Validity and reliability of a Dutch version of the Foot and Ankle Ability Measure.

PURPOSE: The aim of the study was to develop a Dutch language version of the Foot and Ankle Ability Measure (FAAM) and evaluate its measurement properties according to the consensus-based standards for the selection of health measurement instruments (COSMIN) definitions. METHODS: A forward-backward translation procedure was performed and subsequently the Dutch version of the FAAM was evaluated for its reliability and validity in 369 patients with a variety of foot and ankle complaints. The reliability was assessed by calculating the intraclass correlation coefficients (ICC, test-retest reliability), Cronbach's alpha (internal consistency), the standard error of measurement and the minimal detectable change (MDC). Additionally, this was done for athletes. The construct validity was assessed by the use of Spearman's correlation coefficient between FAAM domains and similar and contradictory domains of the Foot and Ankle Outcome Score, Short Form 36 and the Numeric Rating Scale for pain. RESULTS: The ICC of the subscales ranged from 0.62 to 0.86. Cronbach's alpha's minimum was 0.97. At individual level, the MDC ranged from 23.9 to 44.7 and at group level from 2.77 to 4.32. In the subgroup of athletes, the reliability was higher. The hypothesized correlations of the construct validity were supported by an 80% confirmation rate. CONCLUSION: The Dutch version of the FAAM met adequate measurement properties, although the reliability is not optimal. The FAAM-Sport subscale is more useful in athletes and the FAAM-Sport % seems not to contribute. In athletes with various foot and ankle symptoms, the FAAM can be used for functional assessment and follow-up at group level. For the general population, the FAAM is less appropriate. LEVEL OF EVIDENCE: Diagnostic study, Level I.

Lamin A/C mutation is independently associated with an increased risk of arterial and venous thromboembolic complications.

BACKGROUND: Lamin A/C (LMNA) mutation carriers suffer from a variety of clinical phenotypes, including dilated cardiomyopathy (DCM). Although it has been suggested that carriers are at risk for thromboembolic complications, it is unknown whether this risk is higher than can be expected from the underlying cardiac abnormalities. The purpose of this study was to determine whether a LMNA mutation is associated with an increased risk of thromboembolic complications. METHODS: We compared a cohort of 76 LMNA mutation carriers with a cohort of 224 idiopathic DCM patients without a LMNA mutation, with respect to the prevalence of arterial and venous thromboembolic complications. Furthermore, we carried out a case-control study to explore whether a prothrombotic phenotype was present in LMNA mutation carriers without DCM or atrial tachyarrhythmias (n=14) and compared this with mutation negative relatives (n=13). RESULTS: The prevalence of thromboembolic complications was higher in the cohort of LMNA mutation carriers than in DCM patients (22 vs 11%; p<0.05), after respectively mean follow-up of 42 ± 12 and 49 ± 12 years. After adjustment for possible confounders, including atrial tachyarrhythmias and left ventricular ejection fraction, LMNA mutation carriership was independently associated with an increased risk of thromboembolic complications (HR 4.8, 95% CI: 2.2-10.6). The results of the case-control study suggested a prothrombotic phenotype in LMNA mutation carriers, as reflected by an altered platelet function and increased thrombin generation. CONCLUSIONS: LMNA mutation is independently associated with an increased risk of arterial and venous thromboembolic complications. Laboratory research in LMNA mutation carriers without severe cardiac abnormalities suggests a prothrombotic phenotype.

Mental quality of life is related to a cytokine genetic pathway.

BACKGROUND: Quality of life (QoL) in patients with chronic disease is impaired and cannot be solely explained by disease severity. We explored whether genetic variability and activity contributes to QoL in patients with Marfan syndrome (MFS), a genetic connective tissue disorder. METHODOLOGY/PRINCIPAL FINDINGS: In 121 MFS patients, patient characteristics (i.e. demographics and MFS-related symptoms) were assessed. Patients completed the SF-36 to measure QoL. In addition, transcriptome wide gene expression and 484 Single Nucleotide Polymorphysms (SNPs) in cytokine genes were available. QoL was first analyzed and associated with patient characteristics. Patients' physical QoL was impaired and weakly related with age and scoliosis, whereas mental quality of life (MCS) was normal. To explain a largely lacking correlation between disease severity and QoL, we related genome wide gene expression to QoL. Patients with lower MCS scores had high expression levels of CXCL9 and CXCL11 cytokine-related genes (p=0.001; p=0.002); similarly, patients with low vitality scores had high expression levels of CXCL9, CXCL11 and IFNA6 cytokine-related genes (p=0.02; p=0.02; p=0.04), independent of patient characteristics. Subsequently, we associated cytokine related SNPs to mental QoL (MCS and vitality). SNP-cluster in the IL4R gene showed a weak association with MCS and vitality (strongest association p=0.0017). Although overall mental QoL was normal, >10% of patients had low scores for MCS and vitality. Post-hoc analysis of systemic inflammatory mediators showed that patients with lowest MCS and vitality scores had high levels of CCL11 cytokine (p=0.03; p=0.04). CONCLUSIONS/SIGNIFICANCE: Variation in the cytokine genetic pathway and its activation is related to mental QoL. These findings might allow us to identify and, ultimately, treat patients susceptible to poor QoL.