Is progestin an independent risk factor for incident venous thromboembolism? A population-based case-control study

Introduction

Because the risk of venous thromboembolism (VTE) associated with progestin is uncertain, we tested oral contraceptives, estrogen and progestin as independent VTE risk factors.

Materials and Methods

Using longitudinal, population-based Rochester Epidemiology Project resources, we identified all Olmsted County, MN women with objectively-diagnosed incident VTE over the 13-year period, 1988-2000 (n = 726) and one to two Olmsted County women per case matched on age, event year and duration of prior medical history (n = 830), and reviewed their complete medical history in the community for previously-identified VTE risk factors (i.e., hospitalization with or without surgery, nursing home confinement, trauma/fracture, leg paresis, active cancer, varicose veins and pregnancy/postpartum), and oral contraceptive, oral estrogen, and oral or injectable progestin exposure. Using conditional logistic regression we tested these hormone exposures as VTE risk factors, both unadjusted and after adjusting for previously-identified VTE risk factors.

Results

In unadjusted models, oral contraceptives, progestin alone, and estrogen plus progestin were significantly associated with VTE. Individually adjusting for body mass index (BMI) and previously-identified VTE risk factors, these effects remained essentially unchanged except that progestin alone was not associated with VTE after adjusting for active cancer. Considering only case-control pairs without active cancer, progestin alone was positively but non-significantly associated with VTE (OR = 2.49; p = 0.16). Adjusting for BMI and previously-identified VTE risk factors including active cancer, oral contraceptives, estrogen alone, and progestin with or without estrogen were significantly associated with VTE.

Conclusions

Oral contraceptives, estrogen alone, estrogen plus progestin, and progestin with or without estrogen are independent VTE risk factors.     

In vivo quantification of monoamine oxidase A in baboon brain: a PET study using [11C]befloxatone and the multi-injection approach

[¹¹C]befloxatone is a high-affinity, reversible, and selective radioligand for the in vivo visualization of the monoamine oxidase A (MAO-A) binding sites using positron emission tomography (PET). The multi-injection approach was used to study in baboons the interactions between the MAO-A binding sites and [¹¹C]befloxatone. The model included four compartments and seven parameters. The arterial plasma concentration, corrected for metabolites, was used as input function. The experimental protocol—three injections of labeled and/or unlabeled befloxatone—allowed the evaluation of all the model parameters from a single PET experiment. In particular, the brain regional concentrations of the MAO-A binding sites (B′_max) and the apparent in vivo befloxatone affinity (K_d) were estimated in vivo for the first time. A high binding site density was found in almost all the brain structures (170±39 and 194±26 pmol/mL in the frontal cortex and striata, respectively, n=5). The cerebellum presented the lowest binding site density (66±13 pmol/mL). Apparent affinity was found to be similar in all structures (K_dV_R=6.4±1.5 nmol/L). This study is the first PET-based estimation of the B_max of an enzyme.     

Coronary sinus blood flow at rest and during isometric exercise in patients with aortic valve disease: Mechanism of angina pectoris in presence of normal coronary arteries

In 46 patients with aortic valve disease, coronary sinus blood flow was measured using a continuous thermodilution method both at rest and during isometric handgrip excercise. All patients had normal coronary angiograms. The patients were separated into three groups: Group I, 12 patients with aortic stenosis (systolic gradient 72 ± 12 mm Hg); Group II, 15 patients with both aortic stenosis and regurgitation; Group III, 19 patients with aortic regurgitation. At rest, the coronary sinus blood flow was two to three times normal. However, when corrected for left ventricular mass (ml/100 g), flow was within normal limits. The ratio diastolic pressure-time index/systolic pressure-time index ($\text{DPTI}\text{SPTI}$) was decreased in all three groups at rest. During isometric exercise, coronary sinus blood flow increased significantly: by 60 percent in Group I, by 88 percent in Group II and by 118 percent in Group III. There was a significant reduction of the $\text{DPTI}\text{SPTI}$ ratio.Of the 18 patients with angina on effort during the test, 7 were in Group I, 6 in Group II and 5 in Group III. There were no differences in the coronary sinus blood flow between the patients with angina and those who were pain-free, either at rest or during exercise. Angina pectoris does not appear to be caused by a failure of coronary blood flow to increase. There was no discrepancy between myocardial demand, as measured by the pressure-time index and coronary blood flow. However, the $\text{DPTI}\text{SPTI}$ ratio was significantly lower during exercise in the patients with angina than in those who were pain-free. Underperfusion of the subendocardial muscle seems to be a causative factor in the patients with angina.     

Diffusion tensor imaging can localize the epileptogenic zone in nonlesional extra-temporal refractory epilepsies when [(18)F]FDG-PET is not contributive

Surgical outcome in patients with nonlesional refractory partial epilepsies could be improved by a more precise definition of the epileptogenic zone (EZ). The value of interictal FDG-PET hypometabolism, voxel-based-morphometry (VBM) and diffusion tensor imaging (DTI) is still debated. We compared the sensitivity and specificity of these noninvasive techniques in localizing the EZ with stereo-electroencephalography (SEEG) results. Twenty patients with nonlesional partial epilepsy (13 temporal lobe epilepsy (TLE) and 7 extra-temporal (extra-TLE)) underwent structural MRI, DTI and FDG-PET. FDG-PET was analyzed visually (vPET) blinded and unblinded and by statistical parametric mapping (SPM) (sPET). Individual modifications of grey matter volume and mean diffusivity increase were compared to a control group with SPM. The best sensitivity was provided by vPET unblinded (75%) and the best specificity (60%) by DTI. The sensitivity of vPET blinded (55%) was lower and those of sPET (40%) and VBM (35%) were still lower. In TLE, vPET analyzed either blinded or unblinded, performed the best and additional use of the other tools improved slightly the sensitivity. For extra-TLE, combining vPET and DTI results increased the number of pertinent abnormalities detected especially for circumscribed changes in frontal lobe epilepsy (FLE). Combining vPET and DTI was the more efficient strategy for extra-TLE, allowing the detection of pertinent abnormalities in FLE when FDG-PET alone was not contributive. Combining sPET or VBM with vPET was less useful.     

Salivary cortisol profiles in patients remitted from recurrent depression: one-year follow-up of a mindfulness-based cognitive therapy trial

Few studies have examined changes of diurnal cortisol profiles prospectively, in relation to non-pharmacological interventions such as mindfulness-based cognitive therapy (MBCT). Fifty-six patients remitted from recurrent depression (≥3 episodes) were included in an 8-week randomized controlled trial comparing MBCT plus treatment as usual (TAU) with TAU for depression relapse prophylaxis. Saliva samples (0, 15, 30, 45, 60 min post-awakening, 3 PM, 8 PM) were collected on six occasions (pre- and post-intervention, 3-, 6-, 9-, 12-month follow-up). Cortisol awakening response (CAR), average day exposure (AUCday) and diurnal slope were analyzed with mixed effects models (248 profiles, 1-6 per patient). MBCT (n = 28) and TAU groups (n = 28) did not significantly differ with respect to baseline variables. Intra-individual variability exceeded inter-individual variability for the CAR (62.2% vs. 32.5%), AUC(day) (30.9% vs. 23.6%) and diurnal slope (51.0% vs. 34.2%). No time, group and time by group effect was observed for the CAR and diurnal slope. A significant time effect (p = 0.003) was detected for AUCday, which was explained by seasonal variations (p = 0.012). Later wake-up was associated with lower CAR (-11.7% per 1-hour later awakening, p < 0.001) and lower AUCday (-4.5%, p = 0.014). Longer depression history was associated with dampened CAR (-15.2% per 10-year longer illness, p = 0.003) and lower AUCday (-8.8%, p = 0.011). Unchanged cortisol secretion patterns following participation in MBCT should be interpreted with regard to large unexplained variability, similar relapse rates in both groups and study limitations. Further research is needed to address the scar hypothesis of diminished HPA activity with a longer, chronic course of depression.     

The effect of thrombolysis on short-term improvement depends on initial stroke severity

A large number of parameters have been identified as predictors of early outcome in patients with acute ischemic stroke. In the present work we analyzed a wide range of demographic, metabolic, physiological, clinical, laboratory and neuroimaging parameters in a large population of consecutive patients with acute ischemic stroke with the aim of identifying independent predictors of the early clinical course. We used prospectively collected data from the Acute Stroke Registry and Analysis of Lausanne. All consecutive patients with ischemic stroke admitted to our stroke unit and/or intensive care unit between 1 January 2003 and 12 December 2008 within 24 h after last-well time were analyzed. Univariate and multivariate analyses were performed to identify significant associations with the National Institute of Health Stroke Scale (NIHSS) score at admission and 24 h later. We also sought any interactions between the identified predictors. Of the 1,730 consecutive patients with acute ischemic stroke who were included in the analysis, 260 (15.0%) were thrombolyzed (mostly intravenously) within the recommended time window. In multivariate analysis, the NIHSS score at 24 h after admission was associated with the NIHSS score at admission (β = 1, p < 0.001), initial glucose level (β = 0.05, p < 0.002) and thrombolytic intervention (β = −2.91, p < 0.001). There was a significant interaction between thrombolysis and the NIHSS score at admission (p < 0.001), indicating that the short-term effect of thrombolysis decreases with increasing initial stroke severity. Thrombolytic treatment, lower initial glucose level and lower initial stroke severity predict a favorable early clinical course. The short-term effect of thrombolysis appears mainly in minor and moderate strokes, and decreases with increasing initial stroke severity.     

Motor unit number index (MUNIX) versus motor unit number estimation (MUNE): a direct comparison in a longitudinal study of ALS patients

ObjectiveTo evaluate how the motor unit number index (MUNIX) is related to high-density motor unit number estimation (HD-MUNE) in healthy controls and patients with amyotrophic lateral sclerosis (ALS).MethodsBoth MUNIX and HD-MUNE were performed on the thenar muscles in 18 ALS patients and 24 healthy controls. Patients were measured at baseline, within 2 weeks, and after 4 and 8 months. Clinical evaluation included Medical Research Council (MRC) scale and the ALS functional rating scale (ALSFRS).ResultsThere was a significant positive correlation between MUNE and MUNIX values in ALS patients (r = 0.49 at baseline; r = 0.56 at 4 months; r = 0.56 at 8 months, all p < 0.05), but not in healthy controls. After 8 months, both MUNE and MUNIX values of the ALS patients decreased significantly more compared to MRC scale, ALS functional rating scale (ALSFRS) and compound muscle action potential (CMAP) (p < 0.05). There was no significant difference in relative decline of MUNIX and HD-MUNE values.ConclusionsIn ALS patients, MUNIX and HD-MUNE are significantly correlated. MUNIX has an almost equivalent potential in detecting motor neuron loss compared to HD-MUNE.SignificanceMUNIX could serve as a reliable and sensitive marker for monitoring disease progression in ALS.     

Increasingly certain about uncertainty: Intolerance of uncertainty across anxiety and depression

Intolerance of uncertainty (IU) - a dispositional characteristic resulting from negative beliefs about uncertainty and its implications - may be an important construct in anxiety disorders and depression. Despite the potential importance of IU, clinical data on the construct remains relatively scant and focused on generalized anxiety disorder and obsessive-compulsive disorder. The present study systematically investigated IU, as measured by the Intolerance of Uncertainty Scale-12 (IUS-12), across groups diagnosed with anxiety disorders (i.e., social anxiety disorder, panic disorder, generalized anxiety disorder, obsessive-compulsive disorder) or depression (clinical sample: n=376; 61% women), as well as undergraduate (n=428; 76% women) and community samples (n=571; 67% women). Analysis of variance revealed only one statistically significant difference in IUS-12 scores across diagnostic groups in the clinical sample; specifically, people with social anxiety disorder reported higher scores (p<.01; η(2)=.03) than people with panic disorder. People diagnosed with an anxiety disorder or depression reported significantly and substantially higher IUS-12 scores relative to community and undergraduate samples. Furthermore, IUS-12 score distributions were similar across diagnostic groups as demonstrated by Kernel density estimations, with the exception of panic disorder, which may have a relatively flat distribution of IU. Response patterns were invariant across diagnostic groups as demonstrated by multi-group confirmatory factor analyses, but varied between clinical and nonclinical samples. Overall, the findings suggest IU may serve as an important transdiagnostic feature across anxiety disorders and depression. In addition, robust support was found for the proposed 2-factor model of the IUS-12. Comprehensive findings, implications, and future research directions are discussed.     

Impaired recognition of musical emotions and facial expressions following anteromedial temporal lobe excision

We have shown that an anteromedial temporal lobe resection can impair the recognition of scary music in a prior study (Gosselin et al., 2005). In other studies ( [Adolphs et?al., 2001] and [Anderson et?al., 2000] ), similar results have been obtained with fearful facial expressions. These findings suggest that scary music and fearful faces may be processed by common cerebral structures. To assess this possibility, we tested patients with unilateral anteromedial temporal excision and normal controls in two emotional tasks. In the task of identifying musical emotion, stimuli evoked either fear, peacefulness, happiness or sadness. Participants were asked to rate to what extent each stimulus expressed these four emotions on 10-point scales. The task of facial emotion included morphed stimuli whose expression varied from faint to more pronounced and evoked fear, happiness, sadness, surprise, anger or disgust. Participants were requested to select the appropriate label. Most patients were found to be impaired in the recognition of both scary music and fearful faces. Furthermore, the results in both tasks were correlated, suggesting a multimodal representation of fear within the amygdala. However, inspection of individual results showed that recognition of fearful faces can be preserved whereas recognition of scary music can be impaired. Such a dissociation found in two cases suggests that fear recognition in faces and in music does not necessarily involve exactly the same cerebral networks and this hypothesis is discussed in light of the current literature.