J. Clin. Med.2015, 4(5), 1156-1170; doi:10.3390/jcm4051156 (registering DOI) - published 21 May 2015 Show/Hide Abstract
Abstract: Multidisciplinary interventions have been developed for patients with atopic dermatitis (AD) and their families, with the aim of improving outcomes such as disease control, adherence, and quality of life. We reviewed the content of different multidisciplinary approaches to intervention for AD and evidence for their impact on key outcome measures. We also provided data from our multidisciplinary outpatient program for pediatric AD. Studies included in the review suggest benefits of multidisciplinary interventions as models of treatment or adjuncts to standard medical care, with a positive impact on outcomes including disease severity and itching/scratching. There were limitations to existing studies, including heterogeneous methods used to assess quality of life outcomes across studies and lack of controlled studies assessing the outcome of clinical care programs. Further research will be useful in assessing the impact of multidisciplinary interventions on important outcomes such as treatment adherence and sleep, identifying the elements of multidisciplinary interventions that are most critical for improved outcomes, and identifying the best candidates for multidisciplinary intervention approaches.
J. Clin. Med.2015, 4(5), 1126-1155; doi:10.3390/jcm4051126 (registering DOI) - published 21 May 2015 Show/Hide Abstract
Abstract: Human papillomaviruses (HPVs) are small DNA viruses; some oncogenic ones can cause different types of cancer, in particular cervical cancer. HPV-associated carcinogenesis provides a classical model system for RNA interference (RNAi) based cancer therapies, because the viral oncogenes E6 and E7 that cause cervical cancer are expressed only in cancerous cells. Previous studies on the development of therapeutic RNAi facilitated the advancement of therapeutic siRNAs and demonstrated its versatility by siRNA-mediated depletion of single or multiple cellular/viral targets. Sequence-specific gene silencing using RNAi shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments. However, siRNA-based targeting requires further validation of its efficacy in vitro and in vivo, for its potential off-target effects, and of the design of conventional therapies to be used in combination with siRNAs and their drug delivery vehicles. In this review we discuss what is currently known about HPV-associated carcinogenesis and the potential for combining siRNA with other treatment strategies for the development of future therapies. Finally, we present our assessment of the most promising path to the development of RNAi therapeutic strategies for clinical settings.
J. Clin. Med.2015, 4(5), 1113-1125; doi:10.3390/jcm4051113 (registering DOI) - published 21 May 2015 Show/Hide Abstract
Abstract: Demand for hospital resources may increase over time; we have examined all emergency admissions (51,136 episodes) from 2005 to 2013 for underlying trends and whether resource utilization and clinical risk are correlated. We used logistic regression of the resource indicator against 30-day in-hospital mortality and adjusted this risk estimate for other outcome predictors. Generally, resource indicators predicted an increased risk of a 30-day in-hospital death. For CT Brain the Odds Ratio (OR) was 1.37 (95% CI: 1.27, 1.50), CT Abdomen 3.48 (95% CI: 3.02, 4.02) and CT Chest, Thorax, Abdomen and Pelvis 2.50 (95% CI: 2.10, 2.97). Services allied to medicine including Physiotherapy 2.57 (95% CI: 2.35, 2.81), Dietetics 2.53 (95% CI: 2.27, 2.82), Speech and Language 5.29 (95% CI: 4.57, 6.05), Occupational Therapy 2.65 (95% CI: 2.38, 2.94) and Social Work 1.65 (95% CI: 1.48, 1.83) all predicted an increased risk. The in-hospital 30-day mortality increased with resource utilization, from 4.7% (none) to 27.0% (five resources). In acute medical illness, the use of radiological investigations and allied professionals increased over time. Resource utilization was calibrated from case complexity/30-day in-hospital mortality suggesting that complexity determined the need for and validated the use of these resources.
J. Clin. Med.2015, 4(5), 1102-1112; doi:10.3390/jcm4051102 (registering DOI) - published 21 May 2015 Show/Hide Abstract
Abstract: Myeloid sarcoma (MS) of the central nervous system (CNS) is a rare presentation of leukemic mass infiltration outside of the bone marrow. It may involve the subperiosteum and dura mater and, on rare occasions, can also invade the brain parenchyma. The disease is most commonly seen in children or young adults; however, it has been described in multiple age groups. MS can be seen in patients with acute myeloid leukemia (AML), chronic myeloid leukemia and other myeloproliferative disorders. This entity has the potential to be underdiagnosed if the MS appearance precedes the first diagnosis of leukemia. The main reason is that their appearance on CT and MRI has a broad differential diagnosis, and proper diagnosis of MS can only be made if the imaging findings are correlated with the clinical history and laboratory findings. Herein, we describe the intracranial CNS manifestations of MS in patients with AML on CT and MRI involving the brain and/or meninges. This study is based on a systematic review of the literature. In addition, three case reports from the author’s institution with AML and intracranial involvement of MS are included. Our aim is to enhance the awareness of this entity among both clinicians and radiologists.
J. Clin. Med.2015, 4(5), 1079-1101; doi:10.3390/jcm4051079 (registering DOI) - published 21 May 2015 Show/Hide Abstract
Abstract: The widespread use of drugs that bind diffusible vascular endothelial growth factor (VEGF) has revolutionized the treatment of neovascular age-related macular degeneration (AMD). The pivotal ranibizumab and aflibercept registration trials featured monthly intravitreal injections for 12 months, during which visual acuities and macular edema rapidly improved for the first 3 months and modest gains or stabilization continued until the primary endpoint. In many subsequent trials, patients were evaluated monthly and treated as-needed (PRN) according to the results of visual acuity (VA) testing, fundus examinations and optical coherence tomography scans. Compared to monthly-treated control groups, PRN treated patients require fewer injections during the first year but they also experience smaller VA gains (1–3 letters). A small number of prospective trials that directly compared monthly with PRN therapy showed that VA gains with discontinuous therapy lag slightly behind those achieved with monthly injections. Physicians recognize that monthly office visits with frequent intraocular injections challenge patients’ compliance, accrue high drug and professional service costs, and clog office schedules with frequently returning patients. To decrease the numbers of both office visits and anti-VEGF injections without sacrificing VA gains, physicians have embraced the treat-and-extend strategy. Treat-and-extend has not been studied as rigorously as PRN but it has become popular among both vitreoretinal specialists and patients. Despite the possible risks associated with discontinuous therapy (decreased VA and increased macular fluid), most physicians individualize treatment (PRN or treat-and-extend) for the majority of their patients. This review chapter explores the many advantages of individualized therapy, while balancing these against suboptimal responses due to the decreased frequency of anti-VEGF injections.
J. Clin. Med.2015, 4(5), 1063-1078; doi:10.3390/jcm4051063 - published 20 May 2015 Show/Hide Abstract
Abstract: Drug-induced liver injury (DILI) is major problem for both the drug industry and for clinicians. There are two basic categories of DILI: intrinsic and idiosyncratic. The former is the chief cause of acute liver failure in several developed countries, while the latter is the most common reason for post-marketing drug withdrawal and a major reason for failure to approve new drugs in the U.S. Although considerably more progress has been made in the study of intrinsic DILI, our understanding of both forms of drug hepatotoxicity remains incomplete. Recent work involving microRNAs (miRNAs) has advanced our knowledge of DILI in two ways: (1) possible roles of miRNAs in the pathophysiological mechanisms of DILI have been identified, and (2) circulating miRNA profiles have shown promise for the detection and diagnosis of DILI in clinical settings. The purpose of this review is to summarize major findings in these two areas of research. Taken together, exciting progress has been made in the study of miRNAs in DILI. Possible mechanisms through which miRNA species contribute to the basic mechanisms of DILI are beginning to emerge, and new miRNA-based biomarkers have the potential to greatly improve diagnosis of liver injury and prediction of patient outcomes.