RESUMO
BACKGROUND: Arm pain is common amongst working-aged adults and causes substantial work disability. The results of a population-based randomized controlled trial (the ARM trial) suggested that advice to remain active reduced disability after 6 months. AIMS: To verify ARM trial results amongst people in paid employment. METHODS: The ARM trial recruited adults with distal arm pain referred for physiotherapy and randomized equally to three groups: wait-listed for physiotherapy (advised to rest); wait-listed for physiotherapy (advised to remain active) or early physiotherapy. The primary outcome was absence of disability at 26 weeks. Secondary analyses were undertaken amongst participants in paid employment. RESULTS: Amongst 538 trial participants, 347 (64%) were in paid employment, mean age 46.1 years and 47% in manual work. Employed participants were randomized equally to the three arms. Amongst the 271 (78% workers with 26-week data), 43% of those advised to remain active were free from disability, as compared with 37% of those advised to rest. Forty per cent of those who waited for physiotherapy were disability-free as compared with 35% of those treated rapidly. Advice to rest was associated with lower chances of recovery amongst workers who lift/carry weights and those who believed work had caused their symptoms (P = 0.023). CONCLUSIONS: Although not powered as a trial for workers only, our findings suggest that advising activity was as beneficial for people currently in paid work and may be superior to advice to rest in reducing disability. Addressing harmful beliefs about causation of symptoms has the potential to reduce disability.
Assuntos
Pessoas com Deficiência , Dor , Adulto , Humanos , Pessoa de Meia-Idade , Modalidades de Fisioterapia , Análise Custo-Benefício , Qualidade de VidaRESUMO
Abdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemizygous knockout mice (Col4a1/a2+/-, 129Svj background) we show that partial Col4a1/a2 deficiency augmented AAA formation. Although unchallenged aortas were morphometrically and biomechanically unaffected by genotype, explorative proteomic analyses of aortas revealed a clear reduction in BM components and contractile vascular smooth muscle cell (VSMC) proteins, suggesting a central effect of the BM in maintaining VSMCs in the contractile phenotype. These findings were translated to human arteries by showing that COL4A1/A2 correlated to BM proteins and VSMC markers in non-lesioned internal mammary arteries obtained from coronary artery bypass procedures. Moreover, in human AAA tissue, MYH11 (VSMC marker) was depleted in areas of reduced COL4 as assessed by immunohistochemistry. Finally, circulating COL4A1 degradation fragments correlated with AAA progression in the largest Danish AAA cohort, suggesting COL4A1/A2 proteolysis to be an important feature of AAA formation. In sum, we identify COL4A1/A2 as a critical regulator of VSMC phenotype and a protective factor in AAA formation.
Assuntos
Aneurisma da Aorta Abdominal/etiologia , Membrana Basal/metabolismo , Colágeno Tipo IV/deficiência , Predisposição Genética para Doença , Alelos , Animais , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Biomarcadores , Biópsia , Colágeno Tipo IV/genética , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Estudos de Associação Genética , Genótipo , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Knockout , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Proteólise , Proteoma , Proteômica/métodosRESUMO
BACKGROUND: Abdominal aortic aneurysm (AAA) rupture carries a high fatality rate. AAAs can be detected before rupture by abdominal ultrasound imaging, allowing elective repair. Population-based screening for AAA in older men reduces AAA-related mortality by about 40 per cent. The UK began an AAA screening programme offering one-off scans to men aged 65 years in 2009. Sweden has a similar programme. Currently, there is no AAA screening programme in New Zealand. This cost-utility analysis aimed to assess the cost-effectiveness of a UK-style screening programme in the New Zealand setting. METHODS: The analysis compared a formal AAA screening programme (one-off abdominal ultrasound imaging for about 20 000 men aged 65 years in 2011) with no systematic screening. A Markov macrosimulation model was adapted to estimate the health gains (in quality-adjusted life-years, QALYs), health system costs and cost-effectiveness in New Zealand. A health system perspective and lifetime horizon was adopted. RESULTS: With New Zealand-specific inputs, the adapted model produced an estimate of about NZ $15 300 (7746) per QALY gained, with a 95 per cent uncertainty interval (UI) of NZ $8700 to 31 000 (4405 to 15 694) per QALY gained. Health gains were estimated at 117 (95 per cent UI 53 to 212) QALYs. Health system costs were NZ $1·68 million (850 535), with a 95 per cent UI of NZ $820 200 to 3·24 million (415 243 to 1·65 million). CONCLUSION: Using New Zealand's gross domestic product per capita (about NZ $45 000 or 22 100) as a cost-effectiveness threshold, a UK-style AAA screening programme would be cost-effective in New Zealand.
Assuntos
Aneurisma da Aorta Abdominal/diagnóstico , Programas de Rastreamento/métodos , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/economia , Aneurisma da Aorta Abdominal/mortalidade , Análise Custo-Benefício , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Programas de Rastreamento/economia , Programas de Rastreamento/mortalidade , Nova Zelândia/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Ultrassonografia/economiaRESUMO
OBJECTIVE: The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were 'expert opinion'. METHODS: A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations. RESULTS: 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only 'strong for' therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as 'weak for' based on meta-analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability). CONCLUSIONS: These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.
Assuntos
Atividades Cotidianas , Fadiga/terapia , Fibromialgia/terapia , Guias de Prática Clínica como Assunto , Sono , Terapia por Acupuntura , Amitriptilina/análogos & derivados , Amitriptilina/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Biorretroalimentação Psicológica , Capsaicina/uso terapêutico , Terapia Cognitivo-Comportamental , Europa (Continente) , Medicina Baseada em Evidências , Terapia por Exercício , Fadiga/fisiopatologia , Fibromialgia/fisiopatologia , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Hidroterapia , Hipnose , Manipulação Quiroprática , Massagem , Terapias Mente-Corpo , Atenção Plena , Inibidores da Monoaminoxidase/uso terapêutico , Dor/fisiopatologia , S-Adenosilmetionina/uso terapêutico , Fármacos do Sistema Sensorial/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Sociedades Médicas , Oxibato de Sódio/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Epidemiological studies on chronic pelvic pain (CPP) have focused on women of reproductive age. We aimed to determine the prevalence of chronic pelvic pain (CPP) in adult women and the differences in associated factors among women of reproductive age and older women. In addition, to determine whether distinct subgroups existed among CPP cases. METHODS: A cross-sectional postal survey was conducted among 5300 randomly selected women aged ≥25 years resident in the Grampian region, UK. Multivariable logistic regression was used to determine pregnancy-related and psychosocial factors associated with CPP. To identify subgroups of CPP cases, we performed cluster analysis using variables of pain severity, psychosocial factors and pain coping strategies. RESULTS: Of 2088 participants, 309 (14.8%) reported CPP. CPP was significantly associated with being of reproductive age (odds ratios (OR) 2.43, 95% CI 1.69-3.48), multiple non-pain somatic symptoms (OR 3.58 95% CI 2.23-5.75), having fatigue (OR mild 1.74 95% CI 1.24-2.44, moderate/severe 1.82, 95% CI 1.25-2.63) and having depression (OR 1.61, 95% CI 1.09-2.38). CPP was less associated with multiple non-pain somatic symptoms in women of reproductive age compared to older women (interaction OR 0.51, 95% CI 0.28-0.92). We identified two clusters of CPP cases; those having little/no psychosocial distress and those having high psychosocial distress. CONCLUSION: CPP is common in both age groups, though women of reproductive age are more likely to report it. Heightened somatic awareness may be more strongly associated with CPP in older women. There are distinct groups of CPP cases characterized by the absence/presence of psychosocial distress. SIGNIFICANCE: Heightened somatic awareness may be more strongly associated with CPP in women of post-reproductive years compared to women of reproductive years. Two subgroups of CPP cases can be differentiated by the absence/presence of psychosocial distress suggesting that stratified management approach may be more efficient.
Assuntos
Dor Pélvica/epidemiologia , Adaptação Psicológica , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Dor Crônica , Estudos Transversais , Depressão/etiologia , Depressão/psicologia , Feminino , Nível de Saúde , Humanos , Saúde Mental , Pessoa de Meia-Idade , Medição da Dor , Dor Pélvica/psicologia , População , Prevalência , Fatores Socioeconômicos , Inquéritos e Questionários , Reino Unido/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Abdominal aortic aneurysm (AAA) continues to be a significant health burden yet few countries have implemented a comprehensive screening programme. Screening typically places emphasis on men aged over 65 years; however, there is concern that other at-risk groups may be underidentified. The present study examined three potential screening strategies based on cardiovascular risk. METHODS: The prevalence of AAA was determined by abdominal ultrasound imaging in over 50-year-olds of either sex undergoing coronary angiography, vascular laboratory assessment of peripheral arterial disease, or community-based cardiovascular disease (CVD) event risk assessment. A fourth group, consisting of volunteers aged over 60 years who had no symptoms or signs of cardiovascular disease, was used as a comparator group. RESULTS: A total AAA prevalence of 4·4 per cent was detected across all three strategies (137 of 3142 individuals), compared with 1·0 per cent in the CVD-free group. Male sex, age and smoking were all associated with greater AAA prevalence. Although AAA prevalence was lowest using the community-based strategy, those with an AAA detected were on average 7 years younger than those with AAAs detected with the other two strategies (P < 0·001). CONCLUSION: Different strategies, based on CVD risk, resulted in AAA prevalence rates that were significantly greater than that in CVD-free individuals. This may provide opportunities for a targeted approach to community AAA screening in parts of the world where more sophisticated national screening programmes do not exist.
Assuntos
Aneurisma da Aorta Abdominal/diagnóstico , Tomada de Decisão Clínica/métodos , Programas de Rastreamento/métodos , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/epidemiologia , Estudos de Casos e Controles , Angiografia Coronária , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Prevalência , Medição de Risco , Fatores de Risco , UltrassonografiaRESUMO
OBJECTIVES: There is little consensus regarding the burden of pain in the UK. The purpose of this review was to synthesise existing data on the prevalence of various chronic pain phenotypes in order to produce accurate and contemporary national estimates. DESIGN: Major electronic databases were searched for articles published after 1990, reporting population-based prevalence estimates of chronic pain (pain lasting >3â months), chronic widespread pain, fibromyalgia and chronic neuropathic pain. Pooled prevalence estimates were calculated for chronic pain and chronic widespread pain. RESULTS: Of the 1737 articles generated through our searches, 19 studies matched our inclusion criteria, presenting data from 139â 933 adult residents of the UK. The prevalence of chronic pain, derived from 7 studies, ranged from 35.0% to 51.3% (pooled estimate 43.5%, 95% CIs 38.4% to 48.6%). The prevalence of moderate-severely disabling chronic pain (Von Korff grades III/IV), based on 4 studies, ranged from 10.4% to 14.3%. 12 studies stratified chronic pain prevalence by age group, demonstrating a trend towards increasing prevalence with increasing age from 14.3% in 18-25â years old, to 62% in the over 75 age group, although the prevalence of chronic pain in young people (18-39â years old) may be as high as 30%. Reported prevalence estimates were summarised for chronic widespread pain (pooled estimate 14.2%, 95% CI 12.3% to 16.1%; 5 studies), chronic neuropathic pain (8.2% to 8.9%; 2 studies) and fibromyalgia (5.4%; 1 study). Chronic pain was more common in female than male participants, across all measured phenotypes. CONCLUSIONS: Chronic pain affects between one-third and one-half of the population of the UK, corresponding to just under 28 million adults, based on data from the best available published studies. This figure is likely to increase further in line with an ageing population.
Assuntos
Dor Crônica/epidemiologia , Fibromialgia/epidemiologia , Neuralgia/epidemiologia , Distribuição por Idade , Fibromialgia/complicações , Humanos , Neuralgia/complicações , Medição da Dor , Prevalência , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: Twenty-eight genetic loci are associated with serum urate levels in Europeans. Evidence for association with gout at most loci is absent, equivocal or not replicated. Our aim was to test the loci for association with gout meeting the American College of Rheumatology gout classification criteria in New Zealand European and Polynesian case-control sample sets. METHODS: 648 European cases and 1550 controls, and 888 Polynesian (Ma¯ori and Pacific) cases and 1095 controls were genotyped. Association with gout was tested by logistic regression adjusting for age and sex. Power was adequate (>0.7) to detect effects of OR>1.3. RESULTS: We focused on 24 loci without previous consistent evidence for association with gout. In Europeans, we detected association at seven loci, one of which was the first report of association with gout (IGF1R). In Polynesian, association was detected at three loci. Meta-analysis revealed association at eight loci-two had not previously been associated with gout (PDZK1 and MAF). In participants with higher Polynesian ancestry, there was association in an opposing direction to Europeans at PRKAG2 and HLF (HLF is the first report of association with gout). There was obvious inconsistency of gout association at four loci (GCKR, INHBC, SLC22A11, SLC16A9) that display very similar effects on urate levels. CONCLUSIONS: We provide the first evidence for association with gout at four loci (IGF1R, PDZK1, MAF, HLF). Understanding why there is lack of correlation between urate and gout effect sizes will be important in understanding the aetiology of gout.
Assuntos
Gota/sangue , Gota/genética , Havaiano Nativo ou Outro Ilhéu do Pacífico/genética , Ácido Úrico/sangue , População Branca/genética , Proteínas Quinases Ativadas por AMP/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética , Proteínas de Transporte/genética , Estudos de Casos e Controles , Genótipo , Humanos , Subunidades beta de Inibinas/genética , Proteínas de Membrana , Transportadores de Ácidos Monocarboxílicos/genética , Nova Zelândia , Transportadores de Ânions Orgânicos Sódio-Independentes/genética , Proteínas Proto-Oncogênicas c-maf/genética , Receptor IGF Tipo 1 , Receptores de Somatomedina/genéticaRESUMO
BACKGROUND: Predicting long-term survival following repair is essential to clinical decision making when offering abdominal aortic aneurysm (AAA) treatment. A systematic review and a meta-analysis of pre-operative non-modifiable prognostic risk factors influencing patient survival following elective open AAA repair (OAR) and endovascular aneurysm repair (EVAR) was performed. METHODS: MEDLINE, Embase and Cochrane electronic databases were searched to identify all relevant articles reporting risk factors influencing long-term survival (≥1 year) following OAR and EVAR, published up to April 2015. Studies with <100 patients and those involving primarily ruptured AAA, complex repairs (supra celiac/renal clamp), and high risk patients were excluded. Primary risk factors were increasing age, sex, American Society of Anaesthesiologist (ASA) score, and comorbidities such as ischaemic heart disease (IHD), cardiac failure, hypertension, chronic obstructive pulmonary disease (COPD), renal impairment, cerebrovascular disease, peripheral vascular disease (PVD), and diabetes. Estimated risks were expressed as hazard ratio (HR). RESULTS: A total of 5,749 study titles/abstracts were retrieved and 304 studies were thought to be relevant. The systematic review included 51 articles and the meta-analysis 45. End stage renal disease and COPD requiring supplementary oxygen had the worst long-term survival, HR 3.15 (95% CI 2.45-4.04) and HR 3.05 (95% CI 1.93-4.80) respectively. An increase in age was associated with HR of 1.05 (95% CI 1.04-1.06) for every one year increase and females had a worse survival than men HR 1.15 (95% CI 1.07-1.27). An increase in ASA score and the presence of IHD, cardiac failure, hypertension, COPD, renal impairment, cerebrovascular disease, PVD, and diabetes were also factors associated with poor long-term survival. CONCLUSION: The result of this meta-analysis summarises and quantifies unmodifiable risk factors that influence late survival following AAA repair from the best available published evidence. The presence of these factors might assist in clinical decision making during discussion with patients regarding repair.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Fatores Etários , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/mortalidade , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Comorbidade , Procedimentos Cirúrgicos Eletivos , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE/BACKGROUND: There is compelling level 1 evidence in support of screening men for abdominal aortic aneurysm (AAA) to reduce AAA mortality. However, New Zealand (NZ) lacks data on AAA prevalence, and national screening has not been implemented. The aim of this study was to determine the prevalence of AAA in a population undergoing a computed tomography colonography (CTC) for gastrointestinal symptoms. METHODS: This was an observational study; all consecutive CTCs performed in three regions of the South Island of NZ over a 4 year period were reviewed. Data on abdominal and thoracic aorta diameters ≥30 mm, and iliac and femoral aneurysms ≥20 mm were recorded. Previous aortic surgical grafts or endovascular stents were also documented. Demographics, survival, and AAA related outcomes were collected and used for analysis. RESULTS: Included were 4,893 scans on 4,644 patients (1,933 men [41.6%], 2,711 women [58.4%]) with a median age of 69.3 years (range 17.0-97.0 years). There were 309 scans on 289 patients (75.4% men) who had either an aneurysm or a previous aortic graft with a median age of 79.6 years (range 57.0-96.0 years). Of these, 223 had a native AAA ≥30 mm. The prevalence of AAA rose with age from 1.3% in men aged 55-64 years, to 9.1% in 65-74 year olds, 16.8% in 75-84 year olds, and 22.0% in ≥85 year olds. The corresponding figures in women were 0.4%, 2%, 3.9%, and 6.2%, respectively. CONCLUSION: In this observational study, the prevalence of AAA was high and warrants further evaluation. The results acquired help to define a population that may benefit from a national AAA screening programme.
Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/epidemiologia , Colonografia Tomográfica Computadorizada , Achados Incidentais , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Valor Preditivo dos Testes , Prevalência , Estudos Retrospectivos , Distribuição por Sexo , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: This study aims to determine whether older adults reporting back pain (BP) are at increased risk of premature mortality, specifically, to examine the association with disabling/non-disabling pain separately. METHODS: Participants aged ≥75 years were recruited to the Cambridge City over-75s Cohort (CC75C) study. Participants answered interviewer-administered questions on BP and were followed up until death. The relationship between BP and mortality was examined using Cox regression, adjusted for potential confounding factors. Separate models were computed for men and women. RESULTS: From 1174 individuals with BP data, the date of death was known for 1158 (99%). A significant association was found between disabling BP and mortality (hazard ratio: 1.4; 95% confidence interval: 1.1-1.8) and this remained, albeit of borderline significance, following adjustment for socio-demographic variables and potential disease markers (1.3; 0.99-1.7). Further, this association was found to vary with sex: women experienced a 40% increase in the risk of mortality associated with disabling BP (1.4; 1.1-1.9), whereas no such increase was observed for men (1.0; 0.5-1.9). Participants with non-disabling BP were not at increased risk of mortality. CONCLUSIONS: This study confirmed previous findings regarding the relationship between pain and excess mortality. Further, we have shown that, among older adults, this association is specific to disabling pain and to women. Clinicians should be aware not only of the short-term implications of disabling BP but also the longer-term effects. Future research should attempt to understand the mechanisms underpinning this relationship to avoid excess mortality and should aim to determine why the relationship differs in men and women.
Assuntos
Dor nas Costas/epidemiologia , Dor nas Costas/mortalidade , Pessoas com Deficiência , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Fatores de Risco , Caracteres SexuaisRESUMO
OBJECTIVES: Increased chronic postprocedural levels of active matrix metalloproteinase-9 (MMP-9) have been associated retrospectively with a history of in-stent restenosis (ISR). This study aimed to determine whether index or post-percutaneous coronary intervention (PCI) plasma levels of active MMP-9 are a predictor of subsequent clinical ISR, in a standard population of patients treated with bare metal coronary stents. METHODS: Four hundred thirty-two patients were prospectively recruited and sampled at index and 3 and 6 months after PCI. Those who developed symptomatic angiographically confirmed ISR were compared to randomly selected, asymptomatic controls, stratified by index presentation in a nested case-control design. Plasma samples were analyzed for the active form of MMP-9. RESULTS: In all, 35 patients (8.1%) developed ISR, and these were compared to 98 controls. The increase in active MMP-9 over 3 months was significantly greater in the ISR group (p = 0.030) and independent of the established risk factors. Index clinical presentation was not associated with acute changes in active MMP-9; however, patients with ST-elevation myocardial infarction had greater increases in active MMP-9 at 3 months. CONCLUSIONS: The change in active MMP-9 over 3 months after bare metal coronary stent placement appears to be independently associated with the development of ISR in a standard PCI population.
Assuntos
Reestenose Coronária/etiologia , Metaloproteinase 9 da Matriz/metabolismo , Stents , Reestenose Coronária/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Fatores de RiscoRESUMO
There is a strong body of circumstantial evidence which implicates genetics in the aetiology and pathology of varicose veins and venous ulcer disease. The aim of this review is to consider the current knowledge of the genetic associations and the ways in which new genetic technologies may be applied to advancing our understanding of the cause and progression of these venous diseases. A number of publications have used a candidate gene approach to identify genes implicated in venous disease. Although these studies have opened up important new insights, there has been a general failure to replicate results in an independent cohort of patients. With our limited knowledge of the biological pathways involved in the pathogenesis of venous disease we are not in a strong position to formulate truly erudite a priori candidate gene hypothesis-directed studies. A genome-wide association study should therefore be considered to help further our understanding of the genetic basis of venous disease. Due to the large sample sizes required for discovery and validation, using the new generations of molecular technologies, it will be necessary to form collaborating groups in order to successfully advance the field of venous disease genetics.
Assuntos
Varizes/genética , Insuficiência Venosa/genética , Doença Crônica , Progressão da Doença , Fatores de Transcrição Forkhead/genética , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Genética Populacional , Estudo de Associação Genômica Ampla , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Trombomodulina/metabolismoRESUMO
OBJECTIVE: The aim was to examine the relationship between gestational age and birthweight and adult chronic widespread pain (CWP). DESIGN AND PARTICIPANTS: A prospective cohort study of 18,558 participants recorded birthweight and gestation at birth. EXPOSURE: Participants were categorised by gestation (fullterm ≥37 weeks; preterm <37 week) and birthweight (full birthweight (FBW) ≥2.5 kg; low birthweight (LBW) 1.5-2.5 kg; and very low birthweight (VLBW) <1.5 kg). OUTCOME: The presence or absence of CWP was measured by self-completed questionnaire in 8572 participants at age 45 yrs. Risk ratios were calculated using Poisson regression. Adjustment was made for potential confounding factors. RESULTS: Premature birth was associated with a 26% increase in the risk of CWP compared to fullterm birth, although this was not statistically significant (risk ratio 1.26, 95% confidence interval 0.95-1.67). This increased risk was robust to adjustment for sex, social class at birth and age 42 yrs, or birthweight, but was completely attenuated when adjusted for childhood behavioural problems and adult psychiatric disorder. LBW was not associated with an increased risk of CWP (RR 1.01, 95%CI 0.78-1.32). VLBW was associated with a non-significant increased risk (RR 1.48, 0.42-5.22) although there was insufficient study power to examine this relationship in the context of other factors. CONCLUSIONS: Premature birth and VLBW are associated with increased risk of adult CWP although these effects are modest, and not statistically significant. Although not conclusive in itself, this study lends support to the theory that adult chronic pain may have its origins - at least in part - in very early life.
Assuntos
Dor Crônica/epidemiologia , Recém-Nascido de Baixo Peso , Recém-Nascido Prematuro , Adulto , Peso ao Nascer/fisiologia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Pessoa de Meia-Idade , Medição da Dor , Distribuição de Poisson , Gravidez , Estudos Prospectivos , Medição de Risco , Inquéritos e Questionários , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: To determine if the pro-MMP-9/TIMP-1 ratio is an accurate surrogate for endogenously active MMP-9 levels. METHODS: Plasma active MMP-9, pro-MMP-9 and TIMP-1 were measured in 295 patients. RESULTS: There was a weak negative correlation between the pro-MMP-9/TIMP-1 ratio and active MMP-9. TIMP-1 was more closely correlated with active MMP-9 than pro-MMP-9. CONCLUSION: Pro-MMP-9/TIMP-1 ratio measured with ELISA is not a good surrogate measure for active MMP-9, and direct measurements of active MMP-9 are therefore recommended.
Assuntos
Doença da Artéria Coronariana/sangue , Precursores Enzimáticos/sangue , Metaloproteinase 9 da Matriz/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/enzimologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estatísticas não ParamétricasRESUMO
OBJECTIVE: To determine whether active matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 displayed seasonal variation and were stable in storage. METHODS: Plasma active MMP-9 and TIMP-1 were measured at three time-points in 163 individuals. RESULT: There was no evidence for seasonal variation or declining levels for up to three years of storage at -80°C. CONCLUSION: Active MMP-9 and TIMP-1 appear to be stable seasonally, and in storage for at least three years.
Assuntos
Metaloproteinase 9 da Matriz/sangue , Plasma/química , Plasma/enzimologia , Inibidor Tecidual de Metaloproteinase-1/sangue , Biomarcadores/sangue , Preservação de Sangue , Estabilidade Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estações do Ano , Manejo de Espécimes , TempoRESUMO
OBJECTIVE: This study aimed to determine whether plasma levels of active matrix metalloproteinases (MMP) are predictors of in-stent restenosis (ISR) in New Zealand patients treated with bare-metal coronary stents. METHODS: A group of 152 patients with a history of ISR were compared with 151 symptom free 1-year post-stenting patients (non-ISR). Demographic and angiographic characteristics were collected. Plasma samples were analyzed for the active forms of MMP-1, -2, -3 and -9 as well as tissue inhibitor of metalloproteinases (TIMP-1) using ELISA-based isoform sensitive assays. RESULTS: Both active MMP-9 and active MMP-3 were independently associated with history of ISR. Elevated levels of both active MMP-3 and -9 had an adjusted odds ratio of 11.8 (95% CI: 4-35, p<0.0001) for association with ISR, with 37% of ISR patients having such levels versus 11% on non-ISR. The addition of both of the MMP biomarkers significantly increased the area under the curve (AUC) of a receiver operator characteristic (ROC) analysis incorporating the significant demographic and angiographic variables (AUC 0.85 versus 0.78, p<0.005). CONCLUSION: Measures of plasma active MMP isoforms appear to be independently associated with ISR, and assessment of multiple MMP markers yields cumulative utility.
Assuntos
Angioplastia Coronária com Balão/instrumentação , Doença da Artéria Coronariana/terapia , Reestenose Coronária/enzimologia , Metaloproteinase 3 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Stents , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Área Sob a Curva , Biomarcadores/sangue , Estudos de Casos e Controles , Angiografia Coronária , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Ativação Enzimática , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Metaloproteinase 2 da Matriz/sangue , Metais , Pessoa de Meia-Idade , Nova Zelândia , Razão de Chances , Desenho de Prótese , Curva ROC , Medição de Risco , Fatores de Risco , Inibidor Tecidual de Metaloproteinase-1/sangue , Resultado do TratamentoRESUMO
BACKGROUND: Previous studies have suggested a role for transforming growth factor (TGF) beta and its receptor in thoracic aortic aneurysm, but their role in abdominal aortic aneurysm (AAA) is unknown. This study examined the possible association between TGF-beta receptor 1 and 2 (TGFBR-1 and -2) single nucleotide polymorphisms (SNPs) and serum TGF-beta1 with AAA. METHODS: Serum concentrations of TGF-beta1 and 58 SNPs for TGFBR-1 and -2 were examined in 1003 and 1711 men respectively from the Health In Men Study. Validation of SNPs was examined in a second referral cohort of 1043 subjects from New Zealand, of whom 654 had an AAA. RESULTS: Serum TGF-beta1 was not associated with AAA. Only one SNP in TGFBR-2 was weakly associated with AAA; TGFBR2 g.42917C > T, SNP ID rs1078985CC; odds ratio 0.64 (95 per cent confidence interval (c.i.) 0.45 to 0.93); P = 0.020 uncorrected; but this association did not hold after adjusting for multiple testing and was not validated in the New Zealand cohort: odds ratio 0.98 (95 per cent c.i. 0.50 to 1.94); P = 0.960. CONCLUSION: These findings suggest there is no important role of genetic polymorphisms in the main receptors for TGF-beta and circulating TGF-beta1 in AAA in older individuals. (c) 2009 British Journal of Surgery Society Ltd.