Adherence to treatment guidelines for cancer-associated thrombosis: a French hospital-based cohort study.

PURPOSE: French 2008 treatment guidelines recommend low-molecular-weight heparins (LMWH) for the treatment of cancer-associated thrombosis (CAT) with treatment duration of at least 3 months and up to 6 months and beyond if cancer remains active. Our aim was to assess adherence to guidelines in hospital clinical practice. METHODS: The French hospital database (PMSI) was used to identify patients with CAT admitted to three hospitals of the Paris region to be included in a retrospective cohort study. Adherence to guidelines was assessed in patients included from different treatment periods following the venous thromboembolism (VTE) episode i.e. first 10 days (T1), day 10 to 3 months (T2), months 3 to 6 (T3) and beyond 6 months (T4) when applicable. RESULTS: A total of 240 patients with CAT were included from January 2012 to December 2012 of whom 204 were analyzable. Treatment was adherent to guidelines in 55, 31 and 34 % of patients in T1, T2 and T3 treatment periods, respectively, while overall treatment adherence was found in 52 % of patients. Adherence rates were the highest among patients with pulmonary embolism (PE, 60.5 %), catheter-related thrombosis (62.5 %), class III/IV extended cancer (58.0 %) and metastatic malignancy (60.3 %) while only 40 % with deep vein thrombosis (DVT) received a treatment consistent with guidelines. CONCLUSION: Adherence to guidelines appears insufficient since only half of patients received an appropriate treatment. Adherence dropped significantly across treatment periods T2 and T3. VTE diagnosis and cancer characteristics influenced the anticoagulant prescription. Management of patients with CAT requires further education and information of health care professionals.

Botulinum toxin A for treating spasticity in adults: costly for French hospitals?

INTRODUCTION: Intramuscular injection of botulinum toxin (BoNTA) is one of the primary treatments for focal spasticity. This treatment is considered costly and the level of reimbursement by health insurance has been decreasing in many countries for several years. The aim of this study was to determine the real cost of treating spasticity with BoNTA and to compare this with the level of reimbursement by the national health insurance in France in 2008 and with a new fee, specific to the injection of BoNTA in ambulatory services. METHOD: A single-center, retrospective study using the 2008 database from a French secondary-care day-hospital unit (treating spasticity in adults with sequelae of stroke, multiple sclerosis or traumatic brain injuries). The level of reimbursement by the French ministry of health for BoNTA treatment for adults with spasticity constituted the "calculated cost" and corresponded to the hospital's "budget". The "real cost" (incurred by the hospital) included the sum of staffing and material costs as well as the number of toxin vials used. The calculated costs for 2009 and 2013 were based on the levels of reimbursement during those years. The difference between real and calculated cost for 2009 and 2013 was estimated considering that the real cost of 2008 was stable. RESULTS: In 2008, 364 patients received BoNTA, resulting in 870 day-hospital admissions. The calculated cost was 459,056€/year and the real cost was 567,438€/year (equivalent to 4.27€/day/patient). The total budget deficit (hospital income minus hospital costs) was 108,383€. The deficit was estimated at 222,892€ in 2009 and 241,188€ in 2013. CONCLUSION: The daily cost of BoNTA treatment for spasticity is reasonable; however, because of the level of reimbursement by the national health insurance in France, the treatment is costly for French hospitals.

[Modalities for the functionning of a Care Center for women at high risk for breast and ovarian cancers: The French experience of Tenon Hospital]. / Modalités de fonctionnement d'un centre de suivi des femmes à haut risque de cancer du sein et de l'ovaire : une expérience à l'hôpital Tenon.

High risk may be defined as either an absolute risk greater than 20 % or a relative risk greater than 4. Concerning breast and ovarian cancer, high risk patients include carriers of a constitutive deleterious mutation of BRCA1 or BRCA2 genes, patients with a significant family history of breast or ovarian cancer, and patients who have been diagnosed a benign breast lesion with a high risk of degeneration, i.e. atypical hyperplasia. Following up such patients relies on specific strategies. A center including a large panel of physicians involved in the various modalities for patients' management (geneticians, radiologists, gynecologists, plastic surgeons, pathologists, endocrinologists, psychologists, medical oncologists) has been created at Tenon Hospital with this purpose. The collaboration of these different specialists with the referent physician of the patient allows for the definition and the implementation of a patient-centered follow-up continuously updated to take into account the different periods of a woman's life, according to best practices recommendations and the evolving state-of-the art.

[Heart arrest caused by CO2 embolism during a laparoscopic cholecystectomy]. / Paro cardíaco por embolia por CO2 en una colecistectomía laparoscópica.

A 41-year-old woman developed a gas embolism while inserting a Veress needle to achieve pneumoperitoneum for laparoscopic cholecystectomy. The embolism led to asystole, which was corrected after advanced cardiopulmonary resuscitation maneuvers, and was followed by sequelae and a prolonged hospital stay. The anesthesiologist should be vigilant during laparoscopic surgery and be ready and able to act in case of major complications.

Paro cardíaco por embolia por CO2 en una colecistectomía laparoscópica / Heart failure due to carbon dioxide embolism during laparoscopic cholecystectomy

Una mujer de 41 años sufrió una embolia gaseosa durante la colocación de la aguja de Veress, para iniciación del neumoperitoneo, en una colecistectomía laparoscópica. La embolia provocó una asistolia que se remontó tras maniobras de reanimación cardiopulmonar avanzada y ocasionó morbilidad y una estancia hospitalaria prolongada. En la cirugía laparoscópica el anestesiólogo debe extender su vigilancia a aspectos técnicos de la cirugía, estar capacitado y en un medio adecuado, para actuar frente a complicaciones mayores (AU)

A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.

Autosomal dominant hypercholesterolemia (ADH), one of the most frequent hereditary disorders, is characterized by an isolated elevation of LDL particles that leads to premature mortality from cardiovascular complications. It is generally assumed that mutations in the LDLR and APOB genes account for ADH. We identified one large French pedigree (HC2) and 12 additional white families with ADH in which we excluded linkage to the LDLR and APOB, implicating a new locus we named "FH3." A LOD score of 3.13 at a recombination fraction of 0 was obtained at markers D1S2892 and D1S2722. We localized the FH3 locus to a 9-cM interval at 1p34.1-p32. We tested four regional markers in another set of 12 ADH families. Positive LOD scores were obtained in three pedigrees, whereas linkage was excluded in the others. Heterogeneity tests indicated linkage to FH3 in approximately 27% of these non-LDLR/non-APOB ADH families and implied a fourth locus. Radiation hybrid mapping located four candidate genes at 1p34.1-p32, outside the critical region, showing no identity with FH3. Our results show that ADH is genetically more heterogeneous than conventionally accepted.

Genotype-phenotype correlations in familial hypertrophic cardiomyopathy. A comparison between mutations in the cardiac protein-C and the beta-myosin heavy chain genes.

BACKGROUND: The gene involved in familial hypertrophic cardiomyopathy on chromosome 11 was recently identified as the cardiac myosin binding protein-C (MyBP-C) gene. The phenotype of two families associated with mutation in this gene is described here and compared to that of five families with mutations in the beta-myosin heavy chain gene. METHODS AND RESULTS: In adults (n = 33) bearing a splice acceptor site mutation in the MyBP-C gene, penetrance of familial hypertrophic cardiomyopathy was incomplete (69%) and ventricular hypertrophy mild. Among 37 clinical, electrocardiographic and echocardiographic parameters analysed, the only difference with the beta-MHC group (n = 35) was a shorter acceleration time of systolic flow in the pulmonary artery (P < 0.05). Sensitivity and specificity of diagnostic criteria were similar for the two genes. Cumulative survival rate for the splice acceptor site mutation (90% at 50 years old) was mid-way between that observed with a malignant (Arg403Leu: 42%) and a benign mutation (Arg403Trp: 100%) in the beta myosin heavy chain gene (P = 0.002). CONCLUSIONS: The detailed phenotype associated with a mutation in the MyBP-C gene was no different from that associated with mutations in the beta myosin heavy chain gene, except for prognosis which appeared more benign. These preliminary results suggest that there is no locus-specific genotype-phenotype correlation for the two genes analysed.

Empirical affected-sib-pair statistics: two simulation strategies.

We compare two simulation procedures used to determine empirical distributions of three affected sib-pair test-statistics in family samples with missing parental marker information. P1 and P2 procedures differ according to whether affected sibs' genotypes are ignored (P1) or accounted for (P2) to generate the unknown parental genotypes. Overall, our results show that P2 procedure performs better than P1, particularly when marker heterozygosity is high (H = 75%) or when marker data from unaffected siblings are available with low marker heterozygosity (H = 50%). These results are similar for all affected sib-pair tests.

[The PROGENE study, the French project of genetic analysis of familial prostatic cancer: recruitment and analysis]. / Etude PROGENE, project français d'analyse génétique du cancer de la prostate familial: recrutement et analyse.

OBJECTIVES: To initiate a genetic linkage study in order to localize one or several predisposition gene(s) for hereditary prostatic cancer (PC), as various epidemiological studies have demonstrated a possible family aggregation in about 25% of cases. A family segregation study [14] has also shown that a genetic predisposition, with autosomal dominant transmission and high penetrance (88% at 85 years) could be responsible for 9% of all PC. METHODS: A national collection of families with at least 2 cases of PC allowed: 1) identification of families with hereditary forms of PC, 2) creation of a constitutional DNA bank after collecting blood samples from subjects belonging to these families, and 3) a simulation study of genetic linkage analysis prior to microsatellite genotyping. RESULTS: From July 1994 to September 1995, we included 67 families (180 cases of PC). Another 45 families are currently being included. 24 of these 67 families (89 PC, 54 survivors) satisfied at least one of the criteria defined in the study by CARTER et al. for hereditary forms of familial PC. Two families were also included as the 3 patients with PC were second degree relatives. A total of 26 families therefore presented a hereditary form, 18 of which (73 PC, 46 survivors) were considered to be informative for a genetic linkage study (lod score = 4 for theta = 0.001 with an 8 allele marker). The constitutional DNA of 271 individuals of these informative families was extracted from circulating cells obtained from blood samples, immortalized lymphocytes, and the genotyping was initiated for 216 microsatellite markers distributed throughout the genome, an average of every 20 cM. CONCLUSION: Although the recruitment allowed us to identify many informative families for an inherited risk of PC, the predictive study suggested a high probability for localization of a predisposition gene by genetic linkage analysis. It would therefore be possible to identify, within the families concerned, the subjects carrying the genetic anomaly and consequently at high-risk of PC. Finally, the demonstration of the locus would allow cloning and identification of the gene (s) involved.