Impact of methodological choices on a meta-analysis of real-world evidence comparing non-vitamin-K antagonist oral anticoagulants with vitamin K antagonists for the treatment of patients with non-valvular atrial fibrillation

Objective: The aim of this study was to investigate the impact of methodological choices in a meta-analysis of real-world evidence (RWE) comparing three non-vitamin-K antagonist oral anticoagulants with vitamin K antagonists (VKAs) for the treatment of patients with non-valvular atrial fibrillation (NVAF).

Methods: The meta-analysis was based on a systematic review of RWE studies enrolling incident and prevalent patients aged ≥18 years with NVAF and receiving either rivaroxaban, dabigatran, apixaban or a VKA. Five different scenarios were considered to explore the impact of the initial meta-analysis assumptions: (1) using studies that involved only incident patients; (2) excluding studies that only reported crude values and did not consider any adjustment; (3) including all studies independently of possible database overlap; (4) using studies with data on different dosages for rivaroxaban and dabigatran; and (5) assigning quality weights to studies to assess quality of reporting. These scenarios were run on three outcomes: ischemic stroke (IS), myocardial infarction (MI) and intracranial hemorrhage (ICH).

Results: Across all scenarios, rivaroxaban was associated with significantly lower risks of IS and ICH than VKAs. In most scenarios, dabigatran was associated with significantly lower risks of IS and ICH. In all scenarios, apixaban was associated with a significantly lower risk of ICH.

Conclusions: Sensitivity analyses showed the impact of similar assumptions was different depending on the outcome and the drug considered. The development of recommendations and guidelines for the inclusion of RWE in meta-analyses could prove useful in evaluating the effectiveness of health care interventions.     

Management of patients with essential thrombocythemia: current concepts and perspectives

Essential thrombocythemia must now be regarded as a heterogeneous disease. Recent availability of clonality studies have repeatedly shown that a significant number of female patients diagnosed as E.T. according the most stringent criteria had a definitely polyclonal myelopoiesis. Although the incidence of patients newly diagnosed every year is low, there is in fact a conspicuous population of E.T., followed as outpatients in every department of hematology or internal medicine, including a large number of young females. These eventualities should be integrated in further discussions of the benefit/risk ratio of cytoreduction with the presently available drugs. The combination of several evidence-based data is the basis of a widely accepted stratification of high-risk patients defined by any of the following features. Age > 60 to 65. History of thrombosis or embolic or major ischemic events. Platelet counts in excess of 1000 or 1500 x 10(9)/L. In the question of chemotherapy in E.T., growing concern comes from the potential leukemogenic risk associated with the presently available drugs and extends beyond Melphalan, Busulfan and other alkylating agents and includes non-alkylating agents like Hydroxyurea. At the same time, much attention has been paid to the introduction of very precise initial diagnostic criteria directed to elimination of other myeloproliferative or myelodysplastic disorders with an increased risk of transformation. Present treatment of E.T. is a compromise between prevention of E.T. related thrombotic and bleeding complications on one hand and long term side effects and toxicity of the presently available drugs on the other hand. The recent availability of non mutagenic drugs like Interferon and most of all Anagrelide; the recognition of the role of antiaggregating agents in the treatment of platelet related microvascular ischemic events gives the opportunity for further comparative prospective trials. The use of aspirin in the management of pregnant E.T. patients is now widely accepted but there is still controversies concerning the use of Interferon in this situation.     

Discovery of aryloxy tetramethylcyclobutanes as novel androgen receptor antagonists

An aryloxy tetramethylcyclobutane was identified as a novel template for androgen receptor (AR) antagonists via cell-based high-throughput screening. Follow-up to the initial "hit" established 5 as a viable lead. Further optimization to achieve full AR antagonism led to the discovery of 26 and 30, both of which demonstrated excellent in vivo tumor growth inhibition upon oral administration in a castration-resistant prostate cancer (CRPC) animal model.     

Dissociative symptoms and trauma exposure: specificity, affect dysregulation, and posttraumatic stress

Although dissociation is often described as a posttraumatic response, the actual statistical association between trauma exposure and dissociative symptoms is surprisingly small. This suggests that that some dissociative phenomena may be unrelated to trauma, or may be related in more complex ways. Analysis of the normative data for the Multiscale Dissociation Inventory revealed significant dissociative symptoms in only 8% of trauma-exposed individuals from the general population. However, 90% of those with at least one clinically significant dissociation scale on the Multiscale Dissociation Inventory reported a trauma history, and significant dissociation was found in only 2% of nontraumatized individuals. A history of interpersonal violence, number of different types of trauma exposure, posttraumatic stress, and affect dysregulation were univariate predictors of dissociative symptomatology in trauma-exposed participants, but only posttraumatic stress and affect dysregulation were multivariate predictors. Trauma is probably an important, but insufficient, condition for the development of dissociative symptomatology. Additional risk factors, such as high posttraumatic stress and/or reduced affect regulation capacities, may determine whether trauma exposure results in clinically significant dissociation.     

Fractionated stereotactic radiotherapy for local control of resected brain metastases

Journal of Neuro-Oncology - Postoperative stereotactic radiosurgery (SRS) has been shown to establish local control in patients with resected brain metastases, yet its efficacy may be limited,...     

Quality Improvement Initiative to Prevent Admission Hypothermia in Very-Low-Birth-Weight Newborns

Objective

To decrease rates of admission hypothermia (<36 °C) in very-low-birth-weight (VLBW) newborns (<1,500 g).

Symptomatology in men who were molested as children: a comparison study

Forty male and 40 female crisis center clients, evenly divided in terms of molestation history, were examined for possible long-term sequelae of sexual abuse. Although molestation during childhood was associated with previous suicide attempts and with elevated symptomatology on the Trauma Symptom Checklist, no differences between males and females were found on these variables.     

Functional ability in executive variant Alzheimer's disease and typical Alzheimer's disease

A frontal, or executive, variant of Alzheimer's disease (EAD) has been described in the literature in which frontal dysfunction accompanies temporal and parietal changes in the early stages of the illness. However, no study has empirically investigated associated aspects, such as neuropsychiatric symptoms, instrumental activities of daily living, or caregiver burden in this EAD subgroup. We compared the performance of two subgroups of mild Alzheimer's disease patients (e.g., EAD and typical Alzheimer's disease; TAD) on neuropsychological and associated measures. Results revealed that the EAD group, selected based on poor executive scores, did not significantly differ from the TAD group on nonexecutive neuropsychological tests of intelligence, language, verbal and nonverbal memory, or visual-spatial abilities. However, the EAD group evidenced more severe neuropsychiatric symptoms, impaired activities of daily living, and greater caregiver distress than the TAD group. Thus, the EAD subgroup is characterized by executive dysfunction, neuropsychiatric symptoms, and functional disability in excess of that seen in TAD. Whether our EAD subgroup represents an actual frontal variant of Alzheimer's disease awaits replication in a larger sample including neuroimaging and pathological confirmation, as well as longitudinal assessment of cognition and neuropsychiatric symptoms.     

Adult Sexual Assault: Prevalence, Symptomatology, and Sex Differences in the General Population

The prevalence and impact of adult sexual assault (ASA) were examined in a stratified random sample of the general population. Among 941 participants, ASA was reported by 22% of women and 3.8% of men. Multivariate risk factors for ASA included a younger age, being female, having been divorced, sexual abuse in childhood, and physical assault in adulthood. Childhood sexual abuse was especially common among sexually assaulted men and women (61 and 59%, respectively). ASA victims were more symptomatic than their nonassaulted cohorts on all scales of the Trauma Symptom Inventory (TSI; J. Briere, 1995), despite an average of 14 years having passed since the assault. Assaulted men reported greater symptomatology than assaulted women, whereas nonassaulted men reported less symptomatology than nonassaulted women.