Sulodexide in Patients with Chronic Venous Disease of the Lower Limbs: Clinical Efficacy and Impact on Quality of Life

Introduction

Chronic venous disease (CVD) of the lower limbs is a common problem. It is more prevalent in women than in men and has a significant impact on patients’ quality of life (QoL) and on the healthcare system. The aim of this study was to evaluate the efficacy of sulodexide in adult patients with CVD of the lower limbs and its effect on patients’ QoL.

Methods

Patients with CVD were treated with sulodexide [250 LSU (lipasemic units) twice daily] for 3 months in a setting of real-life clinical practice. The endpoints of this observational non-comparative, open-label prospective study were the clinical efficacy of sulodexide (evaluated by scoring objective and subjective symptoms with a Likert-type scale) and the impact of sulodexide therapy on patients’ QoL [assessed using the chronic venous insufficiency quality of life questionnaire (CIVIQ)].

Results

The study included 450 patients (mean age 46.9 ± 10.5 years, range 17–78 years). A greater percentage of patients were female (65.4%). Three months of treatment with sulodexide significantly improved all objective and subjective symptoms (p < 0.0001). Overall, patients reported a significant improvement in all QoL scores (p < 0.0001). Adverse events were spontaneously reported by two patients (one case of epigastric pain and one of gastric pain with vomiting).

Conclusion

Oral sulodexide significantly improves both objective and subjective symptoms, as well as functional and psychological aspects of QoL in patients with CVD.

Funding

No funding or sponsorship was received for this study. Sponsorship for article processing charges and open access fees was provided by Alfa Wassermann.

     

Association of autoantibodies to heat‐shock protein 60 with arterial vascular events in patients with antiphospholipid antibodies

Objective

Anti–heat shock protein 60 autoantibodies (anti‐Hsp60) are associated with cardiovascular disease and are known to affect endothelial cells in vitro, and we have recently shown that anti‐Hsp60 promote thrombosis in a murine model of arterial injury. Based on those findings, we undertook the present study to investigate the hypothesis that the presence of anti‐Hsp60, alone or in combination with other thrombogenic risk factors, is associated with an elevated risk of vascular events.

Methods

The study population was derived from 3 ongoing cohort studies: 2 independent systemic lupus erythematosus (SLE) registries and 1 cohort comprising SLE patients and non‐SLE patients. Data from a total of 402 participants were captured; 199 of these participants had had confirmed vascular events (arterial vascular events in 102, venous vascular events in 76, and both arterial and venous vascular events in 21). Anti‐Hsp60 were detected by enzyme‐linked immunoassay, and association with vascular events was assessed by regression analysis.

Results

Multiple regression analysis revealed that arterial vascular events were associated with male sex, age, and hypertension. Analyses of the vascular events according to their origin showed an association of anti‐Hsp60 with arterial vascular events (odds ratio 2.26 [95% confidence interval 1.13–4.52]), but not with venous vascular events. Anti‐Hsp60 increased the risk of arterial vascular events (odds ratio 5.54 [95% confidence interval 1.89–16.25]) in antiphospholipid antibody (aPL)–positive, but not aPL‐negative, individuals.

Conclusion

We demonstrate that anti‐Hsp60 are associated with an increased risk of arterial vascular events, but not venous vascular events, in aPL‐positive individuals. These data suggest that anti‐Hsp60 may serve as a useful biomarker to distinguish risk of arterial and venous vascular events in patients with aPL.

     

Tumour-like lesions of the infrapatellar fat pad

Three different tumour-like lesions within the infrapatellar fat pad, an osteochondroma, a localised pigmented villonodular synovitis and a synovial cyst are reported. The osteochondroma and the pigmented villonodular synovitis were treated by marginal excision, and the synovial cyst was resected using arthroscopy.     

Modeling stroke management: a qualitative review of cost-effectiveness analyses

Objective

To review recent economic analyses and determine if means of improving methodology used in modeling stroke management may exist.

Study design and setting

The Medline database was searched for pharmacoeconomic models of treatments or interventions in acute, non-transitory ischemic stroke. Search terms were: stroke, cost, cost-effectiveness, cost analysis, stroke management, model, modeling, and economic. All English-language articles published from January 1997 to January 2008 were reviewed.

Results

Ten Markov models and three decision analytical models were identified. All models had a societal perspective and all but one had lifetime horizons. They were all based on common patient states of disability, mortality and recurrence of stroke. Inputs used in the models were transparent and valid. Intracranial hemorrhage, cardiovascular events and data closely related to local settings were not systematically considered. One-way sensitivity analyses were the most common, but few parameters were tested and these varied between models. Consensus key drivers were therefore difficult to determine.

Conclusion

The overall structure of the models reviewed was sound. However, they should include more systematically cardiovascular events and intracranial hemorrhage, as well as local epidemiological data. Further multi-way sensitivity analyses would help to identify key cost drivers with greater precision and robustness.     

Synthesis and biologic studies of iodinated (I/I) ethidium

An iodinated (¹²⁵I/¹²⁷I) ethidium derivative (3,8-diamino-5-[6′-(p-iodobenzoylamino)-4′-azahexyl]-6-phenylphenanthridinium chloride hydrochloride) was synthesized and characterized. The labeling yield of the ¹²⁵I-labeled derivative was 75% for carrier-free ¹²⁵I, with a radiochemical purity of 95%. The incubation of iodoethidium with calf thymus DNA resulted in a substantial enhancement of fluorescence yield, indicating the intercalation of this compound into DNA. In the presence of iodoethidium, the nuclei of methanol-treated mammalian cells fluoresced, while those of viable cells did not (since the plasma membrane is impermeable to iodoethidium). When viable cells were incubated with the reduced form of the derivative, ¹²⁵I/¹²⁷I-dihydroethidium traversed the plasma membrane, was oxidized in the cytoplasm, and intercalated into nuclear DNA. Finally, we tested the hypothesis that larger malignant solid tumors, containing a relatively greater percentage of degenerating permeable cells, can be targeted with ¹²⁵I-ethidium. In-vivo studies demonstrated a small but positive correlation (R = 0.72) between tumor volume and the uptake of the derivative. Because of the ubiquitous presence of abnormal permeable cells and necrosis in tumors, our results support the belief that radiolabeled DNA-intercalating or DNA-binding molecules may be of diagnostic and therapeutic value for a variety of solid tumors in humans.     

Therapeutic radionuclides: biophysical and radiobiologic principles

Although the general radiobiologic principles underlying external beam therapy and radionuclide therapy are the same, there are significant differences in the biophysical and radiobiologic effects between the 2 types of radiation. In addition to the emission of particulate radiation, targeted radionuclide therapy is characterized by (1) extended exposures and, usually, declining dose rates; (2) nonuniformities in the distribution of radioactivity and, thus, absorbed dose; and (3) particles of varying ionization density and, hence, quality. This review explores the special features that distinguish the biologic effects consequent to the traversal of charged particles through mammalian cells. It also highlights what has been learned when these radionuclides and radiotargeting pharmaceuticals are used to treat cancers.     

Approach to term neonates born after maternal intrapartum fever and unknown maternal group B Streptococcus status: value of serum C-reactive protein and 16S rRNA gene PCR amplification

Thirty-six term neonates born after maternal intrapartum fever, with premature rupture of membranes <18 hours and unknown maternal group B Streptococcus status had blood samples for complete blood count, C-reactive protein, culture, and 16S rRNA gene polymerase chain reaction amplification. Only 2 neonates were symptomatic and none had leukopenia, C-reactive protein >1.0 mg/dL, bacteremia, or positive polymerase chain reaction.