Despite improvements in the management of atrial fibrillation, patients with this condition remain at increased risk for cardiovascular complications. It is unclear whether early rhythm-control ...therapy can reduce this risk.
In this international, investigator-initiated, parallel-group, open, blinded-outcome-assessment trial, we randomly assigned patients who had early atrial fibrillation (diagnosed ≤1 year before enrollment) and cardiovascular conditions to receive either early rhythm control or usual care. Early rhythm control included treatment with antiarrhythmic drugs or atrial fibrillation ablation after randomization. Usual care limited rhythm control to the management of atrial fibrillation-related symptoms. The first primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome; the second primary outcome was the number of nights spent in the hospital per year. The primary safety outcome was a composite of death, stroke, or serious adverse events related to rhythm-control therapy. Secondary outcomes, including symptoms and left ventricular function, were also evaluated.
In 135 centers, 2789 patients with early atrial fibrillation (median time since diagnosis, 36 days) underwent randomization. The trial was stopped for efficacy at the third interim analysis after a median of 5.1 years of follow-up per patient. A first-primary-outcome event occurred in 249 of the patients assigned to early rhythm control (3.9 per 100 person-years) and in 316 patients assigned to usual care (5.0 per 100 person-years) (hazard ratio, 0.79; 96% confidence interval, 0.66 to 0.94; P = 0.005). The mean (±SD) number of nights spent in the hospital did not differ significantly between the groups (5.8±21.9 and 5.1±15.5 days per year, respectively; P = 0.23). The percentage of patients with a primary safety outcome event did not differ significantly between the groups; serious adverse events related to rhythm-control therapy occurred in 4.9% of the patients assigned to early rhythm control and 1.4% of the patients assigned to usual care. Symptoms and left ventricular function at 2 years did not differ significantly between the groups.
Early rhythm-control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients with early atrial fibrillation and cardiovascular conditions. (Funded by the German Ministry of Education and Research and others; EAST-AFNET 4 ISRCTN number, ISRCTN04708680; ClinicalTrials.gov number, NCT01288352; EudraCT number, 2010-021258-20.).
There have been large numbers of studies on anti-HEV IgG seroprevalence in Europe, however, the results of these studies have produced high variability of seroprevalence rates, making interpretation ...increasingly problematic. Therefore, the aim of this study was to develop a clearer understanding of anti-HEV IgG seroprevalence in Europe and identify risk groups for HEV exposure by a meta-analysis of published studies.
All European HEV-seroprevalence studies from 2003 to 2015 were reviewed. Data were stratified by assay, geographical location, and patient cohort (general population, patients with HIV, solid-organ transplant recipients, chronic liver disease patients, and individuals in contact with swine/wild animals). Data were pooled using a mixed-effects model.
Four hundred thirty-two studies were initially identified, of which 73 studies were included in the analysis. Seroprevalence estimates ranged from 0.6% to 52.5%, increased with age, but were unrelated to gender. General population seroprevalence varied depending on assays: Wantai (WT): 17%, Mikrogen (MG): 10%, MP-diagnostics (MP): 7%, DiaPro: 4%, Abbott 2%. The WT assay reported significantly higher seroprevalence rates across all cohorts (p < 0.001). Individuals in contact with swine/wild animals had significantly higher seroprevalence rates than the general population, irrespective of assay (p < 0.0001). There was no difference between any other cohorts. The highest seroprevalence was observed in France (WT: 32%, MP: 16%) the lowest in Italy (WT: 7.5%, MP 0.9%). Seroprevalence varied between and within countries. The observed heterogeneity was attributed to geographical region (23%), assay employed (23%) and study cohort (7%).
Seroprevalcence rates primarily depend on the seroassy that is used, followed by the geographical region and study cohort. Seroprevalence is higher in individuals exposed to swine and/or wild animals, and increases with age.
Optimal selection of liver transplant candidates and early detection of alcohol relapse after orthotopic liver transplantation (OLT) is necessary to improve long‐term outcomes. In this study, urinary ...ethyl glucuronide (uEtG) was prospectively evaluated as a novel screening tool for alcohol detection in the transplant setting. Overall, 141 liver transplant candidates and recipients, visiting the outpatient clinic for a total of 308 times, were included. At each visit, the alcohol markers, uEtG, ethanol, methanol, and carbohydrate‐deficient transferrin (CDT), as well as the state markers, alanine transaminase, aspartate transaminase, gamma glutamyl transpeptidase (GGT), and mean corpuscular volume (MCV), were determined, then compared to patients' self‐reports on alcohol intake. Urinary EtG significantly increased the detection rate of alcohol consumption, compared to the other alcohol markers (P < 0.001). In 93% of patients and at 92.5% of visits with positive alcohol markers, alcohol intake was detected by uEtG and/or CDT. Sensitivity and specificity of uEtG were 89.3% and 98.9% and of CDT were 25% and 98.6%, respectively. Urinary EtG was the best independent predictor of alcohol consumption in univariate and multivariate analysis (positive predictive value: 89.3%; negative predictive value: 98.9%; odds ratio: 761.1; P < 0.001). It showed a superior prediction rate, when compared to established alcohol and state markers, as well as to the combination of CDT with MCV and GGT, assessed by net reclassification improvement (NRI) (NRI: 1.01, P < 0.001; NRI: 1.755, P < 0.001). Conclusion: uEtG is a sensitive, specific, and reliable marker for the detection of recent alcohol intake pre‐ and post‐OLT. In combination with CDT, uEtG should be considered as a tool for routine alcohol screening within the transplant setting. (HEPATOLOGY 2011)
•Romberg posturography and DXA scans were evaluated retrospectively in 1086 patients.•Lower femoral BMD T-score was associated with higher Romberg path length.•Patients with history of fragility ...fracture exhibited higher postural instability.
Although the interactions between balance, falls and fracture risk have been demonstrated in various aspects, the clinical focus of fracture risk evaluation has been on bone properties, e.g., bone mineral density (BMD). Accordingly, the role of balance parameters in the setting of osteoporosis assessment remained to be further explored.
Is postural stability assessed by Romberg quiet stance posturography influenced by BMD or prior fragility fractures in a cohort of more than 1000 patients screened for osteoporosis?
Patients who completed both Romberg test and dual energy X-ray absorptiometry (DXA) were included retrospectively from a large database. Quantification of the Romberg test was performed by using posturography. Center of pressure (CoP) movements were tracked and the corresponding path length for ten seconds as well as an ellipse area including 90 % of all CoP were calculated. To determine potential predictors of posturography, simple and multiple linear regression analyses were performed including DXA results, grip strength, age, sex and BMI. As a secondary outcome, the influence of a previous fragility fracture on postural stability was evaluated.
Overall, 1086 patients (801 women, 285 men) met the inclusion criteria. Lower femoral BMD T-score (p < 0.05), higher age (p < 0.001) and male sex (p < 0.001) were associated with higher Romberg path length (both eyes open and eyes closed). Both women and men with any previous fragility fracture showed significantly increased values in the path length with eyes open (p < 0.05) and eyes closed (women p < 0.001, men p < 0.05) compared to those without a history of a fragility fracture.
Our study indicates that postural stability is affected by femoral BMD, age and sex. As a history of prior fragility fracture was associated with postural instability, assessment and management of impaired balance in everyday clinical practice is advisable for optimal fracture prevention.
Smoking is a strong risk factor for coronary heart disease particularly in women. The risk may be aggravated by dietary habits, though.
The Coronary Risk for Atherosclerosis Study (CORA) compares ...dietary, lifestyle, biochemical, and clinical factors in 200 consecutive pre- and postmenopausal women with incident coronary heart disease to those of 255 age-matched population-based controls. A mixed logistic regression model was used to assess the possible interactions between smoking habits and dietary patterns.
Each increase of 100 kcal energy intake per day was positively associated with coronary risk (OR 1.10, 95% CI 1.03-1.17; p = 0.006). Doubling the intake of alcohol and vegetables was negatively related with coronary risk (alcohol: OR 0.61, 95% CI 0.50-0.73; p < 0.001; vegetables: OR 0.50, 95% CI 0.032-0.080; p = 0.003). In contrast, doubling the intake of meat was associated with an increase of coronary risk, but only in smoking women (OR 2.61, 95%CI 1.58-4.29; p < 0.001). In smoking women a high meat-over-vegetable-ratio indicated an even higher risk (ratio of 2.0: OR 5.77, 95% CI 2.13-15.67; p < 0.001), while a low meat-over-vegetable-ratio did not have a significant impact on coronary risk (ratio of 0.5: OR 1.28, 95% CI 0,78-2.09).
This explorative analysis of the CORA-study indicates that a high intake of meat is significantly associated with an increase in coronary risk particularly in smoking women, and may account for part of the unadjusted risk of smoking.
The Hedgehog pathway plays an important role in stem-cell biology and malignant transformation. Therefore, we investigated the expression and prognostic impact of Hedgehog pathway members in acute ...myeloid leukemia (AML).
Pretreatment samples from 104 newly diagnosed AML patients (AMLSG 07-04 trial) were analyzed by qPCR, and expression of Hedgehog family members was correlated with clinical outcome. Inhibition of GLI by GANT61 or shRNA was investigated in AML cells in vitro and in vivo.
Expression of receptors Smoothened and Patched-1 and their downstream mediators, GLI1, GLI2, and GLI3, was found in AML patients in contrast to Hedgehog ligands. GLI2 expression had a significant negative influence on event-free survival (EFS), relapse-free survival (RFS), and overall survival (OS; P = 0.037, 0.026, and 0.013, respectively) and was correlated with FLT3 mutational status (P < 0.001). Analysis of a second, independent patient cohort confirmed the negative impact of GLI2 on EFS and OS (P = 0.007 and 0.003, respectively; n = 290). Within this cohort, GLI1 had a negative prognostic impact (P < 0.001 for both EFS and OS). Although AML cells did not express Hedgehog ligands by qPCR, AML patients had significantly increased Desert Hedgehog (DHH) plasma levels compared with healthy subjects (P = 0.002), in whom DHH was presumably provided by bone marrow niche cells. Moreover, the GLI inhibitor GANT61 or knockdown of GLI1/2 by shRNA caused antileukemic effects, including induction of apoptosis, reduced proliferation, and colony formation in AML cells, and a survival benefit in mice.
GLI expression is a negative prognostic factor and might represent a novel druggable target in AML.
Background: Mild to moderate depressive symptoms are common but often remain unrecognized and treated inadequately. We hypothesized that an Internet intervention in addition to usual care is superior ...to care as usual alone (CAU) in the treatment of mild to moderate depressive symptoms in adults. Methods: This trial was controlled, randomized and assessor-blinded. Participants with mild to moderate depressive symptoms (Patient Health Questionnaire, PHQ-9, score 5-14) were recruited from clinical and non-clinical settings and randomized to either CAU or a 12-week Internet intervention (Deprexis) adjunctive to usual care. Outcomes were assessed at baseline, 3 months (post-assessment) and 6 months (follow-up). The primary outcome measure was self-rated depression severity (PHQ-9). The main analysis was based on the intention-to-treat principle and used linear mixed models. Results: A total of 1,013 participants were randomized. Changes in PHQ-9 from baseline differed significantly between groups (t825 = 6.12, p < 0.001 for the main effect of group). The post-assessment between-group effect size in favour of the intervention was d = 0.39 (95% CI: 0.13-0.64). It was stable at follow-up, with d = 0.32 (95% CI: 0.06-0.69). The rate of participants experiencing at least minimally clinically important PHQ-9 change at the post-assessment was higher in the intervention group (35.6 vs. 20.2%) with a number needed to treat of 7 (95% CI: 5-10). Conclusions: The Internet intervention examined in this trial was superior to CAU alone in reducing mild to moderate depressive symptoms. The magnitude of the effect is clinically important and has public health implications.
In a retrospective analysis we evaluated the achieved and the predicted survival times according to the Tokuhashi score for patients with spinal metastases of lung cancer (lc).
Our aim was to ...investigate the robustness of the Tokuhashi Score for this group of patients.
The decision on operative versus conservative treatment for cancer patients with vertebral metastases depend on their predicted lifespan. Although the score of Tokuhashi is commonly used for prognostic predictions, it's reliability for specific tumor types (e.g., lc), has not been validated.
Seventy-six patients who had undergone spinal surgery for lc metastases between 1999 and 2004 were verified according to the Tokuhashi score and predicted versus achieved survival times were compared.
The median overall survival (OS) after surgery for all patients was 108 (3-1767) days (102 5-1767 days for patients with NSCLC n = 49; 64.5% and 108 3-473 days for patients with SCLC n = 24; 31.6%). Survival times differed depending on the time period of procedure performance (OS 81 3-435 days for patients operated between 1999 and 2001 n = 38, 135 8-1767 days for patients who received surgery between 2002 and 2004 n = 38). Actual and predicted survival were similar in 51 of 76 cases (67.1%), while there was no correlation in 25 of 76 (32.9%) cases. Results were comparable for all histologic subgroups.
Although the survival time of patients with vertebral metastases from lc has increased over the last 10 years, the overall outcome is still poor. For the prediction of an individual prognosis in the group of lc patients the score of Tokuhashi seems to be a suboptimal tool. We conclude that therapeutic decisions for such patients should be made based on interdisciplinary platforms, especially in the light of improved systemic treatment options.
Nodal metastasis (N1) is a strong prognostic parameter in prostate cancer; however, lymph node evaluation is always incomplete.
To study the prognostic value of lymphatic invasion (L1) and whether it ...might complement or even replace lymph node analysis in clinical practice.
Retrospective analysis of pathological and clinical data from 14 528 consecutive patients.
Radical prostatectomy.
The impact of L1 and N1 on patient prognosis was measured with time to biochemical recurrence as the primary endpoint.
Nodal metastases were found in 1602 (12%) of 13 070 patients with lymph node dissection. L1 was seen in 2027 of 14 528 patients (14%) for whom lymphatic vessels had been visualized by immunohistochemistry. N1 and L1 continuously increased with unfavorable Gleason grade, advanced pT stage, and preoperative prostate-specific antigen (PSA) values (p<0.0001 each). N1 was found in 4.3% of 12 501 L0 and in 41% of 2027 L1 carcinomas (p<0.0001). L1 was seen in 11% of 9868 N0 and in 61% of 1360 N1 carcinomas (p<0.0001). Both N1 and L1 were linked to PSA recurrence (p<0.0001 each). This was also true for 17 patients with isolated tumor cells (ie, <200 unequivocal cancer cells without invasive growth) and 193 metastases ≤1mm. Combined analysis of N and L status showed that L1 had no prognostic effect in N1 patients but L1 was strikingly linked to PSA recurrence in N0 patients. N0L1 patients showed a similar outcome as N1 patients.
Analysis of lymphatic invasion provides comparable prognostic information than lymph node analysis. Even minimal involvement of the lymphatic system has pivotal prognostic impact in prostate cancer. Thus, a thorough search for lymphatic involvement helps to identify more patients with an increased risk for disease recurrence.
Already minimal amounts of tumor cells inside the lymph nodes or intraprostatic lymphatic vessels have a severe impact on patient prognosis.
To replace morbidity-prone lymph node analysis, we tested immunohistochemical analysis of lymphatic vessels to predict prognosis after radical prostatectomy. We found that minimal lymphatic invasion had a pivotal prognostic impact.
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