Tools to study the severity of itch in 8- to 17-year-old children: Validation of TweenItchyQoL and ItchyQuant.

BACKGROUND/OBJECTIVES: Validated pruritus-specific quality of life and self-reported severity instruments exist primarily for adults. Clinical trials to develop therapeutics for children with chronic pruritus are hampered by the paucity of appropriate outcome measures. To address this gap, we aimed to develop validated instruments to measure itch-specific quality of life and self-reported severity in children. METHODS: We conducted in-depth, open-ended interviews of itchy children and generated concepts to develop TweenItchyQoL. We administered TweenItchyQoL, ItchyQuant, a cartoon-annotated self-reported pruritus severity numeric rating scale (NRS), and a non-cartoon NRS to 175 itchy children aged 8-17 years. We analyzed the data for feasibility, preference, reliability, construct validity, and responsiveness. RESULTS: Average completion time was 4.8 minutes for TweenItchyQoL and 33 seconds for ItchyQuant. The majority of patients either preferred ItchyQuant or found no difference between ItchyQuant and the NRS. Cronbach's alpha for TweenItchyQoL total and subscales ranged from 0.84 to 0.95. Test-retest reliability coefficients were ≥0.7 for TweenItchyQoL and 0.4 for ItchyQuant. A 3-dimensional bifactor model was most appropriate (RMSEA = 0.048) on the confirmatory factor analyses. As a function of those reporting worsening, improvement, or no change at their final visit, TweenItchyQoL and ItchyQuant scores in those cohorts changed as expected. CONCLUSIONS: This new set of validated and feasible instruments shows promise to quantify itch severity and QoL impact in older children.

Adapting a National Framework to Inform Curricular Redesign Focused on Enhancing Student Clinical Competency.

Doctor of Pharmacy (PharmD) programs continually engage in curricular redesign to ensure practice readiness of graduates. With ever-increasing demands on clinical competency and curricular time, it is important to be intentional when determining curricular priorities and prioritize contemporary pharmacist practice. This paper describes how to adapt a national framework for pharmacotherapy curricula to emphasize the pharmacist's role within a given topic area in order to facilitate conversations about allotting curricular time during a curricular redesign. Customized Tier descriptions based on various factors expected of student pharmacists during Advanced Pharmacy Practice Experiences (APPEs) were developed (e.g., relative autonomy of the pharmacist in managing the topic, emphasis on licensing exams, frequency with which students can expect to encounter the topic at school-specific experiential placements, and condition-specific information). Topics were also reprioritized to address regional variations in practice and ideologies. Customizing a national framework to determine program-specific considerations for prioritizing topics within the pre-APPE curriculum can help faculty and students alike maintain focus on highly critical and foundational concepts, while also making sure not to completely disregard topics of lower priority. We have proposed such a framework for programs to utilize when facilitating conversations surrounding curricular reforms and topic prioritization.

From biosociality to biosolidarity: the looping effects of finding and forming social networks for body-focused repetitive behaviours.

Anthropological accounts of biosociality reveal the importance of the social relations formed through shared biomedical conditions. In the context of body-focused repetitive behaviours (BFRBs), like compulsive hair pulling (trichotillomania) and skin picking (dermatillomania), biosociality moves people from isolation towards community. After diagnosis, the powerful moment of discovering 'you are not alone' can lead to immense personal transformations, demonstrating the 'looping effects' of diagnosis and biosociality. Yet, biosocial groups do not simply exist, and must first be formed and found and their sustainability requires ongoing work and care from biosocial actors themselves. Biosociality also means different things to different people, often requiring a negotiation between secrecy and disclosure. This article acknowledges the role of stigma in biosociality, differentiating between private and public biosocial experiences. It argues that through biosociality come acts of biosolidarity, where advocacy can improve the visibility and recognition of illness groups. The circular looping effects of biosociality and biosolidarity demonstrate the way that community activism and biosociality reproduce one another. Through reflections from the anthropologist, biosolidarity is considered as a methodological tool that can help scholars to navigate the boundaries between relatedness, sociality and advocacy in the field and beyond.

Distinct compartmentalization of immune cells and mediators characterizes bullous pemphigoid disease.

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by recruitment of leucocytes into skin and release of damaging enzymes, resulting in epidermal detachment and blister formation. To better understand the role of leukotriene B4 (LTB4) and other inflammatory factors in BP pathophysiology, we conducted microscopic and immunohistochemical analyses of preserved skin biopsy sections and conducted flow cytometry and ELISA analyses of matched blood and blister fluid from BP patients. Neutrophils predominated in BP blister fluid, which also contained monocytes/macrophages and T cells, but few to no eosinophils and B cells. In contrast, BP skin histology showed a different pattern, with abundant neutrophils but eosinophils being the predominant immune cell type. LTB4 pathway and neutrophil activation markers were prevalent in BP skin lesions and strongly associated with perivascular neutrophils. Blister fluid neutrophils, monocytes/macrophages and eosinophils all exhibited increased surface expression of leukotriene A4 hydrolase and neutrophil elastase (P = .002 for both). Blister fluid was also enriched in interleukins (IL)-1α, IL-1ß, IL-8, IL-10, IL-18, monocyte colony-stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF). Our findings suggest differential leucocyte recruitment from blood into dermis and from dermis into blister, which correlates with disease activity, and presents potential new treatment opportunities for BP.

Single-Cell Analysis Suggests that Ongoing Affinity Maturation Drives the Emergence of Pemphigus Vulgaris Autoimmune Disease.

Pemphigus vulgaris (PV) is an autoimmune disease characterized by blistering sores on skin and mucosal membranes, caused by autoantibodies primarily targeting the cellular adhesion protein, desmoglein-3 (Dsg3). To better understand how Dsg3-specific autoantibodies develop and cause disease in humans, we performed a cross-sectional study of PV patients before and after treatment to track relevant cellular responses underlying disease pathogenesis, and we provide an in-depth analysis of two patients by generating a panel of mAbs from single Dsg3-specific memory B cells (MBCs). Additionally, we analyzed a paired sample from one patient collected 15-months prior to disease diagnosis. We find that Dsg3-specific MBCs have an activated phenotype and show signs of ongoing affinity maturation and clonal selection. Monoclonal antibodies (mAbs) with pathogenic activity primarily target epitopes in the extracellular domains EC1 and EC2 of Dsg3, though they can also bind to the EC4 domain. Combining antibodies targeting different epitopes synergistically enhances in vitro pathogenicity.

Evaluation of the prescribing practices of nonbenzodiazepine, benzodiazepine receptor agonist hypnotics in adults at a federally qualified health center.

OBJECTIVE: To assess the change in prescribing of nonbenzodiazepine and benzodiazepine receptor agonist hypnotics (Z-drugs) prescribed to adults after U.S. Food and Drug Administration safety warnings. SETTING: Five clinical sites as part of a Federally Qualified Health Center (FQHC). PRACTICE DESCRIPTION: Virginia Garcia Memorial Health Center is an FQHC consisting of 5 patient centered medical homes. PRACTICE INNOVATION: Examine Z-drug use in a vulnerable adult population to confirm appropriate prescribing and quality care. EVALUATION: The primary measure was to determine the percentage of Z-drugs prescribed to patients age 18 years or older during the study period of September 1, 2016, to August 31, 2017. Patients were identified using the electronic health record. Z-drugs included zolpidem, zaleplon, and eszopiclone. Secondary measures included percentage of Z-drug prescribing to adults age 65 years and older, percentage of female patients prescribed zolpidem doses greater than 5 mg, prior behavioral health encounter, and prior pharmacotherapy for insomnia. RESULTS: Of 22,733 adults age 18 years and older, 282 patients (1.3%) received a Z-drug prescription during the study period. Forty-nine (28.9%) female patients received 10 mg of zolpidem nightly, a zolpidem dose higher than the recommended 5 mg nightly. In addition, of 2239 patients age 65 years and older, 34 patients (1.5%) received a prescription for a Z-drug. CONCLUSION: Prescribing rates of zolpidem in 10-mg doses to female patients were high, indicating that providers could benefit from further education on this topic. In the population, and in adults age 65 years and older, Z-drug prescribing in an FQHC was low compared with available prescribing rates.

Disentangling Family Life and Hair Pulling: Trichotillomania and Relatedness.

Trichotillomania (hair pulling) remains a relatively unknown form of body-focused repetitive behavior (BFRB). Sufferers tend to conceal both the action and its effects from others because of stigmatization, which is strong in both public and domestic spheres. Negative responses from close family members can add significantly to the suffering. Based on fieldwork in the United Kingdom and United States, we explore how hair pulling troubles ties even among close family members. We show why ethnographic methods reveal impacts of hair pulling that structured assessments do not yet capture and argue for a more nuanced study of BFRBs through anthropologies of relatedness.

Salivary levels of angiopoietin-2 in infants with infantile haemangiomas treated with and without systemic propranolol.

Infantile haemangiomas (IHs) with functional or cosmetic concerns necessitate systemic treatment for which propranolol is the preferred treatment. However, the mechanism of action is unknown. Mouse models suggest the angiopoietin-2 (Ang2)/Tie-2 system is implicated. Ang2 can promote endothelial growth or induce apoptosis depending on the presence of vascular endothelial growth factor. This pilot study investigates the saliva Ang2 levels in infants with IH treated with and without systemic propranolol. Patients with clinically confirmed IHs were recruited from an academic paediatric dermatology centre. Treatment was based on clinical evaluation. Saliva samples were collected over 6 months. An enzyme-linked immunosorbent assay determined Ang2 levels. Ang2 levels were detectable in 45% of samples. However, by the late time point, only 28% had detectable levels. There were no changes of Ang2 over time, and there were no differences in Ang2 levels between groups. However, Ang2 levels were correlated with baseline size and changes in size from baseline. Ang2 is detectable in saliva of affected infants, but does not decrease with propranolol treatment. However, Ang2 levels are positively correlated with size and changes in size. Thus, Ang2 is not the primary factor in the mechanism of propranolol resulting in IH reduction.

Robust memory responses against influenza vaccination in pemphigus patients previously treated with rituximab.

Rituximab is a therapeutic anti-CD20 monoclonal antibody widely used to treat B cell lymphoma and autoimmune diseases, such as rheumatic arthritis, systemic lupus erythematosus, and autoimmune blistering skin diseases (AIBD). While rituximab fully depletes peripheral blood B cells, it remains unclear whether some preexisting B cell memory to pathogens or vaccines may survive depletion, especially in lymphoid tissues, and if these memory B cells can undergo homeostatic expansion during recovery from depletion. The limited data available on vaccine efficacy in this setting have been derived from rituximab-treated patients receiving concomitant chemotherapy or other potent immunosuppressants. Here, we present an in-depth analysis of seasonal influenza vaccine responses in AIBD patients previously treated with rituximab, who generally did not receive additional therapeutic interventions. We found that, despite a lack of influenza-specific memory B cells in the blood, patients mount robust recall responses to vaccination, comparable to healthy controls, both at a cellular and a serological level. Repertoire analyses of plasmablast responses suggest that they likely derive from a diverse pool of tissue-resident memory cells, refractory to depletion. Overall, these data have important implications for establishing an effective vaccine schedule for AIBD patients and the clinical care of rituximab-treated patients in general and contribute to our basic understanding of maintenance of normal and pathogenic human B cell memory.

The 2016 ACCP Pharmacotherapy Didactic Curriculum Toolkit.

The 2016 American College of Clinical Pharmacy (ACCP) Educational Affairs Committee was charged with updating and contemporizing ACCP's 2009 Pharmacotherapy Didactic Curriculum Toolkit. The toolkit has been designed to guide schools and colleges of pharmacy in developing, maintaining, and modifying their curricula. The 2016 committee reviewed the recent medical literature and other documents to identify disease states that are responsive to drug therapy. Diseases and content topics were organized by organ system, when feasible, and grouped into tiers as defined by practice competency. Tier 1 topics should be taught in a manner that prepares all students to provide collaborative, patient-centered care upon graduation and licensure. Tier 2 topics are generally taught in the professional curriculum, but students may require additional knowledge or skills after graduation (e.g., residency training) to achieve competency in providing direct patient care. Tier 3 topics may not be taught in the professional curriculum; thus, graduates will be required to obtain the necessary knowledge and skills on their own to provide direct patient care, if required in their practice. The 2016 toolkit contains 276 diseases and content topics, of which 87 (32%) are categorized as tier 1, 133 (48%) as tier 2, and 56 (20%) as tier 3. The large number of tier 1 topics will require schools and colleges to use creative pedagogical strategies to achieve the necessary practice competencies. Almost half of the topics (48%) are tier 2, highlighting the importance of postgraduate residency training or equivalent practice experience to competently care for patients with these disorders. The Pharmacotherapy Didactic Curriculum Toolkit will continue to be updated to provide guidance to faculty at schools and colleges of pharmacy as these academic pharmacy institutions regularly evaluate and modify their curricula to keep abreast of scientific advances and associated practice changes. Access the current Pharmacotherapy Didactic Curriculum Toolkit at http://www.accp.com/docs/positions/misc/Toolkit_final.pdf.

Depression in the older adult: What should be considered?

INTRODUCTION: The updated American Geriatrics Society (AGS) 2015 Beers Criteria include the following antidepressant classes as potentially inappropriate medications to be used with caution in older adults: selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, and mirtazapine. METHODS: A search of the medical literature using PubMed and references included in the AGS 2015 Beers Criteria. RESULTS: The treatment of depression in the older adult can additionally be complicated by comorbid conditions, as 80% of older adults have at least 1 comorbid condition and 50% have at least 2. These considerations limit the pharmacologic treatment options for depression in older adults. However, the treatment of major depression should not be overlooked, as it is quite common, with estimates of up to 5% of older adults in the community and up to 13.5% in older adults who receive home health care. DISCUSSION: This article reviews treatment considerations of depression in the older adult, including both available screening tools and a discussion balancing the need for treatment of depression in this population with the concerns addressed in the 2015 Beers Criteria.

Managing depression for residents in nursing facilities.

OBJECTIVE: Review the current Centers for Medicare & Medicaid Services' (CMS) Interpretive Guidelines from the State Operations Manual (SOM) in light of evidence for management of depression found in the literature. DATA SOURCES: Articles indexed in PubMed for the last 20 years, American Psychiatric Association Guidelines, CMS Interpretive Guidelines from the SOM, and The American Medical Directors Association (AMDA) Guidelines. STUDY SELECTION AND DATA EXTRACTION: Forty published papers were reviewed, and criteria supporting the primary objective were used to identify useful resources. DATA SYNTHESIS: The literature included guidelines regarding the management of late-life depression (e.g., dosage and duration of therapy). This literature was examined in relation to the current CMS Interpretive Guidelines, which are provided to state surveyors to help them evaluate whether a nursing facility is in compliance with federal regulations. These guidelines provide explanation and clarification of the actual regulations and so are used during evaluation of the facility. CONCLUSION: Current recommendations indicate that a first episode of depression should be treated for 12 months beyond full remission, according to AMDA guidelines. Longer treatment durations (maintenance phase) are needed depending on the resident's situation (e.g., severity or number of episodes). In addition, evidence suggests that antidepressants should remain at the same dose through the maintenance phase of treatment. The Interpretive Guidelines require a dosage reduction to the lowest effective dose by decreasing the dose two times in the first year unless "clinically contraindicated to discontinuation" is documented. This correlates to a dosage reduction within the first nine months of antidepressant treatment. This necessitates that in the majority of depressive episodes, clinicians document their rationale for continuing treatment. Clinicians must commit to this process, and surveyors must acknowledge this appropriate approach to depression management.

Quality of life of cutaneous disease in the ectodermal dysplasias.

The ectodermal dysplasias are a complex, heritable group of syndromes that affect derivatives of ectoderm. The dermatologist plays an important role in ectodermal dysplasias as the visible defects of skin, hair, and nails are often recognized first. Our objective was to examine how quality of life relates to the degree of skin involvement in ectodermal dysplasias. Subjects (n = 42) with ectodermal dysplasias were surveyed at national and regional conferences hosted by National Foundation for Ectodermal Dysplasias on July 26 to 28, 2007 and November 17, 2007. Severity of hypohidrosis, alopecia, and fingernail involvement were measured using validated Likert scales. The quality of life was measured using the Children's Dermatology Life Quality Index in children, and the Skindex-29 and RAND Short Form-36 in adults. The severity for all subjects (n = 42) was greatest for hypohidrosis, which clinically translated into "little ability to sweat." We found that the greatest impact on quality of life was related to the actual symptoms of ectodermal dysplasias, which is not surprising as almost all participants reported skin involvement (93%), most likely related to hypohidrosis, atopic dermatitis, skin erosions and infections. The symptoms of ectodermal dysplasias may also be related to the nail involvement, as manifested by dystrophic or fragmented nails. Alopecia did not play a significant role in the quality of life burden. The challenge of providing proper skin care emphasizes the benefit of dermatologic involvement, and the need for increased recognition and enhanced awareness of the cutaneous burden in ectodermal dysplasias.

Characterization of mesenchymal stem cells from human vocal fold fibroblasts.

OBJECTIVES/HYPOTHESIS: Mesenchymal stem cells (MSCs) originally isolated from bone marrow (BM), are fibroblast-looking cells that are now assumed to be present in the stromal component of many tissues. MSCs are characterized by a certain set of criteria, including their growth culture characteristics, a combination of cell surface markers, and the ability to differentiate along multiple mesenchymal tissue lineages. We hypothesized that human vocal fold fibroblasts (hVFF) isolated from the lamina propria meet the criteria established to define MSCs and are functionally similar to MSCs derived from BM and adipose tissue. STUDY DESIGN: In vitro study. METHODS: hVFF were previously derived from human vocal fold tissues. MSCs were derived from adipose tissue (AT), and BM of healthy donors based on their attachment to culture dishes and their morphology and expanded in culture. Cells were analyzed for standard cell surface markers identified on BM-derived MSCs and the ability to differentiate into cells of mesenchymal lineage (i.e., fat, bone, and cartilage). We investigated the immunophenotype of these cells before and after interferon-gamma (INF-gamma) stimulation. RESULTS: hVFF displayed cell surface markers and multipotent differentiation capacity characteristic of MSCs. Furthermore, these cells exhibited similar patterns of expression of human leukocyte antigen and costimulatory molecules, after stimulation with INF-gamma compared to MSCs derived from BM and AT. CONCLUSIONS: Based on our findings, hVFF derived from lamina propria have the same cell surface markers, immunophenotypic characteristics, and differentiation potential as BM- and AT-derived MSCs. We propose that vocal fold fibroblasts are MSCs resident in the vocal fold lamina propria.

Treatment of cutaneous T-cell lymphoma/mycosis fungoides.

The cause of mycosis fungoides is unknown and, with the possible exception of very early stage disease, no cure is available. Fortunately, patients with MF have a number of therapeutic options and partial and complete remissions are achievable. Because it is not curable, the burden for patients with this disease involves the need for lifelong therapy and monitoring, and meticulous skin care. Despite its indolent nature in most individuals, the disease has a tremendous psychological impact, not only because of the visible nature of the skin lesions, but also due to the rarity of the disease and its chronicity. Knowledge of this disease, therapeutic options, and expectations of therapy will enhance care of patients afflicted with mycosis fungoides. Ongoing research provides hope that in the future, therapy to induce long-lasting remission, or even cure, will become available. Since the submission of this manuscript, vorinostat (Zolinza), an orally administered histone inhibitor, has been FDA approved for treating skin manifestations in patients with CTCL.