Melanoma developing in a nevoid melanocytoma with myxoid changes: a case report.

Nevoid and myxoid melanoma are rare variants of melanoma; association of the two is a unique finding. Nevoid melanoma is characterized by morphologic resemblance to a nevus, whereas myxoid melanoma demonstrates a basophilic mucinous matrix. We present an atypical case of a melanoma progressing from a nevoid melanocytoma with myxoid changes. A 78-year-old female presented with a pigmented growth on her right thigh. Biopsy demonstrated a biphenotypic melanocytic proliferation composed of a nodule showing epithelioid melanocytes with enlarged nuclei, prominent nucleoli, lack of maturation, and abundant amphophilic cytoplasm with a rare mitotic figure. These findings were suggestive of melanoma along with a nevoid dermal component and myxoid stroma. FISH testing revealed a homozygous loss of 9p21 in the atypical component. SNP-microarray from the nevoid component demonstrated three abnormalities including a gain of whole chromosome 8, as well as loss of a copy of nearly an entire chromosome 9 and 16q most consistent with a melanocytoma.

A review of topical vitamin C derivatives and their efficacy.

Vitamin C is a popular ingredient in over-the-counter cosmeceuticals due to its many biological functions in maintaining and improving skin health by treating UV damage, improving discoloration, and boosting collagen production. Several chemically modified derivatives of vitamin C have been developed in an attempt to increase the stability, percutaneous absorption, and overall activity of this ingredient in topical formulations. The goal of this review is to evaluate the differences between vitamin C derivatives that have been designed for cosmeceutical use and their efficacy.

Alopecia totalis following hand-foot-and-mouth disease.

We present a case of a 13-month-old male patient with alopecia totalis that began two months after an episode of hand-foot-and-mouth disease. It is hypothesized that the viral infection triggered an autoimmune response, which lead to production of lymphocytes targeting an antigen present in the hair bulb. Future research is necessary to determine whether and how the pathophysiology of alopecia totalis may be triggered by viral infection.

Clinical efficacy of popular oral hair growth supplement ingredients.

Hair supplements are a vast and growing industry. Patients often turn to oral supplements to address hair concerns as they are easily accessible. There are numerous products on the market, many with thousands of reviews (both positive and negative). Nutritional supplements are regulated by the FDA as foods instead of drugs, meaning they do not have to prove their efficacy and safety before becoming available to consumers. While some oral supplements have strong evidence supporting their use for hair growth, many ingredients have not been tested in clinical trials, have only in vitro evidence for hair growth, or have only been tested in animals. Given these industry characteristics, it is important for dermatologists to be aware of the safety and utility of these ingredients to provide appropriate counseling to their patients. The goal of this review is to evaluate the efficacy of popular hair growth oral supplement ingredients and formulations. This review does not address the topical formulations of these ingredients and their effects on hair growth.

Acrokeratosis paraneoplastica (Bazex syndrome) as the presenting sign of pancreatic adenocarcinoma.

Acrokeratosis paraneoplastica (Bazex syndrome) is a rare paraneoplastic skin condition characterised by acral psoriasiform plaques, with a predilection for the nose, ears, hands and feet. It typically presents before the discovery of an internal malignancy and is often misdiagnosed as an inflammatory dermatitis that does not respond to treatment. It is associated with squamous cell carcinoma of the aerodigestive tract and lung, as well as adenocarcinoma of the lung, colon and gastrum. Here, we describe the second reported case of Bazex syndrome in the setting of pancreatic adenocarcinoma and the first such case in a patient of African ancestry.

Characteristics of the vaginal microbiome in women with and without clinically confirmed vulvodynia.

BACKGROUND: Vulvodynia (idiopathic vulvar pain) affects up to 8% of women by age 40 years, has a poorly understood etiology, and has variable treatment efficacy. Several risk factors are associated with vulvodynia from a history of yeast infections to depression and allergies. Recent work suggests an altered immune inflammatory mechanism plays a role in vulvodynia pathophysiology. Because the vaginal microbiome plays an important role in local immune-inflammatory responses, we evaluated the vaginal microbiome among women with vulvodynia compared with controls as 1 component of the immune system. OBJECTIVE: The objective of the study was to characterize the vaginal microbiome in women with clinically confirmed vulvodynia and age-matched controls and assess its overall association with vulvodynia and how it may serve to modify other factors that are associated with vulvodynia as well. STUDY DESIGN: We conducted a case-control study of 234 Minneapolis/Saint Paul-area women with clinically confirmed vulvodynia and 234 age-matched controls clinically confirmed with no history of vulvar pain. All participants provided vulvovaginal swab samples for culture-based and non-culture (sequencing)-based microbiological assessments, background and medical history questionnaires on demographic characteristics, sexual and reproductive history, and history of psychosocial factors. Vaginal microbiome diversity was assessed using the Shannon alpha diversity Index. Data were analyzed using logistic regression. RESULTS: Culture and molecular-based analyses of the vaginal microbiome showed few differences between cases and controls. However, among women with alpha diversity below the median (low), there was a strong association between increasing numbers of yeast infections and vulvodynia onset, relative to comparable time periods among controls (age-adjusted odds ratio, 8.1, 95% confidence interval, 2.9-22.7 in those with 5 or more yeast infections). Also among women with low-diversity microbiomes, we observed a strong association between moderate to severe childhood abuse, antecedent anxiety, depression, and high levels of rumination and vulvodynia with odds ratios from 1.83 to 2.81. These associations were not observed in women with high-diversity microbiomes. CONCLUSION: Although there were no overall differences in microbiome profiles between cases and controls, vaginal microbiome diversity influenced associations between environmental and psychosocial risk factors and vulvodynia. However, it is unclear whether vaginal diversity modifies the association between the risk factors and vulvodynia or is altered as a consequence of the associations.

Disseminated cryptococcosis presenting with cutaneous involvement in an immunocompromised patient.

Cryptococcosis is a fungal infection that typically affects immunocompromised patients. It most commonly affects the lungs and may then disseminate to the central nervous system, bone, skin, and adrenal glands. Herein, we describe a 69-year-old man who presented with skin lesions as the initial manifestation of disseminated cryptococcosis. Initial workup led to an assumption that the patient was immunocompetent. Later in the clinical course, idiopathic depletion of CD4 T cells was discovered. This case highlights that disseminated cryptococcosis may present with cutaneous symptoms even when there is no evidence of pulmonary or central nervous system involvement and may be the first sign of an underlying cellular immune dysfunction.

Randomized Phase II Study of Paclitaxel plus Alisertib versus Paclitaxel plus Placebo as Second-Line Therapy for SCLC: Primary and Correlative Biomarker Analyses.

INTRODUCTION: We assessed the Aurora A kinase inhibitor, alisertib, plus paclitaxel (henceforth referred to as alisertib/paclitaxel) as second-line treatment for SCLC. METHODS: In this double-blind study, patients with relapsed or refractory SCLC were stratified by relapse type (sensitive versus resistant or refractory) and brain metastases and randomized 1:1 to alisertib/paclitaxel or placebo plus paclitaxel (henceforth referred to as placebo/paclitaxel) in 28-day cycles. The primary end point was progression-free survival (PFS). Associations of c-Myc expression in tumor tissue (prespecified) and genetic alterations in circulating tumor DNA (retrospective) with clinical outcome were evaluated. RESULTS: A total of 178 patients were enrolled (89 in each arm). The median PFS was 3.32 months with alisertib/paclitaxel versus 2.17 months with placebo/paclitaxel (hazard ratio [HR] = 0.77, 95% confidence limit [CI]: 0.557-1.067, p = 0.113 in the intent-to-treat population versus HR = 0.71, 95% CI: 0.509-0.985, p = 0.038 with corrected analysis applied). Among 140 patients with genetic alternations, patients with cell cycle regulator mutations (cyclin-dependent kinase 6 gene [CDK6], retinoblastoma-like 1 gene [RBL1], retinoblastoma-like 2 gene [RBL2], and retinoblastoma 1 gene [RB1]) had significantly improved PFS with alisertib/paclitaxel versus with placebo/paclitaxel (3.68 versus 1.80 months, respectively [HR = 0.395, 95% CI: 0.239-0.654, p = 0.0003]), and overall survival (7.20 versus 4.47 months, respectively [HR = 0.427, 95% CI: 0.259-0.704, p = 0.00085]). A subset of patients with c-Myc expression showed significantly improved PFS with alisertib/paclitaxel. The incidence of grade 3 or higher drug-related adverse events was 67% (58 patients) with alisertib/paclitaxel versus 22% (25 patients) with placebo/paclitaxel. Twelve patients (14%) versus 11 (12%) died on study, including four versus zero treatment-related deaths. CONCLUSIONS: Efficacy signals were seen with alisertib/paclitaxel in relapsed or refractory SCLC. c-Myc expression and mutations in cell cycle regulators may be potential predictive biomarkers of alisertib efficacy; further prospective validations are warranted.

Improving Care for the Frail in Nova Scotia: An Implementation Evaluation of a Frailty Portal in Primary Care Practice.

BACKGROUND: Understanding and addressing the needs of frail patients has been identified as an important strategy by the Nova Scotia Health Authority (NSHA). Primary care (PC) providers are in a key position to aid in the identification of, and response to frailty as part of routine care. Unlike singular chronic conditions such as diabetes and hypertension which garner a disease-based approach and identification as part of standard practice, frailty is only just emerging as a concept for PC. The web-based Frailty Portal was developed to aid in the identification of, assessment and care planning for frail patients in PC practice. In this study we assess the implementation feasibility and impact of the Frailty Portal by: (1) identifying factors influencing the Frailty Portal's use in community PC practice, and (2) examination of the immediate impact of the 'Frailty Portal' on frail patients, their caregivers and PC providers. METHODS: A convergent mixed method approach was implemented among PC providers in community-based practice in the NSHA, Central Zone. Quantitative and qualitative data were collected concurrently over a 9-month period. A sample of patients who underwent assessment and/or their caregiver were approached for survey participation. RESULTS: Fourteen community PC providers (10 family physicians, 4 nurse practitioners) completed 48 patient assessments and completed or begun 41 care plans; semi-structured interviews were conducted among 9 providers. Nine patients and 5 caregivers participated in the survey. PC providers viewed frailty as an important concept but implementation challenges were met, primarily with respect to the time required for use and lack of fit with traditional practice routines. Additional barriers included tool usability and accessibility, training and care planning steps, and privacy. Impacts of the tools use with respect to confidence and knowledge showed early promise. CONCLUSION: This feasibility study highlights the need for added health system supports, resources and financial incentives for successful implementation of the Frailty Portal in community PC practice. We suggest future implementation integrate the Frailty Portal to practice electronic medical records (EMRs) and target providers with largely geriatric practice populations and those practicing within interdisciplinary, collaborative primary healthcare (PHC) teams.

Bringing Value-Based Perspectives to Care: Including Patient and Family Members in Decision-Making Processes.

BACKGROUND: Recent evidence shows that patient engagement is an important strategy in achieving a high performing healthcare system. While there is considerable evidence of implementation initiatives in direct care context, there is limited investigation of implementation initiatives in decision-making context as it relates to program planning, service delivery and developing policies. Research has also shown a gap in consistent application of system-level strategies that can effectively translate organizational policies around patient and family engagement into practice. METHODS: The broad objective of this initiative was to develop a system-level implementation strategy to include patient and family advisors (PFAs) at decision-making points in primary healthcare (PHC) based on wellestablished evidence and literature. In this opportunity sponsored by the Canadian Foundation for Healthcare Improvement (CFHI) a co-design methodology, also well-established was applied in identifying and developing a suitable implementation strategy to engage PFAs as members of quality teams in PHC. Diabetes management centres (DMCs) was selected as the pilot site to develop the strategy. Key steps in the process included review of evidence, review of the current state in PHC through engagement of key stakeholders and a co-design approach. RESULTS: The project team included a diverse representation of members from the PHC system including patient advisors, DMC team members, system leads, providers, Public Engagement team members and CFHI improvement coaches. Key outcomes of this 18-month long initiative included development of a working definition of patient and family engagement, development of a Patient and Family Engagement Resource Guide and evaluation of the resource guide. CONCLUSION: This novel initiative provided us an opportunity to develop a supportive system-wide implementation plan and a strategy to include PFAs in decision-making processes in PHC. The well-established co-design methodology further allowed us to include value-based (customer driven quality and experience of care) perspectives of several important stakeholders including patient advisors. The next step will be to implement the strategy within DMCs, spread the strategy PHC, both locally and provincially with a focus on sustainability.

Evaluating the Implementation and Feasibility of a Web-Based Tool to Support Timely Identification and Care for the Frail Population in Primary Healthcare Settings.

BACKGROUND: Understanding and addressing the needs of frail persons is an emerging health priority for Nova Scotia and internationally. Primary healthcare (PHC) providers regularly encounter frail persons in their daily clinical work. However, routine identification and measurement of frailty is not standard practice and, in general, there is a lack of awareness about how to identify and respond to frailty. A web-based tool called the Frailty Portal was developed to aid in identifying, screening, and providing care for frail patients in PHC settings. In this study, we will assess the implementation feasibility and impact of the Frailty Portal to: (1) support increased awareness of frailty among providers and patients, (2) identify the degree of frailty within individual patients, and (3) develop and deliver actions to respond to frailtyl in community PHC practice. METHODS: This study will be approached using a convergent mixed method design where quantitative and qualitative data are collected concurrently, in this case, over a 9-month period, analyzed separately, and then merged to summarize, interpret and produce a more comprehensive understanding of the initiative's feasibility and scalability. Methods will be informed by the 'Implementing the Frailty Portal in Community Primary Care Practice' logic model and questions will be guided by domains and constructs from an implementation science framework, the Consolidated Framework for Implementation Research (CFIR). DISCUSSION: The 'Frailty Portal' aims to improve access to, and coordination of, primary care services for persons experiencing frailty. It also aims to increase primary care providers' ability to care for patients in the context of their frailty. Our goal is to help optimize care in the community by helping community providers gain the knowledge they may lack about frailty both in general and in their practice, support improved identification of frailty with the use of screening tools, offer evidence based severity-specific care goals and connect providers with local available community supports.

A Patient-Centred Redesign Framework to Support System-Level Process Changes for Multimorbidities and Chronic Conditions.

Recent trends show an increase in the prevalence and costs associated with managing individuals with multimorbidities. Enabling better care for these individuals requires system-level changes such as the shift from a focus on a single disease or single service to multimorbidities and integrated systems of care. In this paper, a novel patient-centred redesign framework that was developed to support system-level process changes in four service areas has been discussed. The novelty of this framework is that it is embedded in patient perspectives and in the chronic care model as the theoretical foundation. The aims of this paper are to present an application of the framework in the context of four chronic disease prevention and management services, and to discuss early results from the pilot initiative along with an overview of the spread opportunities for this initiative.

Two live attenuated Shigella flexneri 2a strains WRSf2G12 and WRSf2G15: a new combination of gene deletions for 2nd generation live attenuated vaccine candidates.

Shigella infections are a major cause of inflammatory diarrhea and dysentery worldwide. First-generation virG-based live attenuated Shigella strains have been successfully tested in phase I and II clinical trials and are a leading approach for Shigella vaccine development. Additional gene deletions in senA, senB and msbB2 have been engineered into second-generation virG-based Shigella flexneri 2a strains producing WRSf2G12 and WRSf2G15. Both strains harbor a unique combination of gene deletions designed to increase the safety of live Shigella vaccines. WRSf2G12 and WRSf2G15 are genetically stable and highly attenuated in both cell culture and animal models of infection. Ocular immunization of guinea pigs with either strain induces robust systemic and mucosal immune responses that protect against homologous challenge with wild-type Shigella. The data support further evaluation of the second-generation strains in a phase I clinical trial.

Impact of an online alcohol education course on behavior and harm for incoming first-year college students: short-term evaluation of a randomized trial.

OBJECTIVE: The authors assessed short-term effectiveness of a Web-based alcohol education program on entering freshmen. PARTICIPANTS: 3,216 incoming first-year students were randomized to a control or intervention group. METHODS: Controls completed a survey and knowledge test the summer before college; 4 to 6 weeks after arrival on campus, they completed a follow-up survey of behaviors and harms followed by an invitation to complete the online course. Intervention students completed the precourse survey and test, the online course, and final exam prior to coming to campus. This was followed by a survey 4 to 6 weeks after arrival on campus. RESULTS: Although the intervention group showed significantly higher alcohol-related postcourse knowledge compared to the control group, protective behavior, risk-related behavior, high-risk drinking, and alcohol-related harm did not favor the intervention group, with the sole exception of playing drinking games. CONCLUSIONS: Alcohol knowledge alone was insufficient to mitigate alcohol-related high-risk behaviors in this student population.

Rhythms of locomotion expressed by Limulus polyphemus, the American horseshoe crab: II. Relationship to circadian rhythms of visual sensitivity.

In the laboratory, horseshoe crabs express a circadian rhythm of visual sensitivity as well as daily and circatidal rhythms of locomotion. The major goal of this investigation was to determine whether the circadian clock underlying changes in visual sensitivity also modulates locomotion. To address this question, we developed a method for simultaneously recording changes in visual sensitivity and locomotion. Although every animal (24) expressed consistent circadian rhythms of visual sensitivity, rhythms of locomotion were more variable: 44% expressed a tidal rhythm, 28% were most active at night, and the rest lacked statistically significant rhythms. When exposed to artificial tides, 8 of 16 animals expressed circatidal rhythms of locomotion that continued after tidal cycles were stopped. However, rhythms of visual sensitivity remained stable and showed no tendency to be influenced by the imposed tides or locomotor activity. These results indicate that horseshoe crabs possess at least two biological clocks: one circadian clock primarily used for modulating visual sensitivity, and one or more clocks that control patterns of locomotion. This arrangement allows horseshoe crabs to see quite well while mating during both daytime and nighttime high tides.