Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78 , associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

Multiple views detect more radiographic osteoarthritis than single views alone. When different combinations of views are used, the prevalence and compartmental distribution of osteoarthritis changes and this may alter the accepted relationship, or lack of it, between symptoms and radiographic change.

Mild isolated PF OA is significantly associated with symptoms of pain, stiffness and functional limitation. Further research on its recognition in clinical practice and the development of targeted treatments to prevent or slow progression are warranted.

Objectives: Joint pain and radiographic osteoarthritis are often discordant. Aim: To investigate this issue more closely by studying the detailed nature of pain and disability, and how this relates to radiographic osteoarthritis. Methods: Population-based study of 819 adults aged >50 years with knee pain. The severity of knee pain, stiffness and disability was measured using a validated scale (the Western Ontario and McMaster Universities (WOMAC) Score) and pain persistence was recorded. Global severity was measured by the graded chronic pain scale. Three radiographic views of the knees were obtained-weight-bearing posteroanterior metatarsophalangeal, supine skyline and supine lateral. Results: 745 participants with knee pain in the past 6 months were eligible (mean age 65 years, 338 men). Radiographic osteoarthritis was more common in those with a longer history and more persistent symptoms. A strong trend was found of radiographic osteoarthritis being more strongly associated with higher WOMAC scores for pain severity, stiffness and disability (adjusted odds ratio (95% confidence interval (CI)) for highest v lowest WOMAC category: 3.7 (2.0 to 6.7), 3.0 (2.0 to 4.6) and 2.8 (1.6 to 5.0), respectively). Those individual WOMAC items for pain and disability pertaining to weight-bearing mobility were the most strongly associated with radiographic osteoarthritis. Combining pain persistence and global severity, persistent severe pain was associated with a significant increase in the occurrence of radiographic osteoarthritis (2.6 (95% CI 1.5 to 4.7)). Conclusions: A consistent association was found between severity of pain, stiffness and physical function and the presence of radiographic osteoarthritis. This study highlights the potential contribution of underlying joint disease to the degree of pain and disability.

These results suggest a common sequence in the development of radiographic knee OA in symptomatic adults beginning in the PFJ, with subsequent addition and progression of TFJOA. It is proposed that isolated symptomatic PFJOA may be one marker for the future development of TFJOA and a target for the early management of knee OA.

ObjectivesTo explore the views and experiences of patients on the care they have received while enrolled on the Northumberland High Risk Patient Programme (NHRPP). This programme involved case finding of frail patients using a multidisciplinary team (MDT)-led community case management programme, and support of patients through care planning and regular reviews using primary, community, secondary and social care professionals.DesignA qualitative study using semistructured interviews, which were digitally recorded, transcribed and subject to thematic analysis.SettingCommunity patients receiving primary care in the county of Northumberland, England.Participants23 participants took part, of which 16 were patients enrolled on the NHRPP, and 7 carers. GP practices were selected purposively by size, deprivation and location, and patients identified and invited by General Practitioners to participate.Results4 main themes emerged from the data: awareness and understanding of the NHRPP, confidence in the primary healthcare team, limitations of home care and the active role of being a patient. Despite having a low level of awareness of the details of the NHRPP, participants did think that its broad aim made sense. Participants discussed their high level of satisfaction with their care and access to team members. However, some limitations of alternatives to hospital care were identified, including the need to consider psychological as well as medical needs, the importance of overnight care and the needs of those without informal carers. Finally, participants discussed the active nature of being a patient under the NHRPP if they were to contribute fully to planning and managing their own care.ConclusionsThis study has identified that a programme of MDT-led case management was generally very well received by patients and their families. However, a number of factors were identified that could improve the implementation of the programme and further research needs to be undertaken to address these.

IntroductionPatellofemoral joint osteoarthritis (OA) is common and leads to pain and disability. However, current classification criteria do not distinguish between patellofemoral and tibiofemoral joint OA. The objective of this study was to provide empirical evidence of the clinical features of patellofemoral joint OA (PFJOA) and to explore the potential for making a confident clinical diagnosis in the community setting.MethodsThis was a population-based cross-sectional study of 745 adults aged ≥50 years with knee pain. Information on risk factors and clinical signs and symptoms was gathered by a self-complete questionnaire, and standardised clinical interview and examination. Three radiographic views of the knee were obtained (weight-bearing semi-flexed posteroanterior, supine skyline and lateral) and individuals were classified into four subsets (no radiographic OA, isolated PFJOA, isolated tibiofemoral joint OA, combined patellofemoral/tibiofemoral joint OA) according to two different cut-offs: 'any OA' and 'moderate to severe OA'. A series of binary logistic and multinomial regression functions were performed to compare the clinical features of each subset and their ability in combination to discriminate PFJOA from other subsets.ResultsDistinctive clinical features of moderate to severe isolated PFJOA included a history of dramatic swelling, valgus deformity, markedly reduced quadriceps strength, and pain on patellofemoral joint compression. Mild isolated PFJOA was barely distinguished from no radiographic OA (AUC 0.71, 95% CI 0.66, 0.76) with only difficulty descending stairs and coarse crepitus marginally informative over age, sex and body mass index. Other cardinal signs of knee OA - the presence of effusion, bony enlargement, reduced flexion range of movement, mediolateral instability and varus deformity - were indicators of tibiofemoral joint OA.ConclusionsEarly isolated PFJOA is clinically manifest in symptoms and self-reported functional limitation but has fewer clear clinical signs. More advanced disease is indicated by a small number of simple-to-assess signs and the relative absence of classic signs of knee OA, which are predominantly manifestations of tibiofemoral joint OA. Confident diagnosis of even more advanced PFJOA may be limited in the community setting.

Objective. Patients with systemic lupus erythematosus (SLE) are significantly more likely to experience a myocardial infarction or a stroke than age-matched controls. We compared the prevalence of conventional and lupus-specific risk factors in patients with SLE just before a cardiovascular event and in matched controls with SLE but no cardiovascular disease (CVD). Methods. Twenty-nine patients with SLE and CVD were enrolled. For each patient, 2 ethnically-and sex-matched controls were obtained, 1 matched for age and 1 for SLE duration. Data regarding risk factors were collected for the time immediately preceding the relevant cardiovascular event, or at an equivalent time for controls. Results. Patients' median age at event was 49 years (interquartile range 43-54 years) and mean disease duration was 12.0 ؎ 7.1 years. Patients with SLE and CVD were more likely than both age and duration controls to be treated for hypertension (P ‫؍‬ 0.01 and P ‫؍‬ 0.001, respectively) and to have elevated triglyceride levels (P ‫؍‬ 0.05 and P ‫؍‬ 0.01, respectively). Compared with duration controls, CVD patients were more likely to have lupus anticoagulant (P ‫؍‬ 0.03), but less likely to be receiving treatment with hydroxychloroquine (P ‫؍‬ 0.003). Compared with age controls, patients were more likely to be current smokers (P ‫؍‬ 0.03), to have taken a mean dosage >7.5 mg/day of prednisolone (P ‫؍‬ 0.04), and to have been treated with pulsed methylprednisolone (P ‫؍‬ 0.03). In multivariable analysis, only hypertension treatment was an independent risk factor for CVD. Conclusion. We identified significantly increased prevalence of some conventional and lupus-specific risk factors in patients with SLE immediately before a CVD event compared with controls matched for age or disease duration.