Moderate to Severe Osteoarthritis: What is the Economic Burden for Patients and the Health Care System? Insights from the "PONOS" Study.

OBJECTIVE: To assess the economic burden of moderate to severe osteoarthritis (OA) management for patients and the health care system in Greece. DESIGN: A noninterventional, cross-sectional, prospective, epidemiological analysis of data from the medical records of patients with moderate to severe OA, recruited in a single visit from 9 sites in Greece. Outcomes included health care resource use (direct/indirect costs) associated with this patient population. RESULTS: A total of 164 patients were included in the analysis: mean age was 70.5 years, and the majority of participants were females (78.7%). The presence of comorbidities was reported by 87.2% of patients, with hypertension being the most frequently reported (53.7%). Paracetamol was the most commonly used analgesic treatment (96%), followed by systemic nonsteroidal anti-inflammatory drugs (NSAIDs) (75%) and opioids (50%). The mean overall annual direct costs per patient was estimated at 1,675.3€, with approximately half incurred by the National Health Insurance Fund, whereas the mean overall annual indirect cost (absenteeism of patients and informal caregivers) was estimated at 3,501.4€. Joint replacement (JR) procedures and paid care were the major drivers of annual direct costs in this patient population (4,326.3€ and 9,360.0€, respectively). CONCLUSIONS: This real-world analysis of direct and indirect costs confirmed the substantial economic burden imposed by moderate to severe OA to the health care system and the patients. Our findings emphasize the need for interventions to enhance disease management, to improve patients' health outcomes and reduce the global burden of OA on society.

The impact of moderate to severe osteoarthritis on the physical performance and quality of life: a cross-sectional study in Greek patients (PONOS study).

BACKGROUND: Osteoarthritis (OA) represents a leading cause of disability with limited data available for the Greek patients. OBJECTIVES: To evaluate the impact of moderate to severe symptomatic hip/knee OA under treatment on physical performance and quality of life. METHODS: A non-interventional, cross-sectional, epidemiological study of patients with moderate/severe OA, recruited in a single visit from 9 expert sites in Athens, Greece. Assessments were based on commonly used outcome scales: the Hip disability and Osteoarthritis Outcome Score (HOOS), the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the EuroQol-5-Dimensions 3-levels questionnaire (EQ-5D-3L). RESULTS: One hundred sixty-four patients were included in the analysis. Most of the patients were females (78.7%), with a mean age of 70.5 ± 10.2 years. Comorbidities were reported by 87.2% of patients with hypertension being the most frequently reported (53.7%), followed by dyslipidemia (31.1%), obesity (24.4%) and diabetes mellitus (23.2%). Paracetamol was the most common treatment (96%), followed by NSAIDs (75%), opioids (50%) and locally applied medications (42.7%). Both hip and knee OA patients showed substantial deterioration in health-related quality of life (QoL) and health status as reflected by the HOOS/KOOS (Function in sport and recreation was the most impaired subscale, followed by Hip- or Knee-related QoL). The mean EQ-5D-3L index score was 0.396 ± 0.319 and the mean EQ-VAS score was 52.1 ± 1.9. When compared indirectly to the local population norms our OA population had worse QoL indices. CONCLUSION: Our findings suggest the functional disability and impaired QoL of Greek patients with moderate/severe hip/knee OA under treatment emphasizing the need for novel treatments that will reduce the burden of the disease.

Cardiovascular magnetic resonance detects silent heart disease missed by echocardiography in systemic lupus erythematosus.

Background Accurate diagnosis of cardiovascular involvement in systemic lupus erythematosus (SLE) remains challenging, due to limitations of echocardiography. We hypothesized that cardiovascular magnetic resonance can detect cardiac lesions missed by echocardiography in SLE patients with atypical symptoms. Aim To use cardiovascular magnetic resonance in SLE patients with atypical symptoms and investigate the possibility of silent heart disease, missed by echocardiography. Patients/methods From 2005 to 2015, 80 SLE patients with atypical cardiac symptoms/signs (fatigue, mild shortness of breath, early repolarization and sinus tachycardia) aged 37 ± 6 years (72 women/8 men), with normal echocardiography, were evaluated using a 1.5 T system. Left and right ventricular ejection fractions, T2 ratio (oedema imaging) and late gadolinium enhancement (fibrosis imaging) were assessed. Acute and chronic lesions were defined as late gadolinium enhancement-positive plus T2>2 and T2<2, respectively. Lesions were characterized according to late gadolinium enhancement patterns as: diffuse subendocardial, subepicardial and subendocardial/transmural, due to vasculitis, myocarditis and myocardial infarction, respectively. Results Abnormal cardiovascular magnetic resonance findings were identified in 22/80 (27.5%) of SLE patients with normal echocardiography, including 4/22 with recent silent myocarditis, 5/22 with past myocarditis (subepicardial scar in inferolateral wall), 9/22 with past myocardial infarction (six inferior and three anterior subendocardial infarction) and 4/22 with diffuse subendocardial fibrosis due to vasculitis. No correlation between cardiovascular magnetic resonance findings and inflammatory indices was identified. Conclusions Cardiovascular magnetic resonance in SLE patients with atypical cardiac symptoms/signs and normal echocardiography can assess occult cardiac lesions including myocarditis, myocardial infarction and vasculitis that may influence both rheumatic and cardiac treatment.

Lack of efficacy of etanercept in Sjögren syndrome correlates with failed suppression of tumour necrosis factor alpha and systemic immune activation.

OBJECTIVE: To provide insight into the clinical failure of the tumour necrosis factor alpha (TNFalpha) inhibitor, etanercept, in primary Sjögren syndrome (pSS), an extensive analysis of the systemic immune profile of patients with pSS was carried out and the effect of etanercept treatment on these immune parameters monitored. METHODS: Peripheral blood mononuclear cells of patients with pSS and healthy controls were compared by flow cytometry to determine differences in distribution of specific cell populations (T cells, B cells, monocytes), and to determine their expression of activation markers (CD25, HLA-DR), TNF receptors and chemokine receptors (CXCR1, 2) before and after treatment. Systemic cytokine levels were measured by multiplex ELISA assay in plasma and in lipopolysaccharide-stimulated whole blood from healthy controls and from patients with pSS before and after etanercept treatment. Baseline cytokine levels were correlated with clinical markers of disease. RESULTS: Before treatment, salivary gland inflammatory focus scores did not correlate with circulating TNF levels. Furthermore, consistent with the lack of evidence of significant clinical benefit, enhanced markers of immune activation, frequency of cell subpopulations and aberrant cytokine profiles were not restored to normal levels by etanercept treatment. Remarkably, the levels of circulating TNFalpha were significantly increased after treatment. CONCLUSION: Etanercept is an ineffective therapeutic agent in pSS consistent with the absence of suppression of TNFalpha and other indicators of immune activation in this patient population. These data suggest that TNFalpha may not be a pivotal cytokine in the pathogenesis of pSS, impelling continued molecular characterisation of disease parameters to define appropriate intervention targets.

Ovarian failure in systemic lupus erythematosus patients treated with pulsed intravenous cyclophosphamide.

Pulsed intravenous cyclophosphamide is considered as standard therapy for lupus nephritis and several other severe manifestations of systemic lupus erythematosus (SLE). While the response rate to intravenous cyclophosphamide is substantial, concern has arisen about its toxicity. In addition to increased susceptibility to infection, bone marrow suppression, alopecia, hemorrhagic cystitis and malignancy, ovarian failure is an important side effect associated with the use of cyclophosphamide. Prior research on cyclophosphamide-treated women has consistently demonstrated that the risk of sustained amenorrhea depends on the age of the patient and the cumulative dose received. Sustained amenorrhea is difficult to avoid in women 32 years or older, even with very short intravenous cyclophosphamide courses. Younger women seem to have a substantially lower incidence of ovarian failure, but this side effect may be far more problematic for these patients. In these young women the risk may be modulated by the prior SLE disease duration, the presence of anti-U1RNP antibodies and anti-Ro antibodies. Co-treatment with gonadotropin-releasing hormone agonists may preseserve the future fertility and ovarian function in young women. Ovarian banking before administration of cyclophosphamide should be considered in selected patients.

Evaluation of the association of autoantibodies with mortality in the very elderly: a cohort study.

OBJECTIVE: To evaluate whether autoantibodies in the absence of rheumatic diseases increase the risk of mortality among very elderly subjects who are otherwise in good functional condition. METHODS: Autoantibodies were measured in 1987 in 156 elderly nursing home residents (median age 84 yr) who were followed subsequently over 14.6 yr. RESULTS: Eleven subjects had anticardiolipin antibodies, 30 had rheumatoid factor and 19 had antibodies to single-stranded DNA (ssDNA). Other autoantibodies were more rare. During follow-up, 144 subjects died. Adjusting for age as a time-dependent covariate, the hazard ratio for death was 0.71 [95% confidence interval (CI) 0.38-1.32] for anticardiolipin antibodies, 0.93 (95% CI 0.60-1.41) for rheumatoid factor, 1.08 (95% CI 0.65-1.79) for antibodies to ssDNA, and 0.99 (95% CI, 0.70-1.41) for any autoantibody. Hazard ratios were similar when adjusted also for sex and clinical conditions. CONCLUSION: Our results exclude the possibility that the autoantibodies evaluated increase substantially the risk of death among very elderly subjects in good functional condition.

Risk of myelotoxicity with intravenous cyclophosphamide in patients with systemic lupus erythematosus.

OBJECTIVES: To determine the incidence of serious myelotoxicity from intravenous cyclophosphamide (IC) in systemic lupus erythematosus (SLE). METHODS: In a retrospective study, white blood cell (WBC) counts with differential and platelet counts were determined in 92 SLE patients (96 courses) given 1623 doses of IC. RESULTS: Only one patient developed a total leucocyte count <1000/mm3, one developed a neutrophil count <500/mm3, two had a lymphocyte count <100/mm3 and no patients had platelet counts <50000/mm3 during follow-up. The risk of a neutrophil count <500/mm3 was 0.06 per 100 visits [95% confidence interval (CI) 0.00-0.34]. Two patients discontinued IC due to neutropenia [rate of 0.12 per 100 doses (95% CI 0.01-0.44)]. No clinical consequences were recorded in conjunction with low blood cell counts. In multivariate models, both the cumulative number of IC doses and European Consensus Lupus Activity Measurement (ECLAM) score affected neutrophil and lymphocyte counts adversely. For neutrophils, lowering the ECLAM score by 1 point counteracted four additional doses of IC after adjusting for steroid dose. CONCLUSIONS: IC and SLE disease activity have independent effects in lowering white blood cell counts, but serious myelotoxicity of IC is uncommon.

Carboplatin, methotrexate and 5-fluorouracil in combination with medroxyprogesterone acetate (JMF-M) in the treatment of advanced or recurrent endometrial carcinoma: A Hellenic cooperative oncology group study.

Twenty-three patients with advanced or recurrent endometrial carcinoma entered a prospective study of chemotherapy which consisted of carboplatin (300 mg/m2), methotrexate (30 mg/m2), and 5-fluoruracil (500 mg/m2) given on day 1, in a 3-weekly schedule, in combination with medroxyprogesterone acetate (MPA): 300 mg daily, p. o., until progression (JMF-M regimen). None had received prior chemotherapy and/or hormonotherapy for metastatic disease. Ten patients had received radiotherapy. Response to treatment was evaluated every two courses. Objective response was seen in 17 of the 23 patients (74%, 95% confidence interval = 52-90%), with 2 long-lasting complete responses (9%). The median response duration was 10+ months (3-45+). The median survival was 16+ months (2-45+). The 2 complete responders, the first in the lung and the second in groin nodes, are without evidence or recurrence after 32 and 45 months, respectively. The regimen was given on an outpatient basis and was well tolerated. The major toxic effects were myelosuppression (less than 14% leukopenia, anemia and thrombocytopenia). The MPA-related side effects were: weight gain (22%), hypertension (17%) and thromboplebitis (17%). In 2 patients, consolidation treatment with MPA was discontinued because of thromboplebitis. In conclusion, the JMF-M regimen is highly active with an acceptable toxicity in patients with recurrent or metastatic endometrial carcinoma.