Real-world assessment of intravitreal dexamethasone implant (0.7 mg) in patients with macular edema: The CHROME study

© 2015 Lam et al.Background: The purpose of this study was to evaluate the real-world use, efficacy, and safety of one or more dexamethasone intravitreal implant(s) 0.7 mg (DEX implant) in patients with macular edema (ME). Methods: This was a retrospective cohort study of patients with ME secondary to retinal disease treated at ten Canadian retina practices, including one uveitis center. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), glaucoma and cataract surgery, and safety data were collected from the medical charts of patients with ≥3 months of follow-up after the initial DEX implant.Results: One hundred and one patient charts yielded data on 120 study eyes, including diagnoses of diabetic ME (DME) (n=34), retinal vein occlusion (RVO, n=30; branch in 19 and central in 11), and uveitis (n=23). Patients had a mean age of 60.9 years, and 73.3% of the study eyes had ME for a duration of ≥12 months prior to DEX implant injection(s). Baseline mean (± standard error) BCVA was 0.63±0.03 logMAR (20/86 Snellen equivalents) and mean CRT was 474.4±18.2 μm. The mean number of DEX implant injections was 1.7±0.1 in all study eyes; 44.2% of eyes had repeat DEX implant injections (reinjection interval 2.3–4.9 months). The greatest mean peak changes in BCVA lines of vision occurred in study eyes with uveitis (3.3±0.6, P0.05). Significant decreases in CRT were observed: -255.6±43.6 µm for uveitis, -190.9±23.5 µm for DME, and -160.7±39.6 µm for RVO (P<0.0001 for all cohorts). IOP increases of ≥10 mmHg occurred in 20.6%, 24.1%, and 22.7% of DME, RVO, and uveitis study eyes, respectively. IOP-lowering medication was initiated in 29.4%, 16.7%, and 8.7% of DME, RVO, and uveitis study eyes, respectively. Glaucoma surgery was performed in 1.7% of all study eyes and cataract surgery in 29.8% of all phakic study eyes receiving DEX implant(s). onclusion: DEX implant(s) alone or combined with other treatments and/or procedures resulted in functional and anatomic improvements in long-standing ME associated with retinal disease.Link_to_subscribed_fulltex

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A Systematic Review of Directly Applied Biologic Therapies for Acute Spinal Cord Injury

An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are administered as soon as possible after injury with the hope of attenuating secondary damage and maximizing the extent of spared neurologic tissue. In this article, we systematically reviewed the available preclinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we reviewed treatments that have a relatively high potential for translation due to the fact that they are already used in human clinical applications or are available in a form that could be administered to humans. These included: erythropoietin, NSAIDs, anti-CD11d antibodies, minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol, atorvastatin, inosine, and pioglitazone. The literature was systematically reviewed to examine studies in which an in vivo animal model was utilized to assess the efficacy of the therapy in a traumatic spinal cord injury paradigm. Using these criteria, 122 studies were identified and reviewed in detail. Wide variations exist in the animal species, injury models, and experimental designs reported in the preclinical literature on the therapies reviewed. The review highlights the extent of investigation that has occurred in these specific therapies, and points out gaps in our knowledge that would be potentially valuable prior to human translation

A Systematic Review of Non-Invasive Pharmacologic Neuroprotective Treatments for Acute Spinal Cord Injury

An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are administered as soon as possible after injury with the hope of attenuating secondary damage and maximizing the extent of spared neurologic tissue. In this article, we systematically review the available pre-clinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we review treatments that have a relatively high potential for translation due to the fact that they are already used in human clinical applications, or are available in a form that could be administered to humans. These include: erythropoietin, NSAIDs, anti-CD11d antibodies, minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol, atorvastatin, inosine, and pioglitazone. The literature was systematically reviewed to examine studies in which an in-vivo animal model was utilized to assess the efficacy of the therapy in a traumatic SCI paradigm. Using these criteria, 122 studies were identified and reviewed in detail. Wide variations exist in the animal species, injury models, and experimental designs reported in the pre-clinical literature on the therapies reviewed. The review highlights the extent of investigation that has occurred in these specific therapies, and points out gaps in our knowledge that would be potentially valuable prior to human translation

NIH roundtable on emergency trauma research

Study objective: The National Institutes of Health (NIH) formed an NIH Task Force on Research in Emergency Medicine to enhance NIH support for emergency care research. The NIH Trauma Research Roundtable was convened on June 22 to 23, 2009. The objectives of the roundtable are to identify key research questions essential to advancing the scientific underpinnings of emergency trauma care and to discuss the barriers and best means to advance research by exploring the role of trauma research networks and collaboration between NIH and the emergency trauma care community. Methods: Before the roundtable, the emergency care domains to be discussed were selected and experts in each of the fields were invited to participate in the roundtable. Domain experts were asked to identify research priorities and challenges and separate them into mechanistic, translational, and clinical categories. During and after the conference, the lists were circulated among the participants and revised to reach a consensus. Results: Emergency trauma care research is characterized by focus on the timing, sequence, and time sensitivity of disease processes and treatment effects. Rapidly identifying the phenotype of patients on the time spectrum of acuity and severity after injury and the mechanistic reasons for heterogeneity in outcome are important challenges in emergency trauma research. Other research priorities include the need to elucidate the timing, sequence, and duration of causal molecular and cellular events involved in time-critical injuries, and the development of treatments capable of halting or reversing them; the need for novel experimental models of acute injury; the need to assess the effect of development and aging on the postinjury response; and the need to understand why there are regional differences in outcomes after injury. Important barriers to emergency care research include a limited number of trained investigators and experienced mentors, limited research infrastructure and support, and regulatory hurdles. Conclusion: The science of emergency trauma care may be advanced by facilitating the following: (1) development of an acute injury template for clinical research; (2) developing emergency trauma clinical research networks; (3) integrating emergency trauma research into Clinical and Translational Science Awards; (4) developing emergency carespecific initiatives within the existing structure of NIH institutes and centers; (5) involving acute trauma and emergency specialists in grant review and research advisory processes; (6) supporting learn-phase or small, clinical trials; (7) performing research to address ethical and regulatory issues; and (8) training emergency care investigators with research training programs. © 2010 American College of Emergency Physicians

NIH roundtable on emergency trauma research

Study objective: The National Institutes of Health (NIH) formed an NIH Task Force on Research in Emergency Medicine to enhance NIH support for emergency care research. The NIH Trauma Research Roundtable was convened on June 22 to 23, 2009. The objectives of the roundtable are to identify key research questions essential to advancing the scientific underpinnings of emergency trauma care and to discuss the barriers and best means to advance research by exploring the role of trauma research networks and collaboration between NIH and the emergency trauma care community. Methods: Before the roundtable, the emergency care domains to be discussed were selected and experts in each of the fields were invited to participate in the roundtable. Domain experts were asked to identify research priorities and challenges and separate them into mechanistic, translational, and clinical categories. During and after the conference, the lists were circulated among the participants and revised to reach a consensus. Results: Emergency trauma care research is characterized by focus on the timing, sequence, and time sensitivity of disease processes and treatment effects. Rapidly identifying the phenotype of patients on the time spectrum of acuity and severity after injury and the mechanistic reasons for heterogeneity in outcome are important challenges in emergency trauma research. Other research priorities include the need to elucidate the timing, sequence, and duration of causal molecular and cellular events involved in time-critical injuries, and the development of treatments capable of halting or reversing them; the need for novel experimental models of acute injury; the need to assess the effect of development and aging on the postinjury response; and the need to understand why there are regional differences in outcomes after injury. Important barriers to emergency care research include a limited number of trained investigators and experienced mentors, limited research infrastructure and support, and regulatory hurdles. Conclusion: The science of emergency trauma care may be advanced by facilitating the following: (1) development of an acute injury template for clinical research; (2) developing emergency trauma clinical research networks; (3) integrating emergency trauma research into Clinical and Translational Science Awards; (4) developing emergency carespecific initiatives within the existing structure of NIH institutes and centers; (5) involving acute trauma and emergency specialists in grant review and research advisory processes; (6) supporting learn-phase or small, clinical trials; (7) performing research to address ethical and regulatory issues; and (8) training emergency care investigators with research training programs. © 2010 American College of Emergency Physicians

Electrocardiographic Manifestations of Immune Checkpoint Inhibitor Myocarditis

International audienc