GLIM criteria-based identification of severe malnutrition and its relationship with the risk of mortality among older Chinese adults with arthritis or rheumatism.

BACKGROUND: Malnutrition is a well-known risk factor for mortality among older adults. Arthritis and rheumatism are characterized by chronic inflammation and are also related to malnutrition as diagnosed using the Global Leadership Initiative on Malnutrition (GLIM) criteria. This study was thus developed to examine the associations linking malnutrition and all-cause death among older adults in China, employing the GLIM criteria to assess malnutrition. METHODS: Two waves of the China Health and Retirement Longitudinal Study from 2013 and 2018 were used to conduct this study. Moderate malnutrition was defined as low BMI (< 18.5 and < 20 for individuals < 70 and 70 + years of age, respectively), an unintended 10-20% decrease in weight, or low muscle mass based on the sex-specific lowest 20% of the height-adjusted muscle mass as < 5.039 kg/m2 in women and < 6.866 kg/m2 in men. Severe malnutrition was defined as a > 20% unintended decrease in weight only or the combination of both low muscle mass and an unintended reduction of over 10% in weight. Associations between malnutrition and the risk of all-cause death were assessed through Cox regression analyses. RESULTS: Overall, this study enrolled 1766 subjects 60 + years of age, of whom 57.36% (1033/1766) were female. Malnutrition was estimated to affect 418 (23.67%) of these individuals at baseline, with 21.06% and 2.60% affected by moderate and severe malnutrition, respectively. Over the 5-year follow-up, 189 of these individuals died. Covariate-adjusted Cox regression analyses confirmed a significant association between severe malnutrition and the risk of death in this cohort (HR = 2.196, 95%CI 1.125-4.286, P = 0.021). CONCLUSIONS: Severe malnutrition, identified through screening based on the GLIM criteria, was associated with an increased risk of all-cause death among older Chinese adults with arthritis or rheumatism.

Differential interplay between multimorbidity patterns and frailty and their mutual mediation effect on mortality in old age.

BACKGROUND: Multimorbidity and frailty often concurrently occur among older adults. OBJECTIVES: To assess the reciprocal association between multimorbidity (condition count and patterns) and frailty and examine the mutual mediation effect of multimorbidity and frailty in their associations with mortality among Chinese older adults. METHODS: This nationwide population-based longitudinal study included 16,563 participants aged ≥65 years in the Chinese Longitudinal Healthy Longevity Survey who were surveyed in 2008 and followed up in 2011, 2014, and 2018. Frailty phenotype was assessed by the modified Fried criteria and vital status was ascertained from family members. Cross-lagged panel model (CLPM) was used to test bidirectional associations between multimorbidity and frailty. The direct and indirect effects of multimorbidity and frailty on mortality were evaluated using the combined CLPM with survival analysis. RESULTS: Three multimorbidity patterns were identified: cardiometabolic diseases, cognitive-sensory disorder, and arthritis-digestive-respiratory diseases. The number of chronic conditions and cognitive-sensory disease pattern showed bidirectional associations with frailty across waves (range for ß: 0.046-0.109; all P < 0.001), while cardiometabolic and arthritis-digestive-respiratory patterns unidirectionally predicted frailty change. Furthermore, frailty mediated 23%-27% of the association between multimorbidity and mortality. Only the number of conditions and cognitive-sensory disease pattern were significant mediators in the association between frailty and mortality, with the proportion of mediation ranging 4%-12%. CONCLUSIONS: Multimorbidity measures including condition count and cognitive-sensory disease pattern are bi-directionally associated with frailty in older adults. These multimorbidity measures and frailty partially mediated each other's association with mortality, with frailty acting as a more prominent pathway in the association between multimorbidity and mortality.

Cleft palate morphology, genetic etiology, and risk of mortality in infants with Robin sequence.

Robin sequence (RS) has many genetic and nongenetic causes, including isolated Robin sequence (iRS), Stickler syndrome (SS), and other syndromes (SyndRS). The purpose of this study was to determine if the presence and type of cleft palate varies between etiologic groups. A secondary endpoint was to determine the relationship of etiologic group, cleft type, and mortality. Retrospective chart review of patients with RS at two high-volume craniofacial centers. 295 patients with RS identified. CP was identified in 97% with iRS, 95% with SS, and 70% of those with SyndRS (p < .0001). U-shaped CP was seen in 86% of iRS, 82% with SS, but only 27% with SyndRS (p < .0001). At one institution, 12 children (6%) with RS died, all from the SyndRS group (p < .0001). All died due to medical comorbidities related to their syndrome. Only 25% of children who died had a U-shaped CP. The most common palatal morphology among those who died was an intact palate. U-shaped CP was most strongly associated with iRS and SS, and with a lower risk of mortality. RS with submucous CP, cleft lip and palate or intact palate was strongly suggestive of an underlying genetic syndrome and higher risk of mortality.

Have the 10-year outcomes of patients with early inflammatory arthritis improved in the new millennium compared with the decade before? Results from the Norfolk Arthritis Register.

OBJECTIVE: To compare the 10-year outcome (disease activity, disability, mortality) of two cohorts of patients with inflammatory polyarthritis (IP) recruited 10 years apart. METHODS: Patients with IP were recruited to the Norfolk Arthritis Register from 1990 to 1994 (cohort 1 (C1)) and from 2000 to 2004 (cohort 2 (C2)). Demographic and clinical data were collected at baseline and at years 1, 2, 3, 5, 7 and 10. Longitudinal disease activity (swollen/tender 51 joint counts (SJC51/TJC51)) and disability (Health Assessment Questionnaire (HAQ)) were compared between the cohorts using population-average negative binomial regression and generalised estimating equation analysis, respectively. Risk of 10-year mortality was compared between cohorts using Cox models. Risk of cardiovascular disease (CVD) mortality was compared between cohorts using competing risks analysis. Mortality rate ratios (MRR), adjusted for changes in mortality risk of the general population, were calculated using Poisson regression. RESULTS: In total 1653 patients were recruited (C1=1022, C2=631). Patients in C2 had 17% lower SJC51 than C1 over 10 years (95% CI -23% to -10%), whereas TJC51 and HAQ were comparable. C2 patients had reduced risk of all-cause and CVD mortality compared with C1 (all-cause: HR 0.72, 95% CI 0.56 to 0.95; CVD: subhazard ratio 0.58, 95% CI 0.37 to 0.93). After accounting for changes in mortality risk in the general population, the difference in mortality was non-significant (all-cause: MRR 0.78, 95% CI 0.56 to 1.10; CVD: MRR 0.77, 95% CI 0.48 to 1.24). CONCLUSION: Disease activity significantly improved in the new millennium, whereas disability and mortality were unchanged.

Reduced survival for uncemented compared to cemented total hip arthroplasty after operatively treated acetabular fractures.

BACKGROUND: Post traumatic arthritis and avascular necrosis of the femoral head are common complications after operatively treated acetabular fractures. This may cause severe disabilities for the patient, necessitating a total hip arthroplasty. Even though an arthroplasty may provide good symptomatic relief, the long-term results are more uncertain and no consensus exists according to preferred prosthetic designs. With this cohort study, we aimed to investigate the medium to long term arthroplasty survival and clinical results of total hip arthroplasty after operatively treated acetabular fractures. METHODS: We included 52 patients treated with a secondary total hip arthroplasty at a median of 2.4 (0.1-14.1) years after an operatively treated acetabular fracture. The median age was 54 (11-82) years. Cemented arthroplasty was used for 33 patients, 10 patients had an uncemented arthroplasty and 9 patients received a hybrid arthroplasty. Average follow up was 8.0 (SD 5.0) years. RESULTS: Ten-year revision free arthroplasty survival was 79%. Uncemented arthroplasties had a significantly worse 10-year survival of 57%. Arthroplasties performed at a centre without a pelvic fracture service also had a significantly worse 10-years survival of 51%. Cox regression showed similar results with an 8-fold increase in risk of revision for both uncemented arthroplasties and operations performed at a non-pelvic trauma centre. CONCLUSION: Total hip arthroplasty secondary to an operatively treated acetabular fracture provides good symptomatic relief. These patients are, however, complex cases and are probably best treated at specialist centres with both pelvic trauma surgeons and arthroplasty surgeons proficient in complex revisions present.

Pattern and severity of multimorbidity among patients attending primary care settings in Odisha, India.

Multimorbidity is increasingly the primary concern of healthcare systems globally with substantial implications for patient outcomes and resource cost. A critical knowledge gap exists as to the magnitude of multimorbidity in primary care practice in low and middle income countries with available information limited to prevalence. In India, primary care forms the bulk of the health care delivery being provided through both public (community health center) and private general practice setting. We undertook a study to identify multimorbidity patterns and relate these patterns to severity among primary care attendees in Odisha state of India. A total of 1649 patients attending 40 primary care facilities were interviewed using a structured multimorbidity assessment questionnaire. Multimorbidity patterns (dyad and triad) were identified for 21 chronic conditions, functional limitation was assessed as a proxy measure of severity and the mean severity score for each pattern, was determined after adjusting for age. The leading dyads in younger age group i.e. 18-29 years were acid peptic disease with arthritis/ chronic back ache/tuberculosis /chronic lung disease, while older age groups had more frequent combinations of hypertension + arthritis/ chronic lung disease/vision difficulty, and arthritis + chronic back ache. The triad of acid peptic disease + arthritis + chronic backache was common in men in all age groups. Tuberculosis and lung diseases were associated with significantly higher age-adjusted mean severity score (poorer functional ability). Among men, arthritis, chronic backache, chronic lung disease and vision impairment were observed to have highest severity) whereas women reported higher severity for combinations of hypertension, chronic back ache and arthritis. Given the paucity of studies on multimorbidity patterns in low and middle income countries, future studies should seek to assess the reproducibility of our findings in other populations and settings. Another task is the potential implications of different multimorbidity clusters for designing care protocols, as currently the protocols are disease specific, hardly taking comorbidity into account.

Nursing students' death anxiety and fear towards dementia patients.

OBJECTIVE: This study investigated the relationship between death anxiety (DA) and fear towards patients according to the age and illness of the patient. METHODS: A sample of 94 undergraduate nursing students from an Australian university were presented with a hypothetical patient, who varied by age (29 years or 71 years) and illness (arthritis, cancer or dementia). They then completed measures of DA and fear towards the patient. RESULTS: Older patients with dementia were associated with higher DA compared to all other conditions. Greater fear was associated with patients in the dementia target condition. CONCLUSION: The findings from this study are consistent with terror management theory; specifically, older age and terminal illness are associated with greater DA. Implications are discussed regarding the quality of care provided to older people with dementia.

Atherosclerotic cardiovascular disease in patients with chronic inflammatory joint disorders.

Inflammatory joint disorders (IJD), including rheumatoid arthritis (RA), ankylosing spondylitis (ASp) and psoriatic arthritis (PsA), are prevalent conditions worldwide with a considerable burden on healthcare systems. IJD are associated with increased cardiovascular (CV) disease-related morbidity and mortality. In this review, we present an overview of the literature. Standardised mortality ratios are increased in IJD compared with the general population, that is, RA 1.3-2.3, ASp 1.6-1.9 and PsA 0.8-1.6. This premature mortality is mainly caused by atherosclerotic events. In RA, this CV risk is comparable to that in type 2 diabetes. Traditional CV risk factors are more often present and partially a consequence of changes in physical function related to the underlying IJD. Also, chronic systemic inflammation itself is an independent CV risk factor. Optimal control of disease activity with conventional synthetic, targeted synthetic and biological disease-modifying antirheumatic drugs decreases this excess risk. High-grade inflammation as well as anti-inflammatory treatment alter traditional CV risk factors, such as lipids. In view of the above-mentioned CV burden in patients with IJD, CV risk management is necessary. Presently, this CV risk management is still lacking in usual care. Patients, general practitioners, cardiologists, internists and rheumatologists need to be aware of the substantially increased CV risk in IJD and should make a combined effort to timely initiate CV risk management in accordance with prevailing guidelines together with optimal control of rheumatic disease activity. CV screening and treatment strategies need to be implemented in usual care.

Mortality in American Veterans with the HLA-B27 gene.

OBJECTIVE: To compare survival in American veterans with and without the HLA-B27 (B27) gene. METHODS: Mortality was evaluated in a national cohort of veterans with clinically available B27 test results between October 1, 1999, and December 31, 2011. The primary outcome was the mortality difference between B27-positive and B27-negative veterans, adjusted for age, sex, race, and diagnoses codes for diseases that may have influenced both B27 testing and mortality, including psoriasis, inflammatory bowel disease, spondyloarthritis (SpA), and other types of inflammatory arthritis. The secondary outcomes were the adjusted mortality HR for B27+ and B27- veterans, in subgroups with and without SpA. RESULTS: Among veterans with available B27 test results, 27,652 (84.7%) were B27- and 4978 (15.3%) were B27+. The mean followup time was 4.6 years. Mortality was higher in the B27+ group than in the B27- group (HR 1.15, 95% CI 1.03-1.27). Mortality was also higher in the B27+ subgroups with SpA (HR 1.35, 95% CI 1.06-1.72) and without SpA (HR 1.11, 95% CI 0.99-1.24), but the difference was significant only in the subgroup with SpA. CONCLUSION: B27 positivity was associated with an increased mortality rate in a cohort of veterans clinically selected for B27 testing, after adjustment for SpA. In the subgroup with SpA, the mortality rate was associated with B27 positivity, and in the subgroup without SpA, there was a nonsignificant association between B27+ and mortality.

Early remission is associated with improved survival in patients with inflammatory polyarthritis: results from the Norfolk Arthritis Register.

OBJECTIVES: This study aimed to evaluate whether the early achievement of clinical remission influences overall survival in an inception cohort of patients with inflammatory polyarthritis (IP). METHODS: Consecutive early IP patients, recruited to a primary care based inception cohort from 1990 to 1994 and from 2000 to 2004 were eligible for this study. Remission was defined as absence of clinically detectable joint inflammation on a 51-joint count. In sensitivity analyses, less stringent definitions of remission were used, based on 28-joint counts. Remission was assessed at 1, 2 and 3 years after baseline. All patients were flagged with the national death register. Censoring was set at 1 May 2011. The effect of remission on mortality was analysed using the Cox proportional hazard regression model, and presented as HRs and 95% CIs. RESULTS: A total of 1251 patients were included in the analyses. Having been in remission at least once within the first 3 years of follow-up was associated with a significantly lower risk of death: HR 0.72 (95% CI 0.55 to 0.94). Patients who were in remission 1 year after the baseline assessments and had persistent remission over time had the greatest reduction in mortality risk compared with patients who never achieved remission within the first 3 years of follow-up: HR 0.58 (95% CI 0.37 to 0.91). Remission according to less stringent definitions was associated with progressively lower protective effect. CONCLUSIONS: Early and sustained remission is associated with decreased all-cause mortality in patients with IP. This result supports clinical remission as the target in the management of IP.

N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) and mortality risk in early inflammatory polyarthritis: results from the Norfolk Arthritis Registry (NOAR).

BACKGROUND: We measured N-terminal pro-brain natriuretic peptide (NT-pro-BNP), a marker of cardiac dysfunction, in an inception cohort with early inflammatory polyarthritis (IP) and assessed its association with disease phenotype, cardiovascular disease (CVD), all-cause and CVD related mortality. METHODS: Subjects with early IP were recruited to the Norfolk Arthritis Register from January 2000 to December 2008 and followed up to death or until March 2010 including any data from the national death register. The associations of baseline NT-pro-BNP with IP related factors and CVD were assessed by linear regression. Cox proportional hazards models examined the independent association of baseline NT-pro-BNP with all-cause and CVD mortality. RESULTS: We studied 960 early IP subjects; 163 (17%) had prior CVD. 373 (39%) patients had a baseline NT-pro-BNP levels ≥ 100 pg/ml. NT-pro-BNP was associated with age, female gender, HAQ score, CRP, current smoking, history of hypertension, prior CVD and the presence of carotid plaque. 92 (10%) IP subjects died including 31 (3%) from CVD. In an age and gender adjusted analysis, having a raised NT-pro-BNP level (≥ 100 pg/ml) was associated with both all-cause and CVD mortality (adjusted HR (95% CI) 2.36 (1.42 to 3.94) and 3.40 (1.28 to 9.03), respectively). These findings were robust to adjustment for conventional CVD risk factors and prevalent CVD. CONCLUSIONS: In early IP patients, elevated NT-pro-BNP is related to HAQ and CRP and predicts all-cause and CVD mortality independently of conventional CVD risk factors. Further study is required to identify whether NT-pro-BNP may be clinically useful in targeting intensive interventions to IP patients at greatest risk of CVD.

The fate of acutely inflamed joints with a negative synovial fluid culture.

PURPOSE: The purpose of this study was to evaluate the management and fate of acutely inflamed joints with a negative synovial fluid culture. METHODS: Between January and December 2009, all the patients who presented to our institution with an acutely inflamed joint and were subjected to microbiological assessment of their synovial fluid, were included in the study. Patients with a positive synovial fluid culture, a prosthetic joint replacement in situ and where an aspirate was obtained for a rheumatological diagnosis were excluded. This cohort was then divided into two groups depending on whether a diagnosis could be established through the course of their treatment. Group I included patients in whom a diagnosis could be established and group II included patients in whom a diagnosis could not be established. A thorough review of the patients' medical records and the hospital database was performed. Following this, a database consisting of the patient demographics, clinical features, investigations, treatment and outcome was created. RESULTS: A total of 144 patients met the inclusion criteria (group I: 95, group II: 49). The most commonly affected joint in both the groups was the knee. The average time to presentation was shorter in group II. Clinical findings at presentation were comparable in both groups. However, inflammatory markers were more likely to be raised in group II in comparison with group I. Eighty-two percent of group II required antibiotic treatment compared with 15% of group I. The mean duration of antibiotic treatment in group I was ten days and in group II was 26 days. Mean hospital stay differed significantly between the two groups, with group II being more than twice as long as compared with group I (p=0.001). The rate of mortality was also higher in group II (8.2%, p=0.03). CONCLUSION: Our study shows that patients presenting with an acutely inflamed joint and a negative synovial fluid culture in whom a diagnosis cannot be established during their hospital stay have a longer hospital stay and an increased rate of mortality as compared with patients in whom a diagnosis can be established.

A new perspective on the pharmacoeconomics of colchicine.

BACKGROUND: Gout is a common inflammatory arthritis that affects ∼4% of the US population. Most patients with gout are >50 years of age and have multiple comorbidities. Gout is caused by the deposition of monosodium urate crystals in joints secondary to hyperuricemia. Gout typically presents as an acute painful inflammation (flare) involving one or more joint. Left untreated it can progress into a more chronic polyarthritis. Acute gout flare treatment options include colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroids. The safety and efficacy of colchicine, especially in the presence of comorbidity and potential contraindications, has only recently been systematically investigated. METHODS: Through the use of a systematic computer-based literature analysis, this pharmacoeconomic review evaluated costs, risks, and benefits of Colcrys (colchicine) compared with other treatments for gout in the US. RESULTS: Both colchicine and NSAIDs are historically associated with gastrointestinal (GI) adverse events (AEs). Colchicine has very low risk for AEs, even in patients with GI disorders; whereas, NSAIDS are contraindicated in patients with GI disorders, renal insufficiency, and heart failure. The monthly cost of treating 100 patients with Colcrys was $33,100 compared with $3000 for NSAIDs. However, hospitalization for GI complications (1.8%) and heart failure (1.9%) is common with NSAIDs and can increase the monthly cost of treating 100 patients with NSAIDs to $161,000, considering $15,000-20,000 per day of hospitalization. CONCLUSIONS: Considering high costs associated with treating patients with gout, it seems prudent to choose the treatment with greatest benefit, lowest cost, and least risk. Despite higher cost per dose, colchicine appears to be more cost effective for management of gout flares than NSAIDs.

Prosthetic joint infection: recent developments in diagnosis and management.

Over the past years there has been a significant increase in the number of joint prosthesis replacements worldwide. The most serious complication of joint prosthesis is infection with an incidence of 1.5-2.5% for primary interventions and up to 20% for revision procedures. The mortality rate ranges between 1% and nearly 3%. The economic cost of this complication is up to $50,000 per patient and $250,000 million per year. A major issue in the management of prosthetic joint infection (PJI) is the relative difficulty in making a diagnosis so to cause a significant effect on the prognosis. Goals of the treatment are to eradicate infection, prevent its recurrence and preserve mechanical joint function. In this review we focus on the value of traditional and newer diagnostic tests and we discuss management and preventive strategies. European networks are needed to define the best diagnostic and treatment strategies in order to reduce future challenge posed by PJIs.

Association of a rheumatoid arthritis susceptibility variant at the CCL21 locus with premature mortality in inflammatory polyarthritis patients.

OBJECTIVE: To investigate whether recently identified rheumatoid arthritis (RA) susceptibility loci are also associated with disease severity, specifically all-cause and cardiovascular disease (CVD) mortality, in patients with inflammatory polyarthritis (IP). METHODS: Subjects with recent-onset IP were recruited from the Norfolk Arthritis Register. Seventeen RA susceptibility single-nucleotide polymorphisms (SNPs) were tested using Sequenom MassArray iPLEX chemistry. Vital status was ascertained from central records. The association of SNP allele carriage with mortality risk was assessed using Cox proportional hazards models after adjusting by sex. The mortality risks of those SNP alleles found to be associated were then stratified by baseline anti-citrullinated peptide (anti-CCP) antibody and shared epitope (SE) status. RESULTS: All SNPs were successfully genotyped in 2,324 IP subjects. The presence of 2 copies of the risk allele rs2812378 mapping to the CCL21 gene predicted all-cause mortality (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.04-1.87), whereas risk allele carriage also predicted increased CVD mortality (HR 1.33, 95% CI 1.01-1.75). The highest mortality risks were seen in anti-CCP antibody-positive subjects with 2 copies of the CCL21 risk alleles and 2 copies of the SE (all-cause HR 3.20, 95% CI 1.52-6.72; CVD HR 3.73, 95% CI 1.30-10.72). CONCLUSION: In this large study, we found that carriage of CCL21 risk alleles was associated with premature mortality in IP independently of anti-CCP antibody and SE status. Interestingly, CCL21 expression has been reported in atherosclerotic plaques supporting the thesis that the increased CVD mortality in IP patients may be mediated by shared inflammatory mechanisms.

Risk and indicators of condemnation of male turkey broilers in western France, February-July 2006.

A field study was conducted to estimate the sanitary condemnation proportion in male turkey broiler flocks, to describe the reasons for condemnation and the related macroscopic lesions, and to investigate whether primary production information would predict the risk of condemnation. Male turkey standard broiler flocks (117) were randomly selected in the 13 slaughterhouses located in Western France, from February to July 2006. The flocks were monitored from their arrival at the slaughterhouse until the results of the post mortem sanitary inspection. Information about rearing conditions, health history, catching and loading conditions, transportation to the slaughterhouse and slaughtering was also collected. Sampling design was considered in the calculations and the condemnation proportion was modelled using a negative binomial regression, accounting for clustering within slaughterhouse. The within-flock weighted average condemnation proportion was 1.8% (95% confidence interval, 1.3-2.3%). Emaciation, arthritis-polyarthritis and congestion were the main reported official reasons for condemnation, representing 76% of the condemned carcases. Three variables were significantly associated with increased risk of condemnation: observed locomotor disorders on the farm, high cumulative mortality 2 weeks before slaughter, and clinical signs observed by the Veterinary Services during the ante mortem inspection at the slaughterhouse. The final model explained 35% of the total variation in condemnation risk. Half of this explained variation could be attributed to locomotor disorders observed during rearing. The sensitivity and specificity of the model to predict a high flock condemnation risk were 80% and 74%, respectively, when using an optimum threshold of 0.95% to define high risk. The results of this study suggested that the variables found to be associated with condemnation proportion were markers of increased risk and could be used as indicators. These risk indicators can easily be retrieved from the pre-existing regulatory document transmitted before flock arrival at the slaughterhouse and could be used to screen flocks before slaughter, according to their expected risk of condemnation.

Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases.

OBJECTIVES: Clinical trials of tumour necrosis factor antagonists have raised questions about the potential risk of certain serious adverse events (SAE). To assess the safety of adalimumab in rheumatoid arthritis (RA) over time and across five other immune-mediated inflammatory diseases and to compare adalimumab malignancy and mortality rates with data on the general population. METHODS: This analysis included 19,041 patients exposed to adalimumab in 36 global clinical trials in RA, psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD), psoriasis and juvenile idiopathic arthritis (JIA) to 15 April 2007. Events per 100 patient-years were calculated using SAE reported after the first dose to 70 days after the last dose. Standardised incidence rates were calculated for malignancies using national and state-specific databases. Standardised mortality rates (SMR) were calculated for each disease using data from the World Health Organization. RESULTS: Cumulative rates of SAE of interest in RA have remained stable over time. Rates of SAE of interest for PsA, AS, CD, psoriasis and JIA were similar to or lower than rates for RA. Overall malignancy rates for adalimumab-treated patients were as expected for the general population. SMR across all six diseases indicated that no more deaths occurred with adalimumab than expected in the general population. CONCLUSIONS: Based on 10 years of clinical trial experience across six diseases, this safety report and the established efficacy of adalimumab in these diseases provide the foundation for a better understanding of its benefit-risk profile.

An evaluation of the association between C-reactive protein, the change in C-reactive protein over one year, and all-cause mortality in chronic immune-mediated inflammatory disease managed in UK general practice.

OBJECTIVES: To evaluate the association between systemic inflammation, as measured by CRP, and all-cause mortality. To also evaluate the association between change in CRP status (sub-acute, < or =10 mg/l and acute >10 mg/l) and all-cause mortality. METHODS: A cohort of patients was selected from The Health Improvement Network (THIN) data set of anonymized patient-level data from UK general practice. Patients were selected if they had a diagnosis of RA, psoriasis, AS or PsA. Survival was evaluated using Cox proportional hazards regression models (CPHMs). RESULTS: A total of 11 362 cases had at least one CRP measurement. Analysis grouped by each additional unit increase in log-CRP (range 1-6) across the observed range was associated with a 21% increase in the hazard ratio (HR) of death, after controlling for cardiovascular risk factors (P < 0.001). This observation was consistent in separate analysis of cases with either RA or psoriasis. Repeated CRP observations around 1 yr apart were recorded in 2802 subjects. After controlling for confounding factors, in cases whose CRP changed from sub-acute (< or =10 mg/l) to acute (>10 mg/l), the HR for death increased 2-fold (P < 0.001) relative to cases whose CRP remained sub-acute. In comparison, among those subjects whose CRP was reduced from acute to sub-acute, the HR was virtually identical to those who stayed sub-acute (P = 0.571). CONCLUSIONS: CRP level predicted all-cause mortality after standardization for traditional risk factors, as did change in CRP status from sub-acute to acute observed over 1 yr.