humanos , Islândia , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/imunologia
16.
Ann Hematol ; 95(6): 871-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26976017

RESUMO

Infectious complications in chronic lymphocytic leukemia (CLL) represent a major cause of morbidity and mortality. The aim of the study was to investigate temporal trends in bloodstream infections (BSIs) among patients with CLL. Individuals with blood cultures were linked to Swedish Cancer Registry and divided into three time periods (1988-1993, 1994-1999, and 2000-2006) according to year of CLL diagnosis. CLL patients (n = 275) with 1092 blood culture episodes were identified and linked to the nationwide Cause of Death Registry and Swedish Patient Registry (to retrieve information on splenectomies). The most common causes of BSI among CLL patients were Escherichia coli (11/43, 15/78, and 9/33), Streptococcus pneumoniae (7/43, 13/78, and 6/33), Pseudomonas aeruginosa (2/43, 8/78, and 3/33), Staphylococcus aureus (1/43, 6/78, and 6/33), and Viridans streptococci (5/43, 6/78, and 2/33). Coagulase-negative staphylococci was the most frequent microorganism found in blood cultures (22/70, 23/106, and 5/41, respectively) but is a frequent contaminant. Based on the largest study to date on BSI in CLL patients, we found a stable proportion of Gram-positive to Gram-negative bacteria and no temporal change of distribution was observed for BSIs 1988-2006.


Assuntos
Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/sangue , Escherichia coli/isolamento & purificação , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Staphylococcus/isolamento & purificação , Suécia/epidemiologia , Estreptococos Viridans/isolamento & purificação
17.
Arthritis Rheumatol ; 68(5): 1060-71, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26749174

RESUMO

OBJECTIVE: To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA). METHODS: GRAPPA rheumatologists, dermatologists, and PsA patients drafted overarching principles for the management of PsA, based on consensus achieved at face-to-face meetings and via online surveys. We conducted literature reviews regarding treatment for the key domains of PsA (arthritis, spondylitis, enthesitis, dactylitis, skin disease, and nail disease) and convened a new group to identify pertinent comorbidities and their effect on treatment. Finally, we drafted treatment recommendations for each of the clinical manifestations and assessed the level of agreement for the overarching principles and treatment recommendations among GRAPPA members, using an online questionnaire. RESULTS: Six overarching principles had ≥80% agreement among both health care professionals (n = 135) and patient research partners (n = 10). We developed treatment recommendations and a schema incorporating these principles for arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities in the setting of PsA, using the Grading of Recommendations, Assessment, Development and Evaluation process. Agreement of >80% was reached for approval of the individual recommendations and the overall schema. CONCLUSION: We present overarching principles and updated treatment recommendations for the key manifestations of PsA, including related comorbidities, based on a literature review and consensus of GRAPPA members (rheumatologists, dermatologists, other health care providers, and patient research partners). Further updates are anticipated as the therapeutic landscape in PsA evolves.


Assuntos
Corticosteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/terapia , Modalidades de Fisioterapia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Administração Oral , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Humanos , Injeções Intra-Articulares , Ustekinumab/uso terapêutico
18.
J Rheumatol ; 41(11): 2306-14, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25362716

RESUMO

Nail involvement in psoriatic diseases causes significant physical and functional disabilities. Evaluating, measuring, and treating nail involvement is important in improving the health outcomes and quality of life among patients with psoriasis and psoriatic arthritis (PsA). We performed a systematic analysis of the literature on nail psoriasis to help inform an update of treatment recommendations by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).


Assuntos
Doenças da Unha/diagnóstico , Doenças da Unha/terapia , Guias de Prática Clínica como Assunto , Psoríase/diagnóstico , Psoríase/terapia , Administração Oral , Administração Tópica , Terapia Combinada , Medicina Baseada em Evidências , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Terapia a Laser/métodos , Masculino , Terapia PUVA/métodos , Índice de Gravidade de Doença , Resultado do Tratamento
19.
Ann Intern Med ; 160(2): 73-80, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-24592492

RESUMO

BACKGROUND: Involvement of large arteries is well-documented in giant-cell arteritis (GCA), but the risk for cardiovascular events is not well-understood. OBJECTIVE: To evaluate the risks for incident myocardial infarction (MI), cerebrovascular accident (CVA), and peripheral vascular disease (PVD) in individuals with incident GCA in a general population context. DESIGN: Observational cohort study. SETTING: U.K. primary care database. PATIENTS: 3408 patients with incident GCA and 17 027 age- and sex-matched reference participants without baseline cardiovascular disease (MI, CVA, or PVD). MEASUREMENTS: Diagnoses of GCA, outcomes, and cardiovascular risk factors were identified from electronic medical records. One combined and 3 separate cohort analyses were conducted for the outcomes of MI, CVA, and PVD. The association of GCA with study outcomes is expressed with hazard ratios (HRs) with 95% CIs after adjustment for potential cardiovascular risk factors. RESULTS: Among 3408 patients with GCA (73% female; mean age, 73 years), the incidence rates of MI, CVA, and PVD were 10.0, 8.0, and 4.2 events per 1000 person-years, respectively, versus 4.9, 6.3, and 2.0 events per 1000 person-years, respectively, among reference participants. The HRs were 1.70 (95% CI, 1.51 to 1.91) for the combined outcome, 2.06 (CI, 1.72 to 2.46) for MI, 1.28 (CI, 1.06 to 1.54) for CVA, and 2.13 (CI, 1.61 to 2.81) for PVD. The HRs were more pronounced in the first month after GCA diagnosis (combined HR, 4.92 [CI, 2.59 to 9.34]; HR for MI, 11.89 [CI, 2.40 to 59.00]; HR for CVA, 3.93 [CI, 1.76 to 8.79]; HR for PVD, 3.86 [CI, 0.78 to 19.17]). LIMITATION: Information on temporal arterial biopsies was not available, and there was a substantial amount of missing data on cardiovascular risk factors. CONCLUSION: Giant-cell arteritis is associated with increased risks for MI, CVA, and PVD. PRIMARY FUNDING SOURCE: National Institute of Arthritis and Musculoskeletal and Skin Diseases.


Assuntos
Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Arterite de Células Gigantes/complicações , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/epidemiologia , Doenças Vasculares Periféricas/complicações , Doenças Vasculares Periféricas/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia
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