Updates in the treatment of asthma in pediatrics: A review for pharmacists.

PURPOSE: The purpose of this review is to summarize the management of asthma in children and to highlight different guideline-based approaches. This review also discusses literature regarding the use of corticosteroids, both inhaled and systemic, as well as biologic agents, in asthma management. SUMMARY: Asthma is a common chronic respiratory condition in the pediatric population and has evolved into a highly patient-specific disease. Of the 2 main asthma guidelines, one developed by the National Asthma Education and Prevention Program was recently published as a focused update in 2020. The other, from the Global Initiative for Asthma, focuses on a global strategy for management and prevention, with the most recent update in 2023. Both reports discuss diagnosis, assessment, and treatment of asthma in adults and children. Treatment is designed as a stepwise approach in both reports, although there are key differences. This article focuses on gaps in these guidelines, including the use of bronchodilators and inhaled corticosteroids with single maintenance and reliever therapy and long-acting muscarinic antagonists in children. It also reviews treatment in children under 5 years of age, although recommendations are limited due to a lack of evidence in this age group. Finally, this review discusses considerations for emerging treatments, including biologics, for patients who are difficult to treat. CONCLUSION: New treatment strategies and agents have emerged in the treatment of pediatric asthma. Pharmacists play a key role in providing education about, dispensing, and recommending the newest evidence-based treatment options for children.

Evaluating the feasibility and acceptability of home-based urinalysis for albumin-creatinine ratio with smartphone technology: A quality improvement project.

BACKGROUND: Despite albumin-creatinine ratio (urine) testing being recommended for detection of chronic kidney disease among adults with diabetes, testing rates are suboptimal. AIM: We implemented and evaluated a quality improvement project in an inner-city diabetes population in London, UK to assess the feasibility and acceptability of implementing novel home-based urinalysis using smartphone technology. METHODS: After eligible patients were identified and consented, testing kits were sent to the patient's home. Test results and patient feedback were collected through the smartphone application. Focus group discussions were conducted to evaluate primary care staff perspectives on uptake and delivery of the service. RESULTS: In total 2370 patients agreed to take part. Of these, 1244 completed the test (61% of those eligible) and of these, 465 (37%) had clinically significant albuminuria. 98% of patients found the test easy or very easy to use. Staff in primary care found the service to be beneficial for patients, and reported ease of set up and minimal administrative processes. Concerns regarding barriers among patients with lower digital literacy and non-English speakers were raised although these concerns were not substantiated. CONCLUSION: Home-based albumin-creatinine ratio urine testing may improve the testing rates of people with diabetes at higher risk of chronic kidney disease. This is important post-pandemic, as healthcare services are trying to return to pre-pandemic levels of care. The study also found that the use of smartphone technology in an underserved (deprived) community is feasible, despite reservations about levels of digital literacy and possible language barriers. Further evaluation of effectiveness and costs is required.

Just DOAC: Use of direct-acting oral anticoagulants in pediatrics.

PURPOSE: The aim of this article is to provide an overview of the current literature for direct-acting oral anticoagulant (DOAC) use in pediatric patients and summarize ongoing trials. SUMMARY: In treatment of venous thromboembolism (VTE) in pediatric patients, evidence supports use of both dabigatran and rivaroxaban. Dabigatran has been shown to be noninferior to standard of care (SOC) in terms of efficacy, with similar bleeding rates. Similarly, treatment with rivaroxaban in children with acute VTE resulted in a low recurrence risk and reduced thrombotic burden, without increased risk of bleeding, compared to SOC. Treatment of pediatric cerebral venous thrombosis as well as central venous catheter-related VTE with rivaroxaban appeared to be both safe and efficacious and similar to that with SOC. Dabigatran also has a favorable safety profile for prevention of VTE, and rivaroxaban has a favorable safety profile for VTE prevention in children with congenital heart disease. Many studies with several different DOACs are ongoing to evaluate both safety and efficacy in unique patient populations, as well as VTE prevention. CONCLUSION: The literature regarding pediatric VTE treatment and prophylaxis is growing, but the need for evidence-based pediatric guidelines remains. Additional long-term, postauthorization studies are warranted to further elucidate safety and efficacy in clinical scenarios excluded in clinical trials. Additional data on safety, efficacy, and dosing strategies for reversal agents are also necessary, especially as the use of DOACs becomes more common in the pediatric population.

Effectiveness and sustainability of volunteering with older people living in care homes: A mixed methods systematic review.

Older people living in care homes should be considered part of the wider local community; however, little is known about what enables them to connect with people not paid to look after them or family members. Volunteering can complement paid and familial support. While volunteering is common in community settings, care home residents are less likely to benefit from their input. We conducted a mixed methods systematic review and stakeholder consultation that aimed to identify volunteer activities in care homes and evidence for their effectiveness and sustainability. Databases were searched from 2000 to July 2021. Studies of all designs reporting volunteer-led activities with care home residents 65-years or over were included. Data on interventions, study population, study context, outcomes and implementation issues were extracted and synthesised. We identified 36 studies on the use, effectiveness and implementation of volunteering in care homes, although the overall strength of evidence was weak. Resident engagement and mood appeared to improve during volunteer-led activities, but there was little research examining the longer-term impact. Qualitative and stakeholder data suggest considerable investment is needed to initiate and maintain volunteering initiatives, but there are positive benefits for volunteers, residents and staff if an intervention is sustained. Financial cost for care home facilities is unclear. Interventions that address inequalities in accessing volunteer support within the resident population and between facilities should be considered.

An Analysis of Documents Guiding Palliative Care in Five Canadian Provinces.

ABSTRACTThe purpose of this study was to analyse the consistency and extent of palliative content across high-level guiding documents related to the care of persons residing in Canadian long-term care homes. A systematic search was conducted examining documents at the national level and across five provinces (Alberta, Ontario, Saskatchewan, Manitoba, and Quebec). Twenty-five documents were selected based on inclusion criteria from 273 documents identified in the systematic search. The majority of these documents were created nationally (48%) or in Ontario (28%). Documents varied in palliative topics discussed, and long-term care was discussed minimally. A minimal number of palliative care guiding documents were found. Long-term care specific documents were absent, and all documents lacked consistency on palliative topics. It is imperative that palliative principles are present and consistent in high-level documents in order to improve the quality of life and care for long-term care residents across Canada.

Variation in impacts of Tulsa pre-K on cognitive development in kindergarten: The role of instructional support.

Public prekindergarten (pre-K) programs have been a recent focus of policy and research attention, in part because of their empirically documented, positive short-term impacts on child cognitive development and school readiness. However, no studies have explored factors that might explain variation across schools in public pre-K impacts. The current study examines the Tulsa Public School pre-K program's impacts on children's letter-word identification, spelling, and applied problem-solving skills at kindergarten entry. Findings reveal substantial across-school variation in treatment impacts, associated with variation in instructional support. Results are robust to sensitivity checks and are discussed alongside implications for policy and future research. (PsycINFO Database Record

Care of patients with Ebola virus disease.

Caring for patients with Ebola virus disease requires strict biosafety protocols to eliminate exposure and ensure containment. Training and competency verification were critical to creation of a safe environment for nursing staff involved in the direct care of two patients with Ebola virus disease at Emory University Hospital.

Developmental validation of the PowerPlex(®) ESI 16/17 Fast and PowerPlex(®) ESX 16/17 Fast Systems.

The PowerPlex(®) ESI 16 Fast, ESI 17 Fast, ESX 16 Fast, and ESX 17 Fast Systems represent faster cycling versions (50min or less) of the PowerPlex(®) ESI and ESX Systems released by Promega in 2009 to accommodate the ENFSI and EDNAP groups' call for new STR multiplexes for Europe. In addition to amplification of purified DNA samples, these new faster cycling systems allow for direct amplification from single-source blood and buccal samples deposited on FTA(®) and nonFTA paper as well as from SwabSolution™ extracts of buccal swabs without the need for purification and quantitation. There are no changes to the autosomal primer pair sequences in the PowerPlex(®) ESI Fast and ESX Fast Systems compared to the original multiplexes, and full concordance at all autosomal loci and amelogenin was observed with data generated previously with the original PowerPlex(®) ESI and ESX Systems. This paper describes the developmental validation study performed on these new fast systems following guidelines issued by the Scientific Working Group on DNA Analysis Methods (SWGDAM) and those of the DNA Advisory Board (DAB). Validation data demonstrate that these systems are sensitive for detecting low levels of DNA while also being capable of generating robust profiles from the high amount of input DNA present in direct-amplification samples. These systems are also tolerant to both high concentrations of PCR inhibitors as well as to slight variations in the final concentration of master mix and primer pair present in the amplification reaction that might be encountered due to pipetting error. The results of this validation study demonstrate that these systems may be used on multiple thermal cyclers and capillary electrophoresis platforms.

Developmental validation of the PowerPlex(®) Fusion System for analysis of casework and reference samples: A 24-locus multiplex for new database standards.

The original CODIS database based on 13 core STR loci has been overwhelmingly successful for matching suspects with evidence. Yet there remain situations that argue for inclusion of more loci and increased discrimination. The PowerPlex(®) Fusion System allows simultaneous amplification of the following loci: Amelogenin, D3S1358, D1S1656, D2S441, D10S1248, D13S317, Penta E, D16S539, D18S51, D2S1338, CSF1PO, Penta D, TH01, vWA, D21S11, D7S820, D5S818, TPOX, DYS391, D8S1179, D12S391, D19S433, FGA, and D22S1045. The comprehensive list of loci amplified by the system generates a profile compatible with databases based on either the expanded CODIS or European Standard Set (ESS) requirements. Developmental validation testing followed SWGDAM guidelines and demonstrated the quality and robustness of the PowerPlex(®) Fusion System across a number of variables. Consistent and high-quality results were compiled using data from 12 separate forensic and research laboratories. The results verify that the PowerPlex(®) Fusion System is a robust and reliable STR-typing multiplex suitable for human identification.

Toward male individualization with rapidly mutating y-chromosomal short tandem repeats.

Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, >99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RM Y-STRs in identifying and separating unrelated and related males and provides a reference database.

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci.

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.

Developmental validation of the PowerPlex(®) 21 System.

The PowerPlex(®) 21 System is a STR multiplex that has been optimized for casework samples while still being capable of database workflows including direct amplification. The loci included in the multiplex offer increasing overlap with core loci used in different countries and regions throughout the world. The PowerPlex(®) 21 System contains D1S1656, D2S1338, D3S1358, D5S818, D6S1043, D7S820, D8S1179, D12S391, D13S317, D16S539, D18S51, D19S433, D21S11, Amelogenin, CSF1PO, FGA, Penta D, Penta E, TH01, TPOX, and vWA. These loci represent all 13 core CODIS loci in addition to loci commonly used in Asia and Europe. A developmental validation study was completed to document performance capabilities and limitations of the PowerPlex(®) 21 System. Data from this validation work served as the basis for the following conclusions: genotyping of single-source samples was reliable across a range of template DNA concentrations with >95% alleles called at 50 pg. Direct amplification of samples from FTA(®) storage cards was successfully performed using the reagents provided with the system and modified cycling protocols provided in the technical manual. Mixture analysis showed that over 95% of minor alleles were detected at 1:9 ratios. Reaction conditions including volume and annealing temperature as well as the concentrations of primers, DNA polymerase, magnesium, and Master Mix were shown to be optimal and able to withstand moderate variations without affecting system performance. Reproducible results were generated by different users at different sites. Finally, concordance studies showed consistent results when comparing the PowerPlex(®) 21 System with other commercially available STR-genotyping systems.

Characterising the STR locus D6S1043 and examination of its effect on stutter rates.

The forensic analysis of DNA is most often undertaken by the amplification of short tandem repeats (STR) using the polymerase chain reaction (PCR). DNA amplification can result in production of the target allele amplicon and a by-product called stutter. Stutter is the result of the miscopy of the target allele and is typically one repeat smaller. Stutter is traditionally described as a ratio of stutter and allele height; stutter ratio (SR). The challenge to DNA profile interpretation is most serious whenever stutter products are of a similar height to the minor allelic peaks in a mixed DNA profile. An accurate assignment of peaks and the prediction of their height is important when objectively interpreting forensic DNA profiles. The longest uninterrupted stretch (LUS) of tandem repeats within the allele has previously been shown to be a good predictor of stutter ratio. LUS is determined by sequencing a range of observed alleles at a locus. The locus D6S1043 is a relatively new locus to appear in commercial forensic DNA testing kits. To date however, there has been no comprehensive report of sequencing of this locus. In this work, we sequence a sample of D6S1043 alleles to determine LUS values and investigate allele repeat number and LUS as explanatory variables for SR.

Mouse cell line authentication.

The scientific community has responded to the misidentification of human cell lines with validated methods to authenticate these cells; however, few assays are available for nonhuman cell line identification. We have developed a multiplex polymerase chain reaction assay that targets nine tetranucleotide short tandem repeat (STR) markers in the mouse genome. Unique profiles were obtained from seventy-two mouse samples that were used to determine the allele distribution for each STR marker. Correlations between allele fragment length and repeat number were determined with DNA Sanger sequencing. Genotypes for L929 and NIH3T3 cell lines were shown to be stable with increasing passage numbers as there were no significant differences in fragment length with samples of low passage when compared to high passage samples. In order to detect cell line contaminants, primers for two human STR markers were incorporated into the multiplex assay to facilitate detection of human and African green monkey DNA. This multiplex assay is the first of its kind to provide a unique STR profile for each individual mouse sample and can be used to authenticate mouse cell lines.

Haplotype data for 23 Y-chromosome markers in four U.S. population groups.

The PowerPlex Y23 kit contains 23 Y-chromosomal loci including all 17 of the markers in the Yfiler Y-STR kit plus six additional markers: DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643. We have typed 1032 unrelated population samples from four self-declared US groups: African Americans, Asians, Hispanics, and Western European Caucasians. An analysis of the population genetic parameters and the improvement of adding additional Y-STR markers to the dataset are described.

Developmental validation of the PowerPlex® 18D System, a rapid STR multiplex for analysis of reference samples.

As short tandem repeat markers remain the foundation of human identification throughout the world, new STR multiplexes require rigorous testing to ensure the assays are sufficiently robust and reliable for genotyping purposes. The PowerPlex(®) 18D System was created for the direct amplification of buccal and blood samples from FTA(®) storage cards and reliably accommodates other sample materials. The PowerPlex(®) 18D System allows simultaneous amplification of the 13 CODIS loci and amelogenin along with four additional loci: Penta E, Penta D, D2S1338, and D19S433. To demonstrate suitability for human identification testing, the PowerPlex(®) 18D System was tested for sensitivity, concordance, inhibitor tolerance, and performance with thermal cycling and reaction condition variation following SWGDAM developmental validation guidelines. Given these results, PowerPlex(®) 18D System can confidently be used for forensic and human identification testing.

Inhibitory control deficits in rats with ventral hippocampal lesions.

Two experiments are reported in which rats with selective hippocampal lesions were tested on 2 prefrontal-dependent tasks. In Experiment 1, we compared the effects of lesions of the ventral hippocampus (vHC), dorsal hippocampus (dHC), and sham control surgery on the 5-choice reaction time task. Whereas rats with lesions of the dHC were indistinguishable from sham controls, those with vHC lesions showed increased premature responses and reduced accuracy throughout the experiment. The subsequent administration of systemic escitalopram (5 mg/kg), a selective serotonin reuptake inhibitor, reduced the number of premature responses in the vHC animals to control levels. In contrast, systemic injections of GBR 12909, a dopamine reuptake inhibitor, failed to ameliorate the impulsive deficit in the vHC group and, in addition, elevated perseverative responding in the vHC group only. In Experiment 2, we tested a separate group of rats with vHC lesions on a touchscreen visual discrimination and reversal learning task. Rats with vHC lesions acquired the visual discrimination as well as sham controls and showed normal inhibitory control of a previously reinforced response during reversal learning. These data support a role for the vHC in inhibitory control functions, especially in the inhibitory control of impulsive actions.

Capillary electrophoresis and 5-channel LIF detection of a 26plex autosomal STR assay for human identification.

Multiplex polymerase chain reaction (PCR) is a common method used for DNA typing in forensic and paternity cases. There are numerous commercial short tandem repeat (STR) multiplex assays currently available to the forensic community. These assays amplify the core Combined DNA Index System (CODIS) STR loci for entry into the US. DNA database. Additional non-CODIS loci, which are considered genetically unlinked to the CODIS loci, can be useful in resolving challenging cases such as missing persons and mass disaster victim identification, paternity testing, and immigration testing. An STR multiplex has been successfully developed with 25 non-CODIS autosomal loci plus the sex-typing locus amelogenin for a total of 26 loci in a single 26plex amplification reaction. This chapter will focus on the preparation and the use of the 26plex assay with DNA samples for the purpose of human identification.