Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 312
Filtrar
1.
Trials ; 21(1): 524, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539853

RESUMO

BACKGROUND: Scaled-up direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection among people who inject drugs (PWID) is crucial to reach the World Health Organization HCV elimination targets within 2030. One of the critical obstacles to HCV care in this population is the lack of treatment models within specialist healthcare adapted to marginalized individuals. METHODS: OPPORTUNI-C is a pragmatic stepped wedge cluster randomized trial comparing the efficacy of immediate initiation of HCV treatment with the current standard of care among PWID admitted for inpatient care. Screening for HCV RNA will be performed as soon as possible after admission. The intervention includes immediate non-invasive liver disease assessment, counseling, and initiation of pan-genotypic DAA treatment with individualized follow-up. Standard of care is a referral to outpatient care at discharge. To mimic usual clinical practice as closely as possible, we will use a pragmatic clinical trial approach utilizing clinical infrastructure, broad eligibility criteria, flexible intervention delivery, clinically relevant outcomes, and collection of data readily available from the electronic patient files. The stepped wedge design involves a sequential rollout of the intervention over 16 months, in which seven participating clusters will be randomized from standard of care to intervention in a stepwise manner. Randomization will be stratified according to cluster size to keep high prevalence clusters separated. The trial will include approximately 220 HCV RNA positive individuals recruited from departments of internal medicine, addiction medicine, and psychiatry at Akershus University Hospital, Oslo University Hospital, and Lovisenberg Diaconal Hospital, Oslo, Norway. Individuals not able or willing to give informed consent and those with ongoing HCV assessment or treatment will be excluded. The primary outcome is treatment completion, defined as dispensing of the final prescribed DAA package from the pharmacy within 6 months after inclusion. Secondary outcomes include treatment uptake, virologic response, reinfection incidence, and resistance-associated substitutions. DISCUSSION: Representing a novel model of care suited to reach and engage marginalized PWID in HCV care, this study will inform HCV elimination efforts locally and internationally. If the model proves efficacious and feasible, it should be considered for broader implementation, replacing the current standard of care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04220645. Registered on 7 January 2020.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Tratamento de Substituição de Opiáceos , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico , Assistência ao Convalescente , Aconselhamento , Prestação Integrada de Cuidados de Saúde/métodos , Hepatite C/etiologia , Humanos , Noruega , Reação em Cadeia da Polimerase , Ensaios Clínicos Pragmáticos como Assunto , Qualidade de Vida , Recidiva , Abuso de Substâncias por Via Intravenosa/complicações , Resposta Viral Sustentada , Cooperação e Adesão ao Tratamento
2.
Med Hypotheses ; 138: 109575, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32088522

RESUMO

Antibody levels to periodontal pathogens in prediction of cardiovascular disease (CVD) mortality were explored using data from a health survey in Oslo in 2000 (Oslo II-study) with 12 1/2 years follow-up. IgG antibodies to four common periodontal pathogens; Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD) all termed collectively the "red complex", and Aggregatibacter actinomycetemcomitans(AA) were analysed. The study sample consisted of 1172 men drawn from a cohort of 6,530 men who participated in the Oslo II-study, where they provided information on medical and dental history. Of the study sample, 548 men had reported prior myocardial infarction (MI) at baseline whereas the remaining 624 men were randomly drawn from the ostensibly healthy participants for comparative analyses. Dental anamnestic information included tooth extractions and oral infections. An inverse relation was found for trend by the quartile risk level of TF predicting CVD mortality, p-value for trend = 0.017. Comparison of the first to fourth quartile of TF antibodies resulted in hazard ratio (HR) = 1.82, 95% confidence interval 1.12-2.94, p = 0.015, adjusted for age, education, diabetes, daily smoking, and systolic blood pressure. Specificity comparing decile 1 to deciles 2-10 of TF predicting mortality was 92.3%. We found an increased HR by low levels of antibodies to the bacterium T. forsythia predicting CVD mortality in a 12 ½ years follow-up in persons who had experienced an MI but not among non-MI men. This novel finding constitutes a plausible causal link between oral infections and CVD mortality.


Assuntos
Doenças Cardiovasculares , Infarto do Miocárdio , Humanos , Masculino , Estudos Prospectivos , Tannerella , Tannerella forsythia
3.
J Intern Med ; 285(6): 653-669, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30762274

RESUMO

BACKGROUND AND OBJECTIVES: The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures. METHODS: Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. RESULTS: Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. CONCLUSION: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Infliximab/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Anticorpos Monoclonais/efeitos adversos , Método Duplo-Cego , Substituição de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Fatores de Tempo , Resultado do Tratamento
4.
Clin Oral Investig ; 23(8): 3307-3318, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30498980

RESUMO

OBJECTIVES: To describe changes in growth factor mediators in the gingival crevicular fluid (GCF) of patients with aggressive periodontitis (AgP) undergoing regenerative (GTR) and access flap (AF) surgery. MATERIALS AND METHODS: This was a 12-month, single-blind, split-mouth RCT involving 18 AgP patients with a bilateral intrabony defect which was treated with GTR or AF. GCF was collected prior to surgery and at subsequent follow-up visits from 3 days to 12 months post-operatively, and the levels of angiopoietin-1 (Ang-1), vascular-endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), bone morphogenetic protein-2 (BMP-2), osteoprotegerin (OPG), tissue inhibitor of metalloproteinase 1 (TIMP-1), keratinocyte growth factor (KGF) and platelet-derived growth factor-AB (PDGF-AB) were measured. At baseline, 6 and 12 months post-surgery, periodontal clinical parameters were evaluated. ANOVA was applied to test for differences in the amount of mediators (p < 0.05). RESULTS: Higher amounts of BMP-2 and OPG and a higher area under the curve (AUC) of KGF at the GTR versus AF sites were observed. The maximum change in the amount of KGF correlated significantly with periodontal clinical parameters at the GTR sites at 6 and 12 months. The AUC over 30 days of the amount of Ang-1, VEGF and KGF significantly correlated with periodontal clinical parameters at the AF sites at 6 months. CONCLUSIONS: AF and GTR differentially affected the profile of the growth mediators in GCF, and significant correlations between certain GCF mediators and periodontal clinical outcomes were identified. CLINICAL RELEVANCE: GCF components represent attractive prognostic markers for periodontal tissues undergoing repair or regeneration. However, the available evidence is not robust enough to suggest the use of a specific marker, and future adequately powered studies are warranted to identify the most relevant mediators that could be applied in clinical practice.


Assuntos
Periodontite Agressiva , Líquido do Sulco Gengival , Periodontite Agressiva/metabolismo , Líquido do Sulco Gengival/metabolismo , Humanos , Fator de Crescimento Derivado de Plaquetas/metabolismo , Método Simples-Cego , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Scand J Rheumatol ; 46(2): 95-103, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27319613

RESUMO

OBJECTIVES: To explore factors related to sleep disturbance in patients with rheumatoid arthritis (RA). METHOD: Cross-sectional data from 986 patients in the Oslo RA Register (ORAR) collected in 2009 were included. Sleep problems were assessed by four measures: the Medical Outcomes Study (MOS) sleep disturbance scale, and the sleep components of the Rheumatoid Arthritis Impact of Disease (RAID) score, the Multi-Dimensional Health Assessment Questionnaire (MDHAQ), and the 15-dimensional quality of life questionnaire (15D). Patient-reported outcomes (PROs) were recorded using standard questionnaires for physical and mental function [the HAQ and the MOS 36-item Short-Form Health Survey (SF-36), disease activity (the RA Disease Activity Index, RADAI), utility (SF-6D), and visual analogue scales (VAS) for pain, fatigue, and disease activity]. Demographics including comorbidity were collected. Information on use of medication for RA and sleep disturbance was obtained using checklists. Multivariate analyses were used to identify factors independently associated with sleep problems by four different measures. RESULTS: The mean (standard deviation, SD) age of the patients was 59.4 (12.5) years, 76.9% were females, and the mean (SD) disease duration was 13.7 (10.7) years. The correlation between the various sleep measures was high (r2 = 0.71-0.78). Sleep disturbance was moderately correlated to pain (r2 = 0.41-0.61), fatigue (r2 = 0.44-0.58), physical function (r2 = 0.33-0.48), RADAI (r2 = 0.42-0.55), and utility (r2 = 0.49-0.61). RAID sleep demonstrated the highest correlation with other PROs. RADAI, fatigue, the mental component score of SF-36, physical function, body mass index (BMI), and use of Z-drugs/benzodiazepines were independently associated with two or more measures of sleep problems (all p < 0.001). CONCLUSIONS: Sleep disturbance measured by four different measures was independently related to other PROs including fatigue, pain, and disease activity in RA patients.


Assuntos
Artrite Reumatoide/complicações , Fadiga/complicações , Medidas de Resultados Relatados pelo Paciente , Transtornos do Sono-Vigília/etiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia
6.
Clin Transl Sci ; 10(1): 42-49, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27991741

RESUMO

Systemic inflammation has been linked to suppressed CYP3A(4) activity. We determined 4ß-hydroxycholesterol (4ßOHC), an endogenous CYP3A4 metabolite, in patients with rheumatoid arthritis (RA) before and after treatment with biological disease-modifying antirheumatic drugs (bDMARDs). The 4ßOHC was compared in 41 patients before and 2-5 months after initiating TNFα inhibitors (n = 31), IL-6 inhibitors (n = 5), or B-cell inhibitors (n = 5). Correlations between 4ßOHC and inflammatory markers (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) were also tested before and after bDMARDs. 4ßOHC did not differ following bDMARD treatment (P = 0.6), nor in patients who started with IL-6 inhibitors (median 51.6 vs. 50.6 nmol/L). The 4ßOHC and CRP/ESR did not correlate before treatment (P > 0.5), but correlated significantly after bDMARDs (CRP = Spearman r -0.40; P < 0.01; ESR = r -0.34; P = 0.028) suggesting that mainly non-CYP3A4-suppressive cytokines were reduced during treatment. Thus, this study does not support a generally regained CYP3A4 phenotype in patients with RA following initiation of bDMARDs.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Hidroxicolesteróis/sangue , Inflamação/sangue , Adulto , Idoso , Artrite Reumatoide/complicações , Proteína C-Reativa/metabolismo , Feminino , Humanos , Inflamação/complicações , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Int J Cardiol ; 223: 331-336, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27543704

RESUMO

OBJECTIVES: Cardiovascular disease (CVD) risk calculators developed for the general population have been shown to inaccurately predict CVD events in patients with inflammatory joint disease (IJD). European guidelines for CVD prevention recognize the presence of carotid plaques (CP) as a very high CVD risk factor, equivalent of coronary artery disease. Patients with IJD have a high prevalence of CP. We evaluated if CP resulted in reclassification of patients with IJD into a more appropriate CVD risk class and recommended lipid lowering treatment. METHODS: CVD risk evaluation was performed in patients with IJD using SCORE and ACC/AHA risk calculators to predict CVD events. RESULTS: Of the 335 IJD patients evaluated (including rheumatoid arthritis n=201, ankylosing spondylitis n=85 and psoriatic arthritis n=49), 183 and 159 IJD patients had a calculated CVD risk by SCORE and ACC/AHA <5%, indicating no need of lipid lowering treatment (LLT). However, of patients with low to moderate risk calculated by SCORE and ACC/AHA, 67 (36.6%) and 48 (30.2%) had CP and should according to guidelines receive intensive LLT. For patients with high risk, in the LLT considered group, 54.9% and 58.1% were reclassified to correct treatment when adding information on the presence of CP. Our results reveal a considerable reclassification into correct CVD risk category when adding CP in female patients. CONCLUSION: The high frequency of asymptomatic atherosclerosis in patients with IJD has a notable impact on CVD risk stratification. Identification of CP will reclassify patients into recommended CVD preventive treatment group, which may be clinically important.


Assuntos
Doenças Cardiovasculares/epidemiologia , Artropatias/complicações , Medição de Risco/métodos , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Estudos Retrospectivos , Fatores de Risco
8.
Endocr Relat Cancer ; 22(4): 657-64, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26113608

RESUMO

Data on gastroenteropancreatic neuroendocrine neoplasms (NEN) G3 (well-differentiated neuroendocrine tumors (NET G3) and neuroendocrine carcinoma (NEC)) are limited. We retrospectively study patients with NET G3 and NEC from eight European centers. Data examined included clinical and pathological characteristics at diagnosis, therapies and outcomes. Two hundred and four patients were analyzed (37 NET G3 and 167 NEC). Median age was 64 (21-89) years. Tumor origin included pancreas (32%) and colon-rectum (27%). The primary tumor was resected in 82 (40%) patients. Metastatic disease was evident at diagnosis in 88% (liver metastases: 67%). Median Ki-67 index was 70% (30% in NET G3 and 80% in NEC; P<0.001). Median overall survival (OS) for all patients was 23 (95% CI: 18-28) months and significantly higher in NET G3 (99 vs 17 months in NEC; HR=8.3; P<0.001). Platinum-etoposide first line chemotherapy was administered in 113 (68%) NEC and 12 (32%) NET G3 patients. Disease control rate and progression free survival (PFS) were significantly higher in NEC compared to NET G3 (P<0.05), whereas OS was significantly longer in NET G3 (P=0.003). Second- and third-line therapies (mainly FOLFIRI and FOLFOX) were given in 79 and 39 of NEC patients; median PFS and OS were 3.0 and 7.6 months respectively after second-line and 2.5 and 6.2 months after third-line chemotherapy. In conclusion, NET G3 and NEC are characterized by significant differences in Ki-67 index and outcomes. While platinum-based chemotherapy is effective in NEC, it seems to have limited value in NET G3.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Antígeno Ki-67/metabolismo , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/metabolismo , Compostos Organoplatínicos/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Prognóstico , Análise de Sobrevida , Adulto Jovem
9.
Eur J Clin Microbiol Infect Dis ; 34(7): 1303-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25864193

RESUMO

Clavulanate, sulbactam, and tazobactam have been used extensively for the last 30 years, together with ß-lactam antibiotics, to inhibit the effect of ß-lactamases. Although they have been useful as ß-lactamase inhibitors in many cases, their effectiveness is restricted to class A ß-lactamases. With the increasing frequency and breadth of ß-lactamases now threatening public health throughout the world, we need a much broader spectrum of ß-lactamase inhibitors efficient against all classes of ß-lactamases. There are several ß-lactamase inhibitors under development, but only a few of them are able to inhibit class D and even fewer class B metallo-ß-lactamases (MßLs). The latter represent a real threat to the latest generations of ß-lactam antibiotics, including cephalosporins and carbapenems. Only two ß-lactamase inhibitors are, so far, under clinical evaluation, i.e., avibactam and MK-7655. The others are years from being clinically available. Although this has caused cautious optimism, the progress in this field is far too slow. This is particularly so because none of the substances provided are active against MßLs and because new ß-lactamases invariably force their way into our therapeutic armamentarium. While waiting for new antibiotics and new ß-lactamase inhibitors to become available, it is important to carry out accurate clinical and microbiological diagnosis, perform adequate hygiene, and use antibiotics properly. This may save lives and reduce resistance resulting from inappropriate antibiotic treatment.


Assuntos
Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Inibidores de beta-Lactamases/uso terapêutico , Quimioterapia Combinada , Humanos , Resistência beta-Lactâmica/genética , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , beta-Lactamas/farmacologia , beta-Lactamas/uso terapêutico
10.
Arthritis Rheumatol ; 67(7): 1718-28, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25778850

RESUMO

OBJECTIVE: Patients with rheumatoid arthritis (RA) and carotid artery plaques have an increased risk of acute coronary syndromes. Statin treatment with the goal of achieving a low-density lipoprotein (LDL) cholesterol level of ≤1.8 mmoles/liter (≤70 mg/dl) is recommended for individuals in the general population who have carotid plaques. The aim of the ROsuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases (RORA-AS) study was to evaluate the effect of 18 months of intensive lipid-lowering treatment with rosuvastatin with regard to change in carotid plaque height. METHODS: Eighty-six patients (60.5% of whom were female) with carotid plaques and inflammatory joint disease (55 with RA, 21 with AS, and 10 with psoriatic arthritis) were treated with rosuvastatin to obtain the LDL cholesterol goal. Carotid plaque height was evaluated by B-mode ultrasonography. RESULTS: The mean ± SD age of the patients was 60.8 ± 8.5 years, and the median compliance with rosuvastatin treatment was 97.9% (interquartile range [IQR] 96.0-99.4). At baseline, the median number and height of the carotid plaques were 1.0 (range 1-8) and 1.80 mm (IQR 1.60-2.10), respectively. The mean ± SD change in carotid plaque height after 18 months of treatment with rosuvastatin was -0.19 ± 0.35 mm (P < 0.0001). The mean ± SD baseline LDL cholesterol level was 4.0 ± 0.9 mmoles/liter (154.7 ± 34.8 mg/dl), and the mean reduction in the LDL cholesterol level was -2.3 mmoles/liter (95% confidence interval [95% CI] -2.48, -2.15) (-88.9 mg/dl [95% CI -95.9, -83.1]). The mean ± SD LDL cholesterol level during the 18 months of rosuvastatin treatment was 1.7 ± 0.4 mmoles/liter (area under the curve). After adjustment for age/sex/blood pressure, no linear relationship between a reduction in carotid plaque height and the level of LDL cholesterol exposure during the study period was observed. Attainment of the LDL cholesterol goal of ≤1.8 mmoles/liter (≤70 mg/dl) or the amount of change in the LDL cholesterol level during the study period did not influence the degree of carotid plaque height reduction. CONCLUSION: Intensive lipid-lowering treatment with rosuvastatin induced atherosclerotic regression and reduced the LDL cholesterol level significantly in patients with inflammatory joint disease.


Assuntos
Artrite Psoriásica/complicações , Artrite Reumatoide/complicações , Estenose das Carótidas/prevenção & controle , Fluorbenzenos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pirimidinas/uso terapêutico , Espondilite Anquilosante/complicações , Sulfonamidas/uso terapêutico , Síndrome Coronariana Aguda/epidemiologia , Idoso , Estenose das Carótidas/sangue , Estenose das Carótidas/diagnóstico por imagem , LDL-Colesterol/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Rosuvastatina Cálcica , Resultado do Tratamento , Ultrassonografia de Intervenção
11.
Scand J Rheumatol ; 44(2): 118-24, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25756521

RESUMO

OBJECTIVES: Insight into the most important inflammatory pathways in ankylosing spondylitis (AS) could be of importance in risk stratification and the development of treatment strategies. Therefore, we aimed to compare circulating levels of inflammatory biomarkers between AS patients and controls, and explore associations between these biomarkers and clinical measures of disease activity. METHOD: In a cross-sectional study, 143 AS patients were compared with 124 population controls. Blood samples were analysed by immunoassays for interleukin (IL)-6, IL-17a, IL-23, soluble tumour necrosis factor receptor 1 (sTNF-R1) and 2 (sTNF-R2), and osteoprotegerin (OPG). Disease activity was measured by the AS Disease Activity Score (ASDAS) and the Bath AS Disease Activity Index (BASDAI). RESULTS: Analysis of covariance (ANCOVA) demonstrated elevated plasma levels of sTNF-R1 [geometrical mean 0.94 (95% CI 0.88-1.00) vs. 0.83 (95% CI 0.78-0.89) ng/mL, p < 0.01] and OPG (2.3, 95% CI 2.1-2.4 vs. 2.0, 95% CI 1.9-2.2 ng/mL, p = 0.02) and, although not significant, of IL-23 (122, 95% CI 108-139 vs. 106, 95% CI 93-120 pg/mL, p = 0.07) in AS patients vs. CONTROLS: More AS patients had a high level of sTNF-R2 than controls (22 vs. 1, p < 0.01). No differences between the groups were seen for IL-6 and IL-17a. In patients, no significant associations were seen between inflammatory markers and disease activity measures after adjusting for personal characteristics. CONCLUSION: Significantly higher plasma levels of sTNF-R1, sTNF-R2, and OPG and numerically but non-significantly higher levels of IL-23 were found in AS patients compared to controls, indicating that these cytokines and cytokine receptors are important inflammatory pathways. Clinical measures of disease activity were not significantly correlated with circulating inflammatory markers.


Assuntos
Citocinas/sangue , Receptores de Citocinas/sangue , Índice de Gravidade de Doença , Espondilite Anquilosante/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Interleucina-23/sangue , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Receptores Tipo II do Fator de Necrose Tumoral/sangue
12.
Eur J Clin Microbiol Infect Dis ; 34(5): 877-86, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25630538

RESUMO

Biofilms are heterogeneous structures composed of bacterial cells surrounded by a matrix and attached to solid surfaces. The bacteria here are 100 to 1,000 times more tolerant to antimicrobials than corresponding planktonic cells. Biofilms can be difficult to eradicate when they cause biofilm-related diseases, e.g., implant infections, cystic fibrosis, urinary tract infections, and periodontal diseases. A number of phenotypic features of the biofilm can be involved in biofilm-specific tolerance and resistance. Little is known about the molecular mechanisms involved. The current review deals with both phenotypic and molecular mechanisms of biofilm-specific antibiotic tolerance and resistance.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Fenômenos Fisiológicos Bacterianos , Farmacorresistência Bacteriana , Tolerância a Medicamentos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Humanos
13.
Ann Rheum Dis ; 74(1): 148-55, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24130265

RESUMO

OBJECTIVE: To examine changes in patient reported outcome measures (PROs) over 15 years in a representative population of patients with rheumatoid arthritis (RA), with a particular focus on gender differences. PATIENTS AND METHODS: Patients in the Oslo RA register filled in questionnaires including the Modified Health Assessment Questionnaire (MHAQ), the Short-Form 36 (SF-36) with physical (PCS) and mental component summaries and derived utility (SF-6D), visual analogue scales (VAS) for pain, patient global assessment of disease (PtGA) and fatigue, and checklists of medication commonly used in the treatment of RA. Data were collected at five time points during a 15-year period from 1994. Mixed model analyses were used to analyse longitudinal changes in PROs from 1994 to 1996, 2001, 2004 and 2009. RESULTS: Data were available from 829-1025 RA patients at each time point. PROs were statistically significantly improved from 1994 to 2009 (MHAQ, SF-36 PCS, SF-6D, pain VAS, PtGA VAS and fatigue VAS; all p<0.001), and also with clinically important improvement. Men reported significantly better health status than women in 1994, but women improved significantly more than men over 15 years with a reduction of the gender gap in 2009. Antirheumatic medication was increasingly used over 15 years with no gender differences. CONCLUSIONS: RA patients reported statistically significantly improved health status for most PROs from 1994 to 2009. Women improved most, and although they still reported higher disease impact than men, the gender differences were small at the final data collection in 2009.


Assuntos
Atividades Cotidianas , Artrite Reumatoide/fisiopatologia , Nível de Saúde , Avaliação de Resultados da Assistência ao Paciente , Sistema de Registros , Fatores Sexuais , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários
14.
Clin Exp Rheumatol ; 32(5 Suppl 85): S-158-62, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25365108

RESUMO

OBJECTIVES: The use of electronic health records (EHR) is an essential part of modern health care, and electronic data capture (EDC) has become essential for managing clinical trials. Usually, these two entities are independent of each other, and transfer from one system to another is done manually. Our aim was to develop a method to capture data directly from the EHR system and transfer them into an EDC system for the NORwegian Disease-Modifying Anti-Rheumatic Drugs (NOR-DMARD) registry. METHODS: All rheumatology departments contributing to NOR-DMARD had implemented a structured EHR system. Data are extracted locally and securely transferred to the study data management once a month. The study data management then parse the data into a readable format for the EDC and import the data. Once the data is in the EDC, they are available to all authorized researchers and downloadable in a preferred format. RESULTS: From May 2012 to August 2014 almost 6400 visits in 3400 patients treated with biologics have been successfully registered in the EDC system. Previously, NOR-DMARD used standard paper-based case report forms (CRFs), with a substantial cost for data entry. Setting up and maintaining the EDC system required some investments, but the amount saved from avoiding paper handling has made the shift into EDC profitable. In addition to this, gains have been made in administration and data quality. CONCLUSIONS: The transition from paper and pencil format to a fully electronic data management system in NOR-DMARD has had obvious advantages regarding feasibility, cost, data quality and accessibility of the data.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Registros Eletrônicos de Saúde/normas , Armazenamento e Recuperação da Informação/normas , Registro Médico Coordenado/normas , Avaliação de Processos e Resultados em Cuidados de Saúde/normas , Sistema de Registros/normas , Acesso à Informação , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Mineração de Dados , Registros Eletrônicos de Saúde/economia , Humanos , Armazenamento e Recuperação da Informação/economia , Noruega/epidemiologia , Avaliação de Processos e Resultados em Cuidados de Saúde/economia , Fatores de Tempo , Resultado do Tratamento
15.
Eur J Pain ; 18(9): 1271-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24677417

RESUMO

BACKGROUND: Endogenous pain modulation has been studied with the conditioned pain modulation (CPM) paradigm with large differences in the magnitude of the CPM effect. We hypothesized that differences in CPM effects might be associated with differences in blood pressure responses to the conditioning stimulus when comparing the CPM effects using two different conditioning stimuli. METHODS: A single-blind repeated-measures design with block-randomization was applied on 25 healthy male subjects. The test stimulus (TS; tonic heat pain for 120 s) was first presented alone, thereafter in parallel with a conditioning stimulus (CS). Conditioning stimuli were either a cold pressor test (CPT) or equally painful ischaemic muscle pain (ISC), both lasting 120 s. Finger blood pressure and heart rate were recorded continuously. Data were analysed in a linear mixed model framework with CS type (CPT or ISC) and conditioning (TS or TS + CS) as independent factors. RESULTS: An inhibitory CPM effect was found for both types of conditioning (p < 0.001). The CPM effect was larger during CPT conditioning compared with ISC conditioning (p = 0.001). No association with the concomitant cardiovascular response (blood pressure and heart rate) was found (p > 0.34). CONCLUSION: Cold pressor pain CS induces larger CPM effects than ischaemic pain CS. The larger CPM effect is, however, not associated with a larger blood pressure response. Other factors related to the CS should be investigated to understand why different CS modalities give different CPM effects.


Assuntos
Pressão Sanguínea/fisiologia , Condicionamento Psicológico/fisiologia , Percepção da Dor/fisiologia , Dor/fisiopatologia , Adulto , Estudos Cross-Over , Frequência Cardíaca/fisiologia , Humanos , Masculino , Medição da Dor , Método Simples-Cego , Adulto Jovem
16.
Ann Oncol ; 24(1): 152-60, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22967994

RESUMO

BACKGROUND: As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. PATIENTS AND METHODS: Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively registered at 12 Nordic hospitals. RESULTS: The median survival was 11 months in 252 patients given palliative chemotherapy and 1 month in 53 patients receiving best supportive care (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had stable disease. Ki-67<55% was by receiver operating characteristic analysis the best cut-off value concerning correlation to the response rate. Patients with Ki-67<55% had a lower response rate (15% versus 42%, P<0.001), but better survival than patients with Ki-67≥55% (14 versus 10 months, P<0.001). Platinum schedule did not affect the response rate or survival. The most important negative prognostic factors for survival were poor performance status (PS), primary colorectal tumors and elevated platelets or lactate dehydrogenase (LDH) levels. CONCLUSIONS: Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-67<55% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.


Assuntos
Carcinoma Neuroendócrino/terapia , Neoplasias Gastrointestinais/terapia , Análise de Sobrevida , Idoso , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/fisiopatologia , Feminino , Neoplasias Gastrointestinais/fisiopatologia , História do Século XVI , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC
17.
J Comp Pathol ; 148(2-3): 157-72, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22784780

RESUMO

This study describes pathological findings and their association with the production of interferon (IFN)-γ and interleukin (IL)-10 in goats infected naturally with Mycobacterium avium subsp. paratuberculosis (MAP). Twenty-seven goats were subjected to pathological examination. More than half of the animals had severe, diffuse, transmural granulomatous enteritis, often with abundant acid-fast bacilli (AFB), which was most evident in the proximal jejunum. Jejunal strictures and fibrous, peritoneal adhesions were findings that are not often reported in animals with paratuberculosis. Immunohistochemical labelling of IL-10 was seen within diffuse, granulomatous lesions and this may have prevented optimal local IFN-γ production and exacerbated the disease. However, since IFN-γ production was detected in cells from blood, jejunum and jejunal lymph nodes of goats with severe lesions by enzyme-linked immunosorbent assay, intracellular labelling and in-situ hybridization, the up-regulation of IL-10 might have been a consequence rather than a cause of the severe disease. The IL-10 labelling was co-localized with major histocompatibility complex (MHC) class II(+) cells, but rarely with CD4(+) cells. Comparable numbers of CD4(+) and CD8(+) T cells were recruited to both severe, diffuse lesions and small to moderate granulomatous lesions, while few T cells expressing the γδ form of the T-cell receptor were associated with both types of lesions.


Assuntos
Doenças das Cabras/metabolismo , Doenças das Cabras/patologia , Interleucina-10/metabolismo , Doenças do Jejuno/veterinária , Jejuno/patologia , Mycobacterium avium subsp. paratuberculosis/patogenicidade , Paratuberculose/metabolismo , Paratuberculose/patologia , Animais , Anticorpos Antibacterianos/sangue , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Constrição Patológica/metabolismo , Constrição Patológica/patologia , Feminino , Fibrose/metabolismo , Fibrose/patologia , Doenças das Cabras/microbiologia , Cabras , Interferon gama/metabolismo , Doenças do Jejuno/metabolismo , Doenças do Jejuno/patologia , Jejuno/metabolismo , Jejuno/microbiologia , Linfonodos/microbiologia , Linfonodos/patologia , Mycobacterium avium subsp. paratuberculosis/imunologia , Mycobacterium avium subsp. paratuberculosis/isolamento & purificação , Paratuberculose/microbiologia , Aderências Teciduais/metabolismo , Aderências Teciduais/patologia
18.
Am J Transplant ; 12(12): 3316-25, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22946930

RESUMO

The clinical profile of ibandronate as add-on to calcitriol and calcium was studied in this double-blind, placebo-controlled trial of 129 renal transplant recipients with early stable renal function (≤ 28 days posttransplantation, GFR ≥ 30 mL/min). Patients were randomized to receive i.v. ibandronate 3 mg or i.v. placebo every 3 months for 12 months on top of oral calcitriol 0.25 mcg/day and calcium 500 mg b.i.d. At baseline, 10 weeks and 12 months bone mineral density (BMD) and biochemical markers of bone turnover were measured. The primary endpoint, relative change in BMD for the lumbar spine from baseline to 12 months was not different, +1.5% for ibandronate versus +0.5% for placebo (p = 0.28). Ibandronate demonstrated a significant improvement of BMD in total femur, +1.3% versus -0.5% (p = 0.01) and in the ultradistal radius, +0.6% versus -1.9% (p = 0.039). Bone formation markers were reduced by ibandronate, whereas the bone resorption marker, NTX, was reduced in both groups. Calcium and calcitriol supplementation alone showed an excellent efficacy and safety profile, virtually maintaining BMD without any loss over 12 months after renal transplantation, whereas adding ibandronate significantly improved BMD in total femur and ultradistal radius, and also suppressed biomarkers of bone turnover. Ibandronate was also well tolerated.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Difosfonatos/administração & dosagem , Transplante de Rim/efeitos adversos , Osteoporose/tratamento farmacológico , Administração Intravenosa , Reabsorção Óssea/etiologia , Calcitriol/administração & dosagem , Cálcio da Dieta/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Ácido Ibandrônico , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Osteoporose/etiologia , Vitaminas/administração & dosagem
19.
Osteoarthritis Cartilage ; 20(8): 822-8, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22441031

RESUMO

OBJECTIVE: To understand how handling of missing data influences the statistical power and bias of treatment effects in randomised controlled trials of painful knee osteoarthritis (OA). METHODS: We simulated trials with missing data (withdrawals) due to lack-of-efficacy. Outcome measures were response/non-response according to the Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) set of responder criteria, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function from the WOMAC questionnaire, and patient global assessment. We used five methods for managing missing data: ignoring the missing data, last and baseline observation carried forward (LOCF and BOCF), and multiple imputation with two different strategies. The treatment effect was then analysed by appropriate univariate and longitudinal statistical methods, and power, bias and mean squared error (MSE) was assessed by comparing the estimated treatment effect in the trials with missing data with the estimated treatment effect on the trials without missing data. RESULTS: The best imputation method in terms of high power and low bias/MSE was our implementation of regression multiple imputation. The most conservative method was the data augmentation Markov chain Monte Carlo (MCMC) multiple imputation. The LOCF, BOCF and the complete-case methods were not particularly conservative and gave relatively low power and high bias. The analysis on the WOMAC pain scale gave less bias and higher power than the OMERACT-OARSI responder outcome measure. CONCLUSIONS: Multiple imputation of missing data may be used to decrease bias/MSE and increase power in OA trials. These results can guide investigators in the choice of outcome measures and especially how missing data can be handled.


Assuntos
Interpretação Estatística de Dados , Osteoartrite do Joelho/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Viés , Celecoxib , Sulfatos de Condroitina/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Glucosamina/uso terapêutico , Humanos , Medição da Dor/métodos , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Resultado do Tratamento
20.
J Clin Virol ; 53(4): 364-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22261124

RESUMO

BACKGROUND: Human papillomaviruses (HPV) are involved in the etiology of cervix cancer, but it is still unclear whether they play a role in related oral lesions. OBJECTIVES: The presence of HPV in oral leukoplakia biopsies (n=50) and oral squamous carcinoma biopsies (n=50) was compared to normal oral mucosa swabs (n=50) for the purpose of indicating a possible etiological role for the virus. STUDY DESIGN: DNA was extracted from tissue biopsies and from mucosa swabs of control samples. Nested PCR was performed with primers targeting conserved sequences within the capsid gene L1. PCR products were sequenced to identify the HPV genotype. RESULT: The results reveal a profile of low-risk HPV genotypes in oral leukoplakia similar to that in healthy controls, while HPV was less frequently observed in oral squamous carcinoma. CONCLUSIONS: HPV does not seem to represent an important causal factor for the development of oral leukoplakia or oral squamous carcinoma.


Assuntos
Carcinoma de Células Escamosas/virologia , Leucoplasia Oral/virologia , Mucosa Bucal/virologia , Neoplasias Bucais/virologia , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma de Células Escamosas/patologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Papillomaviridae/classificação , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNA , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA