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1.
Occup Med (Lond) ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970820

RESUMEN

BACKGROUND: Fatigue is commonly reported in population surveys and has been identified in patients with health conditions as a key co-morbidity which makes remaining in work challenging. Such patients, however, rarely have access to programmes to help them manage their fatigue. AIMS: To quantify the relationship between fatigue, work impairment and health-related job loss. METHODS: We use data from the Health and Employment After Fifty study, a longitudinal study of people aged 50-64 years when recruited through general practices in England in 2013-14. During follow-up, fatigue was measured using the Fatigue Assessment Scale, work impairment was assessed using the Work Productivity and Activity Impairment scale, and changes in employment status were recorded. RESULTS: A total of 2743 participants were eligible for the current analysis; 23% satisfied criteria for being fatigued. People who were fatigued were less likely to have a partner, university degree, be physically active and were more likely to be obese. Their job was more likely to involve shifts, be perceived as insecure, have reported difficulties coping with job demands, and be unsatisfying. After adjustment for socio-economic, lifestyle and work-related factors, they were almost twice as likely to report both work impairment (relative risk 1.8; 95% confidence interval [CI] 1.6, 2.1) and future health-related job loss, although the latter effect was only in those with other morbidities (incidence rate ratio 1.96; 95% CI 1.03-3.72). CONCLUSIONS: Providing evidence-based support for workers with health conditions who experience fatigue may have an important impact at a population level in terms of extending working lives.

2.
Occup Med (Lond) ; 74(4): 313-322, 2024 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-38781569

RESUMEN

BACKGROUND: Women increasingly work beyond age 50+ but their occupational health is under-researched. AIMS: To investigate what jobs older contemporary women do, when they exit their jobs and what factors predict job exit. METHODS: Data came from the Health and Employment After Fifty cohort, which recruited women aged 50-64 at baseline in 2013-14 and has followed them up annually collecting: demographic, lifestyle and work information. Exits from employment were mapped longitudinally over five follow-ups. Time-to-first event Cox regression analyses were used to identify risk factors for job exit. RESULTS: At baseline, 4436 women participated, 64% of whom were working. The proportions of women working at 50-54, 55-60 and over 60 years were 86%, 79% and 38%, respectively. Amongst all women, after adjustment for age, managing comfortably financially and not coping with the mental demands of the job were associated with exit. Risk factors for job exit differed in the age bands: 50-54; 55-59 and >60 years, reflecting socio-economic status, markers of health (musculoskeletal pain and poor self-rated health) and work factors (under-appreciation, job dissatisfaction, temporary/permanent contracts, coping with work's physical demands). CONCLUSIONS: Factors contributing to exit from work among older women differ by age group, after controlling for perceived financial position, age and mental demands of the job. A number of work characteristics predict job exit and suggest that employers can play an important role in supporting women to continue working until older ages. Identification and treatment of musculoskeletal pain could also enable work amongst older women.


Asunto(s)
Empleo , Jubilación , Humanos , Femenino , Persona de Mediana Edad , Jubilación/estadística & datos numéricos , Jubilación/psicología , Empleo/estadística & datos numéricos , Empleo/psicología , Factores de Riesgo , Satisfacción en el Trabajo , Estado de Salud , Estudios Longitudinales , Estudios de Cohortes , Salud Laboral
3.
Occup Med (Lond) ; 73(8): 492-499, 2023 12 29.
Artículo en Inglés | MEDLINE | ID: mdl-37948123

RESUMEN

BACKGROUND: The impact of long-term occupational exposures on health in older adults is increasingly relevant as populations age. To date, no studies have reported their impact on survival free of disability in older adults. AIMS: We aimed to investigate the association between long-term occupational exposure and disability-free survival (DFS), all-cause mortality and cause-specific mortality in initially healthy older adults. METHODS: We analysed data from 12 215 healthy participants in the ASPirin in Reducing Events in the Elderly (ASPREE) study whose mean age was 75 years. Their work history was collated with the 'ALOHA-plus JEM' (Job Exposure Matrix) to assign occupational exposures. The primary endpoint, DFS, was a composite measure of death, dementia or persistent physical disability. The secondary endpoint, mortality, was classified according to the underlying cause. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals, adjusted for confounders. RESULTS: A total of 1835 individuals reached the DFS endpoint during the median 4.7 years follow-up period. Both ever-high and cumulative exposure to all dusts and all pesticides during a person's working years were associated with reduced DFS. Compared to no exposure, men with high exposure to dusts and pesticides had a reduced DFS. Neither of these exposures were significantly associated with all-cause mortality. Men with high occupational exposure to solvents and women exposed to dusts experienced higher all-cause and cancer-related mortality. CONCLUSIONS: Long-term occupational exposure to all dusts and pesticides was associated with a reduced DFS and increased mortality in community-dwelling healthy older adults.


Asunto(s)
Exposición Profesional , Plaguicidas , Masculino , Humanos , Femenino , Anciano , Aspirina , Exposición Profesional/efectos adversos , Polvo , Factores de Riesgo
4.
Occup Med (Lond) ; 73(5): 268-274, 2023 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-37261458

RESUMEN

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.


Asunto(s)
Personas con Discapacidad , Dolor , Adulto , Humanos , Persona de Mediana Edad , Modalidades de Fisioterapia , Análisis Costo-Beneficio , Calidad de Vida
5.
J Public Health (Oxf) ; 45(2): e285-e295, 2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-35640243

RESUMEN

BACKGROUND: To assess the feasibility and acceptability of conducting a trial of the clinical effectiveness and cost-effectiveness of a new case-management intervention to facilitate the return to work of health care workers, on sick leave, having a common mental disorder (CMD). METHODS: A mixed methods feasibility study. RESULTS: Systematic review examined 40 articles and 2 guidelines. Forty-nine National Health Service Occupational Health (OH) providers completed a usual care survey. We trained six OH nurses as case managers and established six recruitment sites. Forty-two out of 1938 staff on sick leave with a CMD were screened for eligibility, and 24 participants were recruited. Out of them, 94% were female. Eleven participants received the intervention and 13 received usual care. Engagement with most intervention components was excellent. Return-to-work self-efficacy improved more in the intervention group than in the usual care group. Qualitative feedback showed the intervention was acceptable. CONCLUSIONS: The intervention was acceptable, feasible and low cost to deliver, but it was not considered feasible to recommend a large-scale effectiveness trial unless an effective method could be devised to improve the early OH referral of staff sick with CMD. Alternatively, the intervention could be trialled as a new stand-alone OH intervention initiated at the time of usual OH referral.


Asunto(s)
Trastornos Mentales , Reinserción al Trabajo , Femenino , Humanos , Masculino , Personal de Salud , Trastornos Mentales/terapia , Salud Mental , Ausencia por Enfermedad , Medicina Estatal , Estudios de Factibilidad , Ensayos Clínicos como Asunto
6.
Occup Med (Lond) ; 72(7): 470-477, 2022 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-35904117

RESUMEN

BACKGROUND: Governments need people to work to older ages, but the prevalence of chronic disease and comorbidity increases with age and impacts work ability. AIMS: To investigate the effects of objective health diagnoses on exit from paid work amongst older workers. METHODS: Health and Employment After Fifty (HEAF) is a population cohort of adults aged 50-64 years recruited from English GP practices which contribute to the Clinical Practice Research Datalink (CPRD). Participants have completed questionnaires about health and work at baseline and annually for 2 years: their responses were linked with their objective health diagnoses from the CPRD and data analysed using Cox regression. RESULTS: Of 4888 HEAF participants ever in paid work, 580 (25%) men and 642 (25%) women exited employment, 277 of them mainly or partly for a health reason (health-related job loss (HRJL)). Amongst HEAF participants who remained in work (n = 3666) or who exited work but not for health reasons (n = 945), there was a similar prevalence of background health conditions. In men and women, HRJL was associated with inflammatory arthritis, sleep disorders, common mental health conditions and musculoskeletal pain. There were however gender differences: widespread pain and lower limb osteoarthritis were associated with HRJL in women but hypertension and cardiovascular disease in men. CONCLUSIONS: Improved diagnosis and management of common conditions might be expected to increase working lives. Workplace well-being interventions targeting obesity and increasing mobility might contribute to extended working lives. Employers of predominantly female, as compared with male workforces may need different strategies to retain older workers.


Asunto(s)
Empleo , Lugar de Trabajo , Adulto , Femenino , Masculino , Humanos , Encuestas y Cuestionarios , Estudios de Cohortes , Prevalencia
7.
Occup Med (Lond) ; 72(2): 132-141, 2022 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-34927206

RESUMEN

BACKGROUND: UK Biobank (UKB) is a large prospective cohort capturing numerous health outcomes, but limited occupational information (job title, self-reported manual work and occupational walking/standing). AIMS: To create and evaluate validity of a linkage between UKB and a job exposure matrix for physical work exposures based on the US Occupational Information Network (O*NET) database. METHODS: Job titles and UK Standard Occupational Classification (SOC) codes were collected during UKB baseline assessment visits. Using existing crosswalks, UK SOC codes were mapped to US SOC codes allowing linkage to O*NET variables capturing numerous dimensions of physical work. Job titles with the highest O*NET scores were assessed to evaluate face validity. Spearman's correlation coefficients were calculated to compare O*NET scores to self-reported UKB measures. RESULTS: Among 324 114 participants reporting job titles, 323 936 were linked to O*NET. Expected relationships between scores and self-reported measures were observed. For static strength (0-7 scale), the median O*NET score was 1.0 (e.g. audiologists), with a highest score of 4.88 for stone masons and a positive correlation with self-reported heavy manual work (Spearman's coefficient = 0.50). For time spent standing (1-5 scale), the median O*NET score was 2.72 with a highest score of 5 for cooks and a positive correlation with self-reported occupational walking/standing (Spearman's coefficient = 0.56). CONCLUSIONS: While most jobs were not physically demanding, a wide range of physical work values were assigned to a diverse set of jobs. This novel linkage of a job exposure matrix to UKB provides a potentially valuable tool for understanding relationships between occupational exposures and disease.


Asunto(s)
Bancos de Muestras Biológicas , Exposición Profesional , Humanos , Exposición Profesional/efectos adversos , Ocupaciones , Estudios Prospectivos , Reino Unido/epidemiología
8.
Occup Med (Lond) ; 71(9): 429-438, 2021 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-34693446

RESUMEN

BACKGROUND: Night/shift work may be increasing but there are few data about the prevalence amongst older workers. With governments encouraging people to work to older ages, it is important to know how feasible night/shift work is for them and whether there are any adverse health consequences. AIMS: Amongst current older workers (aged 50-64 years), to explore the prevalence of night/shift working and evaluate its health impacts and sustainability over 4 years of follow-up. METHODS: Data from the Health and Employment After Fifty cohort were used to describe the demographic, job and health characteristics of men and women undertaking night/shift work. Longitudinal data were used to examine the number and nature of exits annually thereafter. RESULTS: Amongst the 5409 working at baseline, 32% reported night/shift work in sectors which differed by sex. Night/shift workers were more likely to be: current smokers; doing physically demanding work; struggling to cope at work; dissatisfied with their hours; depressed; sleeping poorly; rating their health poorly. Women whose job involves night work were more likely to exit the workforce over 4 years. CONCLUSIONS: Almost one in three contemporary UK older workers report night/shift work. We found some evidence of adverse impacts on health, sleep and well-being and higher rates of job exit amongst women. More research is needed but night/shift work may be challenging to sustain for older workers and could have health consequences.


Asunto(s)
Horario de Trabajo por Turnos , Empleo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Horario de Trabajo por Turnos/efectos adversos , Sueño , Reino Unido/epidemiología , Tolerancia al Trabajo Programado
9.
J Foot Ankle Res ; 12: 26, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31164925

RESUMEN

OBJECTIVE: The aim of this study was to investigate whether foot and lower limb related symptoms were associated with work participation and poor mobility in people with Systemic Lupus Erythematosus (SLE). METHOD: A quantitative, cross-sectional, self-reported survey design was utilised. People with SLE from six United Kingdom (UK) treatment centres and a national register were invited to complete a survey about lower limb and foot health, work participation and mobility. Data collected included work status and the prevalence of foot symptoms. The focus of the analyses was to explore potential associations between poor foot health work non-participation. RESULTS: In total, 182 useable surveys were returned. Seventy-nine respondents reported themselves as employed and 32 reported work non-participation. The remaining were retired due to age or reported work non-participation for other reasons. Work non-participation due to foot symptoms was significantly associated with difficulty walking (p = 0.024), past episodes of foot swelling (p = 0.041), and past episodes of foot ulceration (p = 0.018). There was a significant increase in foot disability scores amongst those not working (mean 18.13, 95% CI: 14.85-21.41) compared to those employed (mean 10.16, 95% CI: 8.11-12.21). CONCLUSIONS: Twenty-nine% of people with SLE reported work non-participation because of lower limb or foot problems. Our results suggest that foot health and mobility may be important contributors to a persons' ability to remain in work and should be considered as part of a clinical assessment.


Asunto(s)
Empleo/estadística & datos numéricos , Enfermedades del Pie/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Limitación de la Movilidad , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Enfermedades del Pie/etiología , Humanos , Masculino , Persona de Mediana Edad , Autoinforme , Reino Unido/epidemiología , Adulto Joven
10.
Occup Med (Lond) ; 68(9): 572-579, 2018 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-30265338

RESUMEN

BACKGROUND: Job demand-control (DC) and effort-reward imbalance (ERI) are two commonly used measures of work stress which are independently associated with health. AIMS: To test the hypothesis that DC and ERI have different and cumulative effects on health. METHODS: DC and ERI were assessed in the Hertfordshire Cohort Study. The characteristics and occupations of men and women reporting either or both work stresses were compared and the interaction of these with health status were explored. RESULTS: Complete data were available for 1021 men and 753 women, reporting on their most recent or current job. A total of 647 (63%) men and 444 (59%) women reported neither work stress, while 103 (10%) men and 78 (10%) women reported both. Patterns of ERI and DC, alone and in combination, were different by type of occupation and by gender. Men reporting both work stresses (as compared with neither) were more likely to be single. Reported ERI with DC in the most recent or current job was associated with: poorer SF-36 physical function scores (OR 2.3 [95% CI 1.5-3.7] for men; OR 2.0 [95% CI 1.2-3.6] for women) and mental health scores (OR 2.8 [95% CI 1.8-4.4] for men; OR 3.1 [95% CI 1.8-5.3] for women). Moreover, average grip strength was 1.7 kg (95% CI 0.2-3.3) lower among men who described both work stresses. CONCLUSION: DC and ERI are two models of the psychosocial workplace environment which offer different but cumulative insight into the impacts of work on an individual's psychological and physical health, particularly in a population sample.


Asunto(s)
Estrés Laboral/complicaciones , Jubilación/psicología , Anciano , Estudios de Cohortes , Femenino , Humanos , Satisfacción en el Trabajo , Masculino , Estado Civil/estadística & datos numéricos , Persona de Mediana Edad , Estrés Laboral/clasificación , Estrés Laboral/psicología , Psicometría/instrumentación , Psicometría/métodos , Recompensa , Factores de Riesgo , Clase Social , Encuestas y Cuestionarios , Lugar de Trabajo/psicología
11.
Osteoporos Int ; 29(6): 1321-1328, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29479646

RESUMEN

In the large UK Biobank population-based cohort, we found that amongst men, but not women, prior fragility fracture was associated with increased risk of admission with ischaemic heart disease. INTRODUCTION: We aimed to investigate the relationship between prior fracture and risk of incident ischaemic cardiovascular events in a UK population-based cohort. METHODS: UK Biobank is a large prospective cohort comprising 502,637 men and women aged 40-69 years, with detailed baseline assessment. History of fracture was self-reported, and details of hospital admissions for ischaemic heart disease (IHD) (ICD-10:I20-I25) were obtained through linkage to UK Hospital Episode Statistics. Cox proportional hazards models were used to investigate the prospective relationships between prior fracture and hospital admission for men and women, controlling for age, BMI, smoking, alcohol, educational level, physical activity, systolic blood pressure, calcium and vitamin D use, ankle spacing-width, heel BUA and HRT use (women). RESULTS: Amongst men, a fragility fracture (hip, spine, wrist or arm fracture resulting from a simple fall) within the previous 5 years was associated with a 35% increased risk of IHD admission (fully adjusted HR 1.35; 95%CI 1.00, 1.82; p = 0.047), with the relationship predominantly driven by wrist fractures. Associations with hospitalisation for angina in men were similar in age-adjusted models [HR1.54; 95%CI: 1.03, 2.30), p = 0.037], but did not remain statistical significant after full adjustment [HR 1.64; 95%CI: 0.88, 3.07); p = 0.121]. HRs for admission with angina were lower in women, and neither age- nor fully adjusted relationships attained statistical significance. CONCLUSIONS: Prior fragility fracture is an independent risk factor for incident ischaemic cardiovascular events in men. Further work may clarify whether this association is causal or represents shared risk factors, but these findings are likely to be of value in risk assessment of both osteoporosis and cardiovascular disease.


Asunto(s)
Isquemia Miocárdica/epidemiología , Fracturas Osteoporóticas/epidemiología , Adulto , Anciano , Angina de Pecho/epidemiología , Angina de Pecho/etiología , Bancos de Muestras Biológicas , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Isquemia Miocárdica/etiología , Fracturas Osteoporóticas/complicaciones , Medición de Riesgo/métodos , Factores Sexuales , Reino Unido/epidemiología
13.
Bone ; 88: 131-137, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27130873

RESUMEN

Osteoporosis is a major healthcare problem which is conventionally assessed by dual energy X-ray absorptiometry (DXA). New technologies such as high resolution peripheral quantitative computed tomography (HRpQCT) also predict fracture risk. HRpQCT measures a number of bone characteristics that may inform specific patterns of bone deficits. We used cluster analysis to define different bone phenotypes and their relationships to fracture prevalence and areal bone mineral density (BMD). 177 men and 159 women, in whom fracture history was determined by self-report and vertebral fracture assessment, underwent HRpQCT of the distal radius and femoral neck DXA. Five clusters were derived with two clusters associated with elevated fracture risk. "Cluster 1" contained 26 women (50.0% fractured) and 30 men (50.0% fractured) with a lower mean cortical thickness and cortical volumetric BMD, and in men only, a mean total and trabecular area more than the sex-specific cohort mean. "Cluster 2" contained 20 women (50.0% fractured) and 14 men (35.7% fractured) with a lower mean trabecular density and trabecular number than the sex-specific cohort mean. Logistic regression showed fracture rates in these clusters to be significantly higher than the lowest fracture risk cluster [5] (p<0.05). Mean femoral neck areal BMD was significantly lower than cluster 5 in women in cluster 1 and 2 (p<0.001 for both), and in men, in cluster 2 (p<0.001) but not 1 (p=0.220). In conclusion, this study demonstrates two distinct high risk clusters in both men and women which may differ in etiology and response to treatment. As cluster 1 in men does not have low areal BMD, these men may not be identified as high risk by conventional DXA alone.


Asunto(s)
Huesos/diagnóstico por imagen , Huesos/patología , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/patología , Tomografía Computarizada por Rayos X/métodos , Absorciometría de Fotón , Anciano , Análisis por Conglomerados , Demografía , Femenino , Fracturas Óseas/epidemiología , Humanos , Estilo de Vida , Masculino , Oportunidad Relativa , Fenotipo , Factores de Riesgo
14.
Occup Environ Med ; 73(4): 284-6, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26896253

RESUMEN

INTRODUCTION: Reductions in heavy manual work as a consequence of mechanisation might adversely impact muscle strength at older ages. We investigated the association between grip strength at retirement age and lifetime occupational exposure to physically demanding activities. Grip strength is an important predictor of long-term health and physical function in older people. METHODS: Grip strength (maximum of three readings in each hand) was measured in men from the Hertfordshire Cohort Study at a single examination when their mean age was 65.8 (SD 2.9) years. Associations with lifetime occupational exposure (ascertained by questionnaire) to three activities (standing/walking ≥ 4 h/day; lifting ≥ 25 kg; and energetic work sufficient to induce sweating) were assessed by multivariable linear regression with adjustment for various potential confounders. RESULTS: Complete data were available from 1418 men who had worked for at least 20 years. After adjustment for age, height and weight, those with longer exposures to walking/standing and heavy lifting had lower grip strength, but the relationship disappeared after further adjustment for confounders. Working at physical intensity sufficient to induce sweating was not significantly associated with grip strength. CONCLUSIONS: We found no evidence that physically demanding occupational activities increase hand grip strength at normal retirement age. Any advantages of regular physical occupational activity may have been obscured by unmeasured socioeconomic confounders.


Asunto(s)
Envejecimiento/fisiología , Fuerza de la Mano , Músculo Esquelético/fisiología , Exposición Profesional , Esfuerzo Físico , Jubilación , Trabajo , Anciano , Estudios de Cohortes , Estudios Transversales , Humanos , Elevación , Masculino , Persona de Mediana Edad , Ocupaciones , Postura , Reino Unido , Caminata
15.
Blood Cancer J ; 5: e311, 2015 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-25978431

RESUMEN

The vast majority of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ALCL) tumors express the characteristic oncogenic fusion protein NPM-ALK, which mediates tumorigenesis by exerting its constitutive tyrosine kinase activity on various substrates. We recently identified MSH2, a protein central to DNA mismatch repair (MMR), as a novel binding partner and phosphorylation substrate of NPM-ALK. Here, using liquid chromatography-mass spectrometry, we report for the first time that MSH2 is phosphorylated by NPM-ALK at a specific residue, tyrosine 238. Using GP293 cells transfected with NPM-ALK, we confirmed that the MSH2(Y238F) mutant is not tyrosine phosphorylated. Furthermore, transfection of MSH2(Y238F) into these cells substantially decreased the tyrosine phosphorylation of endogenous MSH2. Importantly, gene transfection of MSH2(Y238F) abrogated the binding of NPM-ALK with endogenous MSH2, re-established the dimerization of MSH2:MSH6 and restored the sensitivity to DNA mismatch-inducing drugs, indicative of MMR return. Parallel findings were observed in two ALK+ALCL cell lines, Karpas 299 and SUP-M2. In addition, we found that enforced expression of MSH2(Y238F) into ALK+ALCL cells alone was sufficient to induce spontaneous apoptosis. In conclusion, our findings have identified NPM-ALK-induced phosphorylation of MSH2 at Y238 as a crucial event in suppressing MMR. Our studies have provided novel insights into the mechanism by which oncogenic tyrosine kinases disrupt MMR.


Asunto(s)
Reparación de la Incompatibilidad de ADN/fisiología , Linfoma Anaplásico de Células Grandes/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Quinasa de Linfoma Anaplásico , Western Blotting , Línea Celular Tumoral , Cromatografía Liquida , Humanos , Inmunoprecipitación , Linfoma Anaplásico de Células Grandes/patología , Espectrometría de Masas , Mutagénesis Sitio-Dirigida , Fosforilación , Transfección , Tirosina/metabolismo
16.
Foot (Edinb) ; 25(1): 19-29, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25605413

RESUMEN

BACKGROUND: Most studies of football injuries include professional players and data have been collected in without a single validated, standardised tool. We aimed to develop a new standardised questionnaire for assessing injuries among non-professional footballers and pilot its use. METHOD: A questionnaire was developed using input from footballers, healthcare professionals and triangulation from the literature. The new tool was piloted among players representing amateurs and semi-professionals. Their comments were used iteratively to improve the instrument. RESULTS: The development phase produced a 33-item questionnaire collecting quantitative and qualitative data. In the pilot phase, 42 questionnaires were distributed, 34 (81%) returned. Respondents reported total of 273 football-related injuries, 114 affecting the foot/ankle (70 at the ankle and 44 at the foot). In total, 44% of respondents had suffered one or more foot/ankle injuries in the past 12 months. CONCLUSION: We developed a new standardised tool which we found to be well-completed by young male footballers in semi-professional and amateur settings with an excellent response rate. Our results suggested that foot/ankle injuries were common, larger studies in non-professionals are needed to identify risk factors for injury and develop pragmatic advice for prevention.


Asunto(s)
Traumatismos del Tobillo/epidemiología , Traumatismos de los Pies/epidemiología , Fútbol/lesiones , Encuestas y Cuestionarios , Adolescente , Adulto , Traumatismos del Tobillo/diagnóstico , Traumatismos de los Pies/diagnóstico , Humanos , Masculino , Proyectos Piloto , Reproducibilidad de los Resultados , Factores de Riesgo , Reino Unido , Adulto Joven
17.
Occup Environ Med ; 71(5): 329-31, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24619156

RESUMEN

BACKGROUND: People in sedentary occupations are at increased risk of hip fracture. Hip fracture is significantly associated with low bone mineral density (BMD) measured at the hip. Physical activity is important in the development and maintenance of BMD, but the effects of occupational physical activity on bone health are unclear. We investigated the influence of lifetime physical activity on BMD at the hip. METHODS: This was a cross-sectional epidemiological study of the associations between total hip BMD measured by dual-energy X-ray absorptiometry at retirement age and lifetime exposure to occupational physical workload (standing/walking ≥4 h/day; lifting ≥25 kg; energetic work sufficient to induce sweating and manual work). RESULTS: Complete data on occupational exposures were available for 860 adults (488 men and 372 women) who had worked ≥20 years. Their mean age was 65 years, and many reported heavy physical workplace activities over prolonged durations. There were no statistically significant associations between total hip BMD and any of these measures of lifetime occupational physical activity in men or women. CONCLUSIONS: Lifetime cumulative occupational activity was not associated with hip BMD at retirement age. Our findings suggest that, if sedentary work conveys an increased risk of hip fracture, it is unlikely that the mechanism is through reductions in BMD at the hip and may relate to other physical effects, such as falls risk. Further studies will be needed to test this hypothesis.


Asunto(s)
Densidad Ósea , Cadera , Exposición Profesional , Esfuerzo Físico , Conducta Sedentaria , Caminata , Trabajo , Absorciometría de Fotón , Anciano , Estudios Transversales , Femenino , Fracturas Óseas/etiología , Humanos , Elevación , Masculino , Persona de Mediana Edad , Movimiento , Ocupaciones , Postura , Jubilación , Factores de Riesgo , Factores de Tiempo
18.
Int J STD AIDS ; 25(11): 833-5, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24516081

RESUMEN

A multitude of rheumatologic manifestations have been associated with HIV infection and protease inhibitors use. We describe two cases that display a temporal relationship between initiating Kaletra and developing Achilles tendinopathy. Immediate and dramatic resolution of symptoms occurred on switching from Kaletra to an alternative agent. Clinicians may want to consider a trial of an alternative agent in individuals on Kaletra who experience Achilles tendinopathy. Adverse events must be formally reported so that our understanding of antiretrovirals may continually evolve and aid decisions about antiretroviral prescribing.


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/efectos adversos , Lopinavir/efectos adversos , Ritonavir/efectos adversos , Tendinopatía/inducido químicamente , Tendón Calcáneo/patología , Adulto , Recuento de Linfocito CD4 , Combinación de Medicamentos , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Lopinavir/orina , Imagen por Resonancia Magnética , Masculino , Ritonavir/orina , Resultado del Tratamiento
19.
HIV Med ; 15(3): 182-8, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24025108

RESUMEN

OBJECTIVES: This was a cross-sectional study with a nested case-control analysis among a cohort of HIV-infected adults aiming to explore the prevalence of and risk factors for elective hip surgery (total hip arthroplasty and resurfacing). METHODS: Cases were identified from the out-patient database of HIV-infected adults attending one tertiary hospital service. For each case, five controls from the same database matched by age, gender and ethnicity were identified. From the case notes, information about demographic factors, HIV factors and risk factors for hip surgery attributable to osteoarthritis or avascular necrosis (body mass index, lipids, alcohol, comorbidities and treatment with oral glucocorticoids) was extracted. RESULTS: Among the cohort of 1900 HIV-infected out-patients, 13 cases (12 male) who had undergone hip surgery [0.7%; 95% confidence interval (CI) 0.3-1.1%] were identified, with a median age of 47 years. Eleven of the 13 cases (85%) were Caucasian and seven of the 13 were in stage 3 of HIV infection. Fewer of the cases were in the asymptomatic stage of infection compared with controls [odds ratio (OR) for stage 2 or 3 infection 4.0; 95% CI 0.8-18.5]. Ever having used oral glucocorticoids was highly significantly associated with elective hip surgery (OR 44.6; 95% CI 5.7-347.7). CONCLUSIONS: Among this young cohort, the prevalence of elective hip surgery was 0.7%, with the median age at surgery being 47 years. Ever having been exposed to systemic glucocorticoids was highly significantly associated with elective hip surgery, suggesting that the principal mechanism underlying the need for surgery was avascular necrosis. There may be an increased need for elective hip surgery associated with HIV infection.


Asunto(s)
Glucocorticoides/efectos adversos , Infecciones por VIH/complicaciones , Osteoartritis de la Cadera/etiología , Osteonecrosis/etiología , Adulto , Artroplastia de Reemplazo de Cadera , Estudios de Casos y Controles , Comorbilidad , Estudios Transversales , Femenino , Glucocorticoides/uso terapéutico , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/epidemiología , Osteoartritis de la Cadera/cirugía , Osteonecrosis/epidemiología , Osteonecrosis/cirugía , Factores de Riesgo
20.
Occup Med (Lond) ; 63(8): 579-82, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24213093

RESUMEN

BACKGROUND: Musculoskeletal disorders (MSDs) are a common cause of disability in the workplace. Despite this, there is known to be a wide variation in the assessment of MSDs by UK occupational health (OH) professionals. Therefore we developed a workshop, supported by a bespoke, on-line video, focussing on the assessment and management of MSDs. AIMS: To assess the impact of the training package on the knowledge, confidence and reported behaviour of attendees. METHODS: Workshops were held in two regional centres in England. Delegates completed a questionnaire on arrival to establish their baseline knowledge and confidence and again at the end of the training. A third questionnaire, with one reminder, was e-mailed to delegates 4 months following the workshops. RESULTS: Ninety-two OH professionals (77 nurses, 10 doctors and 5 'others') attended and more than 80% reported that they had no previous training in examining the upper or lower limb or in distinguishing specific from non-specific MSDs. Confidence among delegates in examination, diagnosis and management of MSDs improved after the workshop and these changes were sustained and remained statistically significant from baseline 4 months afterwards. Following the training, 79% (50) of delegates reported that they had shared the knowledge and skills acquired with their colleagues and 71% reported that they had used the examination techniques in their day-to-day practice. CONCLUSIONS: We have developed a training package which resulted in improved knowledge among attendees and gave them confidence to use their skills in practice.


Asunto(s)
Educación Médica Continua/normas , Enfermedades Musculoesqueléticas , Enfermedades Profesionales , Salud Laboral/educación , Actitud del Personal de Salud , Educación Médica Continua/métodos , Inglaterra , Femenino , Humanos , Masculino , Enfermedades Musculoesqueléticas/diagnóstico , Enfermedades Musculoesqueléticas/terapia , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/terapia , Evaluación de Programas y Proyectos de Salud
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