Implementation of a tier system for IVIG indications to address IVIG shortage at a tertiary care pediatric medical center.

BACKGROUND: Drug shortages are a common issue that healthcare systems face and can result in adverse health outcomes for patients requiring inferior alternate treatment. The United States recently experienced a national drug shortage of intravenous immunoglobulin (IVIG). Several reported strategies to address the IVIG and other drug shortages have been proposed; however, there is a lack of evidence-based methods for protocol development and implementation. OBJECTIVE: To evaluate the efficacy of introducing a multidisciplinary task force and tier system of indications and to minimize adverse effects during a shortage of IVIG. METHODS: Faculty members across disciplines with expertise in IVIG use were invited to participate in a task force to address the shortage and ensure adequate supply for emergent indications. A tier system of IVIG indications was established according to the severity of diagnosis, urgency of indication, and quality of supporting evidence. Based on inventory, indications in selected tiers were auto-approved. Orders that could not be automatically approved were escalated for task force review. RESULTS: Overall, there were 342 distinct requests for IVIG during the study period (August 1, 2019 to December 31, 2019). All Tier 1 indications were approved. Of all requests, only 2.6% (9) of requests were denied, none of which resulted in adverse effects based on retrospective chart review. Seven patients who regularly receive IVIG had possible adverse effects due to dose reduction or spacing of treatment; however, each complication was multifactorial and not attributed to the shortage or tier system implementation alone. CONCLUSION: Implementation of a multidisciplinary task force and tier system to appropriately triage high-priority indications for limited pharmaceutical agents should be considered in health institutions faced with a drug shortage.

Beyond health-related quality of life: initial psychometric validation of a new scale for addressing the gap in assessing the full range of alopecia areata psychosocial burden.

BACKGROUND: Patients with alopecia areata (AA) report a broad range of psychosocial outcomes beyond those assessed in existing health-related quality of life measures. Yet, to date, no psychometrically validated scale based on patient-reported outcomes (PROs) appears to exist to comprehensively measure these AA-specific psychosocial outcomes. OBJECTIVES: The objective of this study was to develop such a scale, the Scale of Alopecia Areata Distress (SAAD), and to provide its initial validation evidence. METHODS: Using existing qualitative research on PROs for patients with AA, a pool of 144 items was generated and subsequently reviewed for relevance, redundancy, clarity and comprehensiveness by subject matter experts in AA psychosocial impacts and the research team. This review resulted in a reduced pool of 122 items, which was then administered to adult patients with AA residing in the USA. Exploratory Factor Analysis using Principal Axis Factoring extraction with oblique rotation identified the SAAD's underlying factor structure. To reduce the SAAD item length, additional item-reduction strategies were used. RESULTS: There were 392 participants who responded to the 122 items, each with four or fewer missing item responses. Three iterations of the data analysis plan resulted in a 41-item SAAD with seven underlying factors of psychosocial impact: Emotional and Cognitive Functioning, Romantic Relationships, Family Relationships, Primary Life Responsibilities, Non-Primary Life Responsibility Activities, Stigma, and Self-Perception Change. Each factor demonstrated acceptable to high levels of internal consistency reliability. CONCLUSIONS: Initial validation evidence of the SAAD-41 scale supports its potential as a comprehensive measure of AA-related psychosocial distress for US-based adults. Further scale validation is needed.

Psychosocial impact of pediatric alopecia areata: A survey study.

This study, which aimed to identify distress by sites of hair loss and psychosocial stressors for a pediatric alopecia areata population, enrolled 50 patients (32 females, 18 males, ages 7-17 years) from pediatric dermatology clinics, including a monthly hair disease clinic. Patients completed a 47-question survey. Scalp hair loss was rated as often or always bothersome in 34.7%; eyebrow loss in 24.3%; and eyelash loss in 21.6%, and 6 patients (12%) discontinued a social activity due to hair loss. Referral to behavioral/mental health specialists should be considered to improve psychosocial outcomes.

Assessment of Black Patients' Perception of Their Dermatology Care.

IMPORTANCE: The availability and quality of skin and hair care for black patients in the United States has been a subject of growing interest in dermatology. There is limited understanding of the perceptions of black patients about the care they receive from dermatologists and the factors affecting their care satisfaction. OBJECTIVE: To elucidate black patients' perceptions of their dermatology experience in and outside of a skin of color clinic (SOCC). DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study involving a survey and focus groups was conducted including adult black patients treated in an SOCC. Recruitment was conducted April through June 2015 through clinic-posted flyers. Participants engaged in 1 of 4 focus groups on July 14, 15, 29, or 30, 2015, and completed a survey. Data were analyzed March 2016 through June 2017. MAIN OUTCOMES AND MEASURES: Planned outcomes of the focus groups were black patients' inductively generated themes on their perspectives and experiences in dermatology clinics. Planned outcomes of the survey were patients' ratings of SOCC and non-SOCC dermatologists in terms of interaction style, cultural awareness, and treatment satisfaction. Importance of patient-dermatologist racial concordance was a planned outcome in both measures. Given lack of existing prior research, no specific hypotheses were generated. RESULTS: Of the 19 adult black patients who participated in the study, 18 (95%) were women, and the mean (SD) age was 50.0 (14.2) years. All patients reported positive experiences in the SOCC. Compared with non-SOCC dermatology treatment experiences, patients reported higher levels of overall satisfaction with SOCC dermatologists (t13 = 2.85; P = .01). Patients perceived that SOCC dermatologists were better trained to care for black patients (t13 = 4.42; P = .001); showed patients greater respect and dignity (t13 = 3.37; P = .005), as well as understanding (t13 = 2.56, P = .02); and were more trustworthy (t13 = 3.47; P = .004). The majority of the comments in the focus groups (n = 207) described 2 themes: dermatologists' interaction style (62/207; 30.0%) and knowledge about black skin and hair (42/207; 20.3%). Other themes were partnering with patients on outcomes (17/207; 8.2%), shared life experiences (14/207; 6.8%), and economic sensitivity (7/207; 3.4%). These themes accounted for a large part of the participants' discussion. Of all respondents, 71% (12/17) stated that they would prefer a black (or race concordant) dermatologist; this included 91% (10/11) of the race-concordant group and 33% (2/6) of the race-discordant group. CONCLUSIONS AND RELEVANCE: Participants reported that the SOCC dermatologists provided unique and uniformly beneficial care to black patients. Care satisfaction appeared most related to dermatologists' interpersonal style and specialized knowledge in care of black skin and hair. Findings suggest that black patients' dermatologic care satisfaction would increase if dermatologists underwent enhanced residency training in skin of color, cultural competency, cost-conscious care, and empathic communication skills, and if there were greater dermatology workforce diversity.

Size-adjusted muscle power and muscle metabolism in patients with cystic fibrosis are equal to healthy controls - a case control study.

BACKGROUND: Skeletal muscle function dysfunction has been reported in patients with cystic fibrosis (CF). Studies so far showed inconclusive data whether reduced exercise capacity is related to intrinsic muscle dysfunction in CF. METHODS: Twenty patients with CF and 23 age-matched controls completed an incremental cardiopulmonary cycling test. Further, a Wingate anaerobic test to assess muscle power was performed. In addition, all participants completed an incremental knee-extension test with 31P magnetic resonance spectroscopy to assess muscle metabolism (inorganic phosphate (Pi) and phosphocreatinine (PCr) as well as intracellular pH). In the MRI, muscle cross-sectional area of the M. quadriceps (qCSA) was also measured. A subgroup of 15 participants (5 CF, 10 control) additionally completed a continuous high-intensity, high-frequency knee-extension exercise task during 31P magnetic resonance spectroscopy to assess muscle metabolism. RESULTS: Patients with CF showed a reduced exercise capacity in the incremental cardiopulmonary cycling test (VO2peak: CF 77.8 ± 16.2%predicted (36.5 ± 7.4 ml/qCSA/min), control 100.6 ± 18.8%predicted (49.1 ± 11.4 ml/qCSA/min); p < 0.001), and deficits in anaerobic capacity reflected by the Wingate test (peak power: CF 537 ± 180 W, control 727 ± 186 W; mean power: CF 378 ± 127 W, control 486 ± 126 W; power drop CF 12 ± 5 W, control 8 ± 4 W. all: p < 0.001). In the knee-extension task, patients with CF achieved a significantly lower workload (p < 0.05). However, in a linear model analysing maximal work load of the incremental knee-extension task and results of the Wingate test, respectively, only muscle size and height, but not disease status (CF or not) contributed to explaining variance. In line with this finding, no differences were found in muscle metabolism reflected by intracellular pH and the ratio of Pi/PCr at submaximal stages and peak exercise measured through MRI spectroscopy. CONCLUSIONS: The lower absolute muscle power in patients with CF compared to controls is exclusively explained by the reduced muscle size in this study. No evidence was found for an intrinsic skeletal muscle dysfunction due to primary alterations of muscle metabolism.

Homo- and heteropolymer self-assembly of recombinant trichocytic keratins.

In the past two decades, keratin biomaterials have shown impressive results as scaffolds for tissue engineering, wound healing, and nerve regeneration. In addition to its intrinsic biocompatibility, keratin interacts with specific cell receptors eliciting beneficial biochemical cues. However, during extraction from natural sources, such as hair and wool fibers, natural keratins are subject to extensive processing conditions that lead to formation of unwanted by-products. Additionally, natural keratins suffer from limited sequence tunability. Recombinant keratin proteins can overcome these drawbacks while maintaining the desired chemical and physical characteristics of natural keratins. Herein, we present the bacterial expression, purification, and solution characterization of human hair keratins K31 and K81. The obligate heterodimerization of the K31/K81 pair that results in formation of intermediate filaments is maintained in the recombinant proteins. Surprisingly, we have for the first time observed new zero- and one-dimensional nanostructures from homooligomerization of K81 and K31, respectively. Further analysis of the self-assembly mechanism highlights the importance of disulfide crosslinking in keratin self-assembly.

Cargo delivery on demand from photodegradable MOF nano-cages.

We report the photo-induced degradation of and cargo release from a nanoscale metal-organic framework (nMOF) incorporating photo-isomerizable 4,4'-azobenzenedicarboxylate (AZB) linkers. The structure matches a UiO-type framework where 12 4,4'-azobenzenedicarboxylate moieties are connected to a Zr6O4(OH)4 cluster, referred to as UiO-AZB. Due to the incorporation of photo-isomerizable struts, the degradation of UiO-AZB is accelerated by irradiation with white light (1.3 ± 0.1% h-1 under dark conditions vs. 8.4 ± 0.4% h-1 when irradiated). Additionally, we show slow release of Nile Red (NR) which is triggered by irradiation (0.04 ± 0.01% h-1 under dark conditions vs. 0.36 ± 0.02% h-1 when irradiated).

Seed-mediated biomineralizaton toward the high yield production of gold nanoprisms.

Gold nanotriangles (Au NTs) with tunable edge length were synthesized via a green chemical route in the presence of the designed consensus sequence tetratricopeptide repeat (CTPR) protein, halide anions (Br(-)) and CTPR-stabilized Ag seeds. The well-defined morphologies, tailored plasmonic absorbance from visible-light to the near infrared (NIR) region, colloidal stability and biocompatibility are attributed to the synergistic action of CTPR, halide ions, and CTPR-stabilized Ag seeds.

Effects of a Physical Activity Intervention in Preschool Children.

PURPOSE: This study aimed to evaluate a multicomponent, child-appropriate preschool intervention program led by preschool teachers to enhance physical activity (PA) and motor skill performance (MS) in 4- and 5-yr-old children. METHODS: Evaluation involved 709 children (mean age, 4.7 ± 0.6 yr; 49.5% girls) from 41 preschools (intervention group, n = 21; control group, n = 20) in the rural and urban surroundings of two German cities. Children in the intervention group received a daily PA intervention lasting 30 min and PA homework over one academic year, which was designed by professionals but led by preschool teachers. The intervention included educational components for parents and teachers. Primary outcomes were MS (composite MS score) and objectively measured moderate-to-vigorous PA (MVPA) by accelerometry. Measurements were performed at baseline, midintervention, and postintervention as well as 2-4 months after the end of intervention. Intervention effects were analyzed by repeated measurement analysis adjusted for group, sex, age, baseline outcomes, urban/rural location of the preschool, and cluster (preschool). RESULTS: Compared with controls, children in the intervention group showed positive effects in MS at postintervention (estimate effect, 0.625 z-score points; 95% confidence interval (CI), 0.276-0.975; P = 0.001) and at follow-up (estimate effect, 0.590 z-score points; 95% CI, 0.109-1.011; P = 0.007) and an increase in MVPA from baseline to postintervention by 0.5% of total wearing time (95% CI, 0.002%-1.01%; P = 0.049) at borderline significance. There was no benefit on MVPA for the intervention group between baseline and follow-up. CONCLUSIONS: A child-appropriate, multidimensional PA intervention could sustainably improve MS but not PA. Findings suggest that a change in health-related behaviors is difficult. Future research should implement participatory intervention components in preschool setting and better integrate the families of the children.

Effect of lamellarity and size on calorimetric phase transitions in single component phosphatidylcholine vesicles.

Nano-differential scanning calorimetry (nano-DSC) is a powerful tool in the investigation of unilamellar (small unilamellar, SUVs, or large unilamellar, LUVs) vesicles, as well as lipids on supported bilayers, since it measures the main gel-to-liquid phase transition temperature (Tm), enthalpies and entropies. In order to assign these transitions in single component systems, where Tm often occurred as a doublet, nano-DSC, dynamic light scattering and cryo-transmission electron microscopy (cryo-TEM) data were compared. The two Tms were not attributable to decoupled phase transitions between the two leaflets of the bilayer, i.e. nano-DSC measurements were not able to distinguish between the outer and inner leaflets of the vesicle bilayers. Instead, the two Tms were attributed to mixtures of oligolamellar and unilamellar vesicles, as confirmed by cryo-TEM images. Tm for the oligolamellar vesicles was assigned to the peak closest to that of the parent multilamellar vesicle (MLV) peak. The other transition was higher than that of the parent MLVs for 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and increased in temperature as the vesicle size decreased, while it was lower in temperature than that of the parent MLVs for 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and decreased as the vesicle size decreased. These subtle shifts arose due to small differences in the values of ΔH and ΔS, since Tm is determined by their ratio (ΔH/ΔS). It was not possible to completely eliminate oligolamellar structures for MLVs extruded with the 200 nm pore size filter, even after 120 passes, while these structures were eliminated for MLVs extruded through the 50 nm pore size filter.

Quality of life is associated with physical activity and fitness in cystic fibrosis.

BACKGROUND: Health-related and disease-specific quality of life (HRQoL) has been increasingly valued as relevant clinical parameter in cystic fibrosis (CF) clinical care and clinical trials. HRQoL measures should assess - among other domains - daily functioning from a patient's perspective. However, validation studies for the most frequently used HRQoL questionnaire in CF, the Cystic Fibrosis Questionnaire (CFQ), have not included measures of physical activity or fitness. The objective of this study was, therefore, to determine the cross-sectional and longitudinal relationships between HRQoL, physical activity and fitness in patients with CF. METHODS: Baseline (n = 76) and 6-month follow-up data (n = 70) from patients with CF (age ≥12 years, FEV1 ≥35%) were analysed. Patients participated in two multi-centre exercise intervention studies with identical assessment methodology. Outcome variables included HRQoL (German revised multi-dimensional disease-specific CFQ (CFQ-R)), body composition, pulmonary function, physical activity, short-term muscle power, and aerobic fitness by peak oxygen uptake and aerobic power. RESULTS: Peak oxygen uptake was positively related to 7 of 13 HRQoL scales cross-sectionally (r = 0.30-0.46). Muscle power (r = 0.25-0.32) and peak aerobic power (r = 0.24-0.35) were positively related to 4 scales each, and reported physical activity to 1 scale (r = 0.29). Changes in HRQoL-scores were directly and significantly related to changes in reported activity (r = 0.35-0.39), peak aerobic power (r = 0.31-0.34), and peak oxygen uptake (r = 0.26-0.37) in 3 scales each. Established associates of HRQoL such as FEV1 or body mass index correlated positively with fewer scales (all 0.24 < r < 0.55). CONCLUSIONS: HRQoL was associated with physical fitness, especially aerobic fitness, and to a lesser extent with reported physical activity. These findings underline the importance of physical fitness for HRQoL in CF and provide an additional rationale for exercise testing in this population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00231686.

Validation of activity questionnaires in patients with cystic fibrosis by accelerometry and cycle ergometry.

BACKGROUND: The objective of this study was to validate physical activity questionnaires for cystic fibrosis (CF) against accelerometry and cycle ergometry. METHODS: 41 patients with CF (12-42 years) completed the Habitual Activity Estimation Scale (HAES), the 7-Day Physical Activity Recall questionnaire (7D-PAR) and the Lipid Research Clinics questionnaire (LRC) and performed an incremental exercise test according to the Godfrey protocol up to volitional fatigue. Time spent in moderate and vigorous physical activity (MVPA) assessed objectively by accelerometry was related to the time spent in the respective activity categories by correlation analyses and calculating intraclass correlation coefficients (ICC). Furthermore, the results of the exercise test were correlated with the results of the questionnaires. RESULTS: Time spent in the categories 'hard','very hard' and 'hard & very hard' of the 7D-PAR (0.41 < r < 0.56) and 'active' (r = 0.33) of the HAES correlated significantly with MVPA. The activity levels of the LRC were not related to objectively determined physical activity. Significant ICCs were only observed between the 7D-PAR activitiy categories and MVPA (ICC = 0.40-0.44). Only the LRC showed moderate correlations with the exercise test (Wmax: r = 0.46, p = 0.002; VO2peak: r = 0.32, p = 0.041). CONCLUSIONS: In conclusion, the activity categories 'hard' and 'very hard' of the 7D-PAR best reflected objectively measured MVPA. Since the association was at most moderate, the 7D-PAR may be selected to describe physical activity within a population. None of the evaluated questionnaires was able to generate valid physical activity data exercise performance data at the individual level. Neither did any of the questionnaires provide a valid assessment of aerobic fitness on an invidual level.

Prevention through Activity in Kindergarten Trial (PAKT): a cluster randomised controlled trial to assess the effects of an activity intervention in preschool children.

BACKGROUND: Physical activity and motor skills acquisition are of high importance for health-related prevention and a normal development in childhood. However, few intervention studies exist in preschool children focussing on an increase in physical activity and motor skills. Proof of positive effects is available but not consistent. METHODS/DESIGN: The design, curriculum, and evaluation strategy of a cluster randomised intervention study in preschool children are described in this manuscript. In the Prevention through Activity in Kindergarten Trial (PAKT), 41 of 131 kindergartens of Wuerzburg and Kitzingen, Germany, were randomised into an intervention and a control group by a random number table stratified for the location of the kindergarten in an urban (more than 20,000 inhabitants) or rural area. The aims of the intervention were to increase physical activity and motor skills in the participating children, and to reduce health risk factors as well as media use. The intervention was designed to involve children, parents and teachers, and lasted one academic year. It contained daily 30-min sessions of physical education in kindergarten based on a holistic pedagogic approach termed the "early psychomotor education". The sessions were instructed by kindergarten teachers under regular supervision by the research team. Parents were actively involved by physical activity homework cards. The kindergarten teachers were trained in workshops and during the supervision. Assessments were performed at baseline, 3-5 months into the intervention, at the end of the intervention and 2-4 months after the intervention. The primary outcomes of the study are increases in physical activity (accelerometry) and in motor skills performance (composite score of obstacle course, standing long jump, balancing on one foot, jumping sidewise to and fro) between baseline and the two assessments during the intervention. Secondary outcomes include decreases in body adiposity (BMI, skin folds), media use (questionnaire), blood pressure, number of accidents and infections (questionnaire), increases in specific motor skills (throwing, balancing, complex motor performance, jumping) and in flexibility. DISCUSSION: If this trial proofs the effectiveness of the multilevel kindergarten based physical activity intervention on preschooler's activity levels and motor skills, the programme will be distributed nationwide in Germany. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00623844.