Force Majeure: Therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease

Gaucher disease is the first lysosomal disorder for which clinically effective enzyme replacement therapy has been introduced. Lifelong treatment with imiglucerase, the recombinant glucocerebrosidase manufactured by the Genzyme Corporation (MA, USA), is administered intravenously — usually at biweekly intervals. An acute shortage of imiglucerase (to 20% of prior global supply) has occurred as a result of viral contamination of the production facility; production was halted, and a full supply of imiglucerase is not anticipated until January 2010. An urgent meeting of physicians, researchers, and patients was convened through the agency of the European Working Group for Gaucher Disease; this was instigated by patients internationally represented by the European Gaucher Alliance. Here we present a position statement based on the findings of the group, with key recommendations about identification and monitoring of at-risk patients threatened by the abrupt withdrawal of treatment, the equitable distribution of residual imiglucerase — and access to alternative treatments including those that have completed phase III clinical trials but have not yet been licensed.     

Hunter syndrome in an 11-year old girl on enzyme replacement therapy with idursulfase: brain magnetic resonance imaging features and evolution

Mucopolysaccharidosis type II (MPS-II, Hunter disease) is a X-linked recessive disorder. Affected females are extremely rare, mostly due to skewed X chromosome inactivation. A few papers outline MPS-II brain magnetic resonance imaging (MRI) “gestalt” in males, but neuroradiological reports on females are still lacking. We present an 11-year-old girl affected by the severe form of MPS-II who was followed up over a time span of 8 years, focusing on clinical and brain MRI evolution. In the last 2.5 years, the patient has been treated with enzyme replacement therapy (ERT) with idursulfase (Elaprase?, Shire Human Genetic Therapies AB, Sweden). On brain and cervical MRI examination, abnormalities in our patient did not differ from those detected in male patients: J-shaped pituitary sella, enlargement of perivascular spaces, brain atrophy, mild T2-hyperintensity in the paratrigonal white matter, diffuse platyspondylia, and mild odontoid dysplasia with odontoid cup. Brain atrophy progressed despite ERT introduction, whereas perivascular space enlargement did not change significantly before and after ERT. Cognitive impairment worsened independently from the course of white matter abnormality. Despite a profound knowledge of genetic and biochemical aspects in MPS-II, neuroradiology is still poorly characterized, especially in female patients. Spinal and brain involvement and its natural course and evolution after ERT introduction still need to be clarified.     

Early Results of Endovascular Treatment of the Thoracic Aorta Using the Valiant Endograft

Endovascular repair of the thoracic aorta has been adopted as the first-line therapy for much pathology. Initial results from the early-generation endografts have highlighted the potential of this technique. Newer-generation endografts have now been introduced into clinical practice and careful assessment of their performance should be mandatory. This study describes the initial experience with the Valiant endograft and makes comparisons with similar series documenting previous-generation endografts. Data were retrospectively collected on 180 patients treated with the Valiant endograft at seven European centers between March 2005 and October 2006. The patient cohort consisted of 66 patients with thoracic aneurysms, 22 with thoracoabdominal aneurysms, 19 with an acute aortic syndrome, 52 with aneurysmal degeneration of a chronic dissection, and 21 patients with traumatic aortic transection. The overall 30-day mortality for the series was 7.2%, with a stroke rate of 3.8% and a paraplegia rate of 3.3%. Subgroup analysis demonstrated that mortality differed significantly between different indications; thoracic aneurysms (6.1%), thoracoabdominal aneurysms (27.3%), acute aortic syndrome (10.5%), chronic dissections (1.9%), and acute transections (0%). Adjunctive surgical procedures were required in 63 patients, and 51% of patients had grafts deployed proximal to the left subclavian artery. Comparison with a series of earlier-generation grafts demonstrated a significant increase in complexity of procedure as assessed by graft implantation site, number of grafts and patient comorbidity. The data demonstrate acceptable results for a new-generation endograft in series of patients with diverse thoracic aortic pathology. Comparison of clinical outcomes between different endografts poses considerable challenges due to differing case complexity.     

Development and validation of an enantioselective and chemoselective HPLC method using a Chiralpak IA column to simultaneously quantify (R)-(+)- and (S)-(−)-lansoprazole enantiomers and related impurities

An accurate and reproducible high-performance liquid chromatographic (HPLC) method has been developed and validated for the direct separation of individual enantiomers of lansoprazole, a potent proton pump inhibitor belonging to the family of the substituted benzimidazoles. The enantiomers were resolved on a Chiralpak IA by using a mobile phase consisting of methyl-tert-butyl ether (MtBE)–ethyl acetate (EA)–ethanol (EtOH)–diethylamine (DEA) in the ratio 60:40:5:0.1 (v/v/v/v). Baseline separation of the enantiomers of lansoprazole was obtained with a resolution factor of 8.14. The standard curves for the two enantiomers were linear (r² > 0.999) in the concentration range of 10–80 μg/ml with a working concentration of about 60 μg/ml for each enantiomer. Apparent recovery was 100.8% with a relative standard deviation less than 2%. The limit of quantization for each enantiomer of lansoprazole was 0.22 μg/ml. The intra-day precisions were in the range of 0.21–0.36 and 0.59–0.66 while the inter-day precisions were in the range of 0.55–1.24 and 0.66–1.19% in terms of retention times and area response RSD% for (R)-(+)- and (S)-(−)-lansoprazole, respectively. The method was also able to resolve impurities from the enantiomers of lansoprazole.     

Hemodynamic effects of levobupivacaine after pediatric caudal anesthesia evaluated by transesophageal doppler

Background: The aim of this study is to determine if there are significant differences in hemodynamic effects between combined general‐regional anesthesia using levobupivacaine 0.25% 2 ml·kg^?1 via the caudal route in comparison with balanced general anesthesia using continuous infusion of remifentanil in young children undergoing genitourinary surgery. Patients and methods: 62 ASA I‐II pediatric patients (12 female, 50 male) aged 6 months to 7 years undergoing genitourinary surgery were included in the study. Patients were randomly allocated into one of two groups of 31 patients each. Group Caud received caudal blockade with levobupivacaine 0.25% 2 mg·kg^?1 in combined general‐regional anesthesia and Group Gen received balanced general anesthesia with remifentanil. The noninvasive hemodynamic parameters were measured in each group 5 min after induction of general anesthesia or caudal block (Tcaud), after further 5 min coincident with skin incision (Tsi), 10 min after skin incision (T10i), at the end of surgical procedure (Tend). The time between Tcaud and Tsi was 10 min and the measurements during the interval time T10i‐Tend were performed every 15 min according to the duration of surgical procedures. Results: There was a decrease in all measured hemodynamic parameters at skin incision. The decreases occurred in both groups with those in the caudal group occurring at skin incision and those in the balanced anesthesia group occurring at 10 min after skin incision. These variations showed no significant differences for any of the stated outcomes; neither between the groups at each time point nor in the caudal in comparison with baseline measurements. Conclusions: Using transesophageal Doppler no differences in hemodynamic parameters could be detected between balanced general anesthesia with either caudal levobupivacaine or remifentanil infusion. Both techniques showed good hemodynamic stability with only minor changes from baseline over time which are unlikely to be of clinical significance except possibly in patients with preexisting cardiovascular compromise. Other studies with noninvasive monitoring in a larger population are required to better understand the consequences of caudal blockade on CO and on regional blood flow in infants.     

Soft budget constraints in health care: evidence from Italy

The reforms that have reshaped the public health care systems have often been coupled with devolution. However, this process has frequently been accompanied by widespread soft budget constraint policies. In this paper we argue that the soft budget constraint arises from a cooperative game between local authorities that force Central Government to bail them out. Our theoretical model is tested using data for Italian regions for the period 2002–2006 and our hypothesis is verified. Although the model uses Italy as a benchmark, we believe that the framework we propose could be extended to other federal contexts where resources are distributed unevenly and preferences are asymmetric.     

Prognostic relevance of mitotic activity in patients with node-negative breast cancer.

The prognostic relevance of mitotic activity was analyzed in a series of 306 patients with node-negative breast cancer treated with locoregional therapy alone, until early relapse. Mitotic activity was evaluated as the number of mitotic figures per 10 high-power fields (mitotic activity index) or per 1000 tumor cells (mitotic index). Counting was carried out blindly by two observers. A high correlation was observed between the two determinations (r(s) =.96, P <.001). For clinical analysis, three mitotic activity index subgroups (mitotic figures/field 相似文献   

HIV and metabolic syndrome: a comparison with the general population

OBJECTIVE: To compare the prevalence of metabolic syndrome (MS) in HIV-positive patients with that from a sample of a general Italian population. DESIGN: Cross-sectional study. METHODS: A total of 1263 HIV-infected patients 18 years of age or older were recruited in 18 centers for infectious diseases in northern and central Italy. Controls were 2051 subjects aged 25 to 74 years representative of the residents of Monza, a town in Milan province, who were enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni study. RESULTS: The prevalence of MS in the HIV group was 20.8%, whereas in the control group, it was only 15.8%, with the difference being statistically significant. The age- and gender-adjusted risk of having MS in HIV-infected patients was twice as great as that in controls. Compared with controls, HIV-infected patients had a greater prevalence of the impaired fasting glucose, increased plasma triglycerides, and reduced high-density lipoprotein cholesterol components. MS prevalence was similar in treated and never-treated HIV-infected patients, and so were the various MS components. CONCLUSIONS: The risk of MS is greater in HIV-infected patients compared with the general population because of a greater prevalence of lipid and glucose abnormalities. The prevalence of MS and its components is similar in treated and untreated HIV-positive patients.     

Low Rate of Intrahospital Deep Venous Thrombosis in Acutely Ill Medical Patients: Results From the AURELIO Study

Objective

To evaluate the effect of hospitalization on deep venous thrombosis (DVT) rate by the cumulative incidence of DVT in the proximal venous tract of the lower limbs at admission and discharge.