Frailty in relation to variations in hormone levels of the hypothalamic-pituitary-testicular axis in older men: results from the European male aging study.

OBJECTIVES: To explore the associations between frailty and reproductive axis hormones (as an important regulatory system) in middle aged and older men. DESIGN: Cross-sectional. SETTING: The European Male Aging Study. PARTICIPANTS: Three thousand two hundred nineteen community-dwelling European men aged 40 to 79. MEASUREMENTS: Interviewer-assisted questionnaires to assess physical activity, health status, and mood were administered. Testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) were measured in a fasting morning blood sample. Frailty was assessed as an index (FI) according to the number (out of 43 possible) of health deficits (symptoms, signs, and functional impairments). Relationships between FI and hormone levels (as outcomes) were explored using regression models. RESULTS: Mean FI was 0.12 ± 0.11 (range 0-0.67) was highest in the oldest group. After adjustment for confounders, higher levels of FI were significantly associated with lower levels of total T, free T, and DHEAS and higher levels of gonadotropins and SHBG; a 1-standard deviation cross-sectional increase in FI was associated with a regression coefficient of -0.30 nmol/L (95% confidence interval (CI)=-0.53 to -0.07) decrease in total T and 0.66 U/L (95% CI=0.48-0.83) increase in LH. CONCLUSIONS: The associations between high FI, high gonadotropins, and well-maintained circulating T suggest that these changes are markers of aging-related disruptions of multiple physiological regulation, of which alterations in pituitary-testicular function represent a sensitive marker rather than an underlying pathogenic mechanism for frailty.

Association of the HLA-DRB1 gene with premature death, particularly from cardiovascular disease, in patients with rheumatoid arthritis and inflammatory polyarthritis.

OBJECTIVE: To examine the role of the variants of the PTPN22 and HLA-DRB1 genes as predictors of mortality in inflammatory polyarthritis (IP) and rheumatoid arthritis (RA). METHODS: Patients were recruited from a primary care-based inception cohort of patients with IP and were followed up prospectively. For patients who died, the cause and date of death was obtained. Cox proportional hazards regression models were used to assess the association of the HLA-DRB1 (including the shared epitope [SE]) and PTPN22 genes with the risk of death from all causes and from cardiovascular disease (CVD) and to assess the interactions between SE, smoking, and anti-cyclic citrullinated peptide (anti-CCP) status, adjusted by age at symptom onset and sex. RESULTS: DNA samples were available from 1,022 IP patients. During followup, 751 of them (74%) satisfied the American College of Rheumatology 1987 criteria for RA, and 242 of them (24%) died. Carriage of 2 copies of SE alleles predicted death from all causes (hazard ratio [HR] 1.57 [95% confidence interval (95% CI) 1.1-2.2]) and from CVD (HR 1.68 [95% CI 1.1-2.7]). This effect was most marked for individuals with the HLA-DRB1*01/*04 combination. An interaction of smoking, SE alleles, and anti-CCP antibodies was observed and was associated with the greatest risk of death from CVD (HR 7.81 [95% CI 2.6-23.2]). No association of the PTPN22 gene with mortality was detected. CONCLUSION: SE alleles, particularly compound heterozygotes, are associated with death from all causes and from CVD, independently of autoantibody status. However, the combination of SE, smoking, and anti-CCP antibodies is associated with a high risk of premature death in patients with IP and RA, which raises the possibility of a targeted strategy to prevent CVD in these patients.

Quality of care for people with osteoarthritis: a qualitative study.

AIM: The overall aim of this qualitative study was to explore within primary care the experiences of management and care of individuals with end-stage lower limb osteoarthritis who are on the waiting list for joint replacement. BACKGROUND: Osteoarthritis, one of the most common chronic diseases, causes loss of physical function and severe pain among sufferers. Improving quality of care and service provision for individuals with chronic diseases is high on the UK's NHS agenda. METHODS: Data were collected by semi-structured qualitative interviews with 21 individuals with osteoarthritis who were waiting for a hip or knee replacement operation. Interviews were analysed using framework analysis. RESULTS: Participants had been suffering with osteoarthritis for between seven months and 38 years. The management by health professionals for people on the waiting list for joint replacement was minimal. However, participants spoke of 'hiding' their symptoms from health professionals and were trying to 'self-manage' their symptoms. Families became more involved in helping individuals with osteoarthritis to manage with everyday life. CONCLUSION: Management of individuals' osteoarthritis while on the waiting list needs to be given consideration by health professionals in primary and secondary care. Health professionals need to be working with each other to provide more comprehensive care across the primary and secondary care interface. RELEVANCE TO CLINICAL PRACTICE: Case managers or community matrons could be identified as the co-ordinator and assessor of the needs of patients with osteoarthritis so as to try and improve pain management and service provision for these individuals especially while on the waiting list.

Early functional disability predicts both all-cause and cardiovascular mortality in people with inflammatory polyarthritis: results from the Norfolk Arthritis Register.

OBJECTIVE: To investigate the predictive value of early functional disability in patients with inflammatory polyarthritis (IP), for all-cause and cardiovascular disease (CVD) mortality. METHODS: 1010 subjects with new-onset IP from the Norfolk Arthritis Register were studied. All were seen at baseline and at 1 year. Health Assessment Questionnaire (HAQ) scores were obtained at both time points. Vital status at 10 years from registration was established through central records. Mortality (all-cause and CVD) per 1000 person-years were calculated by HAQ stratum (HAQ scores<1, 1-2 and>or=2). The predictive value of HAQ (per unit increase) at the two time points, adjusted for age at onset of symptom, sex and other factors found to predict mortality, was assessed using Cox regression models. The analysis was repeated for those who satisfied the 1987 American College of Rheumatology criteria for rheumatoid arthritis (RA) by 5 years. RESULTS: By 10 years, 171 (16.9%) subjects had died. 89 deaths (52%) were attributed to CVD. Mortality was greatest in the highest HAQ group at both time points. Following adjustment for other predictors, HAQ score at year 1 remained a significant predictor of all-cause mortality (HR 1.46; 95% CI 1.15 to 1.85) and CVD mortality (HR 1.49; 95% CI 1.12 to 1.97). The predictive value of HAQ at year 1 was similar in the RA subgroup. CONCLUSIONS: Our data show that at 1 year of follow-up, HAQ score is an important independent predictor of subsequent all-cause and CVD mortalities in people with IP and RA. Baseline HAQ scores are of less value.

Mortality in early inflammatory polyarthritis: cardiovascular mortality is increased in seropositive patients.

OBJECTIVE: To determine the degree and causes of any excess mortality observed during the early years of inflammatory polyarthritis (IP). METHODS: Between 1990 and 1994, a total of 1,236 patients were registered with the Norfolk Arthritis Register, a primary care-based inception cohort. All patients were tracked on the National Health Service Central Register for notification of death. The vital status of each patient was determined as of December 31, 1999. Causes of death were coded according to the International Classification of Diseases, Ninth Revision. Expected death rates were calculated using annual death rates for the Norfolk population. Standardized mortality ratios (SMRs) were calculated for all IP patients and for the subgroups of patients who did and did not satisfy the American College of Rheumatology (ACR) 1987 criteria for rheumatoid arthritis (RA) at baseline, as well as for the subgroups who were and were not rheumatoid factor (RF) positive at baseline. RESULTS: By December 31, 1999, 160 patients (13%; 79 women and 81 men) had died. The median duration of followup in the entire cohort was 6.9 years. Mortality rates were not significantly increased in the entire group of patients with IP or in the subgroup who met the ACR 1987 criteria for RA at baseline. In contrast, RF-positive patients had an increased rate of death from all causes (SMR in men 1.51, in women 1.41). Cardiovascular disease was the most common cause of death. The majority of the excess mortality in the RF-positive patients could be attributed to cardiovascular causes (SMR in men 1.34, in women 2.02). CONCLUSION: Excess mortality in the early years of IP is confined to patients who are seropositive for RF. While excess cardiovascular mortality has been described in patients with established RA, this is the first report of premature death from heart disease in the early years of IP.