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1.
Rheumatology (Oxford) ; 62(9): 3075-3083, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36692142

RESUMO

OBJECTIVE: GCA is the commonest primary systemic vasculitis in adults, with significant health economic costs and societal burden. There is wide variation in access to secondary care GCA services, with 34% of hospitals in England not having any formal clinical pathway. Quality standards provide levers for change to improve services. METHODS: The multidisciplinary steering committee were asked to anonymously put forward up to five aspects of service essential for best practice. Responses were qualitatively analysed to identify common themes, subsequently condensed into domain headings, and ranked in order of importance. Quality standards and metrics for each domain were drafted, requiring a minimum 75% agreement. RESULTS: 13 themes were identified from the initial suggestions. Nine quality standards with auditable metrics were developed from the top 10 themes. Patient Access, glucocorticoid use, pathways, ultrasonography, temporal artery biopsy, PET scan access, rheumatology/ophthalmology expertise, education, multidisciplinary working have all been covered in these quality standards. Access to care is a strand that has run through each of the developed standards. An audit tool was developed as part of this exercise. CONCLUSION: These are the first consensus auditable quality standards developed by clinicians from rheumatology and ophthalmology, nursing representatives and involvement of a patient charity. We hope that these standards will be adopted by commissioning bodies to provide levers for change from the improvement of patient care of individuals with GCA.


Assuntos
Arterite de Células Gigantes , Reumatologia , Humanos , Arterite de Células Gigantes/patologia , Atenção Secundária à Saúde , Artérias Temporais/patologia , Tomografia por Emissão de Pósitrons
2.
Org Biomol Chem ; 17(41): 9187-9199, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31595935

RESUMO

A divergent approach has been successfully developed for the synthesis of N-1,2,4-oxadiazole substituted sulfoximines starting from N-cyano sulfoximines. This method has a wide degree of substrate scope that includes aryl, heteroaryl, alkyl, fluoroalkyl and saturated heterocyclic compounds. Excellent functional group tolerability was also observed. Extension of this methodology to nucleosides, amino acids and dipeptides was found to be successful. A gram scale reaction was also established. The major part of this method is metal free and the utility of environmentally friendly solvents such as 2-methyl THF and ionic liquids is an added advantage.

3.
Clin Rheumatol ; 38(12): 3655-3660, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31420810

RESUMO

INTRODUCTION: The frequency of eighth nerve lesions in patients with giant cell arteritis (GCA) has rarely been examined. However, sudden onset deafness has been recorded as a presenting feature of GCA on several occasions. This study sought to establish how common this and other symptoms of eighth nerve involvement are in a large retrospective survey. METHODS: We contacted 170 patients with GCA and 250 matched PMR patients, inviting them to participate in a questionnaire survey of symptoms of eighth nerve dysfunction. We compared the presence of deafness, tinnitus, loss of balance and vertigo in both groups and examined the relationship between the onset of these symptoms and other features of GCA. RESULTS: A total of 317 patients were recruited. The percentage of patients with symptoms of possible vestibulocochlear disease prior to commencement of steroid therapy was significantly greater among GCA patients than PMR patients for all domains. Hearing loss which was twice as common in GCA as in PMR (53% vs 26%) [p = 0.001]. Deafness was concurrent in 35% of GCA patients with other symptoms and 45% reported colocation with headache. Recovery with steroids occurred in 56% of these. CONCLUSION: Symptoms of eighth nerve dysfunction are present in over half of patients with GCA. Recovery with steroids was predicted by concurrence with headache in terms of both timing and location. It appears that eighth nerve involvement, especially acute hearing loss, is a not infrequent feature of GCA and often responds well to steroid therapy. Clinicians should enquire about these symptoms when evaluating a patient for possible GCA.Key Points• Deafness is a frequent presenting feature of giant cell arteritis.• Vertigo, tinnitus and loss of balance are also often reported by GCA sufferers.• Steroid therapy is more likely to relieve these symptoms if they are ipsilateral and concurrent with headache.


Assuntos
Arterite de Células Gigantes/fisiopatologia , Nervo Vestibulococlear/fisiopatologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Polimialgia Reumática/fisiopatologia
4.
J Pharm Bioallied Sci ; 11(Suppl 2): S495-S498, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31198395

RESUMO

With the aim of achieving an optimal aesthetic result, implant dentistry has become a prosthetically driven procedure. Special care is being taken to focus on the details that would lead to this objective. These details may include imitating the natural teeth by harmonizing the structures around the placed implant. The prosthetic and/or surgical parts of the procedure should be performed to reach an optimal outcome. In order to minimize the resorption of hard and soft tissue, which exists around the newly extracted tooth-to create a natural emergence profile of implant born prosthesis-socket preservation procedures were introduced; however, in case of ridge deficiencies, hard and soft tissue augmentation procedures are indicated. In this article, we present a case report using a new approach in socket ridge preservation, which is the socket-shield technique (partial root retention).

5.
Lancet Rheumatol ; 1(2): e85-e94, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38229348

RESUMO

BACKGROUND: Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. METHODS: We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. FINDINGS: In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, ß2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. INTERPRETATION: Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. FUNDING: UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology. VIDEO ABSTRACT.

6.
Swiss Med Wkly ; 148: w14588, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29442344

RESUMO

OBJECTIVES: To assess the use of the Clinical EULAR Sjögren's Syndrome Disease Activity Index (ClinESSDAI), a version of the ESSDAI without the biological domain, for assessing potential eligibility and outcomes for clinical trials in patients with primary Sjögren's syndrome (pSS), according to the new ACR-EULAR classification criteria, from the UK Primary Sjögren's Syndrome Registry (UKPSSR). METHODS: A total of 665 patients from the UKPSSR cohort were analysed at their time of inclusion in the registry. ESSDAI and ClinESSDAI were calculated for each patient. RESULTS: For different disease activity index cut-off values, more potentially eligible participants were found when ClinESSDAI was used than with ESSDAI. The distribution of patients according to defined disease activity levels did not differ statistically (chi2 p = 0.57) between ESSDAI and ClinESSDAI for moderate disease activity (score ≥5 and <14; ESSDAI 36.4%; ClinESSDA 36.5%) or high disease activity (score ≥14; ESSDAI 5.4%; ClinESSDAI 6.8%). We did not find significant differences between the indexes in terms of activity levels for individual domains, with the exception of the articular domain. We found a good level of agreement between both indexes, and a positive correlation between lymphadenopathy and glandular domains with the use of either index and with different cut-off values. With the use of ClinESSDAI, the minimal clinically important improvement value was more often achievable with a one grade improvement of a single domain than with ESSDAI. We observed similar results when using the new ACR-EULAR classification criteria or the previously used American-European Consensus Group (AECG) classification criteria for pSS. CONCLUSIONS: In the UKPSSR population, the use of ClinESSDAI instead of ESSDAI did not lead to significant changes in score distribution, potential eligibility or outcome measurement in trials, or in routine care when immunological tests are not available. These results need to be confirmed in other cohorts and with longitudinal data.


Assuntos
Ensaios Clínicos como Assunto , Avaliação de Resultados em Cuidados de Saúde , Sistema de Registros , Índice de Gravidade de Doença , Síndrome de Sjogren/diagnóstico , Estudos de Coortes , Humanos , Reino Unido
8.
Arthritis Care Res (Hoboken) ; 69(11): 1714-1723, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-27992710

RESUMO

OBJECTIVE: To develop a novel method for capturing the discrepancy between objective tests and subjective dryness symptoms (a sensitivity scale) and to explore predictors of dryness sensitivity. METHODS: Archive data from the UK Primary Sjögren's Syndrome Registry (n = 688) were used. Patients were classified on a scale from -5 (stoical) to +5 (sensitive) depending on the degree of discrepancy between their objective and subjective symptoms classes. Sensitivity scores were correlated with demographic variables, disease-related factors, and symptoms of pain, fatigue, anxiety, and depression. RESULTS: Patients were on average relatively stoical for both types of dryness symptoms (mean ± SD ocular dryness -0.42 ± 2.2 and -1.24 ± 1.6 oral dryness). Twenty-seven percent of patients were classified as sensitive to ocular dryness and 9% to oral dryness. Hierarchical regression analyses identified the strongest predictor of ocular dryness sensitivity to be self-reported pain and that of oral dryness sensitivity to be self-reported fatigue. CONCLUSION: Ocular and oral dryness sensitivity can be classified on a continuous scale. The 2 symptom types are predicted by different variables. A large number of factors remain to be explored that may impact symptom sensitivity in primary Sjögren's syndrome, and the proposed method could be used to identify relatively sensitive and stoical patients for future studies.


Assuntos
Autoavaliação Diagnóstica , Síndrome de Sjogren/diagnóstico , Xeroftalmia/diagnóstico , Xerostomia/diagnóstico , Idoso , Fadiga/diagnóstico , Fadiga/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Dor/epidemiologia , Sistema de Registros , Síndrome de Sjogren/epidemiologia , Reino Unido/epidemiologia , Xeroftalmia/epidemiologia , Xerostomia/epidemiologia
9.
RMD Open ; 2(2): e000282, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27493792

RESUMO

OBJECTIVES: This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS). METHODS: Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels. RESULTS: 14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines-interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)-were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy. CONCLUSIONS: Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.

10.
Rheumatology (Oxford) ; 55(3): 544-52, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26510429

RESUMO

OBJECTIVE: To identify numbers of participants in the UK Primary Sjögren's Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. METHODS: We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. RESULTS: In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren's Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögren's syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögren's Syndrome study (Tocilizumab), 31.6% for the Tolerance and Efficacy of Rituximab in Sjögren's Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögren's Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%. CONCLUSION: The UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters.


Assuntos
Produtos Biológicos/administração & dosagem , Seleção de Pacientes , Sistema de Registros , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico , Adulto , Distribuição de Qui-Quadrado , Ensaios Clínicos como Assunto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Reino Unido
11.
PLoS One ; 10(12): e0143970, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26694930

RESUMO

BACKGROUND: Fatigue is a debilitating condition with a significant impact on patients' quality of life. Fatigue is frequently reported by patients suffering from primary Sjögren's Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms. METHODS: Whole blood samples from 133 fully-phenotyped pSS patients stratified for the presence of fatigue, collected by the UK primary Sjögren's Syndrome Registry, were used for whole genome microarray. The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA) was used as a feature selection technique for input into a support vector machine (SVM) classifier. Classification was assessed using area under curve (AUC) of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W). RESULTS: Although no genes were individually found to be associated with fatigue, 19 metabolic pathways were enriched in the high fatigue patient group using GSEA. Analysis revealed that these enrichments arose from the presence of a subset of 55 genes. A radial kernel SVM classifier with this subset of genes as input displayed significantly improved performance over classifiers using all pathway genes as input. The classifiers had AUCs of 0.866 (SE(W) 0.002) and 0.525 (SE(W) 0.006), respectively. CONCLUSIONS: Systematic analysis of gene expression data from pSS patients discordant for fatigue identified 55 genes which are predictive of fatigue level using SVM classification. This list represents the first step in understanding the underlying pathophysiological mechanisms of fatigue in patients with pSS.


Assuntos
Fadiga/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Síndrome de Sjogren/complicações , Transcriptoma , Adulto , Idoso , Área Sob a Curva , Fadiga/sangue , Fadiga/etiologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Síndrome de Sjogren/sangue
12.
Rheumatology (Oxford) ; 54(4): 655-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25240612

RESUMO

OBJECTIVE: This study sets out to investigate the relationship between health status [EuroQol five-dimensions questionnaire (EQ-5D)] in primary SS and three of the European League Against Rheumatism (EULAR) SS outcome measures-the disease activity index (ESSDAI), the patient reported index (ESSPRI) and the sicca score. In particular, the goal was to establish whether there is a relationship between the EULAR outcome measures and quality of life. METHODS: Health status was evaluated using a standardized measure developed by the EuroQol Group-the EQ5D. This permits calculation of two measures of health status: time trade-off (TTO) values and the EQ-5D visual analogue scale (VAS) scores. We used Spearman's rank correlation analysis to investigate the strength of association between health status and three EULAR measures of physician- and patient-reported disease activity in 639 patients from the UK primary SS registry (UKPSSR) cohort. RESULTS: This study demonstrates that the EULAR SS disease-specific outcome measures are significantly correlated with health outcome values (P < 0.001). Higher scores on the ESSDAI, EULAR sicca score and ESSPRI are associated with poorer health states-i.e. lower TTO values and lower VAS scores. While all three are significantly correlated with TTO values and EQ-5D VAS scores, the effect is strongest for the ESSPRI. CONCLUSION: This study provides further evidence supporting the use of ESSDAI, EULAR sicca score and ESSPRI measures in the clinic. We also discuss the need for disease-specific measures of health status and their comparison with standardized health outcome measures.


Assuntos
Nível de Saúde , Qualidade de Vida , Síndrome de Sjogren/diagnóstico , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Avaliação de Resultados da Assistência ao Paciente , Índice de Gravidade de Doença , Síndrome de Sjogren/fisiopatologia
13.
Rheumatology (Oxford) ; 53(9): 1676-82, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24758887

RESUMO

OBJECTIVES: The prevalence of interstitial lung disease (ILD) in RA is ∼5%. Previous work identified increasing age, active articular disease and articular damage as risk factors for RA-associated ILD (RA-ILD). The roles of high-resolution CT (HRCT) and lung function testing in defining the nature and extent of pulmonary involvement have recently been explored. This study is the first to examine predictive and prognostic factors for the development of RA-ILD and to report on the physiological and radiological characteristics of the condition from a large multicentre UK network. METHODS: We collected data from centres across the UK on patients with both RA and ILD (proved on HRCT) diagnosed over a 25-year period from 1987 to 2012 using a standard pro forma. Potential predictors of RA-ILD were analysed. Baseline lung function data were recorded and related to HRCT findings. We analysed HRCT for subtype and extent of lung involved and examined the relationship between these and both all-cause and pulmonary mortality. We compared our results with case controls matched for age and gender using computer-generated selection from the RA population from one contributing centre. RESULTS: A total of 230 patients were identified from across the UK with proven RA-ILD diagnosed over 25 years. Median age at diagnosis was 64 years and the male:female ratio was 1:1.09. Univariate analysis showed anti-CCP antibody titres to be the single most strongly associated predictor of RA-ILD. Male gender, age at onset, smoking and RF were all independently associated with RA-ILD on multivariate analysis. Vital capacity (VC) was preserved in limited disease but reduced in extensive disease, while gas transfer was reduced in both. Usual interstitial pneumonia (UIP) was the most common subtype on HRCT and both this and extensive disease were associated with increased all-cause mortality. CONCLUSION: This is the largest study of RA-ILD in the UK. Anti-CCP antibodies were strongly associated with RA-ILD in both sexes. Smoking was strongly associated with ILD in males, which may explain the higher frequency of RA-ILD in men. The predominant HRCT pattern was UIP and most patients had limited disease at presentation. The presence of UIP and extensive disease are associated with increased mortality. Baseline gas transfer is a useful screening tool for ILD, while the preservation of VC at baseline might predict limited disease on HRCT.


Assuntos
Artrite Reumatoide/complicações , Doenças Pulmonares Intersticiais/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/epidemiologia , Autoanticorpos/sangue , Estudos de Casos e Controles , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/imunologia , Prognóstico , Fatores de Risco , Tomografia Computadorizada por Raios X , Reino Unido/epidemiologia , Capacidade Vital/fisiologia
14.
Ann Rheum Dis ; 70(7): 1289-91, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21515601

RESUMO

INTRODUCTION: Immunisation against pneumococcus has been shown to reduce pneumonia in rheumatoid arthritis (RA). There is concern that methotrexate may reduce its efficacy. There are very few objective data on the effect of methotrexate on the efficacy of pneumococcal vaccination with pneumovax, and no objective evidence on whether revaccination is necessary in RA patients on methotrexate. METHODS: The authors collected information from 180 RA patients on methotrexate relating to their vaccination status and assayed their pneumococcal antibody levels. Data on pulmonary infection were retrieved in the same patients over the preceding decade. RESULTS: Full data were available for 152 patients, of whom 28 had never been vaccinated against pneumococcus. Median levels were significantly higher in those who had been vaccinated. Unvaccinated patients and those taking oral prednisone were more likely to have had pneumonia in the previous 10 years. The RR for developing pneumonia among non-vaccinated patients was 9.7 (p=0.005) and among steroid-treated patients was 6.5 (p=0.001), after adjusting for age, gender, disease duration and comorbidity. No significant correlation was found between pneumococcal antibody levels and time since vaccination. CONCLUSIONS: This study suggests that a single administration of pneumovax early in RA offers up to 10 years protection against the development of pneumococcal pneumonia in RA patients on methotrexate.


Assuntos
Anticorpos Antibacterianos/sangue , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Metotrexato/uso terapêutico , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Idoso , Antirreumáticos/administração & dosagem , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Esquema de Medicação , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Infecções Oportunistas/complicações , Infecções Oportunistas/prevenção & controle , Pneumonia Pneumocócica/complicações , Pneumonia Pneumocócica/prevenção & controle , Vacinação
15.
Clin Rheumatol ; 29(10): 1093-8, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20544244

RESUMO

Oral methotrexate is the benchmark against which other disease-modifying anti rheumatic drugs are measured. The use of parenteral methotrexate for those failing to tolerate or respond to oral therapy is accepted, but indications for its use and its place in the therapeutic ladder have not been fully investigated. We assessed the use of parenteral methotrexate (MTX) in our rheumatoid arthritis (RA) population and compared the characteristics of these patients to a matched group of those on oral therapy. We compared response rates to each approach using DAS 28 scores, ESR and visual analogue scales. Inferences on costs of parenteral therapy were made and predictors of response defined. We found that 10% of our total RA patient population were on parenteral methotrexate, having failed to tolerate or respond to oral therapy. Seventy-five percent of these met the criteria for the use of anti-tumour necrosis factor (TNF) agents. Overall response rates were equivalent to those obtained by responders to oral MTX. Patients on parenteral therapy were younger and were more likely to have extreme values of body mass index (BMI) than those on oral therapy. The approach was economically viable, although many patients unnecessarily attended hospital to receive their injections. We advocate consideration of parenteral MTX in all RA patients unresponsive to oral therapy prior to treatment with anti-TNF therapy. Response to parenteral therapy can be predicted by low BMI (below 22 kg/m(2)), possibly as a result of malabsorption, or by high BMI (over 30) as a result of gastrointestinal intolerance. A mechanism to deliver this option through self-administration in the community should be encouraged.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Metotrexato/administração & dosagem , Fatores Etários , Idoso , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Índice de Massa Corporal , Esquema de Medicação , Feminino , Humanos , Infusões Parenterais , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento
16.
Eur J Intern Med ; 20(7): 718-21, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19818294

RESUMO

INTRODUCTION: An increased prevalence of musculoskeletal disease is recognised in diabetes and is a common source of disability. It is known to predominantly affect the upper limbs especially the hand and shoulder. The relationship with other complications of diabetes and glycaemic control is uncertain. We designed this study to clarify these relationships, and to assess differences between types 1 and 2 diabetes. METHODS: We identified a group of 96 people with established diabetes and examined them for the presence of locomotor disease focussing on the upper limbs. We recorded the mean HbA1c and the presence of diabetic complications, together with the health assessment questionnaire (HAQ) score. We explored correlations between locomotor disease and these variables using logistic regression. We compared data between type 1 and type 2 diabetics and contrasted the amalgamated data with that of a matched control population of medical out patients using Students t tests. RESULTS: Locomotor disease was present in 75% of diabetics with the upper limb the commonest site for abnormalities. This prevalence was significantly higher than that seen in the controls (53%) [p=0.02]. Shoulder capsulitis (25%), carpal tunnel syndrome (20%), tenosynovitis (29%), limited joint mobility (28%) and Dupuytrens contracture (13%) were the most frequent findings and were much commoner than in controls. Capsulitis usually coexisted with other upper limb abnormalities and best predicted the presence of retinopathy and/or neuropathy. The mean HbA1c was significantly higher in patients with combined shoulder and hand problems (9.1%) than in those with no upper limb problems (8.0%) [p=0.018]. The pattern of results was similar in type 1 and type 2 diabetes, although the prevalence of abnormalities and mean HAQ were significantly greater in type 2 patients, which may be in part a function of their greater mean age. CONCLUSION: Upper limb locomotor abnormalities are very common in diabetes and are associated with worse glycaemic control and more diabetic complications. Assessment of upper limb locomotor disease in diabetes should include an estimate of glycaemic control and a search for other complications.


Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Hiperglicemia/epidemiologia , Doenças Musculoesqueléticas/epidemiologia , Braço , Síndrome do Túnel Carpal/epidemiologia , Síndrome do Túnel Carpal/metabolismo , Complicações do Diabetes/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Avaliação da Deficiência , Contratura de Dupuytren/epidemiologia , Contratura de Dupuytren/metabolismo , Feminino , Humanos , Hiperglicemia/metabolismo , Artropatias/epidemiologia , Artropatias/metabolismo , Masculino , Pessoa de Meia-Idade , Movimento , Doenças Musculoesqueléticas/metabolismo , Prevalência , Tenossinovite/epidemiologia , Tenossinovite/metabolismo
17.
Expert Opin Pharmacother ; 9(18): 3221-30, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19040342

RESUMO

This review article describes our present understanding of interstitial lung disease (ILD) complicating rheumatoid arthritis (RA). It discusses its high prevalence and clinical relevance, our recent improvement in understanding both its pathology and physiology, and our expectations of ongoing research into the immunology and genetics of the disease. An important section relates to the effects of drugs routinely used in the treatment of the articular manifestations of RA on the lung, especially in the presence of ILD. The major focus of the article is on therapeutic intervention, and here we discuss traditional and often unsuccessful approaches to treatment, leading on to discuss newly introduced therapeutic options such as anticoagulation and oral N-acetylcysteine. In the later sections, we focus our attention on several promising new therapeutic agents, including mycophenolate and new monoclonal antibody therapies, reviewing the limited literature available to support the use of these agents, concluding with a number of other aspects of treatment that are worthy of consideration.


Assuntos
Artrite Reumatoide/terapia , Doenças Pulmonares Intersticiais/terapia , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/imunologia , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/imunologia , Transplante de Pulmão , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Guias de Prática Clínica como Assunto , Vacinação
18.
Bioorg Med Chem Lett ; 17(22): 6387-91, 2007 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-17889535

RESUMO

A facile, one-pot synthesis of thio and selenourea derivatives from amines using tetrathiomolybdate 1 and tetraselenotungstate 2 as sulfur and selenium transfer reagents, respectively, is reported. The compounds were tested for their activity as urease inhibitors and some of the compounds showed potent activity in the nanomolar range towards jack bean urease.


Assuntos
Molibdênio/química , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/farmacologia , Tioureia/síntese química , Tioureia/farmacologia , Ureia/análogos & derivados , Urease/antagonistas & inibidores , Canavalia/enzimologia , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Modelos Moleculares , Estrutura Molecular , Compostos Organosselênicos/química , Tioureia/química , Ureia/síntese química , Ureia/química , Ureia/farmacologia
19.
J Rheumatol ; 34(9): 1832-6, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17659759

RESUMO

OBJECTIVE: To determine whether drugs used in the treatment of rheumatoid arthritis (RA) contribute to the increased risk of respiratory infection or influence its outcome. METHODS: We identified all episodes of lower respiratory tract infection (LRTI) in our RA population over a 12 month period. A detailed drug history was recorded in each case, together with the clinical outcome. Premorbid illnesses and admission data were collected and analyzed to assess the influence of oral steroids and disease modifying antirheumatic drugs (DMARD) on outcome. RESULTS: The overall annual incidence of LRTI in patients with RA was 2.3% with a mortality rate of 22.5%. Demographic factors predicting LRTI included older age and male sex. Oral steroids and not taking DMARD were also associated with an increased risk of hospital admission with LRTI. Being male and having RA for over 10 years trended to the prediction of death as a result of infection. Taking DMARD was not associated with any adverse outcome. CONCLUSION: Respiratory infection is common in patients with RA and carries a high mortality. Oral steroids predispose to infection, while DMARD do not. Increasing age and male sex also predispose to respiratory tract infection.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/complicações , Pneumonia/complicações , Fatores Etários , Idoso , Artrite Reumatoide/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , Pneumonia/mortalidade , Prednisolona/efeitos adversos , Fatores de Risco , Fatores Sexuais , Reino Unido/epidemiologia
20.
J Rheumatol ; 33(7): 1250-3, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16758510

RESUMO

OBJECTIVE: There is little information on the natural history of patients with rheumatoid arthritis (RA) and associated interstitial lung disease (ILD). Cryptogenic fibrosing alveolitis (CFA) is known to have a poor longterm prognosis, and we compared the 2 conditions through a longitudinal prospective study. METHODS: We previously compared baseline clinical, physiological, and radiological characteristics in 18 RA-ILD patients with 18 case controls with CFA. Clinical, physiological, and radiological assessment was repeated in all survivors at 5 years, and data on treatment and mortality were collected. RESULTS: The median age in each group was 77 years and 10 patients in each group were male. More patients with RA-ILD survived to 5 years (8 RA-ILD vs 2 CFA; p = 0.03), and median survival was significantly longer for patients with RA-ILD (60 mo) compared to CFA (27 mo; p

Assuntos
Artrite Reumatoide/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Fibrose Pulmonar/diagnóstico , Idoso , Artrite Reumatoide/mortalidade , Artrite Reumatoide/fisiopatologia , Artrografia , Comorbidade , Feminino , Humanos , Estudos Longitudinais , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Estudos Prospectivos , Fibrose Pulmonar/mortalidade , Fibrose Pulmonar/fisiopatologia , Testes de Função Respiratória , Taxa de Sobrevida , Reino Unido/epidemiologia
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