Ludwig Erlacher

Analysing cell-free plasma DNA and SLE disease activity.

Eur J Clin Invest 2011; 41 (6): 579–583

Health-related quality of life in patients with osteopenia or osteoporosis with and without fractures in a geriatric rehabilitation department

ZusammenfassungGRUNDLAGEN: Lebensqualität ist ein wichtiger Gesichtpunkt bei Patientinnen und Patienten mit Osteoporose. Ziel der Studie war es, Unterschiede in der Lebensqualität mittels zweier international standardisierter Fragebögen bei Männern und Frauen zu verifizieren, die an einer Osteopenie oder einer Osteoporose mit oder ohne Fraktur erkrankt sind. METHODIK: Bei Patientinnen und Patienten an einer akutgeriatrischen Abteilung wurde mittels einer DXA-Messung (Dual X-ray Energy Absorptiometry) eine Osteopenie oder Osteoporose festgestellt. Die Lebensqualität wurde mittels zweier standardisierter Fragebögen erfasst, einem allgemeinen, dem SF-36 und einem krankheitsspezifischen, dem QUALEFFO 41, entwickelt von der Internationalen Osteoporosis Foundation. Alle Teilnehmerinnen und Teilnehmer haben die Fragebögen komplett ausgefüllt. Das Schmerzempfinden wurde mittels einer VAS (Visual Analogue Scale) quantifiziert. ERGEBNISSE: 173 Frauen und 49 Männer mit einem Durchschnittsalter von 79,3 ± 8,5 Jahren wurden in die Analysen inkludiert. 85 Teilnehmerinnen und Teilnehmer hatten eine Wirbelkörper- oder Schenkelhalsfraktur in der Anamnese. Der QUALEFFO 41 Score betrug 49,8 ± 19,2 bei Patientinnen und Patienten mit einer Osteopenie und war signifikant höher (58,1 ± 13,3) bei Personen mit einer Osteoporose ohne einer Fraktur (p < 0,05). Bei Patientinnen und Patienten mit Osteoporose und einer Fraktur lag der durchschnittliche Wert bei 63,8 ± 13,6 und war damit signifikant höher (p < 0,05) als bei Patienten mit Osteopenie und auch Patienten mit Osteoporose ohne einer Fraktur. Der Mittelwert des Summenscores des SF-36 war bei Personen mit Osteopenie und bei Patientinnen und Patienten mit Osteoporose ohne Fraktur annähernd gleich (314 ± 117 und 312 ± 99), jedoch bei Personen mit Osteoporose und Fraktur deutlich niedriger, mit Werten von 276 ± 88 (p < 0,05). Die Auswertung des VAS ergab keine signifikanten Unterschiede in den drei evaluierten Gruppen. SCHLUSSFOLGERUNGEN: Osteoporose hat beträchtlich höhere Auswirkungen auf die Lebensqualität von Patientinnen und Patienten als eine Osteopenie. Die Lebensqualität von Personen mit Osteoporose und Wirbelkörper- oder Schenkelhalsfraktur ist noch deutlicher erniedrigt. Diese großen Unterschiede in der Lebensqualität sollten in der Bewertung und in der Behandlung von Patientinnen und Patienten mit Osteoporose Einfluss nehmen.SummaryBACKGROUND: Health-related quality of life (HRQOL) is an important aspect in the management of patients with osteoporosis. The objective of this study was to estimate differences in HRQOL in women and men with osteopenia and osteoporosis with and without a fracture history and to assess HRQOL with a generic and disease-specific instrument. METHODS: Women and men were recruited from a geriatric rehabilitation department. Osteopenia or osteoporosis was diagnosed by Dual X-Ray Energy Absorptiometry (DXA). HRQOL was evaluated with the generic SF-36 questionnaire and the quality of life questionnaire of the International Osteoporosis Foundation (QUALEFFO-41). All subjects were instructed to complete these questionnaires. The level of pain was documented with a VAS (Visual Analogue Scale). RESULTS: 173 women and 49 men at a mean age of 79.3 ± 8.5 years were enrolled. 85 participants reported a history of vertebral or hip fractures. The QUALEFFO score was 49.8 ± 19.2 in patients with osteopenia, but significantly higher in osteoporotic patients without fractures (mean 58.1 ± 13.3; p < 0.05). In osteoporotic patients with a fracture history the mean QUALEFFO score was significantly higher still, i.e. 63.8 ± 13.6 (p < 0.05). The mean SF-36 summation scores of osteopenic patients and osteoporotic patients without fractures were similar (314 ± 117 and 312 ± 99, respectively). Osteoporotic patients with a fracture history showed lower mean scores (276 ± 88; p < 0.05). VAS scores did not differ significantly. CONCLUSIONS: Osteoporosis has a considerably greater impact on HRQOL than osteopenia. Patients with a history of vertebral or hip fractures have a significantly poorer quality of life. These differences should be taken into account when prioritizing health care management.

A randomized, double-blind, parallel, single-site pilot trial to compare two different starting doses of methotrexate in methotrexate-naïve adult patients with rheumatoid arthritis.

BACKGROUND Methotrexate (MTX) is a cornerstone in the treatment of rheumatoid arthritis. Despite its widespread use, expert opinions differ about the optimal MTX starting dosage to achieve rapid onset of action while averting increased occurrence of adverse effects. Plasma concentrations have not been assessed in previous studies that monitored clinical efficacy. OBJECTIVE This study was performed to compare the pharmacokinetic parameters and clinical response of a standard (15 mg) and an accelerated (25 mg) dosing regimen, each administered orally once a week. METHODS This randomized, controlled, double-blind, parallel, single-site study included 19 MTX-naïve patients older than 18 years with rheumatoid arthritis. Patients participated for 16 weeks. Disease activity was assessed using the Disease Activity Score in 28 joints (DAS-28) as the primary outcome parameter. Plasma MTX concentrations were measured using HPLC at weeks 1, 5, 10, and 16. Tolerability was assessed via routine blood analysis (hematology and clinical chemistry) and a patient questionnaire to monitor adverse events. Reported or observed adverse events were recorded along with information about their severity and causal relationship to the study medication. RESULTS Nineteen white patients (13 women and 6 men; mean age, 56 years; and mean weight, 74 kg) participated. At study entry, mean (SD) DAS-28-4v (erythrocyte sedimentation rate) was 4.73 (1.02). Health Assessment Questionnaire scores were 1.45 (0.85); for C-reactive protein, 11.45 (10.04) mg/dL; for alkaline phosphatase, 73.58 (19.91) U/L; for aspartate aminotransferase, 23.32 (7.13) U/L; and for creatinine, 0.87 (0.22) mg/dL. Although pharmacokinetic parameters such as AUC and C(max) were significantly higher after the accelerated dosing regimen, clinical activity scores (DAS-28) and inflammation parameters (C-reactive protein) did not indicate a significant benefit of an accelerated starting regimen. Considering toxicity, no elevation in liver function enzymes and no decrease in renal function were observed using the accelerated dosing (statistical significance set at P ≤ 0.05). No serious adverse events were noted. All observed adverse events were classified as study related. Overall, adverse events were noted in 58% of patients. Comparison of the two doses revealed that 60% of patients receiving the standard dosing regimen and 56% of patients receiving the accelerated dosing regimen reported adverse events, the most frequent being gastrointestinal. These events were generally self-limiting. CONCLUSIONS Differences in clinical response between these two small selected patient groups who received an initial oral dose of either 15 or 25 mg MTX per week did not reach the level of statistical significance. The overall incidence of adverse effects, all classified as study related, was 58%, with 60% of patients receiving the standard dosage and 56% of patients receiving the accelerated dosing regimen reporting adverse effects. However, because of the small sample size, this study was not powered to detect differences in the incidence of adverse events between the two dosing groups. ClinicalTrials.gov identifier: NCT00695188.

Sleep Quality in Patients with Rheumatoid Arthritis and Associations with Pain, Disability, Disease Duration, and Activity

We aimed to assess the subjective sleep quality in patients with rheumatoid arthritis (RA) and its correlation with disease activity, pain, inflammatory parameters, and functional disability. In a cross-sectional study, patients with confirmed RA diagnosis responded to a questionnaire (consisting of socio-demographic data, the Health Assessment Questionnaire Disability Index, and the Medical Outcome Study Sleep Scale). Disease activity was assessed with the Clinical Disease Activity Index, and pain levels using the visual analogue scale. In addition, inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor alpha) were analyzed. Ninety-five patients were analyzed, predominantly female, with an average age of 50.59 (9.61) years. Fifty-seven percent reported non-optimal sleep duration, where functional disability (92.7% vs. 69.8%; p = 0.006) and higher median pain levels (3.75 (2.3–6.0) vs. 2.5 (2.0–3.5); p = 0.003) were also more prevalent. No differences in sociodemographic variables, disease duration or activity, inflammatory parameters, or use of biological and corticosteroid therapy were observed. The multivariate regression analysis showed that more intense pain was associated with a lower likelihood of optimal sleep (odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.47–0.98, p = 0.038). Patients with RA report a high prevalence of non-optimal sleep, which is linked to pain level. Clinicians need to be aware of this issue and the potential effects on health and functional status.

Work Ability and Employment in Rheumatoid Arthritis: A Cross-Sectional Study on the Role of Muscle Strength and Lower Extremity Function

Objective The aim of the present study was to assess the association between muscle strength, lower extremity function, employment status, and work ability in RA patients. Methods One hundred seropositive RA outpatients of working age were included in this cross-sectional study. Employment status was assessed by interview and work ability by the Work Ability Index-Single Item Scale (WAS). Muscle strength was determined using dynamometer measurement of isometric hand grip and knee extensor strength. Lower extremity function was measured using the short physical performance battery (SPPB). Regression models estimate the association between unemployment, work ability and muscle strength, and lower extremity function, controlling for sociodemographic and disease-related factors. Results Forty-one percent of the RA patients were not gainfully employed, and their median work ability had a good WAS value (7.00 [4.00-7.00]). Patients with better knee extensor strength (OR=1.07, 95% CI [1.02-1.12) and better physical performance (OR=1.71, 95% CI [1.18-2.49]) had a significantly better chance of gainful employment. The odds for hand grip strength remained significant when adjusted for sociodemographic (OR=1.5, 95% CI [1.00-1.09]), but not for disease-specific variables. Better hand grip strength (β=0.25, p=0.039) and better knee extensor strength (β=0.45, p=0.001) as well as better lower extremity function (SPPB) (β=0.51, p<0.001) remained significantly associated with work ability following adjustment for sociodemographic and disease-specific variables. Conclusions The association of employment status and work ability with parameters of physical fitness suggests that improvement in muscle strength and lower extremity function may positively influence work ability and employment in individuals with RA.

Short-chain methotrexate polyglutamate MTXPG2 as outcome parameter in rheumatoid arthritis

Background Due to its positive benefit-risk-ratio, methotrexate (MTX) is a first-line therapy in the treatment of rheumatoid arthritis (RA). Although MTX is very effective, the large interpatient variability in drug response is a major drawback in clinical practice. Erythrocyte methotrexate polyglutamates (MTXPG1–7) — intracellular storage products of methotrexate — are supposed to correlate with clinical efficacy. In particular, long-chain polyglutamates (MTXPG4–5) are strongly retained in the cells and are therefore discussed to be potential markers for clinical response in rheumatoid arthritis. We hypothesized that concentrations of methotrexate polyglutamates could correlate with clinical response parameters in rheumatoid arthritis.