Research on post-traumatic stress disorder (PTSD) course finds a substantial proportion of cases remit within 6 months, a majority within 2 years, and a substantial minority persists for many years. ...Results are inconsistent about pre-trauma predictors.
The WHO World Mental Health surveys assessed lifetime DSM-IV PTSD presence-course after one randomly-selected trauma, allowing retrospective estimates of PTSD duration. Prior traumas, childhood adversities (CAs), and other lifetime DSM-IV mental disorders were examined as predictors using discrete-time person-month survival analysis among the 1575 respondents with lifetime PTSD.
20%, 27%, and 50% of cases recovered within 3, 6, and 24 months and 77% within 10 years (the longest duration allowing stable estimates). Time-related recall bias was found largely for recoveries after 24 months. Recovery was weakly related to most trauma types other than very low odds-ratio (OR) 0.2-0.3 early-recovery (within 24 months) associated with purposefully injuring/torturing/killing and witnessing atrocities and very low later-recovery (25+ months) associated with being kidnapped. The significant ORs for prior traumas, CAs, and mental disorders were generally inconsistent between early- and later-recovery models. Cross-validated versions of final models nonetheless discriminated significantly between the 50% of respondents with highest and lowest predicted probabilities of both early-recovery (66-55% v. 43%) and later-recovery (75-68% v. 39%).
We found PTSD recovery trajectories similar to those in previous studies. The weak associations of pre-trauma factors with recovery, also consistent with previous studies, presumably are due to stronger influences of post-trauma factors.
Aims To develop and validate a non-invasive method for measuring myocardial iron in order to allow diagnosis and treatment before overt cardiomyopathy and failure develops. Methods and Results We ...have developed a new magnetic resonance T2-star (T2*) technique for the measurement of tissue iron, with validation to chemical estimation of iron in patients undergoing liver biopsy. To assess the clinical value of this technique, we subsequently correlated myocardial iron measured by this T2* technique with ventricular function in 106 patients with thalassaemia major. There was a significant, curvilinear, inverse correlation between iron concentration by biopsy and liver T2* (r=0·93,P <0·0001). Inter-study cardiac reproducibility was 5·0%. As myocardial iron increased, there was a progressive decline in ejection fraction (r=0·61, P<0·001). All patients with ventricular dysfunction had a myocardial T2* of <20ms. There was no significant correlation between myocardial T2* and the conventional parameters of iron status, serum ferritin and liver iron. Multivariate analysis of clinical parameters to predict the requirement for cardiac medication identified myocardial T2* as the most significant variable (odds ratio 0·79,P <0·002). Conclusions Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment. Myocardial iron content cannot be predicted from serum ferritin or liver iron, and conventional assessments of cardiac function can only detect those with advanced disease. Early intensification of iron chelation therapy, guided by this technique, should reduce mortality from this reversible cardiomyopathy.
Pregnancy outcomes following in utero exposure to antiepileptic drugs (AEDs) are uncertain, limiting an evidenced-based approach.
To determine if fetal outcomes vary as a function of different in ...utero AED exposures.
This ongoing prospective observational study across 25 epilepsy centers in the USA and UK enrolled pregnant women with epilepsy from October 1999 to February 2004 to determine if differential long-term cognitive and behavioral neurodevelopmental effects exist across the four most commonly used AEDs. This initial report focuses on the incidence of serious adverse outcomes including major congenital malformations (which could be attributable to AEDs) or fetal death. A total of 333 mother/child pairs were analyzed for monotherapy exposures: carbamazepine (n = 110), lamotrigine (n = 98), phenytoin (n = 56), and valproate (n = 69).
Response frequencies of pregnancies resulting in serious adverse outcomes for each AED were as follows: carbamazepine 8.2%, lamotrigine 1.0%, phenytoin 10.7%, and valproate 20.3%. Distribution of serious adverse outcomes differed significantly across AEDs and was not explained by factors other than in utero AED exposure. Valproate exhibited a dose-dependent effect.
More adverse outcomes were observed in pregnancies with in utero valproate exposure vs the other antiepileptic drugs (AEDs). These results combined with several recent studies provide strong evidence that valproate poses the highest risk to the fetus. For women who fail other AEDs and require valproate, the dose should be limited if possible.
To assess progesterone treatment of intractable seizures in women with partial epilepsy.
This randomized, double-blind, placebo-controlled, phase III, multicenter, clinical trial compared the ...efficacy and safety of adjunctive cyclic natural progesterone therapy vs placebo treatment of intractable seizures in 294 subjects randomized 2:1 to progesterone or placebo, stratified by catamenial and noncatamenial status. It compared treatments on proportions of ≥50% responders and changes in seizure frequency from 3 baseline to 3 treated menstrual cycles.
There was no significant difference in proportions of responders between progesterone and placebo in the catamenial and noncatamenial strata. Prespecified secondary analysis showed that the level of perimenstrual seizure exacerbation (C1 level) was a significant predictor of responders for progesterone but not placebo. With increasing C1 levels, responders increased from 21% to 57% with progesterone vs 19% to 20% with placebo. Reductions in seizure frequency correlated with increasing C1 levels for progesterone but not placebo, progressing from 26% to 71% for progesterone vs 25% to 26% for placebo. A prespecified clinically important separation between progesterone and placebo responders (37.8% vs 11.1%; p = 0.037) was realized among 21.4% of women who had C1 level ≥3.
There was no difference in the primary outcome of ≥50% responder rates between progesterone vs placebo for catamenial or noncatamenial groups. Post hoc findings suggest that the level of perimenstrual seizure exacerbation is a significant predictor of responder rate with progesterone and that progesterone may provide clinically important benefit for a subset of women with perimenstrually exacerbated seizures.
This study provides Class III evidence that cyclic progesterone is ineffective in women with intractable partial epilepsy. Post hoc analysis identified a subset of women with higher levels of perimenstrual seizure exacerbation that were responsive to treatment.
Aims To prospectively compare the agreement of left ventricular volumes and ejection fraction by M-mode echocardiography (echo), 2D echo, radionuclide ventriculography and cardiovascular magnetic ...resonance performed in patients with chronic stable heart failure. It is important to know whether the results of each technique are interchangable, and thereby how the results of large studies in heart failure utilizing one technique can be applied using another. Some studies have compared cardiovascular magnetic resonance with echo or radionuclude ventriculography but few contain patients with heart failure and none have compared these techniques with the current fast breath-hold acquisition cardiovascular magnetic resonance. Methods and Results Fifty two patients with chronic stable heart failure taking part in the CHRISTMAS Study, underwent M-mode echo, 2D echo, radionuclude ventriculography and cardiovascular magnetic resonance within 4 weeks. The scans were analysed independently in blinded fashion by a single investigator at three core laboratories. Of the echocardiograms, 86% had sufficient image quality to obtain left ventricular ejection fraction by M-mode method, but only 69% by 2D Simpson's biplane analysis. All 52 patients tolerated the radionuclude ventriculography and cardiovascular magnetic resonance, and all these scans were analysable. The mean left ventricular ejection fraction by M-mode cube method was 39±16% and 29±15% by Teichholz M-mode method. The mean left ventricular ejection fraction by 2D echo Simpson's biplane was 31±10%, by radionuclude ventriculography was 24±9% and by cardiovascular magnetic resonance was 30±11. All the mean left ventricular ejection fractions by each technique were significantly different from all other techniques (P<0·001), except for cardiovascular magnetic resonance ejection fraction and 2D echo ejection fraction by Simpson's rule (P=0·23). The Bland–Altman limits of agreement encompassing four standard deviations was widest for both cardiovascular magnetic resonance vs cube M-mode echo and cardiovascular magnetic resonance vs Teichholz M-mode echo at 66% each, and was 58% for radionuclude ventriculography vs cube M-mode echo, 44% for cardiovascular magnetic resonance vs Simpson's 2D echo, 39% for radionuclide ventriculography vs Simpson's 2D echo, and smallest at 31% for cardiovascular magnetic resonance–radionuclide ventriculography. Similarly, the end-diastolic volume and end-systolic volume by 2D echo and cardiovascular magnetic resonance revealed wide limits of agreement (52ml to 216ml and 11ml to 188ml, respectively). Conclusion These results suggest that ejection fraction measurements by various techniques are not interchangeable. The conclusions and recommendations of research studies in heart failure should therefore be interpreted in the context of locally available techniques. In addition, there are very wide variances in volumes and ejection fraction between techniques, which are most marked in comparisons using echocardiography. This suggests that cardiovascular magnetic resonance is the preferred technique for volume and ejection fraction estimation in heart failure patients, because of its 3D approach for non-symmetric ventricles and superior image quality.
Objective: To investigate the role of cardiovascular magnetic resonance (CMR) in a series of patients with ECG repolarisation changes and normal echocardiography. Patients and design: 10 patients ...with anterolateral T wave inversion for which there was no obvious pathological cause who had normal routine echocardiography without contrast for the exclusion of hypertrophic cardiomyopathy (HCM) also had CMR that was diagnostic of apical HCM. Results: Apical HCM detected by CMR could be morphologically severe with wall thickness up to 28 mm, or mild. The extent of repolarisation abnormalities did not correlate to the morphological severity. Conclusions: In patients with unexplained repolarisation abnormalities, a normal routine echocardiogram without contrast does not exclude apical HCM. Further imaging with CMR or contrast echocardiography may be required. The reliance on routine echocardiography to exclude apical HCM may have led to underreporting of this condition.
Epigenetics links perinatal influences with later obesity. We identifed differentially methylated CpG (dmCpG) loci measured at 17 years associated with concurrent adiposity measures and examined ...whether these were associated with hsCRP, adipokines, and early life environmental factors. Genome-wide DNA methylation from 1192 Raine Study participants at 17 years, identified 29 dmCpGs (Bonferroni corrected p < 1.06E-07) associated with body mass index (BMI), 10 with waist circumference (WC) and 9 with subcutaneous fat thickness. DmCpGs within Ras Association (RalGDS/AF-6), Pleckstrin Homology Domains 1 (RAPH1), Musashi RNA-Binding Protein 2 (MSI2), and solute carrier family 25 member 10 (SLC25A10) are associated with both BMI and WC. Validation by pyrosequencing confirmed these associations and showed that MSI2 , SLC25A10 , and RAPH1 methylation was positively associated with serum leptin. These were also associated with the early environment; MSI2 methylation (β = 0.81, p = 0.0004) was associated with pregnancy maternal smoking, SLC25A10 (CpG2 β = 0.12, p = 0.002) with pre- and early pregnancy BMI, and RAPH1 (β = −1.49, p = 0.036) with gestational weight gain. Adjusting for perinatal factors, methylation of the dmCpGs within MSI2, RAPH1, and SLC25A10 independently predicted BMI, accounting for 24% of variance. MSI2 methylation was additionally associated with BMI over time (17 years old β = 0.026, p = 0.0025; 20 years old β = 0.027, p = 0.0029) and between generations (mother β = 0.044, p = 7.5e-04). Overall findings suggest that DNA methylation in MSI2, RAPH1, and SLC25A10 in blood may be robust markers, mediating through early life factors.
Correct diagnosis must be made before appropriate treatment can be given. The aim of cardiac imaging is to establish cardiac diagnosis as accurate as possible and to avert unnecessary invasive ...procedures. There are many different modalities of cardiac imaging and each of them has advanced tremendously throughout the past decades. Echocardiography, as the first-line modality in most clinical circumstances, has progressed from two-dimensional, single-planed M-mode in the 1960s to three-dimensional speckle tracking echocardiography nowadays. Cardiac computed tomography angiogram (CCTA) has revolutionised the management of coronary artery disease as it allows clinicians to visualise the coronary arteries without performing an invasive angiogram. Because of the high negative predictive value, CCTA plays an important reassuring role in acute chest pain management. The greatest strength of cardiovascular magnetic resonance (CMR) is that it provides information in tissue characterization. It is the modality of choice in assessing myocardial viability and myocardial infiltration such as haemochromatosis or amyloidosis. Each of these modalities has its own strengths and limitations. In fact, they are complementing each other in different clinical settings. Cardiac imaging will continue to advance and, not long from now, we will not need invasive procedures to make an accurate cardiac diagnosis.
This study was performed to clarify alterations in lamotrigine (LTG) clearance during pregnancy and childbirth. Fourteen women on LTG monotherapy had LTG concentration samples obtained before ...conception and monthly. LTG apparent clearance, weight-adjusted relative clearance, and percentages of baseline clearance significantly differed between preconception baseline and each trimester and between trimesters. LTG clearance progressively increased until 32 weeks' gestational age, reaching a peak of >330% of baseline, and then began to decline.
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