Development and Validation of a Species-specific PCR Method for the Identification of Ginseng Species Using Orthogonal Approaches.

When testing botanical ingredients of herbal medicines and dietary supplements, the complexity of botanical matrixes often requires the use of orthogonal methods to establish identification procedures suitable for quality control purposes. Genomic-based botanical identification methods are evolving and emerging as useful quality control tools to complement traditional morphological and chemical identification methods. Species-specific polymerase chain reaction methods are being evaluated for botanical quality control and as a cost-effective approach to identify and discriminate between closely related botanical species. This paper describes orthogonal identification of Panax ginseng, P. quinquefolius, and P. notoginseng materials in commerce as an example of the development and validation of a set of species-specific polymerase chain reaction methods to establish botanical identity in ginseng roots. This work also explored the possibility of extending the application of species-specific polymerase chain reaction methods to provide species identity information for processed materials, such as steamed roots and hydroalcoholic extracts, and showed success with this approach. Finally, the paper provides recommendations for an out-of-specification investigation of samples that may pass some of the orthogonal tests and fail others.

SaVanT: a web-based tool for the sample-level visualization of molecular signatures in gene expression profiles.

BACKGROUND: Molecular signatures are collections of genes characteristic of a particular cell type, tissue, disease, or perturbation. Signatures can also be used to interpret expression profiles generated from heterogeneous samples. Large collections of gene signatures have been previously developed and catalogued in the MSigDB database. In addition, several consortia and large-scale projects have systematically profiled broad collections of purified primary cells, molecular perturbations of cell types, and tissues from specific diseases, and the specificity and breadth of these datasets can be leveraged to create additional molecular signatures. However, to date there are few tools that allow the visualization of individual signatures across large numbers of expression profiles. Signature visualization of individual samples allows, for example, the identification of patient subcategories a priori on the basis of well-defined molecular signatures. RESULT: Here, we generate and compile 10,985 signatures (636 newly-generated and 10,349 previously available from MSigDB) and provide a web-based Signature Visualization Tool (SaVanT; http://newpathways.mcdb.ucla.edu/savant ), to visualize these signatures in user-generated expression data. We show that using SaVanT, immune activation signatures can distinguish patients with different types of acute infections (influenza A and bacterial pneumonia). Furthermore, SaVanT is able to identify the prominent signatures within each patient group, and identify the primary cell types underlying different leukemias (acute myeloid and acute lymphoblastic) and skin disorders. CONCLUSIONS: The development of SaVanT facilitates large-scale analysis of gene expression profiles on a patient-level basis to identify patient subphenotypes, or potential therapeutic target pathways.

Assessing Disaster Preparedness Among Select Children's Summer Camps in the United States and Canada.

OBJECTIVE: Children's summer camps are at risk for multiple pediatric casualties during a disaster. The degree to which summer camps have instituted disaster preparedness is unknown. We assessed disaster preparedness among selected camps nationally for a range of disasters. METHODS: We partnered with a national, web-based electronic health records system to send camp leadership of 315 camp organizations a 14-question online survey of disaster preparedness. One response from each camp was selected in the following order of importance: owner, director, physician, nurse, medical technician, office staff, and other. The results were analyzed using descriptive statistics. RESULTS: A total of 181 camps responses were received, 169 of which were complete. Camp types were overnight (60%), day (21%), special/medical needs (14%), and other (5%). Survey respondents were directors (52%), nurses (14%), office staff (10%), physicians (5%), owners (5%), emergency medical technicians (2%), and other (12%). Almost 18% of camps were located >20 mi from a major medical center, and 36% were >5 mi from police/fire departments. Many camps were missing emergency supplies: car/booster seats for evacuation (68%), shelter (35%), vehicles for evacuation (26%), quarantine isolation areas (21%), or emergency supplies of extra water (20%) or food (17%). Plans were unavailable for the following: power outages (23%); lockdowns (15%); illness outbreaks (15%); tornadoes (11%); evacuation for fire, flood, or chemical spill (9%); and other severe weather (8%). Many camps did not have online emergency plans (53%), plans for children with special/medical needs (38%), methods to rapidly communicate information to parents (25%), or methods to identify children for evacuation/reunification with parents (40%). Respondents reported that staff participation in disaster drills varied for weather (58%), evacuations (46%), and lockdowns (36%). The majority (75%) of respondents had not collaborated with medical organizations for planning. CONCLUSIONS: A substantial proportion of camps were missing critical components of disaster planning. Future interventions must focus on developing summer camp-specific disaster plans, increasing partnerships, and reassessing national disaster plans to include summer camp settings.

Mental Health Screening Outcomes in a Pediatric Specialty Care Setting.

OBJECTIVE: To evaluate whether a psychosocial screening program that included free and flexible access to mental health (MH) consultation resulted in increased rate of consultations. STUDY DESIGN: This is a post hoc review of a clinical screening program in a pediatric food allergy clinic in New York City. Screening was limited to 2 days per week, providing an opportunity to compare screened and nonscreened cohorts. Previous results from more than 1000 other families were analyzed to create the 1-page screening questionnaire. Participants were children with allergies and their parents who sought care at the clinic between March and September 2013. Parents were screened for distress and quality of life burden related to their child's allergy, and children were screened for anxiety, bullying, and quality of life. The predefined primary outcome was the percentage of families who received the free MH consultation after screening vs no-screening days in the allergy clinic. RESULTS: The 3143 encounters during the study period included 1171 on screening days and 1972 on no-screening days. Most (86%) eligible families completed the screen. Almost one-half (44%) met the initial screening thresholds. A total of 71 families (6.1% of screening days encounters) were referred to a MH consultation after a secondary review, but only 11 (1% of screening days encounters) scheduled a MH appointment. Eighteen families from the no-screening days came to a MH evaluation (1% of no-screening days encounters). CONCLUSION: Screening did not lead to enhanced MH follow-up. Resources may be better used on ensuring the availability of MH care rather than on screening in pediatric specialty clinics.

Early Acetabular Fracture Repair Through an Anterior Approach Is Associated With Increased Blood Loss.

OBJECTIVES: To determine whether the timing of acetabular fracture fixation through an anterior approach influences estimated and calculated perioperative blood loss. DESIGN: Retrospective cohort study. SETTING: Level 1 trauma center from 2013 to 2021. PATIENT SELECTION CRITERIA: Patients aged ≥18 years treated with acetabular fracture fixation through an anterior-based approach. OUTCOME MEASURES AND COMPARISONS: The primary outcome was calculated blood loss (CBL). Secondary outcomes were estimated blood loss reported by surgeon and anesthesia, and blood transfusion requirements. Comparisons of blood loss were made at discrete postinjury time thresholds (24, 36, and 48 hours) and on a continuous basis. RESULTS: One hundred eight patients were studied. The mean age was 65 years, and 73% of patients were male. Earlier fixation of acetabular fractures resulted in greater CBL and estimated blood loss (surgeon and anesthesia) compared with later fixation when analyzed on a continuum and at specific time points (24, 36, and 48 hours). Mean CBL in patients treated earlier (<48 hours, 2539 ± 1194 mL) was significantly greater than those treated later (≥48 hours, 1625 ± 909 mL; P < 0.001). Fracture repair before 48 hours postinjury was associated with a 3 times greater risk of >2000 mL of CBL ( P = 0.006). This did not result in differences in transfusion rates between groups at 24 hours ( P = 0.518), 36 hours ( P = 1.000), or 48 hours ( P = 0.779). CONCLUSIONS: Delaying fixation of acetabular fractures treated through an anterior approach for 48 hours postinjury may significantly reduce perioperative blood loss. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Potential association of posttraumatic stress disorder and decreased bone mineral density in repatriated prisoners of war.

OBJECTIVE: We conducted a retrospective evaluation of bone mineral density data collected during routine medical follow-up evaluations of 241 Vietnam-era male repatriated prisoners of war, with and without the lifetime diagnosis of posttraumatic stress disorder (PTSD), and 79 subjects in a comparison group. METHODS: Dual-energy X-ray absorptiometry scans evaluated total hip and lumbar spine T-scores. A multivariate analysis of covariance was performed on the data using age, body mass index, ethnicity, and reported alcohol consumption as covariates. RESULTS: There was a significant effect of group on total hip, but not lumbar spine, T-scores. Pairwise comparisons revealed statistically lower total hip T-scores in repatriates with a lifetime history of PTSD in comparison to both the comparison group and repatriates without a lifetime history of PTSD. CONCLUSION: In this study of elderly repatriated prisoners of war, we noted an association between a lifelong history of PTSD and decreased bone mineral density at the hip.

Ensuring public trust in digital therapeutics: a pharmacopeial perspective.

DISCLOSURES: No funding supported the writing of this commentary. The author is employed by US Pharmacopeia. This article was requested by JMCP as a response to the companion Viewpoints article "Decision Makers Need an Approach to Determine Digital Therapeutic Product Quality, Access, and Appropriate Use" by Parcher and Coder (see page 536). Digital Therapeutics Alliance, which is mentioned in this article, is a member of the USP Convention.

The genetic diversity and evolution of field pea (Pisum) studied by high throughput retrotransposon based insertion polymorphism (RBIP) marker analysis.

BACKGROUND: The genetic diversity of crop species is the result of natural selection on the wild progenitor and human intervention by ancient and modern farmers and breeders. The genomes of modern cultivars, old cultivated landraces, ecotypes and wild relatives reflect the effects of these forces and provide insights into germplasm structural diversity, the geographical dimension to species diversity and the process of domestication of wild organisms. This issue is also of great practical importance for crop improvement because wild germplasm represents a rich potential source of useful under-exploited alleles or allele combinations. The aim of the present study was to analyse a major Pisum germplasm collection to gain a broad understanding of the diversity and evolution of Pisum and provide a new rational framework for designing germplasm core collections of the genus. RESULTS: 3020 Pisum germplasm samples from the John Innes Pisum germplasm collection were genotyped for 45 retrotransposon based insertion polymorphism (RBIP) markers by the Tagged Array Marker (TAM) method. The data set was stored in a purpose-built Germinate relational database and analysed by both principal coordinate analysis and a nested application of the Structure program which yielded substantially similar but complementary views of the diversity of the genus Pisum. Structure revealed three Groups (1-3) corresponding approximately to landrace, cultivar and wild Pisum respectively, which were resolved by nested Structure analysis into 14 Sub-Groups, many of which correlate with taxonomic sub-divisions of Pisum, domestication related phenotypic traits and/or restricted geographical locations. Genetic distances calculated between these Sub-Groups are broadly supported by principal coordinate analysis and these, together with the trait and geographical data, were used to infer a detailed model for the domestication of Pisum. CONCLUSIONS: These data provide a clear picture of the major distinct gene pools into which the genus Pisum is partitioned and their geographical distribution. The data strongly support the model of independent domestications for P. sativum ssp abyssinicum and P. sativum. The relationships between these two cultivated germplasms and the various sub-divisions of wild Pisum have been clarified and the most likely ancestral wild gene pools for domesticated P. sativum identified. Lastly, this study provides a framework for defining global Pisum germplasm which will be useful for designing core collections.

Camp Leadership Perspectives on Food Allergy-Related Anaphylaxis Events and Training for Camp Staff: A National Survey of Summer Camps.

BACKGROUND: Training of camp staff to recognize and treat anaphylaxis is recommended because food allergies are prevalent among summer campers. The frequency of food allergy anaphylaxis events and the extent of anaphylaxis training for camp staff are unknown. OBJECTIVE: To estimate the frequency of food-allergic reactions in camps across the United States and to assess the state of food allergy anaphylaxis training for camp staff. METHODS: We partnered with CampDoc.com to send a 20-question survey in February 2016 to camp leadership representing 528 camps. Questions addressed demographic characteristics, food allergy policies, training, medication availability, anaphylaxis events, and confidence in staff to recognize and treat anaphylaxis. RESULTS: A total of 559 responses were received, representing 258 camps. The majority surveyed (n = 529 [94.6%]) reported food-allergic children attending their camps. Only 47.6% (n = 266) respondents reported requiring individualized emergency action plans as required for camper attendance. Anaphylaxis treated with epinephrine was reported by 24% (n = 134) of leadership within the previous 2 years at their camp. These respondents were more likely to have a training session for staff (odds ratio, 2.46; 95% CI, 1.4-4.3). A total of 63.3% (n = 354) reported training session presence. However, 15.6% (n = 87) of leadership were unsatisfied with training materials and one-third were not confident in staff to manage anaphylaxis. CONCLUSIONS: Appropriate policies to manage food anaphylaxis events and anaphylaxis management training were missing in a substantial proportion of camps. Camp-tailored food allergy training is needed given the number of camps reporting food allergy reactions requiring epinephrine.

Pediatric Head Injuries in Summer Camps.

Summer camps have a unique supervisory environment that may lead to increased head injury risk for children. The epidemiology of head injuries in camps is unclear. We partnered with CampDoc.com to review head injury reports from camp nurses in 2016 from 197 camps in 36 states. A total of 4290 (92%) reports were coded as definite head injuries, 47% (n = 2002) in female campers, with median camper age of 10 years. Head injury severity was coded as mild (94%, n = 4040), moderate (6%, n = 248), or severe (<1%, n = 2). Only 3% (n = 134) were medically evaluated, and 29% (n = 1221) were sports-related. Head injuries were categorized as definite (3%, n = 137) and probable (13%, n = 572) concussions, with 39% (n = 277) being sports-related and 61% (n = 83) of definite concussions incurred by female campers. Summer camps, while an important location of head injury risk, appear to be a safe environment for youth.

Improving Health and Safety at Camp.

The American Academy of Pediatrics has created recommendations for health appraisal and preparation of young people before participation in day, resident, or family camps and to guide health and safety practices at camp. These recommendations are intended for parents and families, primary health care providers, and camp administration and health center staff. Although camps have diverse environments, there are general guidelines that apply to all situations and specific recommendations that are appropriate under special conditions. This policy statement has been reviewed and is supported by the American Camp Association and Association of Camp Nursing.

Food Allergy Trends and Epinephrine Autoinjector Presence in Summer Camps.

BACKGROUND: Pediatric campers with food allergies are at greater risk for exposure and anaphylaxis. A diagnosis of asthma increases risk for anaphylaxis. Epidemiological investigations of food-allergic children at high risk for allergic reactions requiring intervention in camp settings are lacking. OBJECTIVE: The objectives of this study were to estimate the prevalence of food allergies among otherwise healthy campers in summer camps throughout the United States and Canada, and to assess asthma comorbidity and determine rates of epinephrine autoinjector prescriptions present in this population. METHODS: We partnered with CampDoc.com, a web-based camp electronic health record system. Deidentified data were abstracted from 170 camps representing 122,424 campers. Only food allergies with a parental report of symptoms requiring intervention or with a camp prescription for an epinephrine autoinjector were included, whereas gluten, lactose intolerance, and food dyes were excluded. Asthma status and epinephrine presence on the camp medication list were assessed. RESULTS: Overall, 2.5% of campers (n = 3055) had documented food allergies. Of these campers, 22% had multiple food allergies. Median age was 11 years; 52% were female. Nuts (81%), seafood (17.4%), egg (8.5%), fruit (8.1%), and seeds (7.2%) were the top 5 food allergies reported. Of food-allergic campers, 44.3% had concurrent asthma and 34.7% of those campers were taking multiple asthma medications. Less than half (39.7%) of food-allergic children brought an epinephrine autoinjector to the camp. CONCLUSIONS: Life-saving epinephrine is not necessarily available for food-allergic children in camp settings. A substantial proportion of food-allergic campers are at higher risk for anaphylaxis based on concurrent asthma status.

Insertional polymorphism and antiquity of PDR1 retrotransposon insertions in pisum species.

Sequences flanking 73 insertions of the retrotransposon PDR1 have been characterized, together with an additional 270 flanking regions from one side alone, from a diverse collection of Pisum germ plasm. Most of the identified flanking sequences are repetitious DNAs but more than expected (7%) lie within nuclear gene protein-coding regions. The approximate age of 52 of the PDR1 insertions has been determined by measuring sequence divergence among LTR pairs. These data show that PDR1 transpositions occurred within the last 5 MY, with a peak at 1-2.5 MYA. The insertional polymorphism of 68 insertions has been assessed across 47 selected Pisum accessions, representing the diversity of the genus. None of the insertions are fixed, showing that PDR1 insertions can persist in a polymorphic state for millions of years in Pisum. The insertional polymorphism data have been compared with the age estimations to ask what rules control the proliferation of PDR1 insertions in Pisum. Relatively recent insertions (< approximately 1.5 MYA) tend to be found in small subsets of the Pisum accessions set, "middle-aged" insertions (between approximately 1.5 and 2.5 MYA) vary greatly in their occurrence, and older insertions (> approximately 2.5 MYA) are mostly found in small subsets of Pisum. Finally, the average age estimate for PDR1 insertions, together with an existing data set for PDR1 retrotransposon SSAP markers, has been used to derive an estimate of the effective population size for Pisum of approximately 7.5 x 10(5).

Allocation of food allergy responsibilities and its correlates for children and adolescents.

This study examined the degree to which children and adolescents with food allergy accept responsibility for their own care, and the extent to which greater self-management is associated with past history of a life-threatening allergic reaction or anxiety. For children (n = 190), caregiver and patient report of self-management was consistent, but agreement was poor for adolescent dyads (n = 59). History of a life-threatening allergic reaction was associated with greater self-management for children only, while among adolescents, it was associated with greater anxiety. Given that shifting to self-management may be challenging, discussion and preparation about this process is warranted.

Mental health and quality-of-life concerns related to the burden of food allergy.

As food allergy increases, more research is devoted to its influence on patient and family mental health and quality of life (QoL). This article discusses the effects on parent and child QoL, as well as distress, while appraising the limitations of knowledge given the methods used. Topics include whether QoL and distress are affected compared with other illnesses, assessment of distress and QoL in parents compared with children, concerns about food allergy-related bullying, and the necessity for evidence-based interventions. Suggestions are offered for how to improve QoL and reduce distress on the way to better coping with food allergy.

Utilizing physician screening questions for detecting anxiety among food-allergic pediatric patients.

OBJECTIVE: To explore the utility of clinician screening for anxiety in pediatric food-allergic patients. STUDY DESIGN: In Phase I, 39 patients completed an anxiety questionnaire while their allergists completed a companion questionnaire estimating their patient's responses. Allergists then attended an educational workshop to improve their anxiety detection. In Phase II, following the workshop, questionnaires were completed by an additional 39 patients and their allergists. RESULTS: The percentage of clinician questionnaires with a "do not know" response decreased from 70% to 5% after the workshop. Correlation between allergists' and children's responses remained nonsignificant (r = .314, P = .321) before the workshop and after (r = .303, P = .068) and only 25% of patients who reported elevated anxiety were identified. Additionally, clinicians expressed poor acceptability of the screening. CONCLUSIONS: After the workshop, clinicians did not more accurately detect anxiety and found the process intrusive. Alternative methods for uncovering anxiety among high-risk patients are needed.

Role of public standards in the safety and efficacy of biologic medicines.

In this report, we emphasize the importance of public monographs with reference materials, coupled with careful process and change control and attention to GMPs, as a means of advancing access to good quality, safe, and effective medicines, with emphasis on available and incoming biologic medicines. With adequate control of articles covered by a monograph, these public standards can form the basis for a global public quality platform that covers reference products, non-interchangeable reference products, biosimilars, and interchangeable biosimilars. Working collaboratively with all stakeholders, new approaches allow these public standards to emerge nationally and globally in a timely way. Yet, there are increasing limitations in the availability of public standards for biologic medicines, which may reverse many decades of progress. Solutions are considered in this report.

Child and parental reports of bullying in a consecutive sample of children with food allergy.

OBJECTIVE: The social vulnerability that is associated with food allergy (FA) might predispose children with FA to bullying and harassment. This study sought to quantify the extent, methods, and correlates of bullying in a cohort of food-allergic children. METHODS: Patient and parent (83.6% mothers) pairs were consecutively recruited during allergy clinic visits to independently answer questionnaires. Bullying due to FA or for any cause, quality of life (QoL), and distress in both the child and parent were evaluated via questionnaires. RESULTS: Of 251 families who completed the surveys, 45.4% of the children and 36.3% of their parents indicated that the child had been bullied or harassed for any reason, and 31.5% of the children and 24.7% of the parents reported bullying specifically due to FA, frequently including threats with foods, primarily by classmates. Bullying was significantly associated with decreased QoL and increased distress in parents and children, independent of the reported severity of the allergy. A greater frequency of bullying was related to poorer QoL. Parents knew about the child-reported bullying in only 52.1% of the cases. Parental knowledge of bullying was associated with better QoL and less distress in the bullied children. CONCLUSIONS: Bullying is common in food-allergic children. It is associated with lower QoL and distress in children and their parents. Half of the bullying cases remain unknown to parents. When parents are aware of the bullying, the child's QoL is better. It is important to proactively identify and address cases in this population.