De novo missense variants in FBXO11 alter its protein expression and subcellular localization.

Recently, others and we identified de novo FBXO11 (F-Box only protein 11) variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant constructs in HEK293 and HeLa cells. We found that the majority of missense variants resulted in subcellular mislocalization and/or reduced FBXO11 protein expression levels. For instance, variants located in the nuclear localization signal and the N-terminal F-Box domain lead to altered subcellular localization with exclusion from the nucleus or the formation of cytoplasmic aggregates and to reduced protein levels in western blot. In contrast, variants localized in the C-terminal Zn-finger UBR domain lead to an accumulation in the cytoplasm without alteration of protein levels. Together with the mutational data, our functional results suggest that most missense variants likely lead to a loss of the original FBXO11 function and thereby highlight haploinsufficiency as the most likely disease mechanism for FBXO11-associated NDDs.

Sharps Disposal Practices Among People With Diabetes in a Community Care Clinic.

Objectives: The primary objective of this study was to determine sharps disposal practices among people with diabetes in a community care clinic. Secondary objectives were to identify patterns of sharps use and barriers to proper use. Methods: Surveys were distributed to patients at a community care clinic in person and via mail. Survey questions focused on how sharps are used and disposed of, the frequency of sharps changes, sharps disposal training, sharps identification, and confidence in sharps disposal. Participant demographics and diabetes profiles were also collected. Findings: Among 89 respondents, mean age was 60 years (range 29-93 years), 61.8% were Caucasian, 88.8% had type 2 diabetes, and 60.7% had had a diabetes diagnosis for ≤10 years, with diverse diabetes management methods; 57.3% did not receive or were unsure of sharps training, 25.8% discarded used sharps without a designated sharps container, and 37.1% properly disposed of sharps containers at sharps disposal facilities. Barriers to proper sharps practices included perceived safety of reusing sharps and waste with single use, cost, and the hassle of disposal. Those with prior sharps training were more likely to properly use and discard sharps; however, gaps in knowledge were still evident in this population. Conclusion: Results indicate gaps in proper sharps use and disposal knowledge among people with diabetes. Responses revealed sharps practices that are inconsistent with current federal and state regulations and are potentially dangerous for those handling improperly discarded sharps. Targeted sharps usage and disposal education resources are needed for individuals with and without prior sharps training.

Twelve-month supply of short-acting contraception methods: Pharmacists' perspectives on implementation of new state law.

BACKGROUND: Oral contraceptives and other short-acting reversible contraceptive (SARC) methods such as the patch, vaginal ring, and medroxyprogesterone injections are used by approximately 30% of people using contraception. People may face barriers in obtaining a timely and adequate supply of their SARCs. It is well established that dispensing more than 1-month supply at a time is more convenient for patients, improves continuation, and decreases the risk of unintended pregnancy. Given the potential for public health impact, 20 states, including Massachusetts, have expanded access to a 12-month supply of SARCs. OBJECTIVES: The goal of this qualitative study was to explore Massachusetts pharmacists' general awareness and specific knowledge of the state's 2017 Act Advancing Contraceptive Coverage and Economic Security in Our State (ACCESS) law, explore barriers to the implementation of the law, and elicit recommendations to improve uptake of this practice. METHODS: Semistructured interviews were conducted with a purposeful sample of community pharmacists in Massachusetts between September 2020 and May 2021 using a pretested interview guide. Interviews were audio recorded and professionally transcribed. Data collection ceased when theoretical saturation was achieved. Data were analyzed using modified grounded theory, including code book development and line-by-line and axial coding. RESULTS: Sixteen pharmacists from diverse practice settings participated in the interviews. All the pharmacists (100%) reported that they had received no training on the ACCESS law, and only 1 pharmacist reported having complete knowledge of the specifics of the law. We identified key themes and subthemes related to pharmacists' concerns about implementation of the law at the system, pharmacy, and patient level, including insurance coverage, communication of new laws, stocking, supply, and misuse by patients. CONCLUSION: Addressing the need for pharmacist training and communication regarding new regulations may improve provision of an extended supply of SARC methods.

Comparison of Discounted and Undiscounted Cash Prices for Cardiovascular Medications by Type of US Community Pharmacy.

BACKGROUND: Cash prices for prescription drugs vary among community pharmacies in the USA. GoodRx is a discount platform that provides coupons for use in community pharmacies without a membership requirement. Analytical pharmacy is a new type of pharmacy that tests drugs before dispensing to verify medication quality. OBJECTIVE: To compare undiscounted and GoodRx-discounted cash prices for common cardiovascular (CV) drugs by pharmacy type. DESIGN: A cross-sectional study. SETTING: GoodRx-discounted and GoodRx-undiscounted cash price data; analytical pharmacy cash price data (all data collected in July 2020). MEASUREMENTS: GoodRx cash price data for 30 units of 41 generic and 16 brand-name common cardiovascular medications at mass merchandiser, regional supermarket, two national chains, and analytical pharmacy (only one of its kind in the USA). RESULTS: The average (SD) undiscounted generic CV medication cash price was $42.41 (44.1). The average GoodRx-discounted generic CV medication cash prices were $11.01 (8.6), $9.88 (6.7), $17.85 (10.5), and $21.73 (14.1) in mass merchandiser, supermarket, and two national chain pharmacies, respectively. The average generic CV medication cash price was $20.84 (25.7) at the analytical pharmacy. The average (SD) undiscounted brand-name CV medication cash price was $368.33 (127.00). The average GoodRx-discounted brand-name CV medication cash prices were $269.16 (118.1), $258.84 (108.6), $270.28 (118.4), and $274.60 (122.50) for mass merchandiser, supermarket, and two national chain pharmacies, respectively. The average (SD) brand-name CV medication cash price was $365.12 (116.20) at the analytical pharmacy. CONCLUSIONS: GoodRx-discounted cash prices of generic CV medications were significantly lower than undiscounted cash prices at supermarket, mass merchandiser, and national chain pharmacies. Analytical pharmacy cash prices too were significantly lower than traditional pharmacy undiscounted cash prices. GoodRx-discounted prices for brand-name CV medications did not differ significantly from undiscounted cash prices and between pharmacy types.

Looking Back at US Pharmacy's Past to Help Discern Its Future.

Objective: To review specific literature that aimed to predict the future of US pharmacy, beginning in the late 1980s. Data Sources: Articles were identified from searching MEDLINE, CINAHL, Google Scholar, and references of relevant articles. The following combinations of search terms were used: future, pharmacy, prediction, and forecast. Study Selection and Data Extraction: The following inclusion criteria were applied: (1) full-text commentary, review, or original research and (2) focused predominantly on the pharmacy in the United States. Data on predictions for the future of pharmacy were extracted. Data Synthesis: We selected 3 articles published between 1988 and 2006, with each aiming to project the future for the following decade. We examined each prediction in light of the current knowledge. Relevance to Patient Care and Clinical Practice: Educators, practitioners, and other stakeholders should consider reflecting on the changes in pharmacy for the past 3 decades and applying both historical and emerging trends to improve patient care and sustain practice in the third decade of the 21st century and beyond. Conclusion: Most of the predictions for the future of pharmacy from the past 3 decades materialized, with some still in progress (reimbursement for pharmacy services), whereas others manifested in unexpected ways (transition from shortage to excess of pharmacists). Current forces shaping pharmacy include, but are not limited to, growing spending and use of specialty drugs, automation of pharmacy operations, growth of pharmacy in the digital health enterprise, and growing consumer interest in the use of analytical pharmacy that tests drugs before dispensing.

Multiplex pcr assay for chlamydia-like bacteria detection.

OBJECTIVE: Introduction: Waddlia chondrophila and Parachlamydia acanthamoebae are well-known and best-studied representatives of Сhlamydia-related bacteria carrying a potential zoonotic threat. These bacteria are associated with miscarriage, ectopic pregnancy, diseases of the respiratory system in both humans and animals. Despite the importance of these Сhlamydia-like organisms for human medicine along with veterinary medicine, studies on their prevalence in Ukraine were not conducted due to the lack of available tests. The aim of our work was to create relatively cheap and easy method for detection Waddlia chondrophila and Parachlamydia acanthamoebae. PATIENTS AND METHODS: Materials and methods: GenBank database was used to find nucleotide sequences of the 16S rRNA gene of bacteria Chlamydiales' order. Alignment was performed using the MEGA7 software, in order to detect the presence of polymorphic hybridization sites specifically attributed to Waddlia chondrophila and Parachlamydia acanthamoebae. PrimerBLAST software was used to design oligonucleotide primers, to evaluate the critical parameters of the primer, in particular, the melting temperature, difference between melting temperatures for the primer pairs, the GC content, the self-complementarity, etc. RESULTS: Results and conclusions: The amplification of control DNA of Parachlamydia acanthamoebae and Waddlia chrondophila in single PCR using the corresponding primers and subsequent gel electrophoresis of PCR products determined the size of the amplified DNA fragments 88 b.p. and 123 b.p, respectively; the fragments were in line with the expected sizes.The analytical specificity test was performed by amplifying the control DNA of 15 species of the order Chlamydiales.

Treatment Persistence Among Insured Patients Newly Starting Buprenorphine/Naloxone for Opioid Use Disorder.

BACKGROUND: Persistence with medication-assisted therapy among patients with opioid use disorder has been associated with reduced likelihood of illicit opioid use. OBJECTIVE: We aimed to describe treatment persistence and identify factors associated with 1-year persistence among insured patients newly initiating buprenorphine-containing pharmacotherapy. METHODS: The retrospective observational cohort included employer-sponsored and managed Medicaid patients newly started on buprenorphine-containing therapy between June 30, 2010, and January 1, 2015. Persistence was measured as both a continuous and dichotomous variable (proportion of patients persistent for 1 year). Multivariable logistic regression analysis was used to identify factors associated with 1-year persistence. RESULTS: A total of 302 patients met inclusion criteria. The median [range] number of treatment episodes was 1 [1-4]. Mean number of days on therapy during the first episode was 206 (SD = 152) days, with 40.4% (n = 122) of patients persisting for 1 year. Presence of concomitant fills of prescription opioid analgesics (odds ratio [OR] = 0.25; 95% CI = 0.12-0.51), being in care of an addiction specialist (OR = 0.40; 95% CI = 0.21-0.76), and Medicaid insurance coverage (OR = 0.33; 95% CI = 0.13-0.84) were significantly and negatively associated with 1-year persistence. There was also a strong inverse relationship between persistence and inpatient hospitalization (OR = 0.30; 95% CI = 0.12-0.76). CONCLUSIONS: Several health care delivery and use variables were significantly associated with nonpersistence. Concomitant use of prescription opioids is the most easily modifiable risk factor that health care providers and policy makers may act on to improve treatment continuation.

Current Practice Patterns in the Management Of Alcohol Withdrawal Syndrome.

OBJECTIVE: The aim of this study was to examine current practice patterns surrounding the management of alcohol withdrawal syndrome (AWS) in the Northeast region of the United States. METHODS: A survey questionnaire with several treatment options related to current practice in the management of AWS was developed. All hospitals with 100 beds or more located in the Northeast region were selected, and 512 surveys were mailed to pharmacy directors of those hospitals. RESULTS: Responses from 90 hospitals in nine states were included in the analyses. For the treatment of mild, moderate, and severe AWS, most institutions utilized protocols or guidelines (66%, 73%, and 67%, respectively). However, two-thirds of the hospitals indicated that guidelines or protocols were not in place to treat benzodiazepine (BZD)-refractory AWS. A BZD-only treatment strategy was selected as the first choice for mild and moderate AWS (74% and 54%, respectively), whereas a BZD regimen in combination with a variety of other agents, including haloperidol, dexmedetomidine, phenobarbital, or propofol, was frequently used in the treatment of severe and BZD-refractory AWS. CONCLUSION: The findings suggest that considerable heterogeneity exists, particularly in the treatment of severe and BZD-refractory AWS, among hospitals in the Northeast. Given that current guidelines focus mainly on BZD therapy, the results of this survey highlight the need for updated practice guidelines utilizing other treatment strategies.

High Total Failures of the North American Pharmacist Licensure Examination (NAPLEX) Warrant Monitoring of Professional Pharmacy Programs.

From 2021 to 2023, 7978 graduates of pharmacy programs failed the North American Pharmacist Licensure Examination on the first attempt. Presently, the Accreditation Council for Pharmacy Education monitors programs with a passage rate of ≥ 2 SDs below the national mean pass rate. In 2023, this should lead to monitoring 7 programs that produced 140 failures out of the total of 2472 failures (5.7 %). In our view, this is neither equitable nor demonstrative of sufficient accountability. Analysis of failure counts among the 144 programs reported by the National Association of Boards of Pharmacy demonstrates a distribution curve highly skewed to the right. The evaluation of average failure counts across all programs suggests that schools with absolute failures ≥ 2 SDs higher than the average number of failures should be identified for monitoring, in addition to those falling ≥ 2 SDs below the national mean pass rate. Based on the 2023 data, this additional criterion corresponds to ≥ 35 failures/program. This threshold would prompt monitoring of 18 programs and 36.5 % of the total failures. Of the 7 programs that will be monitored based on the current Accreditation Council for Pharmacy Education criteria, only 1 would be captured by the ≥ 35 failure method of selection; the remaining 6 contribute 85 total failures to the pool. Thus, if both criteria were to be applied, ie, ≥ 35 failures and ≥ 2 SDs below the national mean pass rate, a total of 24 programs would be monitored (16.6 % of the 144 programs) that contribute 987 of the total failures (39.9 %).

Drivers of citations in social pharmacy and practice research articles.

BACKGROUND: Research in Social and Administrative Pharmacy has been expanding in the last decade. The recently published Granada Statements offer key recommendations to improve the quality of research in this field. OBJECTIVES: To identify the factors associated with the citations of articles in the field of social, administrative, clinical pharmacy and practice research. METHODS: This study was a retrospective, observational analysis of articles published in three leading journals. Per article Google Scholar citations was the dependent variable. Predictor variables were extracted from all articles published from 2013 to 2015. The dependent variable was dichotomized using sample's median Google Scholar citations. Logistic regression analysis was performed to identify independent predictors of citations ≥ median. RESULTS: The median number of citations per article was 17 (range 0-341), with a mean of 24.2 (SD 27.6). The number of references included in the articles (OR 1.03, CI 1.02-1.04), the year of publication (OR 0.31 CI 0.21-0.46 for articles published 2015), article social media mentions (OR = 1.01, CI 1.01-1.03 and OR 1.10 CI 1.04-1.18 for Facebook and X, respectively), the topic area of research namely pharmacy services (OR 1.65, CI 1.06-2.57) and medication adherence (OR 2.22 CI 1.13-4.33) were independently associated with article having citations ≥ median. CONCLUSIONS: The number of references, the year of publication, social media mentions and the topic area of research, namely pharmacy services and medication adherence, were associated with citations above median in the leading journals of social and administrative pharmacy research. Authors may consider providing a thorough literature review in their articles, while researchers, editors, and publishers are advised to use social media to promote newly published work. This article complements the Granada Statements and may contribute to fostering wider dissemination of the discipline's outputs.