Pharmacy-based CLIA-waived testing in the United States: Trends, impact, and the road ahead.

BACKGROUND: Federal authorization of the use of Clinical Laboratory Improvement Amendments of 1988 (CLIA) waived point-of-care tests for SARS-CoV-2 by pharmacists during the pandemic resulted in a dramatic rise in the number of community pharmacies that became CLIA-waived test sites. Now as we exit the pandemic, the wide-ranging expansion of the scope of practice facilitated currently by the PREP Act is set to expire in fall 2024. As a result, American pharmacists' ability to offer CLIA-waived testing services will revert to a patchwork of state laws. OBJECTIVE: This study aims to examine both the number of pharmacies in the United States with CLIA Certificates of Waiver before and after the SARS-CoV-2 pandemic and the state-by-state differences in the percentage of pharmacies with CLIA Certificates of Waiver. METHODS: Data were collected from the U.S. Centers for Disease Control and Prevention CLIA Laboratory Search website on May 3rd, 2015, August 4th, 2019, November 26th, 2020, October 6th, 2021, November 23rd, 2022, and December 4th, 2023. The website allows for the exportation of demographic data on all CLIA-waived facilities by state. RESULTS: The total number of pharmacies with a CLIA-waiver grew from 10,626 (17.9%) locations in 2015 to 12,157 (21.4%) locations in 2019, to 15,671 (27.6%) locations in 2020, and to 29,011 (51.6%) locations in 2023. States demonstrated considerable variability in the percentage of pharmacies possessing a CLIA certificate of waiver in 2023, with a range of 10.7%-87.9%. CONCLUSIONS: Use of CLIA-waived tests in pharmacies has grown by 140% since 2019. The time period from 2019 to 2021 witnessed a 92.5% increase in pharmacies that possessed a certificate of waiver which was largely driven by the pandemic. Interestingly, from 2021 to 2023 the was continued growth in the market of 31.6%. This suggests that pharmacies continue to see opportunity in offering CLIA-waived testing services beyond those that had been extended as a result of the pandemic.

Developing a core outcome set for the health outcomes for children and adults with congenital oesophageal atresia and/or tracheo-oesophageal fistula: OCELOT task group study protocol.

INTRODUCTION: Heterogeneity in reported outcomes of infants with oesophageal atresia (OA) with or without tracheo-oesophageal fistula (TOF) prevents effective data pooling. Core outcome sets (COS) have been developed for many conditions to standardise outcome reporting, facilitate meta-analysis and improve the relevance of research for patients and families. Our aim is to develop an internationally-agreed, comprehensive COS for OA-TOF, relevant from birth through to transition and adulthood. METHODS AND ANALYSIS: A long list of outcomes will be generated using (1) a systematic review of existing studies on OA-TOF and (2) qualitative research with children (patients), adults (patients) and families involving focus groups, semistructured interviews and self-reported outcome activity packs. A two-phase Delphi survey will then be completed by four key stakeholder groups: (1) patients (paediatric and adult); (2) families; (3) healthcare professionals; and (4) researchers. Phase I will include stakeholders individually rating the importance and relevance of each long-listed outcome using a 9-point Likert scale, with the option to suggest additional outcomes not already included. During phase II, stakeholders will review summarised results from phase I relative to their own initial score and then will be asked to rescore the outcome based on this information. Responses from phase II will be summarised using descriptive statistics and a predefined definition of consensus for inclusion or exclusion of outcomes. Following the Delphi process, stakeholder experts will be invited to review data at a consensus meeting and agree on a COS for OA-TOF. ETHICS AND DISSEMINATION: Ethical approval was sought through the Health Research Authority via the Integrated Research Application System, registration no. 297026. However, approval was deemed not to be required, so study sponsorship and oversight were provided by Alder Hey Children's NHS Foundation Trust. The study has been prospectively registered with the COMET Initiative. The study will be published in an open access forum.

How to implement a "standard of care" regulatory model for pharmacists.

National pharmacy associations have increasingly explored regulation according to a "standard of care." In such a model, pharmacists can provide a wide range of clinical services aligned with their education and training. Based on Idaho's experience implementing this model, there are five critical steps states must take to enact a standard of care: 1) Adopt a broad definition of "practice of pharmacy;" 2) Allow elasticity for practice innovation over time; 3) Decide which limited instances still necessitate prescriptive regulation; 4) Eliminate all unnecessary regulations; and 5) Strengthen accountability for deviations from the standard of care. States wishing to adopt a standard of care approach can follow this five-step process to enhance patient care and mitigate the lag that is otherwise constant between laws and practice.

ST-Segment Elevation Myocardial Infarction Caused by 5-Fluorouracil-Related Cardiotoxicity.

5-Fluorouracil (5-FU) and its prodrug, capecitabine, are commonly used chemotherapeutic agents for solid tumor management. While these agents can present with adverse side effects such as nausea, vomiting, diarrhea, and myelosuppression, they can also, less commonly, cause cardiovascular toxicity. This toxicity may manifest as cardiac arrhythmias, myocarditis, heart failure, myocardial infarction, and even death. The management of 5-FU-related cardiotoxicity includes early recognition of symptom manifestation so that medication can be discontinued promptly and symptoms can be addressed appropriately. Here, we describe the case of a 72-year-old male who developed coronary vasospasm and ST-segment elevation myocardial infarction shortly after the initiation of chemotherapy with 5-FU.

Altered DNA methylation within DNMT3A, AHRR, LTA/TNF loci mediates the effect of smoking on inflammatory bowel disease.

This work aims to investigate how smoking exerts effect on the development of inflammatory bowel disease (IBD). A prospective cohort study and a Mendelian randomization study are first conducted to evaluate the association between smoking behaviors, smoking-related DNA methylation and the risks of Crohn's disease (CD) and ulcerative colitis (UC). We then perform both genome-wide methylation analysis and co-localization analysis to validate the observed associations. Compared to never smoking, current and previous smoking habits are associated with increased CD (P = 7.09 × 10-10) and UC (P < 2 × 10-16) risk, respectively. DNA methylation alteration at cg17742416 [DNMT3A] is linked to both CD (P = 7.30 × 10-8) and UC (P = 1.04 × 10-4) risk, while cg03599224 [LTA/TNF] is associated with CD risk (P = 1.91 × 10-6), and cg14647125 [AHRR] and cg23916896 [AHRR] are linked to UC risk (P = 0.001 and 0.002, respectively). Our study identifies biological mechanisms and pathways involved in the effects of smoking on the pathogenesis of IBD.

The Human GP130 Cytokine Receptor and Its Expression-an Atlas and Functional Taxonomy of Genetic Variants.

Genetic variants in IL6ST encoding the shared cytokine receptor for the IL-6 cytokine family GP130 have been associated with a diverse number of clinical phenotypes and disorders. We provide a molecular classification for 59 reported rare IL6ST pathogenic or likely pathogenic variants and additional polymorphisms. Based on loss- or gain-of-function, cytokine selectivity, mono- and biallelic associations, and variable cellular mosaicism, we grade six classes of IL6ST variants and explore the potential for additional variants. We classify variants according to the American College of Medical Genetics and Genomics criteria. Loss-of-function variants with (i) biallelic complete loss of GP130 function that presents with extended Stüve-Wiedemann Syndrome; (ii) autosomal recessive hyper-IgE syndrome (HIES) caused by biallelic; and (iii) autosomal dominant HIES caused by monoallelic IL6ST variants both causing selective IL-6 and IL-11 cytokine loss-of-function defects; (iv) a biallelic cytokine-specific variant that exclusively impairs IL-11 signaling, associated with craniosynostosis and tooth abnormalities; (v) somatic monoallelic mosaic constitutively active gain-of-function variants in hepatocytes that present with inflammatory hepatocellular adenoma; and (vi) mosaic constitutively active gain-of-function variants in hematopoietic and non-hematopoietic cells that are associated with an immune dysregulation syndrome. In addition to Mendelian IL6ST coding variants, there are common non-coding cis-acting variants that modify gene expression, which are associated with an increased risk of complex immune-mediated disorders and trans-acting variants that affect GP130 protein function. Our taxonomy highlights IL6ST as a gene with particularly strong functional and phenotypic diversity due to the combinatorial biology of the IL-6 cytokine family and predicts additional genotype-phenotype associations.

Implementation of the California advanced practice pharmacist and the continued disappointment of tiered licensure.

The Advanced Practice Pharmacist (APh) designation in California was created via legislation 10 years ago. California pharmacists who meet certain criteria can be designated as an APh and unlock additional practice authority. Just 1065 pharmacists, or 2% of licensed California pharmacists, have obtained the APh designation through 2022. APhs did not report benefiting from the designation as it relates to expanded scope of practice. This experience of low uptake and minimal benefit mirrors the tiered licenses created by three other states. More recent legislation broadened the independent prescriptive authority of APhs, but this increased value proposition aligns with the practice authority adopted by other states who have imposed fewer barriers to entry. Given the track record observed to date, we doubt that tiered licensure will ever prove successful in the pharmacy profession. Instead, state policymakers and pharmacy advocates should consider adopting a "standard of care" regulatory approach to improve patient access to safe and beneficial pharmacist services.

Toward collaborative practice, not collaborative practice agreements.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Expunging Board of Pharmacy Disciplinary Actions.

Boards of pharmacy have the authority to discipline licensees whose actions fall short of practice standards. Disciplinary action may include license suspension, revocation, practice restrictions, fines and reprimands. Once discipline is levied against a board of pharmacy licensee, it is usually part of the licensee's permanent record. At least four states have created a pathway for individuals to seek expungement of previous disciplinary actions levied by a board of pharmacy. These states have variations on what violations may be expunged and when. Given the evolving approach to the regulation of pharmacists, more states may want to consider expungement pathways in the years ahead.

The Basis for Elimination of the Jurisprudence Examination as a Condition of Pharmacist Licensure in Idaho.

Some national pharmacy associations have recently joined in advocacy for a more portable pharmacist license. One impediment to accomplishing this is the state-specific nature of the pharmacy jurisprudence examination, leading to calls for the exploration of alternatives to, or outright elimination of, such examinations. This manuscript reviews the rationale for the elimination of the pharmacy jurisprudence examination in Idaho. The Idaho Board of Pharmacy reviewed the absence of similar jurisprudence examinations in other health professions, the role schools of pharmacy and employers play in preparing pharmacists for lawful practice, and how the adoption of a "standard of care" regulatory model changed thinking about the need for a jurisprudence examination. Idaho eliminated the examination in 2018, and no evidence demonstrating a public safety impact has yet materialized, while the number of Idaho licensed pharmacists has grown at a higher rate than its border states. State boards of pharmacy are in a position to decide whether keeping the pharmacy jurisprudence examination is necessary, and this manuscript reviews key considerations for other states.

Regulating Pharmacist Clinical Services: Is Legal Silence Golden or Deafening?

In the United States, the scope of practice of pharmacists is determined primarily at the state level. Not all state laws expressly permit or prohibit pharmacists from providing certain services; in between is a grey area of legal silence. Does legal silence permit pharmacists to perform a service that is not specifically permitted, but not expressly prohibited? Point-of-care testing provides a useful case study in legal silence: there are 1536 pharmacies currently holding a CLIA-waiver to administer tests in states reporting that pharmacists are not expressly permitted to administer tests. Legal silence may even provide a better framework for pharmacy based testing as it is naturally inclusive of any point-of-care test and no laws need updated when a new test comes to the market. Other health professions navigate this legal silence by governing according to a "standard of care." Rather than specifying a list of services a health professional can or cannot provide in law, it provides a flexible framework for the health professional to provide any service that other similarly situated health professionals would provide in the same or similar situation. A standard of care regulatory framework should thus be the target of the pharmacy profession in order to advance patient care.

Pharmacist Prescribing Models for HIV Pre-exposure and Post-exposure Prophylaxis.

State strategies for pharmacist prescribing exist on a continuum from most restrictive to least restrictive. Using human immunodeficiency virus (HIV) pre-exposure prophylaxis and post-exposure prophylaxis as a case study, there are 3 viable pharmacist prescribing models: (1) population-based collaborative practice agreements; (2) government protocols; and (3) standard of care prescribing. The advantages and disadvantages of these 3 models are reviewed.

Pediatric Diving-Related Injuries in Swimming Pools Presenting to US Emergency Departments: 2008-2020.

OBJECTIVES: Recreational swimming/diving is among the most common physical activities in US children and a significant cause of morbidity across the United States. This study updates the national epidemiology of diving-related injuries. METHODS: The Consumer Product Safety Commission's National Electronic Injury Surveillance System database was queried for patients aged 0 to 19 from 2008 to 2020 who presented to any of the 100 National Electronic Injury Surveillance System-participating emergency departments for a diving-related injury. Dive characteristics such as dive height, dive skill, dive direction, and dive sequence were determined from case narratives. RESULTS: A total of 1202 cases were identified for analysis corresponding to a total national estimate of 37,387 diving related injuries during the period from 2008 to 2020 and a national incidence of 3.6 injuries per 100,000 population. Males accounted for 64% of injuries. The average yearly incidences of injury in the 10 to 14 and 15 to 19 age groups were identical at 5.8 per 100,000. Contact with the diving board or platform was the most common cause of injury (34%). Diving backwards or attempting a flip or handstand dive were associated with increased odds of sustaining an injury resulting from contact with the diving board or platform (odds ratio, 16.0 and 6.9, respectively). In 2020, the incidence of diving-related injury fell to 1.6 per 100,000 population. CONCLUSIONS: Diving injuries are common in children and adolescents, especially in boys aged 10 to 19. There was a significant reduction in diving-related injury corresponding with the COVID-19 pandemic.

Revisiting the continuum of pharmacist prescriptive authority.

Pharmacists in all states have prescriptive authority in some form. We identify two broad categories of pharmacist prescribing: dependent and independent. There are gradients within these broad categories that allow us to chart pharmacist prescribing on a continuum from most restrictive to least restrictive. Independent prescribing has seen the most innovation in recent years at the state level, with at least three states adopting a "standard of care" prescribing framework that allows pharmacists to exercise broad prescriptive authority including for conditions that require a diagnosis. Each of the approaches to pharmacist prescriptive authority have perceived advantages and disadvantages as it relates to improving patient care.

Opportunities for pharmacist prescriptive authority of buprenorphine following passage of the Mainstreaming Addiction Treatment (MAT) Act.

In December 2022, Congress passed the Mainstreaming Addiction Treatment Act, which removed the federal legal barrier to pharmacist buprenorphine prescribing. As a result, each state can now decide whether or not to allow pharmacists to prescribe buprenorphine as an additional access point to reduce fatal opioid overdoses. At least 10 states allow pharmacists to prescribe controlled substances under collaborative practice agreements. Two states (California and Idaho) have also created pathways for independent prescribing of buprenorphine by pharmacists. Additional states should seek to enable pharmacists to prescribe buprenorphine to increase access to a proven beneficial treatment and help reduce fatal opioid overdoses.

Extending COVID-19 Pharmacy Technician Duties: Impact on Safety and Pharmacist Jobs.

Background: The 2019 coronavirus pandemic (COVID-19) led to an expanded scope of practice for pharmacy technicians. As the pandemic wanes, state governments are faced with the decision of whether or not to make permanent the authority of pharmacy technicians to perform extended duties. Objective: Determine the impacts on patient safety and job market demands preadoption and postadoption of Idaho's expanded technician duties in 2017 as a natural experiment for expanded technician duties. Methods: Data from the National Practitioner Data Bank (NPDB) is used to explore patient safety outcomes in Idaho preadoption and postadoption and as compared with its border states. Data from Pharmacy Demand Reports is used to compare job postings in Idaho and its border state, and National Association of Boards of Pharmacy census data are used to compare growth in the number of pharmacists and technicians in Idaho and its border states over time. Results: For Idaho pharmacists, the average number of disciplinary actions reported against both pharmacists and technicians dropped after implementation of expanded technician duties. Idaho also had a lower rate of discipline for pharmacists and technicians than its border states. Idaho had the third highest job postings for pharmacists and the second highest for technicians among its border states. Idaho also had the largest growth in the number of licensed pharmacists and technicians of the observed states in the study period. Conclusion: Available statewide data from Idaho as compared with its border states suggests that expanded technician duties did not adversely impact patient safety outcomes or the pharmacist job market. Additional states may wish to expand pharmacy technician duties in the years ahead.

Genome-Wide Methylation Profiling in 229 Patients With Crohn's Disease Requiring Intestinal Resection: Epigenetic Analysis of the Trial of Prevention of Post-operative Crohn's Disease (TOPPIC).

BACKGROUND & AIMS: DNA methylation alterations may provide important insights into gene-environment interaction in cancer, aging, and complex diseases, such as inflammatory bowel disease (IBD). We aim first to determine whether the circulating DNA methylome in patients requiring surgery may predict Crohn's disease (CD) recurrence following intestinal resection; and second to compare the circulating methylome seen in patients with established CD with that we had reported in a series of inception cohorts. METHODS: TOPPIC was a placebo-controlled, randomized controlled trial of 6-mercaptopurine at 29 UK centers in patients with CD undergoing ileocolic resection between 2008 and 2012. Genomic DNA was extracted from whole blood samples from 229 of the 240 patients taken before intestinal surgery and analyzed using 450KHumanMethylation and Infinium Omni Express Exome arrays (Illumina, San Diego, CA). Coprimary objectives were to determine whether methylation alterations may predict clinical disease recurrence; and to assess whether the epigenetic alterations previously reported in newly diagnosed IBD were present in the patients with CD recruited into the TOPPIC study. Differential methylation and variance analysis was performed comparing patients with and without clinical evidence of recurrence. Secondary analyses included investigation of methylation associations with smoking, genotype (MeQTLs), and chronologic age. Validation of our previously published case-control observation of the methylome was performed using historical control data (CD, n = 123; Control, n = 198). RESULTS: CD recurrence in patients following surgery is associated with 5 differentially methylated positions (Holm P < .05), including probes mapping to WHSC1 (P = 4.1 × 10-9, Holm P = .002) and EFNA3 (P = 4.9 × 10-8, Holm P = .02). Five differentially variable positions are demonstrated in the group of patients with evidence of disease recurrence including a probe mapping to MAD1L1 (P = 6.4 × 10-5). DNA methylation clock analyses demonstrated significant age acceleration in CD compared with control subjects (GrimAge + 2 years; 95% confidence interval, 1.2-2.7 years), with some evidence for accelerated aging in patients with CD with disease recurrence following surgery (GrimAge +1.04 years; 95% confidence interval, -0.04 to 2.22). Significant methylation differences between CD cases and control subjects were seen by comparing this cohort in conjunction with previously published control data, including validation of our previously described differentially methylated positions (RPS6KA2 P = 1.2 × 10-19, SBNO2 = 1.2 × 10-11) and regions (TXK [false discovery rate, P = 3.6 × 10-14], WRAP73 [false discovery rate, P = 1.9 × 10-9], VMP1 [false discovery rate, P = 1.7 × 10-7], and ITGB2 [false discovery rate, P = 1.4 × 10-7]). CONCLUSIONS: We demonstrate differential methylation and differentially variable methylation in patients developing clinical recurrence within 3 years of surgery. Moreover, we report replication of the CD-associated methylome, previously characterized only in adult and pediatric inception cohorts, in patients with medically refractory disease needing surgery.

Defining Interactions Between the Genome, Epigenome, and the Environment in Inflammatory Bowel Disease: Progress and Prospects.

Recent advances in our understanding of the pathogenesis of inflammatory bowel disease (IBD) have highlighted the complex interplay between the genome, the epigenome, and the environment. Despite the exciting advances in genomics that have enabled the identification of over 200 susceptibility loci, these only account for a small proportion of the disease variance and the estimated heritability in IBD. It is likely that gene-environment (GxE) interactions contribute to "missing heritability" and these may act through epigenetic mechanisms. Several environmental factors, such as the microbiome, nutrition, and tobacco smoking, induce alterations in the epigenome of children and adults, which may impact disease susceptibility. Other mechanisms for GxE interactions are also directly pertinent in early life. We discuss a model in which environmental factors imprint disease risk in a window of susceptibility during infancy that may contribute to later disease onset, whereas other elements of the exposome act later in life and contribute directly to the pathogenesis and course of the disease. Understanding the mechanisms underlying GxE interactions may provide the basis for new therapeutic targets or preventative strategies for IBD.

Federal pharmacist Paxlovid prescribing authority: A model policy or impediment to optimal care?

The U.S federal government leveraged emergency authority to allow pharmacists to prescribe Paxlovid (nirmatrelvir and ritonavir) during the COVID-19 pandemic. While heralded by pharmacy associations, the FDA framework included restrictions that arguably ran counter to clinical guidelines and evidence-based research and recommendations. These restrictions will limit the utility of pharmacist prescriptive authority for Paxlovid in practice. The experience of Paxlovid prescribing and a similar recent federal action illustrate the challenges inherent in federal oversight of pharmacist prescriptive authority. While initially more difficult to navigate for stakeholders, working with state legislatures and state boards of pharmacy has much stronger long-term potential to enable broad pharmacist prescriptive authority and benefit patient care. This commentary uses Idaho's pharmacist prescribing regulations as a comparison to the federal actions.