Anticonvulsants and suicide attempts in bipolar I disorders.

OBJECTIVE: To identify risk factors for suicide attempts (SA) in individuals commencing treatment for a manic or mixed episode. METHOD: A total of 3390 manic or mixed cases with bipolar disorder (BD) type I recruited from 14 European countries were included in a prospective, 2-year observational study. Poisson regression models were used to identify individual and treatment factors associated with new SA events. Two multivariate models were built, stratified for the presence or absence of prior SA. RESULTS: A total of 302 SA were recorded prospectively; the peak incidence was 0-12 weeks after commencing treatment. In cases with a prior history of SA, risk of SA repetition was associated with younger age of first manic episode (P = 0.03), rapid cycling (P < 0.001), history of alcohol and/or substance use disorder (P < 0.001), number of psychotropic drugs prescribed (P < 0.001) and initiation of an anticonvulsant at study entry (P < 0.001). In cases with no previous SA, the first SA event was associated with rapid cycling (P = 0.02), lifetime history of alcohol use disorder (P = 0.02) and initiation of an anticonvulsant at study entry (P = 0.002). CONCLUSION: The introduction of anticonvulsants for a recent-onset manic or mixed episode may be associated with an increased risk of SA. Further BD studies must determine whether this link is causal.

Using admixture analysis to examine birth-cohort effects on age at onset of bipolar disorder.

OBJECTIVE: It is suggested that age at onset (AAO) of bipolar I disorder (BP-I) is decreasing. We tested for a birth-cohort effect on AAO using admixture analysis. METHOD: A clinical sample of 3896 BP-I cases was analysed using two approaches: (i) in a subsample with untruncated AAO × birth year distribution (n = 1865), we compared the best-fitting model for the observed AAO in patients born ≤1960 and >1960, (ii) to control for potential confounders, two separate subsamples born ≤1960 and >1960 were matched for age at interview (n = 250), and a further admixture analysis was undertaken. RESULTS: The two approaches indicated that the proportion of cases in the early AAO category was significantly greater in cases born >1960; manic onsets were also more frequent in the early onset BP-I cases born >1960. CONCLUSION: The decrease in AAO of BP-I in recent birth-cohorts appears to be associated with an increase in the proportion of cases in the early onset subgroup; not with a decrease in the mean AAO in each putative subgroup. This could indicate temporal changes in exposure to risk factors for mania.

Role of the lean body mass and of pharmacogenetic variants on the pharmacokinetics and pharmacodynamics of sunitinib in cancer patients.

INTRODUCTION: Sunitinib is a multikinase inhibitor active in various cancers types including renal cancers and endocrine tumors. The study analyzed the influence of the lean body mass (LBM) and of pharmacogenetic variants on the exposure to sunitinib and its active metabolite, SU12662, and on sunitinib toxicity and clinical activity. MATERIALS AND METHODS: Exposure to sunitinib and SU12662 was assessed on days 10 and 21 during the first treatment cycle. Acute toxicity was graded using the NCI 4.0 CTCAE ver. 4.0. The LBM and 14 common single nucleotide polymorphisms in the CYP3A4/3A5, NR1I2, NR1I3, ABCB1, and ABCG2 genes were analyzed according to the drug exposure at day 10. Determinants (including sunitinib exposure and pharmacogenetic variants) for toxicities were assessed, as well as the relationship between drug exposure and survival in renal cancer patients. RESULTS: Ninety-two patients (60 % with renal cancer) were assessable for pharmacokinetics, toxicity and survival, and 66 for genetic analysis. The LBM (p < 0.0001) and a polymorphism in the ABCG2 transporter (421C>A) (p = 0.014) were two independent parameters accounting for the variability of composite (sunitinib + SU12662) exposure. Advanced age (OR = 1.47 [1.01-2.15], p = 0.048) and high sunitinib exposure (OR = 1.16 [1.05-1.28], p = 0.005) were independently associated with any grade ≥ 3 acute toxicity, and high SU12662 exposure was associated with grade ≥ 2 thrombocytopenia (OR = 1.27 [1.03-1.57], p = 0.028). A high composite area under the curve (AUC) >1,973 ng/mL∙h at day 21 was associated with a doubled survival (35.2 vs 16.7 months; log-rank p = 0.0051) in renal cancer patients. CONCLUSIONS: This study indicates that LBM and drug monitoring may be helpful in the management of sunitinib-treated patients.

Adapted treatment of Epstein-Barr virus infection to prevent posttransplant lymphoproliferative disorder after heart transplantation.

Up to 35% of posttransplant lymphoproliferative disorder (PTLD) cases occur within 1 year of transplantation, and over 50% are associated with Epstein-Barr virus (EBV). EBV primary infection and reactivation are PTLD predictive factors, but there is no consensus for their treatment. We conducted a prospective single-center study on 299 consecutive heart-transplant patients treated with the same immunosuppressive regimen and monitored by repetitive EBV viral-load measurements and endomyocardial biopsies to detect graft rejection. Immunosuppression was tapered on EBV reactivation with EBV viral loads >10(5) copies/mL or primary infection. In the absence of response at 1 month or a viral load >10(6) copies/mL, patients received one rituximab infusion (375 mg/m(2) ). All patients responded to treatment without increased graft rejection. One primary infection case developed a possible PTLD, which completely responded to diminution of immunosuppression, and one patient, whose EBV load was unevaluable, died of respiratory complications secondary to PTLD. Compared with a historical cohort of 820 patients, PTLD incidence was decreased (p = 0.033) by a per-protocol analysis. This is the largest study on EBV primary infection/reactivation treatment, the first using rituximab following solid organ transplantation to prevent PTLD and the first to demonstrate an acceptable tolerability profile in this setting.

[Evaluation of the impact of a training program on vitamin K antagonists (VKA) implemented by pharmacy students aiming at improving the knowledge of patients receiving vitamin K antagonists during their hospital clinical training course]. / Évaluation de l'impact d'un programme de formation aux antagonistes de la vitamine K (AVK) pour les étudiants en pharmacie sur l'amélioration des connaissances des patients traités par AVK pris en charge au cours de leur stage clinique hospitalier.

INTRODUCTION: We developed a training program for pharmacy students aiming at supporting patients receiving vitamin K antagonists (VKAs). The objective was to estimate how the program impacts VKA-treated patient knowledge acquisition and/or improvement on their anticoagulant treatment. METHOD: Using dedicated tools, pharmacy students received education on VKA treatment. Once appointed to clinical wards of Assistance publique-Hôpitaux de Paris, they were in charge of evaluating patient's knowledge on VKA treatment before and after training. Evaluation was conducted using a face-to-face standardized interview (14-item questionnaire). A global score was calculated for each patient. An univariate and multivariate analysis was performed to identify potential variables influencing score result. RESULTS: One hundred and seventy VKA-treated patients were recruited in seven hospitals for evaluation of their knowledge on VKA treatment and on clinical at risk situations. Before intervention, patients obtained an average score of 12.3±3.2 (maximum: 18). Factors significantly associated with the score were possession of a VKA information booklet, VKA treatment duration, treatment initiation and age. Fifty-two patients with a low score were further trained by the pharmacy student. After intervention, their initial score was improved significantly, from 9.9±3.3 to 13.5±2.3 (P<0.0001). DISCUSSION AND CONCLUSION: Increasing patient knowledge is a way to decrease the rate of adverse effects. This study demonstrates that patients with primary poor knowledge improved it significantly thanks to pharmacy students' intervention. This may contribute to lower the VKA-associated risk of adverse events and consequently to the improvement of patients quality of life and healthcare expenditures.

Influence of genetics and non-genetic factors on acenocoumarol maintenance dose requirement in Moroccan patients.

WHAT IS KNOWN AND OBJECTIVE: Coumarin derivatives such as acenocoumarol represent the therapy of choice for the long-term treatment and prevention of thromboembolic diseases. Many genetic, clinical and demographic factors have been shown to influence the anticoagulant dosage. Our aim was to investigate the contribution of genetic and non-genetic factors to variability in response to acenocoumarol in Moroccan patients. METHODS: Our study included 114 adult Moroccan patients, receiving long-term acenocoumarol therapy for various indications. Tests for VKORC1 -1639G>A promoter polymorphism (rs9923231), CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, and CYP4F2 rs2108622 alleles were undertaken using Taq Man(®) Pre-Developed Assay Reagents for allelic discrimination. The statistical analysis was performed using the SAS V9 statistical package. RESULTS AND DISCUSSION: Genotyping showed that the allele frequencies for the SNPs studied were no different to those found in Caucasians population. A significant association was observed between the weekly maintenance dose and the VKORC1 (P = 0·0027) and CYP2C9 variant genotypes (P = 0·0082). A final multivariate regression model that included the target International Normalized Ratio, VKORC1 and CYP2C9 genotypes explained 36·2% of the overall interindividual variability in acenocoumarol dose requirement. WHAT IS NEW AND CONCLUSION: Our study shows large interindividual variability in acenocoumarol maintenance dose requirement in our population. VKORC1 and CYP2C9 variants significantly affected acenocoumarol dose, in-line with results in other populations. For the Moroccan population, the SNPs that have the largest effect on acecoumarol dose are CYP2C9 rs1799853, CYP2C9 rs1057910 and VKORC1 rs9923231.

[An evaluation of fatigue in patients with glioblastoma relapse treated with the combination of irinotecan-bevacizumab]. / Évaluation de la fatigue dans les glioblastomes en récidive traités par l'association irinotécan-bévacizumab.

OBJECTIVE: The combination of irinotecan-bevacizumab is effective in patients with glioblastoma relapse but fatigue is a commonly reported side effect. The objective of this study was to evaluate the level and evolution of fatigue in a series of patients treated with therapeutic combination. PATIENTS AND METHODS: We used two self-evaluation tools to quantify the physical and emotional aspects of this fatigue. The Norris Visual Analog Scale (VAS Norris) and the Multidimensional Fatigue Inventory-20 (MFI) tools were undertaken by 39 patients with glioblastoma relapse treated with irinotecan-bevacizumab, initially before the first cycle and thereafter with each cycle up until tumor progression. RESULTS: Analysis of the results of the VAS Norris scale did not demonstrate an increase in emotional fatigue but did show an increase in physical fatigue that did not reach statistical significance. With regards to the MFI 20 tool, analysis of the results demonstrated a significant increase in general (P=0.0260) as well as physical (P=0.0141) fatigue but there was no difference in the other indices. CONCLUSION: This study demonstrated a progressive increase in physical fatigue in patients with glioblastoma relapse treated with irinotecan-bevacizumab. We suspect that this is as a direct consequence of the treatment. There are however other confounding factors: insidious tumour progression not detected on follow-up imaging or delayed side effects of the initial radiotherapy-chemotherapy.

Segmental progression of early untreated Parkinson's disease: a novel approach to clinical rating.

OBJECTIVE: To assess the ability of potentially neuroprotective compounds to slow the progression of Parkinson's disease (PD), sensitive rating scales are needed to detect clinically meaningful effects. The topographical progression of motor signs in early untreated PD was evaluated to complement current clinical ratings and enhance the sensitivity to detect disease progression. METHODS: 12 patients referred for diagnostic evaluation of untreated de novo PD underwent detailed clinical assessment of motor parkinsonian signs at baseline and after 6 and 12 months of follow-up using the Unified Parkinson's Disease Rating Scale, motor part (UPDRS-III), and a newly developed approach of detailed segmental rating taking into account the localisation of motor signs in all of the major joints and muscle groups in the body. The progression of PD, as measured with the UPDRS-III, was compared with the segmental ratings. RESULTS: UPDRS-III scores and segmental ratings for rigidity and rest and postural tremor, but not bradykinesia, progressed significantly during the observation period. Progression of normalised segmental ratings for rigidity and tremor was significantly larger than the UPDRS-III ratings over 1 year. The segmental ratings for rigidity and tremor as well as their combination with the UPDRS-III bradykinesia rating were more sensitive a measure for progression of PD than the UPDRS-III. CONCLUSIONS: Taking into account the segmental evolution of parkinsonian signs may be a useful adjunct to UPDRS-III evaluations to measure clinical disease progression of PD. If validated in subsequent larger cohorts, this may be useful in trials of neuroprotective agents.

Influence of 4 preservation solutions on ICU stay, graft and patient survival following liver transplantation.

OBJECTIVE: The goal of this study was to evaluate the prognostic role of four preservation solutions in liver transplantation (LT). PATIENTS AND METHODS: This is a retrospective study originating from 22 French centers performing LT, registered in the prospective databank of the Cristal Biomedicine Agency between 2008 and 2013. The preservation solutions used were Celsior (CS), Institut Georges Lopez (IGL)-1, Solution de Conservation des Organes et des Tissus (SCOT) 15 and University of Wisconsin (UW) solutions. Exclusion criteria were preservation with unknown or inhomogeneous solutions, or Histidine-tryptophan-ketoglutarate (HTK) solution (representing only 3% of LT). Patient survival was the main endpoint. Secondary endpoints were graft survival and duration of stay in intensive care. RESULTS: Of 6347 LT performed, 4928 were included in this study, for which the distribution of preservation solution was CS (30%), IGL-1 (44%), SCOT 15 (10%) and UW (16%). Patient survival was 86%, 80% and 74% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.78). Graft survival was 82%, 75% and 69% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.80). Duration of intensive care was different according to the solution used in univariate analysis (P<0.001), but this effect disappeared in multivariate analysis when the center performing the transplantation was accounted for. CONCLUSION: The type of preservation solution used (CS, IGL-1, SCOT 15 or UW) did not have any influence on patient or graft survival after LT.

Leptin a new biological marker for evaluating malnutrition in elderly patients.

BACKGROUND: There is no single universally accepted biochemical marker of nutritional status in the elderly. Many markers are affected by non-nutritional factors. OBJECTIVE: The purpose of this study was to determine the biological parameters best related to anthropometric markers of malnutrition in an elderly polypathological population, and determine cutoff values for these potential parameters to diagnose malnutrition. DESIGN: This prospective study enrolled 116 elderly hospitalized patients and 76 elderly outpatients. Nutritional status (albumin, transthyretin, body mass index (BMI), skinfold thickness) and biological parameters (leptin, insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1), IGFBP-3, C-reactive protein (CRP), orosomucoid) were assessed. We defined malnutrition according to the lowest quartile of BMI and skinfold thickness measured in a large healthy elderly French sample population. RESULTS: In this sample of elderly patients (age: 85+/-7 years old), leptin concentration was the only biological parameter significantly related to nutrition status. Independent correlations were found between leptin concentration and BMI, skinfold thickness and sex. The relationship between nutritional status and leptin concentration is significantly different in each sex: the more the patients are undernourished, the lower the leptin concentration in both sexes. The optimal leptin cutoff value for the diagnosis of malnutrition in this population was 4 microg/l in men (sensitivity 0.89, specificity 0.82) and 6.48 microg/l in women (sensitivity 0.90, specificity 0.83). CONCLUSION: Leptin concentration is highly correlated with anthropometric data whereas albumin or transthyretin are known to be also influenced by morbidity and inflammatory conditions. Serum leptin concentration could be used for nutritional assessment in elderly patients with acute diseases.

Impact of graft preservation solutions for liver transplantation on early cytokine release and postoperative organ dysfunctions. A pilot study.

INTRODUCTION: During liver transplantation, graft ischemia-reperfusion injury leads to a systemic inflammatory response producing postoperative organ dysfunctions. The aim of this observational and prospective study was to compare the impact of Solution de conservation des organes et tissus (SCOT) 15 and University of Wisconsin (UW) preservation solutions on early cytokine release, postreperfusion syndrome and postoperative organ dysfunctions. METHODS: Thirty-seven liver transplantations were included: 21 in UW Group and 16 in SCOT 15 group. Five cytokines were measured in systemic blood after anesthetic induction, 30minutes after unclamping portal vein and on postoperative day 1. RESULTS: Following unclamping portal vein, cytokines were released in systemic circulation. Systemic cytokine concentrations were higher in UW than in SCOT 15 group: Interleukin-10, Interleukine-6. In SCOT 15 group, significant reduction of postreperfusion syndrome incidence and acute kidney injury were observed. Alanine and aspartate aminotransferase peak concentrations were higher in SCOT 15 group than in UW group. However, from postoperative day 1 to day 10, aminotransferase returned to normal values and did not differ between groups. CONCLUSIONS: Compared to UW, SCOT 15 decreases systemic cytokine release resulting from graft ischemia-reperfusion injury and reduces incidence of postreperfusion syndrome and postoperative renal failure.

[Annuloplasty reduces the mitral leaflets mobility]. / L'annuloplastie réduit la mobilité des deux feuillets mitraux.

The posterior mitral leaflet is usually motionless following mitral valve repair. The aim of this study was to assess (1) the geometric changes of the left ventricular base following prosthetic ring annuloplasty and (2) their impact on the anterior mitral leaflet (AML) mobility. Thirty five patients operated upon for mitral valve repair underwent an intraoperative transesophageal echographic study before and after annuloplasty. A posterior leaflet resection was achieved in 29 cases and ring annuloplasty alone in 6 cases. No repair technique was performed on the AML. Four parameters were assessed: the anteroposterior mitral annulus diameter, the aortomitral angle, the opening and closure angles of the AML. Annuloplasty resulted in a drastic reduction of the mitral annulus from 36.8 +/- 5.6 mm to 20.9 +/- 3.8 mm (systole, long axis view) (p < 0.0001). The aortomitral angle decreased following annuloplasty from 115.1 +/- 8.3 to 108.0 +/- 9.60 (systole, long axis view) (p < 0.0001). No difference was observed between systolic and diastolic measurments concerning the mitral annulus or the aortomitral angle. The opening angle of the AML remained unchanged whereas the closure angle increased from 17.8 +/- 6.10 to 26.6 +/- 6.70 (long axis view) (p = 0.0001) resulting in a displacement of the coaptation point towards the apex. Consequently, the excursion of the anterior leaflet throughout the cardiac cycle decreased following annuloplasty from 43 +/- 130 to 32.5 +/- 11 (long axis view) (p < 0.0001).

Effects of haemolysis, icterus and lipaemia on coagulation tests as performed on Stago STA-Compact-Max analyser.

INTRODUCTION: Haemolysis, icterus and lipaemia (HIL) may affect haemostasis test results. This may be influenced by the level of interfering substance and the reagents and end-point detection system used. METHODS: We assessed the influence of HIL on prothrombin time, activated partial thromboplastin time and fibrinogen assay using a viscosity-based detection analyser. RESULTS: Spontaneous haemolysis that occurred during sample collection and processing had no effect on PT with either a rabbit tissue factor extract or recombinant human tissue factor reagents. In contrast, addition of mechanically haemolysed cells impacted on PT for the highest haemoglobin concentration. For APTTs determined with STA®-Cephascreen® reagent, there was no significant difference between results in haemolysed and nonhaemolysed samples. For the other two reagents studied, APTTs were statistically significantly shorter in haemolysed samples compared with nonhaemolysed samples. This bias was clinically significant only for STA®-PTT Automate. For all three APTT reagents, the impact of haemolysis was sufficient to impact patient management decisions, and in some samples, the effects of lipaemia and icterus were not clinically significant. CONCLUSION: Overall, our results confirm that PT and fibrinogen were not clinically significantly affected by HIL. The APTTs of some haemolysed samples were falsely normal. Haemolysed samples for APTT determination should be rejected.

Impact of prior use or recent withdrawal of oral antiplatelet agents on acute coronary syndromes.

BACKGROUND: Oral antiplatelet agents (OAAs) can prevent further vascular events in cardiovascular disease. How prior use or recent discontinuation of OAA affects clinical presentation of acute coronary syndromes (ACS) and clinical outcomes (death, myocardial infarction [MI]) is unclear. METHODS AND RESULTS: We studied and followed up for up to 30 days a cohort of 1358 consecutive patients admitted for a suspected ACS; of these, 930 were nonusers, 355 were prior users of OAA, and 73 had recently withdrawn OAA. Nonusers were at lower risk, more frequently presented with ST-elevation MI on admission, and more frequently had Q-wave MI at discharge than prior users (36.6% versus 17.5%, P<0.001; and 47.8% versus 28.2%, P<0.001, respectively). However, there was no difference regarding the incidence of death or MI at 30 days between nonusers and prior users (10.3% versus 12.4%, P=NS). In addition, prior users experienced more major bleeds within 30 days compared with nonusers (3.4% versus 1.4%, respectively; P=0.04). Recent withdrawers were admitted on average 11.9+/-0.8 days after OAA withdrawal. Interruption was primarily a physician decision for scheduled surgery (n=47 of 73). Despite a similar cardiovascular risk profile, recent withdrawers had higher 30-day rates of death or MI (21.9% versus 12.4%, P=0.04) and bleedings (13.7% versus 5.9%, P=0.03) than prior users. After multivariate analysis, OAA withdrawal was found to be an independent predictor of both mortality and bleedings at 30 days. CONCLUSIONS: Among ACS patients, prior users represent a higher-risk population and present more frequently with non-ST-elevation ACS than nonusers. Although patients with a recent interruption of OAA resemble those chronically treated by OAA, they display worse clinical outcomes.

Efficacy of streptokinase, but not tissue-type plasminogen activator, in achieving 90-minute patency after thrombolysis for acute myocardial infarction decreases with time to treatment. PERM Study Group. Prospective Evaluation of Reperfusion Markers.

OBJECTIVES: We sought to examine the relation between time to treatment and 90-min patency rates in patients receiving intravenous streptokinase (SK) or accelerated tissue-type plasminogen activator (t-PA). BACKGROUND: Early patency of the infarct-related artery is a major determinant of survival after thrombolysis for acute myocardial infarction. Some data suggest that time to treatment may influence the efficacy of nonfibrin-specific thrombolytic agents in restoring early patency of the infarct-related vessel. METHODS: We performed a retrospective analysis of a cohort of 481 patients receiving thrombolytic therapy for acute myocardial infarction <6 h after pain onset, all of whom underwent 90-min coronary angiography. Patency of the infarct-related artery was graded by two observers who had no knowledge of the treatment received or the time between pain and therapy. RESULTS: There was no difference in baseline clinical or angiographic characteristics according to the timing or nature of treatment. Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 patency rate after SK correlated negatively with the time between onset of pain and thrombolysis (r = 0.8, p = 0.05), whereas the 90-min patency rate after t-PA appeared stable as a function of time to treatment. When patients were categorized as having received treatment <3 or > or = 3 h after pain onset, the patency rate was similar with t-PA, but significantly higher when SK was administered early rather than late, regardless of whether TIMI flow grades 2 and 3 were pooled (86.9% vs. 59.4%, p = 0.0001) or TIMI flow grade 3 alone was considered to indicate patency (81.7% vs. 53.6%, p = 0.0001). Multivariate logistic regression analysis showed a negative effect of time to treatment on the patency probability for SK (p = 0.0001) but not for t-PA. CONCLUSIONS: The efficacy of streptokinase but not t-PA in restoring early coronary patency after intravenous thrombolysis is markedly lower when patients are treated later after onset of pain.

Can we provide reperfusion therapy to all unselected patients admitted with acute myocardial infarction?

OBJECTIVES: This study sought to assess the maximal rate of acute Thrombolysis in Myocardial Infarction (TIMI) grade 3 patency that can be achieved in unselected patients. BACKGROUND: Early and complete (TIMI grade 3 flow) reperfusion is an important therapeutic goal during acute myocardial infarction. However, thrombolysis, although widely used, is often contraindicated or ineffective. The selective use of primary and rescue percutaneous transluminal coronary angioplasty (PTCA) may increase the number of patients receiving reperfusion therapy. METHODS: A cohort of 500 consecutive unselected patients with acute myocardial infarction were prospectively treated using a patency-oriented scheme: Thrombolysis-eligible patients received thrombolysis (n = 257) and underwent 90-min angiography to detect persistent occlusion for treatment with rescue PTCA. Emergency PTCA (n = 193) was attempted in patients with contraindications to thrombolysis, cardiogenic shock or uncertain diagnosis and in a subset of patients admitted under "ideal conditions." A small group of patients (n = 38) underwent acute angiography without PTCA. Conventional medical therapy was used in 12 patients with contraindications to both thrombolysis and PTCA. RESULTS: Ninety-eight percent of patients received reperfusion therapy (thrombolysis, PTCA or acute angiography), and angiographically proven early TIMI grade 3 patency was achieved in 78%. Among patients with TIMI grade 3 patency, thrombolysis alone was the strategy used in 37%, emergency PTCA in 40% and rescue PTCA after failed thrombolysis in 15%; spontaneous patency occurred in 8%. CONCLUSIONS: Reperfusion therapy can be provided to nearly every patient (98%) with acute myocardial infarction. Rescue and direct PTCA provided effective early reperfusion to patients in whom thrombolysis failed or was excluded.

Percutaneous transluminal angioplasty in severe diabetic foot ischemia: outcomes and prognostic factors.

OBJECTIVES: To evaluate the outcomes of severe ischemic diabetic foot ulcers for which percutaneous transluminal angioplasty (PTA) was considered as the first-line vascular procedure. Factors associated with successful PTA were sought. RESEARCH DESIGN AND METHODS: In 32 consecutive diabetic patients with foot ulcers and severe limb ischemia, PTA was performed if feasible; if not, primary bypass grafting was done when feasible. All patients were followed until healing or for at least one year. Patients with worsening ulcers after PTA underwent bypass grafting. Clinical and angiographic factors influencing outcomes after PTA were sought by univariate and multivariate analysis. RESULTS: PTA was done in 25 of the 32 (78%) patients, and considered clinically successful in 13 (52%). After 1 year, the healing rate was 70% and the limb salvage rate 90%. Successful PTA was significantly associated with a higher post-PTA transcutaneous oxygen pressure (P = 0.03) and presence of at least one patent pedal vessel (P = 0.03) in the univariate analysis; only a patent pedal vessel was significant in the multivariate analysis. CONCLUSION: Primary PTA in diabetic patients with severe ischemic foot ulcers provides similar outcomes to usual results obtained in severe ischemia in absence of diabetes. The presence of one patent pedal vessel on arteriography before PTA is the best prognostic factor.

[Relationship between maintenance dosages of fluindione (Préviscan) and warfarin (Coumadin) for patients 70 years and older]. / Nomogramme d'équivalence entre les posologies de fluindione (Préviscan) et de warfarine (Coumadine) pour des patients de 70 ans et plus.

INTRODUCTION: Switching from fluindione, an indanedione vitamin K antagonist derivative, to warfarin, a coumarin one, or vice versa, requires to know the relationships between dosages of these two molecules. METHODS: We conducted a prospective study in 288 consecutive patients aged 70 years and over, converted from fluindione to warfarin. Patients who were retained for the analysis were those for whom maintenance dosages were obtained for both vitamin K antagonists. RESULTS: Eighty-two patients, mean aged 83 ± 6 years, were analysed. The average daily maintenance dosages were 13.8 ± 6.7 mg (range 5-35) and 3.7 ± 1.7 mg (range 1-8) for fluindione and warfarin, respectively. Using a linear regression model, we built a transition algorithm for the maintenance dosages of warfarin and fluindione. CONCLUSION: This is the first study to propose a conversion algorithm to help prescribers to estimate the maintenance dosage when it is necessary for a patient to switch from fluindione to warfarin or conversely.

Chimerism analysis in peripheral blood using indel quantitative real-time PCR is a useful tool to predict post-transplant relapse in acute leukemia.

Detection of increasing mixed chimerism (IMC) using standard PCR correlates with relapse after allo-SCT for acute leukemias (ALs). Quantitative real-time PCR of insertion/deletion polymorphism (indel qrtPCR) is a much more sensitive method, which can be performed on peripheral blood. We studied the significance of low increases of recipient cells (0.1%) detected by indel qrtPCR in a cohort of 89 transplants. We did not observe relapse among the 32 patients with no IMC. Fifty-seven patients presented a first IMC, which was followed by four different scenarios: a decreasing MC (26 cases, no relapse), a stable MC (1 case, 1 relapse), a second IMC (24 cases, 15 relapse) or no control of chimerism (6 cases, 5 relapses). In multivariate analysis, detection of two successive IMCs was strongly associated with relapse (hazard ratio (HR): 9.4, 95% confidence interval (CI): 3.8-23; P<0.0001). Among the 57 patients who presented at least one IMC, 27 underwent immunomodulation (tapering of immunosuppression or donor lymphocyte injection), leading to a 1-year relapse rate of 15.7% vs 57.6% in the 30 other patients (P=0.0007). Altogether, these results indicate that chimerism analysis using indel qrtPCR in peripheral blood is a useful tool for detection of relapse in patients transplanted for AL.

Parkinson's disease and sleepiness: an integral part of PD.

OBJECTIVE: To investigate the potential causes of excessive daytime sleepiness in patients with PD-poor sleep quality, abnormal sleep-wakefulness control, and treatment with dopaminergic agents. METHODS: The authors performed night-time polysomnography and daytime multiple sleep latency tests in 54 consecutive levodopa-treated patients with PD referred for sleepiness, 27 of whom were also receiving dopaminergic agonists. RESULTS: Sleep latency was 6.3 +/- 0.6 minutes (normal >8 minutes), and the Epworth Sleepiness score was 14.3 +/- 4.1 (normal <10). A narcolepsy-like phenotype (> or = 2 sleep-onset REM periods) was found in 39% of the patients, who were sleepier (4.6 +/- 0.9 minutes) than the other 61% of patients (7.4 +/- 0.7 minutes). Periodic leg movement syndromes were rare (15%, range 16 to 43/h), but obstructive sleep apnea-hypopnea syndromes were frequent (20% of patients had an apnea-hypopnea index >15/h; range 15.1 to 50.0). Severity of sleepiness was weakly correlated with Epworth Sleepiness score (r = -0.34) and daily dose of levodopa (r = 0.30) but not with dopamine-agonist treatment, age, disease duration, parkinsonian motor disability, total sleep time, periodic leg movement, apnea-hypopnea, or arousal indices. CONCLUSIONS: In patients with PD preselected for sleepiness, severity of sleepiness was not dependent on nocturnal sleep abnormalities, motor and cognitive impairment, or antiparkinsonian treatment. The results suggest that sleepiness-sudden onset of sleep-does not result from pharmacotherapy but is related to the pathology of PD.