The impact of nurse navigation on timeliness to treatment for benign high-risk breast pathology.

PURPOSE: High-risk breast pathology is a breast cancer risk factor for which timely treatment is crucial. Nurse navigation programs have been implemented to minimize delays in patient care. This study evaluated nurse navigation in terms of timeliness to surgery for patients with high-risk breast pathology. METHODS: This was a single-institution, retrospective review of patients with identified high-risk breast pathology undergoing lumpectomy between January 2017 and June 2019. Patients were stratified into cohorts based on periods with and without nurse navigation. Preoperative and postoperative time to care as well as demographic and tumor characteristics were compared using univariate and multivariate analysis. RESULTS: 100 patients had assigned nurse navigators and 29 patients did not. Nurse navigation was associated with reduced time from referral to date of surgery (DOS) by 16.9 days (p = 0.003). Patients > 75 years had a shorter time to first appointment (p = 0.03), and patients with Medicare insurance had a reduced time from referral to DOS (p = 0.005). 20% of all patients were upstaged to cancer on final surgical pathology. CONCLUSION: Nurse navigation was significantly associated with decreased time to care for patients with high-risk breast pathology undergoing lumpectomy. We recommend nurse navigation programs as part of a comprehensive approach for patients with high-risk breast pathology.

Hidradenitis suppurativa presenting as mammillary fistula in a teenage girl.

Hidradenitis suppurativa (HS) is a common skin disease in children and young adults. In this report, we describe an unusual case of HS presenting as a mammillary fistula (MF) in a teenage female. A thorough dermatologic history and exam resulted in diagnosis of HS. Identifying the underlying disease is key to appropriate treatment of a relapsing MF in the setting of HS.

Treatment of Pediatric Pyoderma Gangrenosum With Modified Negative Pressure Wound Therapy and Intralesional Corticosteroids: A Case Report.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare ulcerative skin disease; its etiology is unknown, though it is often associated with autoimmune diseases. Pyoderma gangrenosum results in significant morbidity and exquisite pain that affects health-related quality of life. Wound healing is delayed, and patients often experience relapse. Pyoderma gangrenosum is susceptible to pathergy and deterioration with surgical intervention or other trauma; therefore, treatment includes atraumatic wound care, infection management, and local or systemic immunosuppression. CASE: We describe the use of modified negative pressure wound therapy (NPWT) with intralesional and topical steroids for the treatment of PG in a 15-year-old female patient with ulcerative colitis and a staged J-pouch ileoanal reconstruction. The patient and her family refused all systemic therapy due to prior steroid-associated weight gain. She was unable to tolerate conscious dressing changes, further complicating the treatment plan. Procedural interventions such as NPWT have been used previously for PG; however, they can cause wound pathergy and subsequent wound deterioration. Modified NPWT in conjunction with topical and intralesional steroids induced wound healing without producing pathergy. CONCLUSION: Timely recognition of PG is crucial to appropriate delivery of care. Modified NPWT and localized corticosteroid treatment were key to promoting wound healing in this case of pediatric PG.

Where is the evidence? The use of routinely-collected patient data to retain adults on antiretroviral treatment in low and middle income countries-a state of the evidence review.

Retention rates in antiretroviral treatment (ART) in low- and middle-income countries are suboptimal for meeting global "90-90-90" treatment targets. Interventions using routinely collected patient data to follow up with ART defaulters is recommended to improve retention; yet, little is documented on how these data are used in practice. This state of the evidence review summarizes how facilities and programmes use patient data to retain adults on ART in low- and middle-income countries, and what effect, if any, these interventions have on retention. The authors searched peer-reviewed and grey literature in PubMed, POPLINE, OVID, Google Scholar, and select webpages; screened publications for relevance; and applied eligibility criteria to select articles for inclusion. Over 4,000 records were found, of which 19 were eligible. Interventions assessed within the studies were sorted into three categories: patient tracing (18), data reviews (3), and improved data capture systems (9). Nine studies demonstrated increased retention or reduced lost to follow-up; however, the quality of evidence was weak. We recommend that future research investigates how various combinations of these interventions are being implemented and their effectiveness on ART retention across diverse country contexts, taking into account cultural, social and economic barriers and differences in countries' HIV epidemics and health information systems.

The relationship between health worker stigma and uptake of HIV counseling and testing and utilization of non-HIV health services: the experience of male and female sex workers in Kenya.

The barrier HIV-stigma presents to the HIV treatment cascade is increasingly documented; however less is known about female and male sex worker engagement in and the influence of sex-work stigma on the HIV care continuum. While stigma occurs in all spheres of life, stigma within health services may be particularly detrimental to health seeking behaviors. Therefore, we present levels of sex-work stigma from healthcare workers (HCW) among male and female sex workers in Kenya, and explore the relationship between sex-work stigma and HIV counseling and testing. We also examine the relationship between sex-work stigma and utilization of non-HIV health services. A snowball sample of 497 female sex workers (FSW) and 232 male sex workers (MSW) across four sites was recruited through a modified respondent-driven sampling process. About 50% of both male and female sex workers reported anticipating verbal stigma from HCW while 72% of FSW and 54% of MSW reported experiencing at least one of seven measured forms of stigma from HCW. In general, stigma led to higher odds of reporting delay or avoidance of counseling and testing, as well as non-HIV specific services. Statistical significance of relationships varied across type of health service, type of stigma and gender. For example, anticipated stigma was not a significant predictor of delay or avoidance of health services for MSW; however, FSW who anticipated HCW stigma had significantly higher odds of avoiding (OR = 2.11) non-HIV services, compared to FSW who did not. This paper adds to the growing evidence of stigma as a roadblock in the HIV treatment cascade, as well as its undermining of the human right to health. While more attention is being paid to addressing HIV-stigma, it is equally important to address the key population stigma that often intersects with HIV-stigma.

The HIV Treatment Gap: Estimates of the Financial Resources Needed versus Available for Scale-Up of Antiretroviral Therapy in 97 Countries from 2015 to 2020.

BACKGROUND: The World Health Organization (WHO) released revised guidelines in 2015 recommending that all people living with HIV, regardless of CD4 count, initiate antiretroviral therapy (ART) upon diagnosis. However, few studies have projected the global resources needed for rapid scale-up of ART. Under the Health Policy Project, we conducted modeling analyses for 97 countries to estimate eligibility for and numbers on ART from 2015 to 2020, along with the facility-level financial resources required. We compared the estimated financial requirements to estimated funding available. METHODS AND FINDINGS: Current coverage levels and future need for treatment were based on country-specific epidemiological and demographic data. Simulated annual numbers of individuals on treatment were derived from three scenarios: (1) continuation of countries' current policies of eligibility for ART, (2) universal adoption of aspects of the WHO 2013 eligibility guidelines, and (3) expanded eligibility as per the WHO 2015 guidelines and meeting the Joint United Nations Programme on HIV/AIDS "90-90-90" ART targets. We modeled uncertainty in the annual resource requirements for antiretroviral drugs, laboratory tests, and facility-level personnel and overhead. We estimate that 25.7 (95% CI 25.5, 26.0) million adults and 1.57 (95% CI 1.55, 1.60) million children could receive ART by 2020 if countries maintain current eligibility plans and increase coverage based on historical rates, which may be ambitious. If countries uniformly adopt aspects of the WHO 2013 guidelines, 26.5 (95% CI 26.0 27.0) million adults and 1.53 (95% CI 1.52, 1.55) million children could be on ART by 2020. Under the 90-90-90 scenario, 30.4 (95% CI 30.1, 30.7) million adults and 1.68 (95% CI 1.63, 1.73) million children could receive treatment by 2020. The facility-level financial resources needed for scaling up ART in these countries from 2015 to 2020 are estimated to be US$45.8 (95% CI 45.4, 46.2) billion under the current scenario, US$48.7 (95% CI 47.8, 49.6) billion under the WHO 2013 scenario, and US$52.5 (95% CI 51.4, 53.6) billion under the 90-90-90 scenario. After projecting recent external and domestic funding trends, the estimated 6-y financing gap ranges from US$19.8 billion to US$25.0 billion, depending on the costing scenario and the U.S. President's Emergency Plan for AIDS Relief contribution level, with the gap for ART commodities alone ranging from US$14.0 to US$16.8 billion. The study is limited by excluding above-facility and other costs essential to ART service delivery and by the availability and quality of country- and region-specific data. CONCLUSIONS: The projected number of people receiving ART across three scenarios suggests that countries are unlikely to meet the 90-90-90 treatment target (81% of people living with HIV on ART by 2020) unless they adopt a test-and-offer approach and increase ART coverage. Our results suggest that future resource needs for ART scale-up are smaller than stated elsewhere but still significantly threaten the sustainability of the global HIV response without additional resource mobilization from domestic or innovative financing sources or efficiency gains. As the world moves towards adopting the WHO 2015 guidelines, advances in technology, including the introduction of lower-cost, highly effective antiretroviral regimens, whose value are assessed here, may prove to be "game changers" that allow more people to be on ART with the resources available.

Botanical Briefs: Fig Phytophotodermatitis (Ficus carica).

Patients presenting with a linear, erythematous, blistering eruption may experience a sudden painful sunburn that seems to get worse rather than better with time. In warm climates, exposure to the common fig tree (Ficus carica) may be the culprit. Dermatologists should recognize fig phytophotodermatitis as a possible cause and help the patient connect their symptoms with the inciting agent as well as administer proper treatment.

Botanical Briefs: Handling the Heat From Capsicum Peppers.

Capsicum peppers-including chili peppers, paprika, and red peppers-are native to the Americas but used worldwide in spicy dishes. Capsaicin, the active ingredient of Capsicum peppers, is used topically to treat musculoskeletal pain, neuropathy, and other conditions. Capsaicin binds the transient receptor potential vanilloid 1 (TRPV1), releasing substance P and desensitizing nerves with long-term use. Capsicum peppers and capsaicin products (eg, medications, cosmetics, pepper sprays) can provoke an irritant contact dermatitis, causing erythema and cutaneous burning. Capsaicin-induced dermatitis can be relieved by washing the area with soap, detergents, or oily compounds. Ice water or high-potency topical steroids also can help. Capsaicin is available in creams, lotions, and patches. Synthetic TRPV1-agonist injectables based on capsaicin are in clinical trials for use in localized pain. Capsaicin is a neuropeptide-active compound found in Capsicum peppers with many promising applications; however, dermatologists should be aware of possible skin reactions to these plants and medications derived from them.

Dermatology practice updates in mycobacterial disease.

Atypical mycobacterial infections are commonly acquired through exposure to water, and tuberculosis remains highly endemic in many parts of the world. In this era of global connection, travel, and immigration, it is more important than ever to maintain a high index of suspicion for infection from cutaneous tuberculosis and atypical mycobacteria. Epidemics related to surgical procedures have been related to inadequate sterilization, as almost 50% of public water supplies harbor mycobacteria. Improved diagnostic techniques for these microbes, including Auramine-Rhodamine staining and rapid detection of mycobacteria and drug susceptibilities through PCR and MALDI-TOF, have improved detection and treatment outcomes. Given an increasing number of patients on immunosuppressive therapies, clinicians must remain vigilant.

Botanical Briefs: Ginkgo (Ginkgo biloba).

Ginkgo biloba is an ancient tree that originated in China and is now cultivated worldwide for its ornamental foliage and resistance to disease and pollution. Direct or indirect interaction with the ginkgo tree can cause allergic contact dermatitis, with erythematous papules, vesicles, and edema on exposed areas due to ginkgolic acids. On the other hand, ginkgo extract, produced from the tree leaves, has long been used in Chinese traditional medicine and is now a popularly consumed herbal medicine. Components of the ginkgo tree can cause dermatitis, but active ingredients in ginkgo extract may be beneficial; research on its safety and potential uses is ongoing.

Aberrant IgA1 glycosylation is inherited in familial and sporadic IgA nephropathy.

IgA nephropathy (IgAN) is a complex trait determined by genetic and environmental factors. Most IgAN patients exhibit a characteristic undergalactosylation of the O-glycans of the IgA1 hinge region, which promotes formation and glomerular deposition of immune complexes. It is not known whether this aberrant glycosylation is the result of an acquired or inherited defect, or whether the presence of aberrant IgA1 glycoforms alone can produce IgAN. A newly validated lectin enzyme-linked immunosorbent assay (ELISA) was used to determine the serum level of galactose-deficient IgA1 (Gd-IgA1) in a cohort of 89 IgAN patients and 266 of their relatives. High Gd-IgA1 levels (> or =95th percentile for controls) were observed in all 5 available patients with familial IgAN, in 21 of 45 (47%) of their at-risk relatives (assuming autosomal dominant inheritance), and in only 1 of 19 (5%) of unrelated individuals who married into the family. This provides evidence that abnormal IgA1 glycosylation is an inherited rather than acquired trait. Similarly, Gd-IgA1 levels were high in 65 of 84 (78%) patients with sporadic IgAN and in 50 of 202 (25%) blood relatives. Heritability of Gd-IgA1 was estimated at 0.54 (P = 0.0001), and segregation analysis suggested the presence of a major dominant gene on a polygenic background. Because most relatives with abnormal IgA1 glycoforms were asymptomatic, additional cofactors must be required for IgAN to develop. The fact that abnormal IgA1 glycosylation clusters in most but not all families suggests that measuring Gd-IgA1 may help distinguish patients with different pathogenic mechanisms of disease.

Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage.

Topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and meiosis and is a highly attractive target for chemotherapeutic agents. We have identified previously topoisomerase II and heat shock protein 90 (Hsp90) as part of a complex. In this paper we demonstrate that drug combinations targeting these two enzymes cause a synergistic increase in apoptosis. The objective of our study was to identify the mode of cell killing and the mechanism behind the increase in topoisomerase II mediated DNA damage. Importantly we demonstrate that Hsp90 inhibition results in an increased topoiosmerase II activity but not degradation of topoisomerase II and it is this, in the presence of a topoisomerase II poison that causes the increase in cell death. Our results suggest a novel mechanism of action where the inhibition of Hsp90 disrupts the Hsp90-topoisomerase II interaction leading to an increase in and activation of unbound topoisomerase II, which, in the presence of a topoisomerase II poison leads to the formation of an increased number of cleavable complexes ultimately resulting in rise in DNA damage and a subsequent increase cell death.

Can differentiated care models solve the crisis in HIV treatment financing? Analysis of prospects for 38 countries in sub-Saharan Africa.

INTRODUCTION: Rapid scale-up of antiretroviral therapy (ART) in the context of financial and health system constraints has resulted in calls to maximize efficiency in ART service delivery. Adopting differentiated care models (DCMs) for ART could potentially be more cost-efficient and improve outcomes. However, no study comprehensively projects the cost savings across countries. We model the potential reduction in facility-level costs and number of health workers needed when implementing two types of DCMs while attempting to reach 90-90-90 targets in 38 sub-Saharan African countries from 2016 to 2020. METHODS: We estimated the costs of three service delivery models: (1) undifferentiated care, (2) differentiated care by patient age and stability, and (3) differentiated care by patient age, stability, key vs. general population status, and urban vs. rural location. Frequency of facility visits, type and frequency of laboratory testing, and coverage of community ART support vary by patient subgroup. For each model, we estimated the total costs of antiretroviral drugs, laboratory commodities, and facility-level personnel and overhead. Certain groups under four-criteria differentiation require more intensive inputs. Community-based ART costs were included in the DCMs. We take into account underlying uncertainty in the projected numbers on ART and unit costs. RESULTS: Total five-year facility-based ART costs for undifferentiated care are estimated to be US$23.33 billion (95% confidence interval [CI]: $23.3-$23.5 billion). An estimated 17.5% (95% CI: 17.4%-17.7%) and 16.8% (95% CI: 16.7%-17.0%) could be saved from 2016 to 2020 from implementing the age and stability DCM and four-criteria DCM, respectively, with annual cost savings increasing over time. DCMs decrease the full-time equivalent (FTE) health workforce requirements for ART. An estimated 46.4% (95% CI: 46.1%-46.7%) fewer FTE health workers are needed in 2020 for the age and stability DCM compared with undifferentiated care. CONCLUSIONS: Adopting DCMs can result in significant efficiency gains in terms of reduced costs and health workforce needs, even with the costs of scaling up community-based ART support under DCMs. Efficiency gains remained flat with increased differentiation. More evidence is needed on how to translate analyzed efficiency gains into implemented cost reductions at the facility level.

The identification and characterisation of a functional interaction between arginyl-tRNA-protein transferase and topoisomerase II.

Topoisomerase II is required for the viability of all eukaryotic cells. It plays important roles in DNA replication, recombination, chromosome segregation, and the maintenance of the nuclear scaffold. Proteins that interact with and regulate this essential enzyme are of great interest. To investigate the role of proteins interacting with the N-terminal domain of the Saccharomyces cerevisiae topoisomerase II, we used a yeast two-hybrid protein interaction screen. We identified an interaction between arginyl-tRNA-protein transferase (Ate1) and the N-terminal domain of the S. cerevisiae topoisomerase II, including the potential site of interaction. Ate1 is a component of the N-end rule protein degradation pathway which targets proteins for degradation. We also propose a previously unidentified role for Ate1 in modulating the level of topoisomerase II through the cell cycle.

The topoisomerase II-Hsp90 complex: a new chemotherapeutic target?

The modulation of DNA topology by topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and has thus become a highly attractive target for chemotherapeutic drugs. However, these drugs are highly toxic, and so new approaches are required. One such strategy is to target topoisomerase II-interacting proteins. Here we report the identification of potential topoisomerase II-associated proteins using immunoprecipitation, followed by 1-D and 2-D gel electrophoresis and MALDI-TOF mass spectrometry. A total of 23 proteins were identified and, of these, 17 were further validated as topoisomerase IIalpha-associated proteins by coimmunoprecipitation and Western blot. Six of the interacting proteins were cellular chaperones, including 3 members of the heat shock protein-90 (Hsp90) family, and so the effect of Hsp90 modulation on the antitumor activity of topoisomerase II drugs was tested using the sulforhodamine B assay, clonogenic assays and a xenograft model. The Hsp90 inhibitors geldanamycin, 17-AAG (17-allylamino-17-demethoxygeldanamycin) and radicicol significantly enhanced the activity of the topoisomerase II poisons etoposide and mitoxantrone in vitro and in vivo. Thus, our method of identifying topoisomerase II-interacting proteins appears to be effective, and at least 1 novel topoisomerase IIalpha-associated protein, Hsp90, may represent a valid drug target in the context of topoisomerase II-directed chemotherapy.