Rab37 in lung cancer mediates exocytosis of soluble ST2 and thus skews macrophages toward tumor‐suppressing phenotype

International Journal of Cancer, EarlyView.


https://ift.tt/2z59tRk

Circadian nutritional behaviours and cancer risk: New insights from the NutriNet‐santé prospective cohort study: Disclaimers

International Journal of Cancer, EarlyView.


https://ift.tt/2tSw5zu

An original micro‐CT study and meta‐analysis of the internal and external anatomy of maxillary molars—implications for endodontic treatment

Clinical Anatomy, EarlyView.


https://ift.tt/2Ksuriy

Variations of the testicular artery and vein: A meta‐analysis with proposed classification

Clinical Anatomy, EarlyView.


https://ift.tt/2INMt9a

Localizing parkinsonism based on focal brain lesions

Abstract

Bradykinesia, rigidity, and tremor frequently co-occur, a clinical syndrome known as parkinsonism. Because this syndrome is commonly seen in Parkinson's disease, symptoms are often attributed to cell loss in the substantia nigra. However, parkinsonism occurs in several other neurological disorders and often fails to correlate with nigrostriatal pathology, raising the question of which brain region(s) cause this syndrome. Here, we studied cases of new-onset parkinsonism following focal brain lesions. We identified 29 cases, only 31% of which hit the substantia nigra. Lesions were located in a variety of different cortical and subcortical locations. To determine whether these heterogeneous lesion locations were part of a common brain network, we leveraged the human brain connectome and a recently validated technique termed lesion network mapping. Lesion locations causing parkinsonism were functionally connected to a common network of regions including the midbrain, basal ganglia, cingulate cortex, and cerebellum. The most sensitive and specific connectivity was to the claustrum. This lesion connectivity pattern matched atrophy patterns seen in Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy, suggesting a shared neuroanatomical substrate for parkinsonism. Lesion connectivity also predicted medication response and matched the pattern of effective deep brain stimulation, suggesting relevance as a treatment target. Our results, based on causal brain lesions, lend insight into the localization of parkinsonism, one of the most common syndromes in neurology. Because many patients with parkinsonism fail to respond to dopaminergic medication, these results may aid the development of alternative treatments.

https://ift.tt/2tZu18k

An Unusual Case of Ototoxicity with Use of Oral Vancomycin

Introduction. Systemic absorption of oral vancomycin is poor due to the size of the molecule and its pharmacokinetics. It has an elimination half life of 5–11 hours in patients with normal renal function. We present a rare case of ototoxicity after oral vancomycin administration and detectable serum vancomycin levels 24 hours after cessation of vancomycin. Case Presentation. A 42-year-old woman with a history of hypertension, diabetes mellitus, and previously treated Clostridium difficile colitis presented with abdominal pain and diarrhea for two weeks. Clostridium difficile infection was confirmed by PCR, and at the time of diagnosis and initiation of therapy, the patient had normal renal function. Vancomycin was initiated at a dose of 125 mg po q6h. After the third dose of oral vancomycin, the patient reported new symptoms of lightheadedness, sensations of "buzzing" and whistling of bilateral ears, and decreased perception of hearing described as "clogged ears." The patient reported to the emergency department the next day due to worsening of these symptoms, and vancomycin dosing was reduced to every 8 hours; however, the patient reported the auditory symptoms persisted. On day three, vancomycin was discontinued with gradual resolution of symptoms over the next 12 hours. On day four, a serum random vancomycin level obtained 24 hours after the last dose was detectable at 2 mcg/dl. Temporal association of the patient's symptoms and improvement with cessation of therapy along with a detectable vancomycin level indicates systemic absorption of oral vancomycin with subsequent ototoxicity. Discussion. The potential for absorption of oral vancomycin is not well described and is attributed to compromised intestinal epithelium allowing for increased drug absorption. Few studies suggested that oral vancomycin may result in therapeutic or even potentially toxic levels of serum vancomycin in patients with impaired renal function. Ototoxicity may be a transient or permanent side effect of vancomycin therapy and is related to high serum levels. Symptoms usually resolve after decreasing the dose or cessation of vancomycin. No detectable serum vancomycin levels were found in 98% of the patients treated with oral vancomycin in a prospective study. The described case is unusual because despite normal renal function, the patient still developed ototoxicity, and systemic absorption of the drug was confirmed with a measurable vancomycin level approximately 24 hours after the drug was stopped. Additionally, the only other medication prescribed to the patient at the time of vancomycin administration was metformin at a dose of 500 mg po bid which has no known idiosyncratic interactions potentiating adverse side effects to vancomycin. This case reflects that some patients may be more susceptible to increased systemic absorption via the oral route, and the possibility for ototoxicity should be considered and discussed with patients while prescribing oral vancomycin.

https://ift.tt/2Krt7MW

Modeling Approaches in Cost-Effectiveness Analysis of Disease-Modifying Therapies for Relapsing–Remitting Multiple Sclerosis: An Updated Systematic Review and Recommendations for Future Economic Evaluations

Abstract

Background

Numerous cost-effectiveness analyses (CEAs) of disease-modifying therapies (DMTs) for relapsing–remitting multiple sclerosis (RRMS) have been published in the last three decades. Literature reviews of the modeling methods and results from these CEAs have also been published. The last literature review that focused on modeling methods, without country or time horizon in the inclusion criteria, included studies published up to 2012. Since then, new DMTs have become available, and new models and data sources have been used to assess their cost effectiveness.

Objective

The aim of this systematic review was to provide a detailed and comprehensive description of the relevant aspects of economic models used in CEAs of DMTs for RRMS, to understand how these models have progressed from recommendations provided in past reviews, what new approaches have been developed, what issues remain, and how they could be addressed.

Methods

EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), the National Health System (NHS) Economic Evaluations Database, the Health Technology Assessment (HTA) Database, and EconLit were searched for cost-effectiveness studies of DMTs for RRMS that used decision-analytic models, published in English between 1 January 2012 and 24 December 2017. The inclusion criteria were as follows: being a full economic evaluation, a decision-analytic model was used, the target population concerned adult patients with RRMS, and being available in full-text format. Studies were not excluded based on the methodological quality. The background information of the included studies, as well as specific information on the components of the economic models related to the areas of recommendation from previous reviews were extracted.

Results

Twenty-three studies from ten countries were included. The model structure of these studies has converged over time, characterizing the course of disease progression in terms of changes in disability and the occurrence of relapses over time. Variations were found in model approach; data sources for the natural course of the disease and comparative efficacy between DMTs; number of lines of treatment modeled; long-term efficacy waning and treatment discontinuation assumptions; type of withdrawal; and criteria for selecting adverse events. Main areas for improvement include using long-term time horizons and societal perspective; reporting relevant health outcomes; conducting scenario analyses using different sources of natural history and utility values; and reporting how the model was validated.

Conclusion

The structure of economic models used in CEAs of DMTs for RRMS has converged over time. However, variation remains in terms of model approach, inputs, and assumptions. Though some recommendations from previous reviews have been incorporated in later models, areas for improvement remain.

https://ift.tt/2zfITp1