Implementation of a comprehensive pharmacy-driven immunization care process model in a pediatric cystic fibrosis clinic.

INTRODUCTION: Members of an integrated pharmacy team (pharmacists and pharmacy technicians) have roles that have been identified in the literature as part of the multi-disciplinary cystic fibrosis (CF) care team. One role that has not specifically addressed is the administration of routine and recommended immunizations to people with CF (PwCF). According to care guidelines, PwCF of all ages should be provided all age-appropriate and recommended immunizations. Pharmacists and pharmacy technicians can administer immunizations per state laws. The Primary Children's CF Center decided to implement a comprehensive pharmacy-driven immunization care process model to impact immunization rates. METHODS: A 24-month retrospective analysis was conducted with pediatric (≤18 years) PwCF at the Primary Children's CF Center. The primary outcome measures were the percentage (%) of PwCF who received PPSV23, and/or HPV, and/or meningococcal conjugate vaccine (MCV) immunizations 1-year post-care process model implementation (October 1, 2021, to September 30, 2022) as compared to baseline values. The secondary outcome measures are the total number of immunizations, the number of each immunization provided, and the financial impact of pharmacy-driven immunization care process model 1-year post-implementation. RESULTS: During the 1-year post-care process model implementation (October 1, 2021, to September 30, 2022), a total of 523 immunizations were provided to 243 pediatric PwCF. The most frequent immunizations provided were PPSV23 (160/523, 31%) and Coronavirus Disease 2019 (COVID-19) (154/523, 29%). The baseline percentages of eligible PwCF of PPSV23, HPV, and MCV were 27% (58/217), 43% (32/74), and 24% (8/34), respectively. The 1-year post-implementation percentages of PPSV23, HPV, and MCV were 99% (217/218, p < 0.00001), 91% (67/74, p < 0.00001), and 97% (33/34, p < 0.00001), respectively. For COVID-19 immunizations, 56% of eligible PwCF (181/321) have received their first dose. Of these 181 PwCF, 70% (126/181) have received at least one dose of their primary series or booster during the 1-year post-implementation period. The rate of those PwCF who have received at least one dose of a COVID-19 immunization from the age of 6 months to 4 years, 5-11 years, and 12-18 years, was 37% (30/82), 60% (78/129), and 66% (73/110), respectively. For the financial impact generated during the 1-year immunization care process model post-implementation period, 404 non-VFC immunizations were given for an estimated profit of $11,930. CONCLUSIONS: The implementation of a pharmacy-driven immunization care process model is a way for integrated pharmacy teams to evolve with the CF center care model and have a role expansion in the care provided to PwCF.

The global prevalence and ethnic heterogeneity of primary ciliary dyskinesia gene variants: a genetic database analysis.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a motile ciliopathy characterised by otosinopulmonary infections. Inheritance is commonly autosomal recessive, with extensive locus and allelic heterogeneity. The prevalence is uncertain. Most genetic studies have been done in North America or Europe. The aim of the study was to estimate the worldwide prevalence and ethnic heterogeneity of PCD. METHODS: We calculated the allele frequency of disease-causing variants in 29 PCD genes associated with autosomal recessive inheritance in 182 681 unique individuals to estimate the global prevalence of PCD in seven ethnicities (African or African American, Latino, Ashkenazi Jewish, Finnish, non-Finnish European, east Asian, and south Asian). We began by aggregating variants that had been interpreted by Invitae, San Francisco, CA, USA, a genetics laboratory with PCD expertise. We then determined the allele frequency of each variant (pathogenic, likely pathogenic, or variant of uncertain significance [VUS]) in the Genome Aggregation Database (gnomAD), a publicly available next-generation sequencing database that aggregates exome and genome sequencing information from a wide variety of large-scale projects and stratifies allele counts by ethnicity. Using the Hardy-Weinberg equilibrium equation, we were able to calculate a lower-end prevalence of PCD for each ethnicity by including only pathogenic and likely pathogenic variants; and upper-end prevalence by also including VUS. This approach was similar to previous work on Li-Fraumeni (TP53 variants) prevalence. We were not diagnosing PCD, but rather estimating prevalence based on known variants. FINDINGS: The overall minimum global prevalence of PCD is calculated to be at least one in 7554 individuals, although this is likely to be an underestimate because some variants currently classified as VUS might be disease-causing and some pathogenic variants might not be detected by our methods. In the overall cohort, Invitae data could be included for variants without gnomAD data for a primary ethnicity. When using only gnomAD allele frequencies to calculate prevalence in individual ethnicities, the estimated prevalence of PCD was lower in each ethnicity compared with the overall cohort. This is because the overall cohort includes additional data from the Invitae database such as copy number variants and other variants not present in gnomAD. With gnomAD we found the expected PCD frequency to be higher in individuals of African ancestry than in most other populations (excluding VUS: 1 in 9906 in African or African American vs 1 in 10 388 in non-Finnish European vs 1 in 14 606 in east Asian vs 1 in 16 309 in Latino; including VUS: 1 in 106 in African or African American vs 1 in 178 in non-Finnish European vs 1 in 196 in Latino vs 1 in 188 in east Asian). In addition, we found that the top 5 genes most commonly implicated in PCD differed across ethnic ancestries and contrasted commonly published findings. INTERPRETATION: PCD appears to be more common than has been recognised, particularly in individuals of African ancestry. We identified gene distributions that differ from those in previous European and North American studies. These results could have an international impact on case identification. Our analytic approach can be expanded as more PCD loci are identified, and could be adapted to study the prevalence of other inherited diseases. FUNDING: None.

An optimized method for histological detection of dopaminergic neurons in Drosophila melanogaster.

Parkinson's disease (PD) affects >1 million Americans and is marked by the loss of dopaminergic neurons in the substantia nigra. PD has been linked to two causative factors: genetic risks (hereditary PD) and environmental toxins (idiopathic PD). In recent years, considerable effort has been devoted to the development of a Drosophila model of human PD that might be useful for examining the cellular mechanisms of PD pathology by genetic screening. In 2000, Feany and Bender reported a Drosophila model of PD in which transgenic flies expressing human mutant alpha-synuclein exhibited shortened life spans, dopaminergic losses, Parkinsonian behaviors, and Lewy bodies in surviving dopaminergic neurons. Since then, a number of studies have been published that validate the model or build on it; conversely, a number report an inability to replicate the results and suggest that most protocols for dopaminergic histology underreport the actual numbers of dopaminergic neurons in the insect brain. Here we report the optimization of dopaminergic histology in Drosophila and identification of new dopaminergic neurons, show the remarkable dendritic complexity of these neurons, and provide an updated count of these neurons in adult brains. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.