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Several new monoclonal antibodies that interfere with interleukin (IL) cascades have come to market in recent years. They follow a generation of drugs that block tumor necrosis factor (TNF). It has been well established that TNF is important in the containment of Mycobacterium tuberculosis (Mtb) and that blocking this cytokine increases the risk of tuberculosis (TB) infection. Thus, judicious screening for Mtb of patients taking TNF blocking drugs has been the standard of care. It remains unclear if the newer monoclonal, interleukin blocking drugs, which affect IL-12, IL-23, and IL-17 pathways are associated with risk of Mtb reactivation. Herein we discuss what is known about the immunologic response to Mtb and discuss the data that is currently available for the new interleukin monoclonal antibody blocking medications regarding the risk of latent TB reactivation or active TB infection.

Hidradenitis suppurativa (HS) is an inflammatory disorder that is characterized by chronic deep-seated nodules, abscesses, fistulae, sinus tracts, and scars in the axilla, inguinal area, submammary folds, and perianal area. This disfiguring condition is accompanied by pain, embarrassment, and a significantly decreased quality of life. Although the mechanism of HS has not been entirely elucidated, lesion formation is believed to center around follicular hyperkeratosis within the pilosebaceous-apocrine unit. Recent research has provided new insight into the role of cytokines in the pathogenesis of HS, helping close some existing knowledge gaps in the development of this condition. The first article in this continuing medical education series reviews HS epidemiology, clinical presentation, and classification. We also provide an update on the most recent understanding of HS pathogenesis, including the central role of inflammatory cytokines and other contributing factors, such as genetics, hormones, and pathogenic microorganisms. [ABSTRACT FROM AUTHOR]

The treatment of hidradenitis suppurativa (HS) has remained challenging because of the many knowledge gaps regarding etiology. However, recent studies into the pathogenesis of HS have enabled the investigation of newer therapies. The second article in this continuing medical education series reviews the evidence for established therapies for HS, including anti-inflammatories, antibiotics, and surgery. New and emerging therapies that specifically target cytokines involved in HS pathogenesis will be covered. The potential therapeutic roles of anticytokine therapies, including both the expanded application of existing molecules as well as the specific development of novel therapies for HS are discussed. With increased attention on HS and with numerous clinical trials currently underway, we hope that the variety of treatment options for HS will be expanded. [ABSTRACT FROM AUTHOR]

Background: The unique health care needs of the homeless population have been well-documented in the literature. However, fewer studies are available assessing the prevalent dermatologic conditions that impact this population. Objective: The purpose of our study was to assess the frequency of dermatologic conditions occurring in a shelter-based homeless population, to understand patient demographic characteristics, and determine the suspected skin malignancy rate. Methods: We completed a retrospective chart review of patients seen at the free dermatology clinic held at the South Park Inn (SPI) homeless shelter in Hartford. Two-hundred-seventy-three patient paper charts from August 2008 to February 2016 were reviewed. Results: The most common dermatologic conditions included acne vulgaris (18.7%), atopic dermatitis (10.6%), tinea pedis (9.2%), xerosis (8.1%), and folliculitis (5.1%). The rate of suspected skin malignancies in this population was 2.5%. Conclusions: Some of our findings mirror the frequency of dermatologic conditions identified in sheltered homeless populations in previous studies. Differences seen may be attributed to geographic and demographic variability. The suspected skin cancer rate, which has been rarely studied, is of particular interest due to this population's risk for chronic sun exposure, lack of consistent sunscreen use, and poor access to dermatologic screening, and should be more thoroughly investigated in future studies. [ABSTRACT FROM AUTHOR]

Background Newer psoriasis treatments tout higher efficacy but are generally more expensive. Objective We sought to estimate the cost efficacy of systemic psoriasis treatments that have been approved by the US Food and Drug Administration (FDA). Methods A literature review of systemic psoriasis treatments that have been approved by the FDA was performed for the primary end point of a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75). Medication cost was referenced by wholesale acquisition cost (WAC), laboratory fees were obtained from the American Medical Association, and office visit fees are standard at our university. Total expenses were standardized by calculating cost per month of treatment considering the number needed to treat (NNT) to achieve PASI 75. Results Methotrexate ($794.05-1502.51) and cyclosporine ($1410.14-1843.55) had the lowest monthly costs per NNT to achieve PASI 75. The most costly therapies were infliximab ($8704.68-15,235.52) and ustekinumab 90 mg ($12,505.26-14,256.75). Monthly costs per NNT to achieve PASI 75 for other therapies were as follows: narrowband ultraviolet B light phototherapy ($2924.73), adalimumab ($3974.61-7678.78), acitretin ($4137.71-14,148.53), ustekinumab 45 mg ($7177.89-7263.99), psoralen plus ultraviolet A light phototherapy ($7499.46-8834.98), and etanercept ($8284.71-10,674.89). Limitations Drug rebates and incentives, potential adverse effects, comorbidity risk reduction, ambassador programs, and combination therapies were excluded. Conclusion Our study provides meaningful cost efficacy data that may influence psoriasis treatment selection. [ABSTRACT FROM AUTHOR]

Objective: To investigate the lost revenue associated with Medicaid patients in a university-based dermatology practice over a one-year period compared to non-Medicaid patients. Specifically, the goal was to investigate the change in revenue if Medicaid visits were associated with a range of copayments. Results: The total billed across all encounters for the 2014 - 2015 fiscal year was $31 017 159, of which $3 715 393 (13.61%) was for Medicaid. The total revenue for all encounters was $12 267 832, of which $420 230 (3.55%) was for Medicaid. After adding potential copayments, the reduced financial impact that such fees would have had on our practice for the past fiscal year ranged from $745.85 at $0.05/visit to $149 170 at $10/visit. Conclusion: Adding a small copayment for Medicaid patients would decrease lost revenue. The degree of financial impact would vary based on the size of the copayment. Broad adoption of such a plan could significantly help hospitals reduce lost revenue. [ABSTRACT FROM AUTHOR]

Background: Opportunity cost is the potential gain or loss when a person chooses to perform an activity over its next best alternative. With respect to surgery, opportunity cost can occur if a less efficient technology uses more operating time than its next best alternative. This additional operating time could be used in a productive way that, when economically valued, adds a “cost” to the less efficient technology. Although fundamental to the economist''s view of costs and widely used in economic assessments, opportunity cost analysis is infrequently used in economic evaluation of surgical technology. Previous cost comparison studies in the surgical literature have not addressed opportunity cost when estimating the efficiency of competing technologies. With increasing healthcare costs and new technologic advancements in surgery, a surgeon''s ability to understand opportunity cost and apply it when choosing between two comparable technologies is essential. Our objective is to present a system to estimate the opportunity cost for given surgical specialties and present a model to demonstrate its principle. Methods: To demonstrate the principle of opportunity cost, our model used a hypothetical scenario comparing two clinically equivalent technologies that differed in that the use of one device (Device A) extended operating time in a hypothetical procedure by 30 minutes compared to its competitor device (Device B). How this extra operating time could potentially be used was then valued using the opportunity cost calculated by our study design. Our study design included 5 surgical procedures from 5 surgical specialties that were elective, profitable, high-volume (performed more than 100 times per year), and had a duration of less than 240 minutes. The data were taken from a university hospital setting in 2007 and included procedure volume, profit margin, and duration. The outcome measure was opportunity cost, which was estimated by dividing the selected procedure''s profit margin by its duration. Results: Surgical specialty results are presented in the accompanying Tables. Otolaryngology has the highest opportunity cost at $38/min. This cost was calculated by using myringotomy as the procedure that was elective, short in duration, performed in high volume, and provided the highest profit margin. By applying our model, the otolaryngology surgeon using the less efficient Device A to perform a hypothetical procedure would incur an opportunity cost of $1,140 ($38/min × 30 min). This is because he could have performed additional myringotomy procedures in the time saved had he instead used the more efficient Device B in his hypothetical cases. General surgery has the lowest opportunity cost at $9/min; laparoscopic inguinal hernia repair was the procedure used for its calculation. Under the same model, the general surgeon using Device A would incur an opportunity cost of $270 ($9/min × 30 min). This is because the general surgeon could have performed additional laparoscopic femoral/hernia repairs had she used the more efficient Device B in her hypothetical cases. Conclusion: In acknowledging opportunity cost, a surgeon can more accurately compare the efficiency of competing surgical devices. This comparison is carried out by estimating and applying a dollar amount to the potential utility of time created by the use of the less efficient device. [Copyright &y& Elsevier]

The delivery of antigenic proteins in the context of a DNA vaccine leads to the intracellular synthesis of antigen and the induction of both humoral and cellular immune responses. Subsequent to immune activation, any transfected cell expressing the immunogenic protein should, by the rules of immunology, become a legitimate target for removal by immune-mediated mechanisms. Herein, we have used an indirect assay of myocyte integrity following intramuscular (i.m.) delivery of a DNA vaccine, in mice with various immune deficiencies, to determine which immunological mechanisms may be involved in destruction of antigenexpressing cells. We demonstrate that destruction of antigenexpressing myocytes following i.m. injection of a DNA vac- cine is dependent on major histocompatability complex (MHC) class II restricted CD4[sup +] T cell activation, but is not mediated solely by MHC I-restricted or perforin-mediated lysis and appears to have a component that is antibodymediated. Although we studied myocytes, the results likely represent what happens to any transfected cell expressing a foreign antigen. This study underscores the ability of DNA vaccines at inducing antigen-specific immune responses that include a number of effector mechanisms. From the perspective of gene therapy, this study highlights the significance of immune activation when considering strategies where maintenance of therapeutic gene expression is desired. [ABSTRACT FROM AUTHOR]

The history of vaccine development spans a relatively short period of time in comparison to the history of human civilization. However, monumental advances in the field of vaccines have been made in effort to combat infectious disease. These advances have led to a reduction, and in one case the complete eradication, of the burden of some infectious diseases of the world. Throughout the history of vaccine development, milestone discoveries can be identified that have shaped the field of vaccine development, as we know it. These milestones include the first official use of a vaccine by Edward Jenner, the attenuation principals observed by Pasteur, the development of cell culture for the propagation of viruses, and the production of first recombinant protein based vaccine for hepatitis B. As vaccine development progresses into the 21st century, it will be important to build on the experience and knowledge generated in the past, in an effort to surpass the limitations that currently hamper the development of new and more effective vaccine technologies. Presented here is an overview on the history of vaccine development and its influence on the positioning of current trends and future considerations.

The development of mucosal vaccines for humans has been hindered by the lack of safe yet effective mucosal adjuvants. Bacterial toxins are commonly used as adjuvants in animal models, but they are too toxic for use in humans. A novel class of adjuvant is CpG DNA, which contains unmethylated CpG dinucleotides in particular base contexts (CpG motifs). CpG DNA is most often coadministered with antigen in the form of synthetic oligodeoxynucleotides (CpG ODN), which are made with a nuclease-resistant phosphorothioate backbone. The vast majority of studies using CpG DNA as adjuvant have been with parenteral delivery; recently, however, mucosal immunization with CpG DNA as adjuvant has also been shown to induce both systemic (humoral and cellular) and mucosal antigen-specific immune responses. This review will highlight the recent uses of CpG DNA as an adjuvant at mucosal surfaces.

CpG DNA has been shown to be a potent adjuvant in many disease models. Most studies using CpG DNA as adjuvant have used parenteral delivery, but more effective protection against mucosal pathogens could be achieved with effective mucosal immunization. Recently, mucosal immunization with CpG DNA as an adjuvant has been shown to induce both systemic (humoral and cellular) and mucosal antigen-specific immune responses. This review will concentrate on the use of CpG DNA as an adjuvant for the induction of mucosal immunity.

Hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. Development of vaccines to prevent HCV infection, or at least prevent progression to chronicity, is a major goal. In mice and rhesus macaques, a DNA vaccine encoding cell-surface HCV-envelope 2 (E2) glycoprotein stimulated stronger immune responses than a vaccine encoding intracellular E2. Therefore, we used DNA encoding surface-expressed E2 to immunize chimpanzees 2768 and 3001. Chimpanzee 3001 developed anti-E2 after the second immunization and antibodies to hypervariable region 1 (HVR1) after the third immunization. Although chimpanzee 2768 had only low levels of anti-E2 after the third immunization, an anamnestic response occurred after HCV challenge. CTL responses to E2 were not detected before challenge, but a strong response was detected after HCV challenge in chimpanzee 2768. An E2-specific CD4+ response was detected in chimpanzee 2768 before challenge and in both chimpanzees postchallenge. Three weeks after the last immunization, animals were challenged with 100 50% chimpanzee-infectious doses (CID(50)) of homologous monoclonal HCV. As a control, a naive chimpanzee was inoculated with 3 CID(50) of the challenge virus. The vaccine did not generate sterilizing immunity because both vaccinated chimpanzees were infected. However, both vaccinated chimpanzees resolved the infection early whereas the control animal became chronically infected. Compared with the control animal, hepatitis appeared earlier in the course of the infection in both vaccinated chimpanzees. Therefore, DNA vaccine encoding cell surface-expressed E2 did not elicit sterilizing immunity in chimpanzees against challenge with a monoclonal homologous virus, but did appear to modify the infection and might have prevented progression to chronicity.

ALX40-4C is an antiretrovirus agent that has been found to have some inhibitory properties against human immunodeficiency virus (HIV) replication in vitro. The compound was designed as a competitor of the HIV Tat protein for TAR binding. In addition to its anti-HIV properties, it has demonstrated the ability to inhibit in vitro replication of herpes simplex virus types 1 and 2 as well as human cytomegalovirus. Subsequently, in vivo pharmacokinetic evaluation of ALX40-4C necessitated the establishment of a detection system for the measurement of ALX40-4C in subject serum. For this purpose, an indirect-competition enzyme-linked immunosorbent assay with generated rabbit anti-ALX40-4C antiserum was developed. The original assay took 12 h to complete and required many manipulations. Herein, we describe alterations to the system that resulted in the overall reduction in assay time and manipulation. We demonstrate that our alterations do not affect the specificity or sensitivity of the assay compared to that of the original system. ALX40-4C levels in spiked serum samples as well as drug levels from patient samples were used to validate the assay.