The presence of cardiovascular disease does not modify the weak impact obesity has on health-related quality of life in patients with hip osteoarthritis in the KHOALA cohort

Objective

In people with hip osteoarthritis (OA), the impact of obesity on health-related quality of life (HRQoL) remains unknown. Also whether cardiovascular conditions can modify the obesity–HRQoL relation has not been explored. We aimed to (1) study the cross-sectional relationship between body mass index (BMI) and HRQoL in symptomatic hip OA patients and determine whether cardiovascular comorbidity modifies this relationship and (2) examine the impact of BMI on the course of HRQoL over time.

Prevalence and distribution of autoimmune diseases in 368 rheumatoid arthritis families

OBJECTIVE: To investigate whether frequency of rheumatoid arthritis (RA) and/or other autoimmune (AI) disorders was increased in RA French Caucasian families among the first- (FDR) and second-degree relatives (SDR), and to test whether the presence of AI disease family history identified a specific RA subset. METHODS: We conducted telephone interviews to obtain histories of AI diseases among the FDR and SDR of 368 RA probands, belonging either to trio or affected sib-pair (ASP) families. All the AI diagnoses were confirmed by the physician of the affected relative. RESULTS: Probands of the ASP families were characterized by older age at RA onset, longer disease duration, and larger family size versus trio families. In the trio families, the prevalence of AI diseases was 6.05% (4.76%-7.57%) in FDR and 2.40% (1.85%-3.06%) in SDR. In ASP families, the prevalence of AI diseases was, respectively, 10.24% (8.68%-11.97%) and 1.79% (1.41%-2.25%). The most frequent AI diseases among relatives were RA, thyroid AI diseases, and vitiligo. In trio families, a proband with a mean age of RA onset < 30 years was associated with AI disease prevalence in the relatives, and male gender was associated with prevalence of RA among the FDR. CONCLUSION: The prevalence of AI diseases is increased, particularly among FDR, in French RA families, and some characteristics of the RA proband seem to be associated with prevalence of AI diseases in families.     

Phrasing of the patient global assessment in the rheumatoid arthritis ACR/EULAR remission criteria: an analysis of 967 patients from two databases of early and established rheumatoid arthritis patients

The ACR/EULAR Boolean remission criteria for rheumatoid arthritis (RA) include a strict cutoff for patient global assessment (PGA, value ≤?1/10). Near-remission corresponds to remission for joint counts and C-reactive protein but with PGA?>?1. The objective was to explore whether the contribution of PGA to remission and near-remission varied according to the wording of the PGA and in relation to disease duration. In patients with early arthritis (N?=?731, French ESPOIR cohort) or established RA (N?=?236 patients from across Europe), frequency of remission versus near-remission was assessed according to the phrasing used for PGA (global health versus disease activity). In 967 patients (mean [standard deviation] age 49.7 [12.7] years, 76.7% women), remission was infrequent: range 12.9–16.7% (according to wording of PGA) in early RA and 6.8–7.2% in established RA. Near-remission was more frequent: 13.0–16.8% in early RA and 13.1–13.6% in established RA. The ratio of remission to near-remission was higher in the early arthritis cohort (0.8–1.3 versus 0.5–0.5 in established RA). Using the disease activity PGA led to more remission and less near-remission than the global health PGA in the early arthritis cohort (12.9 vs 16.7% near-remission, respectively, p?=?0.047) but not in established RA. The proportion of patients who can be classified as remission or near-remission differs in early RA compared to establish RA and depends upon the formulation of the PGA question. PGA referring to disease activity and not global health may be preferred in early disease, if the objective is more alignment with inflammation assessment.     

Succinate-CoA ligase deficiency due to mutations in <Emphasis Type="Italic">SUCLA2</Emphasis> and <Emphasis Type="Italic">SUCLG1</Emphasis>: phenotype and genotype correlations in 71 patients

Background

The encephalomyopathic mtDNA depletion syndrome with methylmalonic aciduria is associated with deficiency of succinate-CoA ligase, caused by mutations in SUCLA2 or SUCLG1. We report here 25 new patients with succinate-CoA ligase deficiency, and review the clinical and molecular findings in these and 46 previously reported patients.

Patients and results

Of the 71 patients, 50 had SUCLA2 mutations and 21 had SUCLG1 mutations. In the newly-reported 20 SUCLA2 patients we found 16 different mutations, of which nine were novel: two large gene deletions, a 1 bp duplication, two 1 bp deletions, a 3 bp insertion, a nonsense mutation and two missense mutations. In the newly-reported SUCLG1 patients, five missense mutations were identified, of which two were novel. The median onset of symptoms was two months for patients with SUCLA2 mutations and at birth for SUCLG1 patients. Median survival was 20 years for SUCLA2 and 20 months for SUCLG1. Notable clinical differences between the two groups were hepatopathy, found in 38 % of SUCLG1 cases but not in SUCLA2 cases, and hypertrophic cardiomyopathy which was not reported in SUCLA2 patients, but documented in 14 % of cases with SUCLG1 mutations. Long survival, to age 20 years or older, was reported in 12 % of SUCLA2 and in 10 % of SUCLG1 patients. The most frequent abnormality on neuroimaging was basal ganglia involvement, found in 69 % of SUCLA2 and 80 % of SUCLG1 patients. Analysis of respiratory chain enzyme activities in muscle generally showed a combined deficiency of complexes I and IV, but normal histological and biochemical findings in muscle did not preclude a diagnosis of succinate-CoA ligase deficiency. In five patients, the urinary excretion of methylmalonic acid was only marginally elevated, whereas elevated plasma methylmalonic acid was consistently found.

Conclusions

To our knowledge, this is the largest study of patients with SUCLA2 and SUCLG1 deficiency. The most important findings were a significantly longer survival in patients with SUCLA2 mutations compared to SUCLG1 mutations and a trend towards longer survival in patients with missense mutations compared to loss-of-function mutations. Hypertrophic cardiomyopathy and liver involvement was exclusively found in patients with SUCLG1 mutations, whereas epilepsy was much more frequent in patients with SUCLA2 mutations compared to patients with SUCLG1 mutations. The mutation analysis revealed a number of novel mutations, including a homozygous deletion of the entire SUCLA2 gene, and we found evidence of two founder mutations in the Scandinavian population, in addition to the known SUCLA2 founder mutation in the Faroe Islands.

     

Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes

Background

Regional musculoskeletal pain such as back or shoulder pain are commonly reported symptoms in the community. The extent of consultation to primary care with such problems is unknown as a variety of labels may be used to record such consultations. The objective was to classify musculoskeletal morbidity codes used in routine primary care by body region, and to determine the annual consultation prevalence of regional musculoskeletal problems.

Methods

Musculoskeletal codes within the Read morbidity Code system were identified and grouped by relevant body region by four GPs. Consultations with these codes were then extracted from the recorded consultations at twelve general practices contributing to a general practice consultation database (CiPCA). Annual consultation prevalence per 10,000 registered persons for the year 2006 was determined, stratified by age and gender, for problems in individual regions and for problems affecting multiple regions.

Results

5,908 musculoskeletal codes were grouped into regions. One in seven of all recorded consultations were for a musculoskeletal problem. The back was the most common individual region recorded (591 people consulting per 10,000 registered persons), followed by the knee (324/10,000). In children, the foot was the most common region. Different age and gender trends were apparent across body regions although women generally had higher consultation rates. The annual consultation-based prevalence for problems encompassing more than one region was 556 people consulting per 10,000 registered persons and increased in older people and in females.

Conclusions

There is an extensive and varied regional musculoskeletal workload in primary care. Musculoskeletal problems are a major constituent of general practice. The output from this study can be used as a resource for planning future studies.     

Plasma and liver hepatitis C virus variability in patients coinfected with human immunodeficiency virus

Liver and plasma hepatitis C virus (HCV) variability was compared by E2 cloning and sequencing in three patients coinfected with HCV and human immunodeficiency virus (HIV) before and after interferon treatment and in three patients solely infected with HCV. The plasma and liver samples contained unique sequences. In the patients coinfected with HIV, accumulated random mutations produced mostly nonsynonymous substitutions in contrast to the reduced HCV genetic variability seen after treatment.     

Serum Markers of Liver Fibrosis: Combining the BIPED Classification and the Neo-Epitope Approach in the Development of New Biomarkers

Background: Fibrosis is a central histological feature of chronic liver diseases and is characterized by the accumulation and reorganization of the extracellular matrix. The gold standard for assessment of fibrosis is histological evaluation of a percutaneous liver biopsy. Albeit a considerable effort have been invested in finding alternative non-invasive approaches, these have not been sufficiently succesfull to replace biopsy assessment. Aim: To identify the extracellular matrix proteins of interest, that as protein degradation fragments produced during extracellular matrix metabolism neo-epitopes, may be targeted for novel biochemical marker development in fibrosis. We used the recently proposed BIPED system (Burden of disease, Investigative, Prognostic, Efficacy and Diagnostic) to characterise present serological markers. Methods: Pubmed was search for keywords; Liver fibrosis, neo-epitopes, biomarkers, clinical trail, extra cellular matrix, protease, degradation, fragment. Results and Conclusion: Implementation of BIPED categorization in the development and validation of fibrosis biomarkers to simplify and standardize the use of existing and future biomarkers seems advantageous. In addition, a systematic use of the neo-epitope approach, i.e. the quantification of peptide epitopes generated from enzymatic cleavage of proteins during extracellular remodeling, may prove productive in the quest to find new markers of liver fibrosis.