Assessment of Clinician-Reported Outcome Measures for Alopecia Areata: A Systematic Scoping Review.

Clinician-reported outcome measures (ClinROMs) are an important part of disease assessment in daily practice and clinical trials. There is a broad disagreement on the most appropriate ClinROM for a comprehensive assessment of alopecia areata (AA) severity. This paper aims to identify the currently available ClinROMs for AA through a systematic literature search, address their practical strengths and weaknesses, and identify the road ahead for future research. A search was conducted of the published, peer-reviewed literature via PubMed (Medline) and EMBASE (via Ovid) databases. Articles published in English within the last 23 years (post-2000) that objectively measured AA severity were included. We did not select scoring systems that were solely based on patient-reported outcomes (PROs). The literature search identified 1376 articles, of which 27 were chosen for full-text review. Based on our eligibility criteria, fourteen articles were identified, describing sixteen different ClinROMs. Five ClinROMs solely measured scalp hair loss (SALT, SALTⅡ, ALODEX, pSALT, and AA-IGA). Three trichoscopy-based ClinROMs assessed disease activity (AAPI, AAPS, and Coudability hair score). Six ClinROMs exclusively assessed non-scalp areas (BETA, BELA, ALBAS, ClinRO for Eyelash, Eyebrow, and Nail assessment). Two ClinROMs assessed both the scalp and beyond-scalp areas (AASI and AASc). The practical strengths and weaknesses of each assessment tool were described. Various practical limitations associated with established tools have impeded their universal implementation in routine clinical practice. There is a significant need for a holistic clinical severity scoring system to capture all the key severity identifiers beyond the involvement of the scalp.

Characteristics Associated with Homeless Pregnant Women in Columbus, Ohio.

INTRODUCTION: The effects of homelessness on pregnant women are substantial. We aim to identify key characteristics of a group of women identified as homeless and pregnant in order to understand their history of housing, family composition, health, and demographics as a first step for future intervention. METHODS: We present cross-sectional survey data on a sample of 100 women reporting homelessness and pregnancy in the prior year in Columbus, Ohio, identified through social service and housing not for profit agencies. Our analysis uses data collected from a survey of health behaviors, housing, employment status, and demographics. Continuous measures are described with means and standard deviations, and categorical variables are described with percentages. RESULTS: The majority (81%) of the women identified as African American. Over 95% of the women were single, and 74 women reported a prior pregnancy. Almost half of the women reported being behind on rent at least one time in the last 6 months, and 43% indicated that they had lived in more than three places in the last year. Approximately 34% of the sample reported cigarette use during pregnancy, while 12% and 30% reported alcohol and illicit drug use, respectively. DISCUSSION: Women who were pregnant and experiencing homelessness in our study reported a multitude of complex and severe problems ranging from high rates of substance use, longstanding housing insecurity and financial stress. Programs hoping to successfully support women will need to address a variety of service needs while recognizing the resilience of many women.

Acceptability of 11 fortified balanced energy-protein supplements for pregnant women in Nepal.

Evidence suggests that multiple micronutrient and balanced energy protein (BEP) supplementation during pregnancy can decrease the risk of stillbirth and small-for-gestational-age births and increase birth weight. We conducted a mixed-methods formative research study to identify the most acceptable among a range of 11 candidates fortified BEP supplements for use in pregnancy and lactation in a rural district in Nepal. Forty pregnant women aged 15-40 years participated in a test meal tasting of 11 different sweet and savoury candidate BEP supplements. Each participant rated the products on organoleptic properties using a 7-point hedonic scale (1 = Dislike it very much to 7 = Like it very much), ranked her 'top 3' most liked supplements, and subsequently discussed each product with peers in focus group discussions (FGDs). Five supplements (sweet lipid-based nutrient supplement (LNS), savoury LNS, sweet vanilla biscuits, vanilla instant drinks and seasoned pillows) achieved the maximum overall median hedonic score of 7, with sweet LNS and seasoned pillows ranking as the top 2. This was consistent with the assessments in FGDs. Women in the FGDs expressed dislike of the smell and taste of the cocoa drink, savoury masala bar, sweet mango bar and savoury curry biscuit, which was consistent with the hedonic scale scores. This study provides valuable insights into our understanding of women's acceptance of different BEP supplements during pregnancy in rural Nepal and has helped identify the two most accepted BEP supplements to be used in a two-month home trial to assess utilisation and compliance in this setting.

Compliance with and acceptability of two fortified balanced energy protein supplements among pregnant women in rural Nepal.

Some evidence suggests that balanced energy protein (BEP) supplements taken during pregnancy and lactation can have positive effects on birth outcomes such as small-for-gestational age and birthweight, but more evidence is needed on the long-term use and acceptability of such supplements. We conducted a mixed-methods formative research study to assess and compare compliance with and acceptability of two BEP supplements, a lipid-based peanut paste and a biscuit, to identify BEP supplements for subsequent inclusion in an efficacy trial. We conducted an 8-week feeding trial of daily supplementation among two groups of 40 pregnant women each in rural Nepal. Compliance data were collected and supplements distributed at the weekly visits. Sensory properties of the supplements were assessed using a 7-point Likert scale. In addition, in-depth interviews with women (n = 16), family members (n = 6) and health workers (n = 6) and focus group discussions (FGDs) (n = 4) were conducted to explore themes related to general use and intention of future use of the supplement. Overall self-reported compliance was high: medians of 91.1% in the lipid-based peanut paste group and 96.4% in the biscuit group. Both supplements were rated highly on overall likability (median score 6/7) and sensory properties. Qualitative findings showed that sustained use of the supplements was attributed to expected health benefits, favourable sensory attributes, and family support. The FGDs suggested providing the option to choose between more than one type/flavour of supplements to improve compliance. Sharing was mostly evident in the first week with higher sharing reported in the biscuit group.

Home consumption of two fortified balanced energy protein supplements by pregnant women in Burkina Faso.

Balanced energy protein (BEP) supplementation for pregnant and lactating women in low- and middle-income countries is a promising strategy to improve birth outcomes and child growth. The objective of this study was to assess and compare the acceptability of new formulations of two fortified BEP supplements, a lipid-based peanut paste and a vanilla biscuit, among 80 pregnant women in rural Burkina Faso, prior to an efficacy trial. A 10-week individually randomized cross-over study was designed, in which women received a weekly supply of each supplement for 4 weeks, and a daily choice between the supplements in the last 2 weeks. Questionnaires to assess daily consumption and supplement acceptability (n = 80) and home observations (n = 20) were combined with focus group discussions (n = 6) and in-depth interviews with women (n = 80) and stakeholders (n = 24). Results showed that the two supplements were well accepted. Quantitative findings indicated high compliance (>99.6%) and high overall appreciation (Likert score >6 out of 7) of both supplements. The assessment of preferred choice in Weeks 9 and 10 indicated a slight preference for the vanilla biscuit. Qualitative findings indicated that perceived health benefits, support from household members and educational messages from health professionals were important drivers for acceptance and compliance. Sharing was not often reported but was identified during interviews as a possible risk. We recommend that future studies use a combination of methods to identify appropriate food supplements and context-specific factors that influence acceptability, compliance and subsequent impact of nutritious food supplements.

Acceptability of 12 fortified balanced energy protein supplements - Insights from Burkina Faso.

Poor maternal nutrition contributes to poor birth outcomes, including low birth weight and small for gestational age births. Fortified balanced energy protein (BEP) supplements may be beneficial, although evidence is limited. This mixed method study, conducted among pregnant women in Burkina Faso, is part of a larger clinical trial that seeks to understand the impact of fortified BEP supplements on pregnancy outcomes and child growth. The formative research reported here, a single-meal rapid assessment of 12 product formulations, sought to understand product preferences for provision of BEP supplements and contextual factors that might affect product acceptability and use. Results indicate a preference for products perceived as sweet rather than salty/savoury and for products perceived as familiar, as well as a sensitivity to product odours. Women expressed a willingness and intention to use the products even if they did not like them, because of the health benefits for their babies. Data also indicate that household food sharing practices may impact supplement use, although most women denied any intention to share the products. Sharing behaviour should therefore be monitored, and strategies to avoid sharing should be developed during the succeeding parts of the research.

Watershed-scale climate influences productivity of Chinook salmon populations across southcentral Alaska.

The ecosystems supporting Pacific salmon (Oncorhynchus spp.) are changing rapidly as a result of climate change and habitat alteration. Understanding how-and how consistently-salmon populations respond to changes at regional and watershed scales has major implications for fisheries management and habitat conservation. Chinook salmon (O. tshawytscha) populations across Alaska have declined over the past decade, resulting in fisheries closures and prolonged impacts to local communities. These declines are associated with large-scale climate drivers, but uncertainty remains about the role of local conditions (e.g., precipitation, streamflow, and stream temperature) that vary among the watersheds where salmon spawn and rear. We estimated the effects of these and other environmental indicators on the productivity of 15 Chinook salmon populations in the Cook Inlet basin, southcentral Alaska, using a hierarchical Bayesian stock-recruitment model. Salmon spawning during 2003-2007 produced 57% fewer recruits than the previous long-term average, leading to declines in adult returns beginning in 2008. These declines were explained in part by density dependence, with reduced population productivity following years of high spawning abundance. Across all populations, productivity declined with increased precipitation during the fall spawning and early incubation period and increased with above-average precipitation during juvenile rearing. Above-average stream temperatures during spawning and rearing had variable effects, with negative relationships in many warmer streams and positive relationships in some colder streams. Productivity was also associated with regional indices of streamflow and ocean conditions, with high variability among populations. The cumulative effects of adverse conditions in freshwater, including high spawning abundance, heavy fall rains, and hot, dry summers may have contributed to the recent population declines across the region. Identifying both coherent and differential responses to environmental change underscores the importance of targeted, watershed-specific monitoring and conservation efforts for maintaining resilient salmon runs in a warming world.

Treatment of alopecia areata: An Australian expert consensus statement.

Alopecia areata (AA) severity varies from a single small patch to complete loss of scalp hair, body hair, eyelashes and eyebrows. While 40% of all affected individuals only ever get one patch and will achieve a spontaneous complete durable remission within 6 months, 27% will develop additional patches but still achieve complete durable remission within 12 months and 33% will develop chronic AA. Without systemic treatment, 55% of individuals with chronic AA will have persistent multifocal relapsing and remitting disease, 30% will ultimately develop alopecia totalis and 15% will develop alopecia universalis. The unpredictable course and psychological distress attributable to AA contributes to the illness associated with AA. Numerous topical, intralesional and systemic agents are currently used to treat AA; however, there is a paucity of data evaluating their use, effectiveness and tolerability. Topical therapy, including topical glucocorticosteroids, minoxidil and immunotherapy, can be used in cases of limited disease. There are no universally agreed indications for initiating systemic treatment for AA. Possible indications for systemic treatment include rapid hair loss, extensive disease (≥50% hair loss), chronic disease, severe distress or a combination of these factors. Currently available systemic treatments include glucocorticosteroids, methotrexate, ciclosporin, azathioprine, dapsone, mycophenolate mofetil, tacrolimus and sulfasalazine. The optimal treatment algorithm has not yet been described. The purpose of this consensus statement is to outline a treatment algorithm for AA, including the indications for systemic treatment, appropriate choice of systemic treatment, satisfactory outcome measures and when to discontinue successful or unsuccessful treatment.

Climate-induced glacier and snow loss imperils alpine stream insects.

Climate warming is causing rapid loss of glaciers and snowpack in mountainous regions worldwide. These changes are predicted to negatively impact the habitats of many range-restricted species, particularly endemic, mountaintop species dependent on the unique thermal and hydrologic conditions found only in glacier-fed and snow melt-driven alpine streams. Although progress has been made, existing understanding of the status, distribution, and ecology of alpine aquatic species, particularly in North America, is lacking, thereby hindering conservation and management programs. Two aquatic insects - the meltwater stonefly (Lednia tumana) and the glacier stonefly (Zapada glacier) - were recently proposed for listing under the U.S. Endangered Species Act due to climate-change-induced habitat loss. Using a large dataset (272 streams, 482 total sites) with high-resolution climate and habitat information, we describe the distribution, status, and key environmental features that limit L. tumana and Z. glacier across the northern Rocky Mountains. Lednia tumana was detected in 113 streams (175 sites) within Glacier National Park (GNP) and surrounding areas. The probability of L. tumana occurrence increased with cold stream temperatures and close proximity to glaciers and permanent snowfields. Similarly, densities of L. tumana declined with increasing distance from stream source. Zapada glacier was only detected in 10 streams (24 sites), six in GNP and four in mountain ranges up to ~600 km southwest. Our results show that both L. tumana and Z. glacier inhabit an extremely narrow distribution, restricted to short sections of cold, alpine streams often below glaciers predicted to disappear over the next two decades. Climate warming-induced glacier and snow loss clearly imperils the persistence of L. tumana and Z. glacier throughout their ranges, highlighting the role of mountaintop aquatic invertebrates as sentinels of climate change in mid-latitude regions.

Hair transplantation in mice: Challenges and solutions.

Hair follicle cells contribute to wound healing, skin circulation, and skin diseases including skin cancer, and hair transplantation is a useful technique to study the participation of hair follicle cells in skin homeostasis and wound healing. Although hair follicle transplantation is a well-established human hair-restoration procedure, follicular transplantation techniques in animals have a number of shortcomings and have not been well described or optimized. To facilitate the study of follicular stem and progenitor cells and their interaction with surrounding skin, we have established a new murine transplantation model, similar to follicular unit transplantation in humans. Vibrissae from GFP transgenic mice were harvested, flip-side microdissected, and implanted individually into needle hole incisions in the back skin of immune-deficient nude mice. Grafts were evaluated histologically and the growth of transplanted vibrissae was observed. Transplanted follicles cycled spontaneously and newly formed hair shafts emerged from the skin after 2 weeks. Ninety percent of grafted vibrissae produced a hair shaft at 6 weeks. After pluck-induced follicle cycling, growth rates were equivalent to ungrafted vibrissae. Transplanted vibrissae with GFP-positive cells were easily identified in histological sections. We established a follicular vibrissa transplantation method that recapitulates human follicular unit transplantation. This method has several advantages over current protocols for animal hair transplantation. The method requires no suturing and minimizes the damage to donor follicles and recipient skin. Vibrissae are easier to microdissect and transplant than pelage follicles and, once transplanted, are readily distinguished from host pelage hair. This facilitates measurement of hair growth. Flip-side hair follicle microdissection precisely separates donor follicular tissue from interfollicular tissue and donor cells remain confined to hair follicles. This makes it possible to differentiate migration of hair follicle cells from interfollicular epidermis in lineage tracing wound experiments using genetically labeled donor follicles.

Safety mechanism assisted by the repressor of tetracycline (SMART) vaccinia virus vectors for vaccines and therapeutics.

Replication-competent viruses, such as Vaccinia virus (VACV), are powerful tools for the development of oncolytic viral therapies and elicit superior immune responses when used as vaccine and immunotherapeutic vectors. However, severe complications from uncontrolled viral replication can occur, particularly in immunocompromised individuals or in those with other predisposing conditions. VACVs constitutively expressing interferon-γ (IFN-γ) replicate in cell culture indistinguishably from control viruses; however, they replicate in vivo to low or undetectable levels, and are rapidly cleared even in immunodeficient animals. In an effort to develop safe and highly effective replication-competent VACV vectors, we established a system to inducibly express IFN-γ. Our SMART (safety mechanism assisted by the repressor of tetracycline) vectors are designed to express the tetracycline repressor under a constitutive VACV promoter and IFN-γ under engineered tetracycline-inducible promoters. Immunodeficient SCID mice inoculated with VACVs not expressing IFN-γ demonstrated severe weight loss, whereas those given VACVs expressing IFN-γ under constitutive VACV promoters showed no signs of infection. Most importantly, mice inoculated with a VACV expressing the IFN-γ gene under an inducible promoter remained healthy in the presence of doxycycline, but exhibited severe weight loss in the absence of doxycycline. In this study, we developed a safety mechanism for VACV based on the conditional expression of IFN-γ under a tightly controlled tetracycline-inducible VACV promoter for use in vaccines and oncolytic cancer therapies.

The additive damage model: a mathematical model for cellular responses to drug combinations.

Mathematical models to describe dose-dependent cellular responses to drug combinations are an essential component of computational simulations for predicting therapeutic responses. Here, a new model, the additive damage model, is introduced and tested in cases where varying concentrations of two drugs are applied with a fixed exposure schedule. In the model, cell survival is determined by whether cellular damage, which depends on the concentrations of the drugs, exceeds a lethal threshold, which varies randomly in the cell population with a prescribed statistical distribution. Cellular damage is assumed to be additive, and is expressed as a sum of separate terms for each drug. Each term has a saturable dependence on drug concentration. The model has appropriate behavior over the entire range of drug concentrations, and is predictive, given single-agent dose-response data for each drug. The proposed model is compared with several other models, by testing their ability to fit 24 data sets for platinum-taxane combinations and 21 data sets for various other combinations. The Akaike Information Criterion is used to assess goodness of fit, taking into account the number of unknown parameters in each model. Overall, the additive damage model provides a better fit to the data sets than any previous model. The proposed model provides a basis for computational simulations of therapeutic responses. It predicts responses to drug combinations based on data for each drug acting as a single agent, and can be used as an improved null reference model for assessing synergy in the action of drug combinations.

Recombinant Rift Valley fever vaccines induce protective levels of antibody in baboons and resistance to lethal challenge in mice.

Rift Valley fever (RVF) is a zoonotic disease endemic in Africa and the Arabian Peninsula caused by the highly infectious Rift Valley fever virus (RVFV) that can be lethal to humans and animals and results in major losses in the livestock industry. RVF is exotic to the United States; however, mosquito species native to this region can serve as biological vectors for the virus. Thus, accidental or malicious introduction of this virus could result in RVFV becoming endemic in North America. Such an event would likely lead to significant morbidity and mortality in humans, and devastating economic effects on the livestock industry. Currently, there are no licensed vaccines for RVF that are both safe and efficacious. To address this issue, we developed two recombinant RVFV vaccines using vaccinia virus (VACV) as a vector for use in livestock. The first vaccine, vCOGnGc, was attenuated by the deletion of a VACV gene encoding an IFN-γ binding protein, insertional inactivation of the thymidine kinase gene, and expression of RVFV glycoproteins, Gn and Gc. The second vaccine, vCOGnGcγ, is identical to the first and also expresses the human IFN-γ gene to enhance safety. Both vaccines are extremely safe; neither resulted in weight loss nor death in severe combined immunodeficient mice, and pock lesions were smaller in baboons compared with the controls. Furthermore, both vaccines induced protective levels of antibody titers in vaccinated mice and baboons. Mice were protected from lethal RVFV challenge. Thus, we have developed two safe and efficacious recombinant vaccines for RVF.

Applicants' choice of an ophthalmology residency program.

OBJECTIVE: To determine the factors most important to applicants when selecting an ophthalmology residency program. DESIGN: Cross-sectional survey. PARTICIPANTS: All 595 applicants who submitted a rank list to the Ophthalmology Residency Matching Program for the 2012 match. METHODS: Participants anonymously completed a 25-item questionnaire after the submission of their rank lists. A multiple-choice format and ordinal scale were used to query applicants on demographics, career plans, and the importance of factors related to program characteristics. One question allowed a free text response to identify factors that caused the applicant to rank a program lower than other programs or not at all (i.e., "red flag"). MAIN OUTCOME MEASURES: Factors important to applicants when creating their rank lists. RESULTS: The response rate was 37% (218/595). The 3 most important factors affecting rank lists were resident-faculty relationships, clinical and surgical volume, and diversity of training. The fourth most important was the interview experience with faculty; poor interview experience was the most frequently cited "red flag." Age, gender, and marital status did not affect how applicants rated factors. Applicants planning a post-residency fellowship or an academic career placed greater importance on opportunities for resident research and a program's prestige (P<0.0001). Female and ethnic minority applicants placed greater importance on the diversity of faculty and residents by gender or ethnicity (P<0.0001). CONCLUSIONS: Applicants rated educational and interpersonal factors as more important than geographic factors when selecting an ophthalmology residency program. Future career plans and demographic factors influenced the rating of specific factors. The results of this study provide a useful resource to programs preparing for the match.

Medications Cost Resources.

High cost of prescription drugs is a common reason why patients stop taking medications, or don't fill a prescription. There are cost savings plans available, but these resources vary by eligibility criteria, and each has advantages and disadvantages. The article reviews some of the available cost saving options.

Erratum: Virtual Ophthalmology Rotation for Visiting Medical Students: An Opportunity to Enhance Diversity in the Workforce.

[This corrects the article DOI: 10.1055/s-0043-1760831.].

Virtual Ophthalmology Rotation for Visiting Medical Students: An Opportunity to Enhance Diversity in the Workforce.

Introduction We created a virtual rotation to facilitate the exposure of ophthalmology to medical students and serve as a pilot program to help attract students from under-represented in medicine (URM) backgrounds. In addition to the rotation eliminating the financial burdens associated with in-person away rotations, we offered a not-for-credit (i.e., drop-in) option that included sessions outside the typical clinic hours. This option reduced scheduling conflicts as a barrier to enrollment and allowed junior medical students and postgraduates to participate and hopefully further develop an interest in ophthalmology. Methods Before the rotation, participants completed a pre-test and a survey to collect data on learners' backgrounds and interest in applying for ophthalmology residency. The rotation included live lectures, case-based discussions, chart reviews, and guided self-study. Following the rotation, participants completed a post-test and a survey to query applicants on the online rotation's utility and delivery. Results Eleven learners enrolled in the course and completed the prerotation survey and test. Approximately one-third (4/11; 36%) were URM students and two-thirds (7/11; 64%) were female. All responded they were planning to apply for ophthalmology residency. All responded they strongly agreed that the rotation increased their general knowledge in ophthalmology, and 89% (9/11) strongly agreed that it improved their ability to diagnose and manage actual patients. Nearly all (7/8; 87.5%) strongly agreed the rotation provided the opportunity to seek support for the residency application process, and all found the online platform reliable and easy to access. Exam scores improved significantly from pre- to post-tests (60 vs. 79%; p < 0.01). Conclusions The rotation attracted a substantial proportion of URM students. Learners reported that the virtual rotation effectively taught and supported their endeavors to become ophthalmologists. Virtual rotations for visiting students can reduce barriers such as travel, financial costs, and time constraints that might otherwise hinder exposure to specialty training that is not offered or is underrepresented at students' home institutions. Increasing exposure and offering mentorship through this novel platform deserves further study to enhance diversity and inclusion in medicine.

Case report: Laryngospasm following ethanol ablation of a parathyroid nodule in a dog with primary hyperparathyroidism.

A 12-year-old female spayed dachshund was presented for emergency assessment of respiratory distress, characterized by inspiratory dyspnea with stridor. Percutaneous ultrasound-guided ethanol ablation of a functional parathyroid tumor was performed 72-h earlier for management of primary hyperparathyroidism. The dog was hypocalcemic (ionized calcium 0.7 mmol/L, reference interval: 0.9-1.3 mmol/L) at the time of presentation and had evidence of laryngospasm on a sedated oral exam. The dog was managed conservatively with supplemental oxygen, anxiolysis, and parenteral calcium administration. These interventions were associated with rapid and sustained improvement in clinical signs. The dog did not demonstrate any recurrence of signs afterwards. To the authors' knowledge, this is the first description of laryngospasm following ethanol ablation of a parathyroid nodule in a dog that developed hypocalcemia.