RESUMO
OBJECTIVE: In this population-based cohort study, we examined the association between the presence of symptomatic osteoarthritis (OA) and risk for cardiovascular (CV) events. METHOD: A cohort aged ≥55 years recruited from 1996 to 98 was followed through provincial health administrative data to 2014. Demographics, joint complaints and functional limitations were collected. Hip, knee and hand OA were defined using a validated definition. Using Cox-regressions, the relationship between OA and a composite CV outcome (myocardial infarction (MI), stroke, angina, heart failure, revascularization) was assessed controlling for age, body mass index (BMI), sex, pre-existing metabolic factors, comorbidities, income status, primary care exposure and functional limitations. RESULTS: 18,490 participants were included: median age was 68 years, 60.3% were female; 24.4% met criteria for OA (10.0% hip, 15.3% knee, 16.0% hand), 16.3% self-reported limitation in grip and 25.4% in walking. Over a median 13.4 years, 31.9% experienced a CV event. Controlling for all but walking limitation, a dose-response relationship was observed between number of joints affected by knee/hip OA and CV risk (HR 2 hips/knees vs none: 1.13, 95% CI 1.03-1.23; 3+ hips/knees: 1.22, 95% CI 1.09-1.36). This relationship became non-significant additionally controlling for difficulty walking. Self-reported difficulty walking was associated with a 30% increased hazard for CV events. The effect of hand OA was not significant. CONCLUSION: In a large population cohort, a greater burden of hip/knee OA was associated with higher CV risk; the relationship was explained by OA-related difficulty walking. Increased attention to management of OA with a view to improving mobility has potential to reduce CV events.
Assuntos
Doenças Cardiovasculares/epidemiologia , Revascularização Miocárdica/estatística & dados numéricos , Osteoartrite do Quadril/epidemiologia , Osteoartrite do Joelho/epidemiologia , Atenção Primária à Saúde , Idoso , Angina Pectoris/epidemiologia , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Articulação da Mão , Insuficiência Cardíaca/epidemiologia , Hospitalização , Humanos , Renda , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Infarto do Miocárdio/epidemiologia , Ontário/epidemiologia , Osteoartrite/epidemiologia , Osteoartrite/fisiopatologia , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Modelos de Riscos Proporcionais , Fatores Sexuais , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND: Erythropoiesis-stimulating agents (ESAs) reduce the need for red blood cell transfusions; however, they increase the risk of thromboembolic events and mortality. The impact of ESAs on quality of life (QoL) is controversial and led to different recommendations of medical societies and authorities in the USA and Europe. We aimed to critically evaluate and quantify the effects of ESAs on QoL in cancer patients. METHODS: We included data from randomised controlled trials (RCTs) on the effects of ESAs on QoL in cancer patients. Randomised controlled trials were identified by searching electronic data bases and other sources up to January 2011. To reduce publication and outcome reporting biases, we included unreported results from clinical study reports. We conducted meta-analyses on fatigue- and anaemia-related symptoms measured with the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) and FACT-Anaemia (FACT-An) subscales (primary outcomes) or other validated instruments. RESULTS: We identified 58 eligible RCTs. Clinical study reports were available for 27% (4 out of 15) of the investigator-initiated trials and 95% (41 out of 43) of the industry-initiated trials. We excluded 21 RTCs as we could not use their QoL data for meta-analyses, either because of incomplete reporting (17 RCTs) or because of premature closure of the trial (4 RCTs). We included 37 RCTs with 10581 patients; 21 RCTs were placebo controlled. Chemotherapy was given in 27 of the 37 RCTs. The median baseline haemoglobin (Hb) level was 10.1 g dl(-1); in 8 studies ESAs were stopped at Hb levels below 13 g dl(-1) and in 27 above 13 g dl(-1). For FACT-F, the mean difference (MD) was 2.41 (95% confidence interval (95% CI) 1.39-3.43; P<0.0001; 23 studies, n=6108) in all cancer patients and 2.81 (95% CI 1.73-3.90; P<0.0001; 19 RCTs, n=4697) in patients receiving chemotherapy, which was below the threshold (≥ 3) for a clinically important difference (CID). Erythropoiesis-stimulating agents had a positive effect on anaemia-related symptoms (MD 4.09; 95% CI 2.37-5.80; P=0.001; 14 studies, n=2765) in all cancer patients and 4.50 (95% CI 2.55-6.45; P<0.0001; 11 RCTs, n=2436) in patients receiving chemotherapy, which was above the threshold (≥ 4) for a CID. Of note, this effect persisted when we restricted the analysis to placebo-controlled RCTs in patients receiving chemotherapy. There was some evidence that the MDs for FACT-F were above the threshold for a CID in RCTs including cancer patients receiving chemotherapy with Hb levels below 12 g dl(-1) at baseline and in RCTs stopping ESAs at Hb levels above 13 g dl(-1). However, these findings for FACT-F were not confirmed when we restricted the analysis to placebo-controlled RCTs in patients receiving chemotherapy. CONCLUSIONS: In cancer patients, particularly those receiving chemotherapy, we found that ESAs provide a small but clinically important improvement in anaemia-related symptoms (FACT-An). For fatigue-related symptoms (FACT-F), the overall effect did not reach the threshold for a CID.
Assuntos
Anemia/tratamento farmacológico , Fadiga/sangue , Hematínicos/uso terapêutico , Neoplasias/sangue , Anemia/sangue , Eritropoese/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: To summarize the available evidence on the effectiveness of psychological interventions for patients with post-traumatic stress disorder (PTSD). METHOD: We searched bibliographic databases and reference lists of relevant systematic reviews and meta-analyses for randomized controlled trials that compared specific psychological interventions for adults with PTSD symptoms either head-to-head or against control interventions using non-specific intervention components, or against wait-list control. Two investigators independently extracted the data and assessed trial characteristics. RESULTS: The analyses included 4190 patients in 66 trials. An initial network meta-analysis showed large effect sizes (ESs) for all specific psychological interventions (ESs between -1.10 and -1.37) and moderate effects of psychological interventions that were used to control for non-specific intervention effects (ESs -0.58 and -0.62). ES differences between various types of specific psychological interventions were absent to small (ES differences between 0.00 and 0.27). Considerable between-trial heterogeneity occurred (τ²= 0.30). Stratified analyses revealed that trials that adhered to DSM-III/IV criteria for PTSD were associated with larger ESs. However, considerable heterogeneity remained. Heterogeneity was reduced in trials with adequate concealment of allocation and in large-sized trials. We found evidence for small-study bias. CONCLUSIONS: Our findings show that patients with a formal diagnosis of PTSD and those with subclinical PTSD symptoms benefit from different psychological interventions. We did not identify any intervention that was consistently superior to other specific psychological interventions. However, the robustness of evidence varies considerably between different psychological interventions for PTSD, with most robust evidence for cognitive behavioral and exposure therapies.
Assuntos
Psicoterapia/normas , Transtornos de Estresse Pós-Traumáticos/terapia , Resultado do Tratamento , HumanosRESUMO
OBJECTIVES: Femoroacetabular impingement is proposed to cause early osteoarthritis (OA) in the non-dysplastic hip. We previously reported on the prevalence of femoral deformities in a young asymptomatic male population. The aim of this study was to determine the prevalence of both femoral and acetabular types of impingement in young females. METHODS: We conducted a population-based cross-sectional study of asymptomatic young females. All participants completed a set of questionnaires and underwent clinical examination of the hip. A random sample was subsequently invited to obtain magnetic resonance images (MRI) of the hip. All MRIs were read for cam-type deformities, increased acetabular depths, labral lesions, and impingement pits. Prevalence estimates of cam-type deformities and increased acetabular depths were estimated, and relationships between deformities and signs of joint damage were examined using logistic regression models. RESULTS: The study included 283 subjects, and 80 asymptomatic females with a mean age of 19.3 years attended MRI. Fifteen showed some evidence of cam-type deformities, but none were scored to be definite. The overall prevalence was therefore 0% [95% confidence interval (95% CI) 0-5%]. The prevalence of increased acetabular depth was 10% (95% CI 5-19). No association was found between increased acetabular depth and decreased internal rotation of the hip. Increased acetabular depth was not associated with signs of labral damage. CONCLUSIONS: Definite cam-type deformities in women are rare compared to men, whereas the prevalence of increased acetabular depth is higher, suggesting that femoroacetabular impingement has different gender-related biomechanical mechanisms.
Assuntos
Impacto Femoroacetabular/epidemiologia , Acetábulo/patologia , Adolescente , Estudos Transversais , Feminino , Impacto Femoroacetabular/diagnóstico , Impacto Femoroacetabular/patologia , Impacto Femoroacetabular/fisiopatologia , Articulação do Quadril/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Prevalência , Amplitude de Movimento Articular , Fatores Sexuais , Suíça/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To determine the performance of a newly developed examination chair as compared with the clinical standard of assessing internal rotation (IR) of the flexed hip with a goniometer. METHODS: The examination chair allowed measurement of IR in a sitting position simultaneously in both hips, with hips and knees flexed 90 degrees, lower legs hanging unsupported and a standardized load of 5 kg applied to both ankles using a bilateral pulley system. Clinical assessment of IR was performed in supine position with hips and knees flexed 90 degrees using a goniometer. Within the framework of a population-based inception cohort study, we calculated inter-observer agreement in two samples of 84 and 64 consecutive, unselected young asymptomatic males using intra-class correlation coefficients (ICC) and determined the correlation between IR assessed with examination chair and clinical assessment. RESULTS: Inter-observer agreement was excellent for the examination chair (ICC right hip, 0.92, 95% confidence interval [CI] 0.89-0.95; ICC left hip, 0.90, 95% CI 0.86-0.94), and considerably higher than that seen with clinical assessment (ICC right hip, 0.65, 95% CI 0.49-0.77; ICC left hip, 0.69, 95% CI 0.54-0.80, P for difference in ICC between examination chair and clinical assessment Assuntos
Articulação do Quadril/fisiologia
, Quadril/anatomia & histologia
, Osteoartrite do Quadril/fisiopatologia
, Amplitude de Movimento Articular
, Fenômenos Biomecânicos
, Desenho de Equipamento
, Equipamentos e Provisões
, Humanos
, Masculino
, Valores de Referência
, Rotação
, Suíça
, Adulto Jovem
RESUMO
OBJECTIVES: To examine gender differences along the care pathway to total hip replacement. METHODS: We conducted a population-based cross-sectional study of 26,046 individuals aged 35 years and over in Avon and Somerset. Participants completed a questionnaire asking about care provision at five milestones on the pathway to total hip replacement. Those reporting hip disease were invited to a clinical examination. We estimated odds ratios (ORs) [95% confidence intervals (CI)] for provision of care to women compared with men. RESULTS: 3169 people reported hip pain, 2018 were invited for clinical examination, and 1405 attended (69.6%). After adjustment for age and disease severity, women were less likely than men to have consulted their general practitioner (OR 0.78, 95%-CI 0.61-1.00), as likely as men to have received drug therapy for hip pain in the previous year (OR 0.96, 95%-CI 0.74-1.24), but less likely to have been referred to specialist care (OR 0.53, 95%-CI 0.40-0.70), to have consulted an orthopaedic surgeon (OR 0.50, 95%-CI 0.32-0.78), or to be on a waiting list for total hip replacement (OR 0.41, 95%-CI 0.20-0.87). Differences remained in the 746 people who had sought care from their general practitioner, and after adjustment for willingness and fitness for surgery. CONCLUSIONS: There are gender inequalities in provision of care for hip disease in England, which are not fully accounted for by gender differences in care seeking and treatment preferences. Differences in referral to specialist care by general practitioners might unwittingly contribute to this inequity. Accurate information about availability, benefits and risks of hip replacement for providers and patients, and continuing education to ensure that clinicians interpret and correct patients' assumptions could help reduce inequalities.
Assuntos
Artroplastia de Quadril , Atenção à Saúde/normas , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Idoso , Procedimentos Clínicos/estatística & dados numéricos , Estudos Transversais , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta/estatística & dados numéricos , Análise de Regressão , Fatores SexuaisRESUMO
OBJECTIVE: To determine whether treatment with spinal manipulative therapy (SMT) administered in addition to standard care is associated with clinically relevant early reductions in pain and analgesic consumption. METHODS: 104 patients with acute low back pain were randomly assigned to SMT in addition to standard care (n = 52) or standard care alone (n = 52). Standard care consisted of general advice and paracetamol, diclofenac or dihydrocodeine as required. Other analgesic drugs or non-pharmacological treatments were not allowed. Primary outcomes were pain intensity assessed on the 11-point box scale (BS-11) and analgesic use based on diclofenac equivalence doses during days 1-14. An extended follow-up was performed at 6 months. RESULTS: Pain reductions were similar in experimental and control groups, with the lower limit of the 95% CI excluding a relevant benefit of SMT (difference 0.5 on the BS-11, 95% CI -0.2 to 1.2, p = 0.13). Analgesic consumptions were also similar (difference -18 mg diclofenac equivalents, 95% CI -43 mg to 7 mg, p = 0.17), with small initial differences diminishing over time. There were no differences between groups in any of the secondary outcomes and stratified analyses provided no evidence for potential benefits of SMT in specific patient groups. The extended follow-up showed similar patterns. CONCLUSIONS: SMT is unlikely to result in relevant early pain reduction in patients with acute low back pain.
Assuntos
Dor Lombar/reabilitação , Manipulação da Coluna , Doença Aguda , Adulto , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Terapia Combinada , Esquema de Medicação , Feminino , Humanos , Dor Lombar/tratamento farmacológico , Masculino , Manipulação da Coluna/efeitos adversos , Pessoa de Meia-Idade , Medição da Dor/métodos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To analyse the performance of a new M. tuberculosis-specific interferon gamma (IFNgamma) assay in patients with chronic inflammatory diseases who receive immunosuppressive drugs, including tumour necrosis factor alpha (TNFalpha) inhibitors. METHODS: Cellular immune responses to the M. tuberculosis-specific antigens ESAT-6, CFP-10, TB7.7 were prospectively studied in 142 consecutive patients treated for inflammatory rheumatic conditions. Results were compared with tuberculin skin tests (TSTs). Association of both tests with risk factors for latent M. tuberculosis infection (LTBI) and BCG vaccination were determined and the influence of TNFalpha inhibitors, corticosteroids, and disease modifying antirheumatic drugs (DMARDs) on antigen-specific and mitogen-induced IFNgamma secretion was analysed. RESULTS: 126/142 (89%) patients received immunosuppressive therapy. The IFNgamma assay was more closely associated with the presence of risk factors (odds ratio (OR) = 23.8 (95% CI 5.14 to 110) vs OR = 2.77 (1.22 to 6.27), respectively; p = 0.009), but less associated with BCG vaccination than the TST (OR = 0.47 (95% CI 0.15 to 1.47) vs OR = 2.44 (0.74 to (8.01), respectively; p = 0.025). Agreement between the IFNgamma assay and TST results was low (kappa = 0.17; 95% CI 0.02 to 0.32). The odds for a positive IFNgamma assay strongly increased with increasing prognostic relevance of LTBI risk factors. Neither corticosteroids nor conventional DMARDs significantly affected IFNgamma responses, but the odds for a positive IFNgamma assay were decreased in patients treated with TNFalpha inhibitors (OR = 0.21 (95% CI 0.07 to 0.63), respectively; p = 0.006). CONCLUSIONS: These results demonstrate that the performance of the M. tuberculosis antigen-specific IFNgamma ELISA is better than the classic TST for detection of LTBI in patients receiving immunosuppressive therapy for treatment of systemic autoimmune disorders.
Assuntos
Imunossupressores/uso terapêutico , Mycobacterium tuberculosis/imunologia , Doenças Reumáticas/tratamento farmacológico , Tuberculose/diagnóstico , Adulto , Anticorpos Monoclonais/uso terapêutico , Antígenos de Bactérias/sangue , Antígenos de Bactérias/imunologia , Vacina BCG , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Testes Imunológicos , Infliximab , Interferon gama/sangue , Modelos Logísticos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Doenças Reumáticas/imunologia , Doenças Reumáticas/microbiologia , Fatores de Risco , Teste Tuberculínico , Tuberculose/complicações , Tuberculose/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
BACKGROUND: Drugs are prescribed for chronic low back pain without knowing in advance whether a patient will respond to them or not. Quantitative sensory tests (QST) can discriminate patients according to sensory phenotype, possibly reflecting underlying mechanisms of pain processing. QST may therefore be a screening tool to identify potential responders to a certain drug. The aim of this study was to investigate whether QST can predict analgesic effects of oxycodone, imipramine and clobazam in chronic low back pain. METHODS: Oxycodone 15 mg (n = 50), imipramine 75 mg (n = 50) and clobazam 20 mg (n = 49) were compared to active placebo tolterodine 1 mg in a randomized, double-blinded, crossover fashion. Electrical, pressure and thermal QST were performed at baseline and after 1 and 2 h. Pain intensity was assessed on a 0-10 numeric rating scale every 30 min for up to 2 h. The ability of baseline QST to predict pain reduction after 2 h was analysed using linear mixed models. Genetic variants of drug-metabolizing enzymes and genes affecting pain sensitivity were examined as covariables. RESULTS: No predictor of analgesic effect was found for oxycodone and clobazam. Thermal QST was associated with analgesic effect of imipramine: patients more sensitive to heat or cold were more likely to experience an effect of imipramine. Pharmacogenetic variants and pain-related candidate genes were not associated with drug efficacy. CONCLUSIONS: Thermal QST have the potential to predict imipramine effect in chronic low back pain. Oxycodone and clobazam effects could not be predicted by any of the selected QST or genetic variants. SIGNIFICANCE: Predicting drug efficacy in chronic low back pain remains difficult. There is some evidence that patients more sensitive to heat and cold pain respond better to imipramine.
Assuntos
Analgésicos/uso terapêutico , Clobazam/uso terapêutico , Imipramina/uso terapêutico , Dor Lombar/tratamento farmacológico , Oxicodona/uso terapêutico , Limiar da Dor/efeitos dos fármacos , Adulto , Idoso , Analgésicos/administração & dosagem , Clobazam/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Estimulação Elétrica , Feminino , Humanos , Imipramina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Oxicodona/administração & dosagem , Medição da Dor , PressãoRESUMO
BACKGROUND: Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low-back pain and on quantitative sensory tests. METHODS: In this double-blind cross-over study, 49 patients with chronic low-back pain received a single oral dose of clobazam 20 mg or active placebo tolterodine 1 mg. Pain intensity on the 0-10 numeric rating scale and quantitative sensory tests were assessed during 2 h after drug intake. RESULTS: Pain intensity in the supine position was significantly reduced by clobazam compared to active placebo (60 min: 2.9 vs. 3.5, p = 0.008; 90 min: 2.7 vs. 3.3, p = 0.024; 120 min: 2.4 vs. 3.1, p = 0.005). Pain intensity in the sitting position was not significantly different between groups. No effects on quantitative sensory tests were observed. CONCLUSIONS: This study suggests that clobazam has an analgesic effect in patients with chronic low-back pain. Muscle relaxation or sedation may have contributed to the effect. Development of substances devoid of these side effects would offer the potential to further investigate the antihyperalgesic action of GABAergic compounds. SIGNIFICANCE: Modulation of GABAergic pain-inhibitory pathways may be a potential future therapeutic target.
Assuntos
Anticonvulsivantes/uso terapêutico , Benzodiazepinas/uso terapêutico , Dor Crônica/tratamento farmacológico , Dor Lombar/tratamento farmacológico , Limiar da Dor/efeitos dos fármacos , Adulto , Idoso , Clobazam , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Resultado do TratamentoRESUMO
Osteoarthritis is one of the most important contributions to the burden of disease. 50% of those aged 65 and 80% of those aged 75 years show radiological signs of osteoarthritis. Risk factors for incidence and progression of osteoarthritis vary considerably according to the type of joint. There is only a modest relationship between the radiographic severity of joint damage and the incidence and severity of pain. Psychosocial and socioeconomic factors play an important role for the development of pain in osteoarthritis.
Assuntos
Osteoartrite/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Europa (Continente)/epidemiologia , Medicina Baseada em Evidências , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem , Osteoartrite/terapia , Medição da Dor , Radiografia , Fatores de RiscoRESUMO
Guided tissue regeneration (GTR) with bioabsorbable collagen membranes (CM) is commonly used for the treatment of periodontal defects. The objective of this systematic review of randomized clinical trials was to assess the clinical efficacy of GTR procedures with CM, with or without bone substitutes, in periodontal infrabony defects compared with that of open flap debridement (OFD) alone. Primary outcomes were tooth loss and gain in clinical attachment level (CAL). Screening of records, data extraction, and risk-of-bias assessments were performed by two reviewers. Weighted mean differences were estimated by random effects meta-analysis. We included 21 reports on 17 trials. Risk of bias was generally high. No data were available for the primary outcome tooth loss. The summary treatment effect for change in CAL for GTR with CM compared with OFD was 1.58 mm (95% CI, 1.27 to 1.88). Despite large between-trial heterogeneity (I2 = 75%, p < .001), all trials favored GTR over OFD. No differences in treatment effects were detected between trials of GTR with CM alone and trials of GTR with CM in combination with bone substitutes (p for interaction, .31). GTR with CM, with or without substitutes, may result in improved clinical outcomes compared with those achieved with OFD alone. Our findings support GTR with CM for the treatment of infrabony periodontal defects.
Assuntos
Implantes Absorvíveis , Colágeno , Regeneração Tecidual Guiada Periodontal/instrumentação , Membranas Artificiais , Perda do Osso Alveolar/cirurgia , Substitutos Ósseos/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Chronic pain is associated with generalized hypersensitivity and impaired endogenous pain modulation (conditioned pain modulation; CPM). Despite extensive research, their prevalence in chronic pain patients is unknown. This study investigated the prevalence and potential determinants of widespread central hypersensitivity and described the distribution of CPM in chronic pain patients. METHODS: We examined 464 consecutive chronic pain patients for generalized hypersensitivity and CPM using pressure algometry at the second toe and cold pressor test. Potential determinants of generalized central hypersensitivity were studied using uni- and multivariate regression analyses. Prevalence of generalized central hypersensitivity was calculated for the 5th, 10th and 25th percentile of normative values for pressure algometry obtained by a previous large study on healthy volunteers. CPM was addressed on a descriptive basis, since normative values are not available. RESULTS: Depending on the percentile of normative values considered, generalized central hypersensitivity affected 17.5-35.3% of patients. 23.7% of patients showed no increase in pressure pain threshold after cold pressor test. Generalized central hypersensitivity was more frequent and CPM less effective in women than in men. Unclearly classifiable pain syndromes showed higher frequencies of generalized central hypersensitivity than other pain syndromes. CONCLUSIONS: Although prevalent in chronic pain, generalized central hypersensitivity is not present in every patient. An individual assessment is therefore required in order to detect altered pain processing. The broad basic knowledge about central hypersensitivity now needs to be translated into concrete clinical consequences, so that patients can be offered an individually tailored mechanism-based treatment.
Assuntos
Dor Crônica/fisiopatologia , Hiperalgesia/epidemiologia , Adulto , Idoso , Dor Crônica/complicações , Feminino , Humanos , Hiperalgesia/complicações , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Limiar da Dor/fisiologia , Pressão , PrevalênciaRESUMO
BACKGROUND: Newer generation everolimus-eluting stents (EES) improve clinical outcome compared to early generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). We investigated whether the advantage in safety and efficacy also holds among the high-risk population of diabetic patients during long-term follow-up. METHODS: Between 2002 and 2009, a total of 1963 consecutive diabetic patients treated with the unrestricted use of EES (n=804), SES (n=612) and PES (n=547) were followed throughout three years for the occurrence of cardiac events at two academic institutions. The primary end point was the occurrence of definite stent thrombosis. RESULTS: The primary outcome occurred in 1.0% of EES, 3.7% of SES and 3.8% of PES treated patients ([EES vs. SES] adjusted HR=0.58, 95% CI 0.39-0.88; [EES vs. PES] adjusted HR=0.29, 95% CI 0.13-0.67). Similarly, patients treated with EES had a lower risk of target-lesion revascularization (TLR) compared to patients treated with SES and PES ([EES vs. SES], 5.6% vs. 11.5%, adjusted HR=0.68, 95% CI: 0.55-0.83; [EES vs. PES], 5.6% vs. 11.3%, adjusted HR=0.51, 95% CI: 0.33-0.77). There were no differences in other safety end points, such as all-cause mortality, cardiac mortality, myocardial infarction (MI) and MACE. CONCLUSION: In diabetic patients, the unrestricted use of EES appears to be associated with improved outcomes, specifically a significant decrease in the need for TLR and ST compared to early generation SES and PES throughout 3-year follow-up.
Assuntos
Diabetes Mellitus/tratamento farmacológico , Stents Farmacológicos/tendências , Paclitaxel/administração & dosagem , Sirolimo/análogos & derivados , Sirolimo/administração & dosagem , Idoso , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Everolimo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The design of randomised controlled trials (RCTs) should incorporate characteristics (such as concealment of randomised allocation and blinding of participants and personnel) that avoid biases resulting from lack of comparability of the intervention and control groups. Empirical evidence suggests that the absence of such characteristics leads to biased intervention effect estimates, but the findings of different studies are not consistent. OBJECTIVES: To examine the influence of unclear or inadequate random sequence generation and allocation concealment, and unclear or absent double blinding, on intervention effect estimates and between-trial heterogeneity, and whether or not these influences vary with type of clinical area, intervention, comparison and outcome measure. DATA SOURCES AND METHODS: Data were combined from seven contributing meta-epidemiological studies (collections of meta-analyses in which trial characteristics are assessed and results recorded). The resulting database was used to identify and remove overlapping meta-analyses. Outcomes were coded such that odds ratios < 1 correspond to beneficial intervention effects. Outcome measures were classified as mortality, other objective or subjective. We examined agreement between assessments of trial characteristics in trials assessed in more than one contributing study. We used hierarchical Bayesian bias models to estimate the effect of trial characteristics on average bias [quantified as ratios of odds ratios (RORs) with 95% credible intervals (CrIs) comparing trials with and without a characteristic] and in increasing between-trial heterogeneity. RESULTS: The analysis data set contained 1973 trials included in 234 meta-analyses. Median kappa statistics for agreement between assessments of trial characteristics were: sequence generation 0.60, allocation concealment 0.58 and blinding 0.87. Intervention effect estimates were exaggerated by an average 11% in trials with inadequate or unclear (compared with adequate) sequence generation (ROR 0.89, 95% CrI 0.82 to 0.96); between-trial heterogeneity was higher among such trials. Bias associated with inadequate or unclear sequence generation was greatest for subjective outcomes (ROR 0.83, 95% CrI 0.74 to 0.94) and the increase in heterogeneity was greatest for such outcomes [standard deviation (SD) 0.20, 95% CrI 0.03 to 0.32]. The effect of inadequate or unclear (compared with adequate) allocation concealment was greatest among meta-analyses with a subjectively assessed outcome intervention effect (ROR 0.85, 95% CrI 0.75 to 0.95), and the increase in between-trial heterogeneity was also greatest for such outcomes (SD 0.20, 95% CrI 0.02 to 0.33). Lack of, or unclear, double blinding (compared with double blinding) was associated with an average 13% exaggeration of intervention effects (ROR 0.87, 95% CrI 0.79 to 0.96), and between-trial heterogeneity was increased for such studies (SD 0.14, 95% CrI 0.02 to 0.30). Average bias (ROR 0.78, 95% CrI 0.65 to 0.92) and between-trial heterogeneity (SD 0.37, 95% CrI 0.19 to 0.53) were greatest for meta-analyses assessing subjective outcomes. Among meta-analyses with subjectively assessed outcomes, the effect of lack of blinding appeared greater than the effect of inadequate or unclear sequence generation or allocation concealment. CONCLUSIONS: Bias associated with specific reported study design characteristics leads to exaggeration of beneficial intervention effect estimates and increases in between-trial heterogeneity. For each of the three characteristics assessed, these effects were greatest for subjectively assessed outcomes. Assessments of the risk of bias in RCTs should account for these findings. Further research is needed to understand the effects of attrition bias, as well as the relative importance of blinding of patients, care-givers and outcome assessors, and thus separate the effects of performance and detection bias. FUNDING: National Institute for Health Research Health Technology Assessment programme.
Assuntos
Viés , Projetos de Pesquisa Epidemiológica , Avaliação de Resultados em Cuidados de Saúde/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Interpretação Estatística de Dados , Bases de Dados Bibliográficas , Humanos , Metanálise como Assunto , Avaliação de Resultados em Cuidados de Saúde/normas , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To explore the regulation of factors involved in lymphocyte trafficking in patients with rheumatoid arthritis (RA) undergoing treatment with tumour necrosis factor alpha (TNF-alpha) inhibitors. METHODS: We examined 14 consecutive patients with RA according to ACR criteria prior to and during treatment with TNF-alpha inhibitors (seven etanercept, seven infliximab) and determined disease activity using the Disease Activity Score (DAS-28). Peripheral blood mononuclear cells were isolated before and after 6 and 14 weeks of treatment and analysed immediately for CD3, CD4 and CD8, expression of chemokine receptors CXCR3 and CCR4, CD45RO phenotype and for expression of interferon gamma (IFN-gamma) and interleukin 4 (IL-4) using four-colour flow cytometry. RESULTS: We found significant increases in CD4 and CD8 T lymphocytes expressing CXCR3 after 6 and 14 weeks. The overall proportion of T lymphocytes expressing CCR4 appeared unchanged. More than half of peripheral CD4 T lymphocytes showed a memory phenotype (CD45RO), with a non-significant increase under TNF-alpha inhibition. Upon activation, up to 30% of CXCR3(+)/CD4 T cells expressed IFN-gamma, while IL-4-expressing cells were rare. There was a robust negative correlation between CXCR3(+)/CD4 T lymphocytes and DAS-28. CONCLUSIONS: TNF-alpha inhibition with infliximab and etanercept results in sustained accumulation of CXCR3 positive T lymphocytes in the peripheral blood of RA patients. This suggests altered lymphocyte trafficking during TNF-alpha inhibition.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Receptores de Quimiocinas/imunologia , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Etanercepte , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Infliximab , Interferon gama/análise , Interleucina-4/análise , Antígenos Comuns de Leucócito/imunologia , Masculino , Pessoa de Meia-Idade , Receptores CCR4 , Receptores CXCR3 , Receptores de Quimiocinas/análise , Receptores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
CONTEXT: Diagrams of the flow of participants through a clinical trial are recommended in the Consolidated Standards for Reporting of Trials (CONSORT) statement, but it is unclear whether such flow diagrams improve the quality of trial reports. OBJECTIVE: To examine the information contributed by flow diagrams and the completeness of reporting overall in reports of randomized controlled trials (RCTs) published in 5 general and internal medicine journals. DESIGN AND SETTING: Analysis of 270 reports of RCTs published in 1998 in the Annals of Internal Medicine (AIM; n = 19), BMJ (n = 42), JAMA (n = 45), The Lancet (n = 81), and The New England Journal of Medicine (NEJM; n = 83). MAIN OUTCOME MEASURES: Proportion of reports that included a flow diagram, information provided in flow diagrams, and completeness of reporting about flow of participants overall in flow diagrams or text. RESULTS: A total of 139 reports (51.5%) of RCTs included a flow diagram, but this varied widely among journals (AIM, 21.0%; BMJ, 38.1%; JAMA, 80.0%; The Lancet, 93.8%; and NEJM, 8.4%). Diagrams generally provided useful information, but only 73 (52.5%) included the number of participants who received allocated interventions and only 32 (23.0%) included the number of participants included in the analysis. In logistic regression analysis, overall completeness of reporting about flow of study participants was associated with publication of a flow diagram. CONCLUSIONS: Flow diagrams are associated with improved quality of reporting of randomized controlled trials. However, the structure of current flow diagrams is less than ideal. We propose a revised flow diagram that includes all important counts through the stages of parallel group trials.