The incidence of recurrent venous thromboembolism after treatment with vitamin K antagonists in relation to time since first event: a meta-analysis

BACKGROUND: After a first episode of venous thromboembolism, patients are treated with vitamin K (phytonadione) antagonists. There are indications that the risk of recurrence after treatment with vitamin K antagonists decreases relative to the time since the first event. The aim of the present meta-analysis is to describe the risk of recurrent venous thromboembolism after treatment with vitamin K antagonist in relation to the time since the index event. METHODS: Computerized searches in MEDLINE and EMBASE databases; reference checks of pertinent articles; personal communication with colleagues to find randomized clinical trials and cohort studies in which patients with venous thromboembolism were treated with vitamin K antagonists. Per treatment arm, 2 reviewers independently extracted data on the number of recurrent events and the duration of follow-up per time period of 3 months. RESULTS: A total of 135 potentially eligible studies were identified. Of these, 18 studies could be included, comprising 25 treatment arms that could be analyzed. Treatment arms were divided into 3 groups based on treatment duration (short, medium, and long). For all 3 groups, the monthly incidence immediately after discontinuation of treatment was high and declined rapidly thereafter. The monthly incidence after 9 months seemed independent of the treatment duration. CONCLUSIONS: There is a diminishing risk of recurrent venous thromboembolism over time and a stabilization after 9 months independent of the duration of the initial treatment with vitamin K antagonists. These findings have important implications for decision making about the optimal duration of treatment with vitamin K antagonists.     

Plasma long-chain polyunsaturated fatty acids and neurodevelopment through the first 12 months of life in phenylketonuria

The aims of the study were to examine the relationship between long-chain polyunsaturated fatty acid (LCPUFA) status at diagnosis of phenylketonuria (PKU) and neurodevelopment through the first 12 months of life, and to assess whether any difference exists between infants breastfed and bottlefed in the first days of life on the basis of LCPUFA status. Twenty infants with PKU were prospectively examined through the first year of life. Plasma fatty acids were measured in infants at diagnosis. Plasma phenylalanine levels were determined monthly. Main outcome measures were the Bayley Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at 5 and 12 months of age, and the visual function at 12 months, evaluated by P100 wave latencies with visual evoked potentials. A higher PDI score was associated with higher plasma arachidonic acid at diagnosis (adjusted correlation coefficient of PDI at 5 months, r=0.38, p=0.05). P100 wave latency at 15 minutes of arc (15') was associated with the early plasma arachidonic acid (adjusted r=-0.56, p=0.02) and phenylalanine levels at 12 months (adjusted r=0.22, p=0.05). No association was found between MDI score and any essential fatty acids. Breastfed infants exhibited higher plasma arachidonic acid (mean difference, delta, =3.4%; 95% confidence interval [CI]=1.2-5.6%) and shorter P100 wave latency at 15' (delta=-21 ms, 95%CI=-30 to -12) than bottlefed infants. Within the population of this study, a weak positive association has been found between plasma LCPUFAs at diagnosis (higher in breastfed infants) and neurodevelopmental indices through the first year of life.     

Treatment-seeking inpatient cocaine abusers show hypothalamic dysregulation of both basal prolactin and cortisol secretion

Cocaine causes neuroendocrine aberrations in cocaine abusers with pituitary stress hormone secretion providing a window to the stress system in the brain. Substance abusers and control participants were hormonally profiled for 3 weeks. Abusers showed significant basal elevations in prolactin in week 1 with normalization over the 3 weeks. No differences in prolactin secretion were seen with either thyrotropin-releasing hormone stimulation or L-dopa suppression testing. Basal afternoon cortisol secretion was significantly elevated during weeks 1 and 2 comparing abusers to controls. Elevated afternoon cortisol secretion is a sensitive indicator of central stress activation. These results point to the hypothalamus, not the pituitary gland, as being primarily altered in cocaine withdrawal. The data demonstrate that both the dopamine-prolactin and hypothalamic-pituitary-adrenal (HPA) axes are affected during cocaine cessation. As medications are developed to modulate activation of a dysfunctional stress system, future therapeutic studies of substance abuse, withdrawal, craving and relapse should employ more sophisticated tests of hypothalamic pituitary function, especially the HPA axis, as this information may be a guide in the diagnosis and predict clinical responses.     

Intravascular hemolysis in patients with new-generation prosthetic heart valves: a prospective study

OBJECTIVE: A prospective clinical study was designed to assess the frequency and severity of intravascular hemolysis in patients with new-generation, normally functioning prosthetic heart valves. METHODS: Hemolysis was evaluated in 172 patients with a mechanical prosthesis (53 CarboMedics and 119 Sorin Bicarbon) and in 106 patients with a bioprosthesis (15 St Jude Medical Toronto, 19 Baxter Perimount, and 72 Medtronic Mosaic) in the aortic position, mitral position, or both. Aortic valve replacement was performed in 206 patients, mitral valve replacement in 59 patients, and double valve replacement in 13 patients. The presence of hemolysis was assessed on the basis of the level of serum lactic dehydrogenase and serum haptoglobin and the presence and amount of reticulocytes and schistocytes in the peripheral blood. Severity of intravascular hemolysis was estimated on the basis of serum lactic dehydrogenase. Clinical, echocardiographic, and hematologic evaluations were performed 1, 6, and 12 months after discharge. RESULTS: None of the 278 patients experienced decompensated anemia, whereas at 12 months, mild subclinical hemolysis was identified in 49 patients, 44 (26%) with a mechanical prosthesis and 5 (5%) with a bioprosthesis (P <.001). At multivariate analysis, independent predictors of the presence of subclinical hemolysis were mitral valve replacement (P <.001), use of a mechanical prosthesis (P =.002), and double valve replacement (P =.02). Frequency of hemolysis in patients with stented aortic bioprostheses was 3%, whereas it was absent in those with stentless valves. Among mechanical valve recipients, double versus single valve replacement (P =.04) and mitral versus aortic valve replacement (P =.05) were correlated with the presence of hemolysis; double valve recipients also showed a more severe degree of hemolysis (P =.03). In patients with a Sorin Bicarbon prosthesis, hemolysis was less frequent (22% vs 34%, P =.09) and severe (P <.001) than in those with a CarboMedics prosthesis. CONCLUSIONS: In normally functioning prosthetic heart valves, subclinical hemolysis is a frequent finding. A low incidence of hemolysis is found in stented biologic prostheses, and it is absent in stentless aortic valves. Modifications of valve design may contribute to minimize the occurrence of hemolysis in mechanical prostheses.     

Changes in bone mineral density, lean body mass and fat content as measured by dual energy x-ray absorptiometry in patients with prostate cancer without apparent bone metastases given androgen deprivation therapy

PURPOSE: We characterize the consequences of androgen deprivation therapy on body composition in elderly men. MATERIALS AND METHODS: Using a dual energy x-ray absorptiometry instrument, we determined the changes in bone mineral density, bone mineral content, fat body mass and lean body mass in 35 patients with prostate cancer without bone metastases who received luteinizing hormone releasing hormone analogue for 12 months. RESULTS: At baseline conditions 46% of cases were classified as osteopenic and 14% as osteoporotic at the lumbar spine and 40% were osteopenic and 4% osteoporotic at the hip. Androgen deprivation significantly decreased bone mineral density either at the lumbar spine (mean gm./cm.2 [SD] 1.00 [0.194], 0.986 [0.172] and 0.977 [0.182] at baseline, and 6 and 12 months, respectively, p <0.002) or the hip (0.929 [0.136], 0.926 [0.144] and 0.923 [0.138], p <0.03). A more than 2% decrease in bone mineral density was found at the lumbar spine in 19 men (54.3%) and at the hip in 15 (42.9%). Bone mineral content paralleled the bone mineral density pattern. Lean body mass decreased (mean gm. [SD] 50,287 [6,656], 49,296 [6,554] and 49,327 [6,345], p <0.003), whereas fat body mass consistently increased (18,115 [6,209], 20,724 [6,029] and 21,604 [5,923] p <0.001). CONCLUSIONS: Serial bone densitometry evaluation during androgen deprivation therapy may allow the detection of patients with prostate cancer at risk for osteoporotic fractures, that is those with osteopenia or osteoporosis at baseline and fast bone loss. The change in body composition may predispose patients to accidental falls, thus increasing the risk of bone fracture.     

Glomerular cell replication and cell loss through apoptosis in experimental diabetes mellitus

AIM: To evaluate changes in the glomerular cell balance between replication and apoptosis in experimental diabetes mellitus (DM) in relation to morphometric data. METHODS: Adult Sprague-Dowley rats with streptozotocin-induced DM and controls of the same age and strain were sacrificed 4 and 8 weeks and 6 months after disease onset. Cell replication was demonstrated with MIB-5, and apoptosis with the terminal uridine nick end labeling technique. Glomerular size and glomerular cell population were estimated morphologically. RESULTS: Diabetic and control rats showed irrelevant MIB-5 positivity at all time points. Glomerular apoptosis was minimal in rats with 4 and 8 weeks of DM and in controls. Rats with 6 months of DM showed significantly higher glomerular apoptosis values than controls (2.49 +/- 0.25 vs. 0.65 +/- 0.16%; p < 0.001). The mean cell count per glomerular profile was significantly lower in these diabetic rats (64.02 +/- 1.93 vs. 78.27 +/- 0.99; p < 0.001), a change that correlated with that in apoptosis. The glomerular cell density was further decreased in diabetic rats because of the diabetic increase in mean glomerular volume (1.598 vs. 0.927 10(6) microm). CONCLUSIONS: Apoptosis is associated with loss of glomerular cells in rats with long-term, streptozotocin-induced DM and - to a considerably lower degree - in controls of the same age and strain. These changes could be relevant to glomerulosclerosis associated with long-term, streptozotocin-induced DM.