Cystic fibrosis improves COVID-19 survival and provides clues for treatment of SARS-CoV-2.

Systemic pools of ATP are elevated in individuals homozygous for cystic fibrosis (CF) as evidenced by elevated blood and plasma ATP levels. This elevated ATP level seems to provide benefit in the presence of advanced solid tumors (Abraham et al., Nature Medicine 2(5):593-596, 1996). We published in this journal a paper showing that IV ATP can elevate the depleted ATP pools of advanced cancer patients up to levels found in CF patients with subsequent clinical, biochemical, and quality of life (QOL) improvements (Rapaport et al., Purinergic Signalling 11(2): 251-262, 2015). We hypothesize that the elevated ATP levels seen in CF patients may be benefiting CF patients in another way: by improving their survival after contracting COVID-19. We discuss here the reasoning behind this hypothesis and suggest how these findings might be applied clinically in the general population.

The job of 'ethics committees'.

What should authorities establish as the job of ethics committees and review boards? Two answers are: (1) review of proposals for consistency with the duly established and applicable code and (2) review of proposals for ethical acceptability. The present paper argues that these two jobs come apart in principle and in practice. On grounds of practicality, publicity and separation of powers, it argues that the relevant authorities do better to establish code-consistency review and not ethics-consistency review. It also rebuts bad code and independence arguments for the opposite view. It then argues that authorities at present variously specify both code-consistency and ethics-consistency jobs, but most are also unclear on this issue. The paper then argues that they should reform the job of review boards and ethics committees, by clearly establishing code-consistency review and disestablishing ethics-consistency review, and through related reform of the basic orientation, focus, name, and expertise profile of these bodies and their actions.

Impact of enhanced pharmacy services on adherence for patients with hypertension.

PURPOSE: To evaluate the impact of UI TEAM RX, a pharmacy-based enhanced services and care model, on adherence in patients with hypertension and prescribed a renin-angiotensin system antagonist (RASA). METHODS: A single-center, retrospective, observational cohort study was conducted in an academic health system, University of Illinois Hospital & Health Sciences System (UI Health). The cohort consisted of patients who utilized UI Health's outpatient pharmacies between May 2016 and December 2018 to fill RASA prescriptions. Patients who were not part of the UI TEAM RX care model served as the control group, while patients enrolled in UI TEAM RX formed the intervention group. The control and intervention groups were matched based on index date, age, gender, and race. The primary outcome was mean change in a rolling 6-month calculation of proportion of days covered (PDC). The secondary outcome was the percentage of patients who had reached their blood pressure goal at follow-up at 12 months. RESULTS: Patients receiving UI TEAM RX intervention showed significant improvement in mean PDC at 6-month follow-up compared to control patients (P < 0.01). The proportion of patients with a PDC above 0.8 was higher in the intervention group, but this difference was not statistically significant. There was also a 16.4% increase in the proportion of patients who reached their blood pressure goal in the intervention group, although this increase was not statistically significant. CONCLUSION: The UI TEAM RX program had a statistically significant impact on patients' mean PDCs. An increase in the number of patients reaching their blood pressure goal was also seen.

A comparison of medication access services at 340B and non-340B hospitals.

BACKGROUND: For patients that face barriers to filling their prescriptions, the availability of medication access services at their site of care can mean the difference between receiving prescribed drug therapy, and undue interruptions in care. Hospitals often provide medication access services that are not reimbursed by payers; however, they can be challenging to sustain. The 340B Drug Pricing Program allows covered entities to generate savings through discounted pricing for certain outpatient medications, which can then be used to provide more comprehensive services, including medication access services. OBJECTIVE: To characterize medication access services provided at hospitals that participate in the 340B Drug Pricing Program compared to hospitals that do not participate in the 340B Program. METHODS: Primary questionnaire response data was collected from a national sample of Directors of Pharmacy at non-federal acute care hospitals from March 2019 to May 2019. American Hospital Association Data Viewer was used to collect demographic information on 1,531 hospitals. Hospitals were excluded if they had 199 beds or fewer, did not have a unique Medicare provider ID, were federally owned, were located outside the continental U.S., or were non-acute care hospitals that served niche patient populations. This study utilized a proportional stratified sampling strategy to administer an electronic questionnaire to 340B and non-340B hospitals to assess the number and type of medication access service offerings. A final randomized sample of 500 hospitals were administered the questionnaire, and data was collected through recorded responses in Qualtrics software. RESULTS: 340B hospitals provided a significantly higher average number of medication access services compared to non-340B hospitals (6.20 vs. 3.91, p = 0.0001), adjusted for differences in hospital size and ownership type. For all nine medication access services that were assessed, a higher percentage of 340B hospitals reported providing the service compared to non-340B hospitals. This difference was statistically significant for six out of nine programs assessed. CONCLUSIONS: 340B hospitals provided more medication access services, on average, than comparably sized non-340B hospitals, suggesting that hospitals participating in the 340B Drug Pricing Program may be better positioned to create and administer programs that support medication access services.

Relationship between fluoroquinolone use and changes in susceptibility to fluoroquinolones of selected pathogens in 10 United States teaching hospitals, 1991-2000.

We retrospectively examined the relationship between fluoroquinolone use and the susceptibilities of 11 bacterial pathogens to fluoroquinolones in 10 US teaching hospitals from 1991 through 2000. Statistical significance was determined by 2-way analysis of variance, with the number of isolates tested each year as a weighting factor. The analysis of baseline-to-end point change in the percentage of susceptibility and the slope of the regression line (trend line) for logit percentage of susceptibility showed that the overall percentage of susceptibility to fluoroquinolones decreased significantly during the study period (P<.05) and that change in percentage of susceptibility was significantly related to change in fluoroquinolone use (P<.05). Particularly notable were the decreases in the susceptibilities of Pseudomonas aeruginosa, Proteus mirabilis, and Escherichia coli (decreases of 25.1%, 11.9%, and 6.8%, respectively).

Balance of academic responsibilities of clinical track pharmacy faculty in the United States: a survey of select American College of Clinical Pharmacy Practice and Research Network Members.

STUDY OBJECTIVES: To characterize the balance of clinical and academic responsibilities of clinical track pharmacy faculty in the United States and evaluate organizational structures that promote satisfactory balance between these responsibilities. DESIGN: Prospective cross-sectional survey. SETTING: A 22-item online survey was developed and distributed via Qualtrics software. PARTICIPANTS: Clinical faculty members of the American College of Clinical Pharmacy Adult Medicine, Ambulatory Care, Cardiology, Critical Care, Gastrointestinal/Liver/Nutrition, Immunology/Transplantation, Infectious Disease, and Pediatrics Practice and Research Networks (PRNs) were invited to participate via the PRN electronic mailing list. MEASUREMENTS AND MAIN RESULTS: The survey comprised questions related to demographics, organizational structure, and balance of clinical and academic responsibilities. A total of 344 participants responded to some or all of the survey questions. The demographics were relatively equally balanced between faculty at state and private academic institutions, academic rank, and practice setting. Expected and actual effort allocations were similar for each of the clinical and academic responsibilities, with direct patient care and clinical teaching representing more than 50% effort allocation cumulatively. Clinical faculty at state institutions devoted a larger proportion of time to clinical service, whereas clinical faculty at private institutions devoted a greater proportion of time to didactic teaching. When asked about time constraints, 157 (69.8%) of the 225 survey participants responding to this question did not believe they had sufficient time to fulfill their nonclinical academic needs. Clinical faculty who were provided "protected time" away from clinical service had a significantly more favorable opinion of this question. CONCLUSION: Most of the clinical track pharmacy faculty indicated that they have insufficient time to fulfill their nonclinical academic responsibilities. Provision of protected time may alleviate some of these time constraints.

Survey of pharmacy staffing levels and vacancy rates in small and rural hospitals in Illinois.

PURPOSE: The results of a survey evaluating pharmacy staffing and vacancies in small and rural hospitals in Illinois are reported. METHODS: Questionnaires were mailed in November 2011 to pharmacy directors at 86 small and rural hospitals in Illinois. The survey included several items regarding human resources and staffing, and it used work-force items and methods similar to surveys conducted in 1991 and 2001. Descriptive analyses were used to assess differences in staffing and vacancies across different hospital sizes (number of staffed beds), and inferential statistics were used to compare selected hospital characteristics. RESULTS: A total of 40 responses were received, yielding a response rate of 46.5%. Most rural hospitals reported having no vacancies in their pharmacy work force (62.5%, n = 25). Vacancy rates in 2011 were very low for pharmacists (1.8%), pharmacy technicians (2.5%), and pharmacy staff overall (2.1%). For several specific occupational titles, vacancy rates were zero. Nonetheless, adverse consequences (sites could report more than one effect) of vacancies included longer hours worked by part-time staff (27.5%, n = 11), reduced time to provide clinical pharmacy services (20.0%, n = 8), job dissatisfaction of remaining staff (17.9%, n = 7), and reduced time to provide drug distribution services (10.0%, n = 4). CONCLUSION: The shortage of pharmacists in small and rural hospitals in Illinois largely subsided from 2001 to 2011, with many hospitals reporting no vacancies at all. The total number of actual full-time equivalent pharmacy staff has sizably increased since 2001.

Pharmacy practice in small and rural hospitals in Illinois--2011.

PURPOSE: The results of a 2011 survey evaluating pharmacy services at small and rural Illinois hospitals are presented and compared with data from similar surveys in 2001 and 1991. METHODS: A questionnaire modeled on the previous survey instruments but updated to reflect contemporary pharmacy practice was mailed to pharmacy directors at 86 small hospitals (i.e., <150 staffed beds) and rural hospitals (i.e., located outside metropolitan areas). RESULTS: The response rate was 46.5%. The survey data indicated that 57.5% of hospitals represented in the 2011 survey had a centralized drug distribution system, 35.0% had a hybrid system, and 7.5% had a decentralized system. The most commonly reported form of technology was automated dispensing cabinets, which were in use at 75.0% of hospitals in 2011, compared with 34.8% of hospitals represented in the 2001 survey. Barcode verification of medication doses before dispensing and at the time of administration was performed at 50% and 70% of hospitals, respectively. While the provision of clinical pharmacy services has risen sharply since 1991, substantial changes were not observed between 2001 and 2011 except in the provision of compliance and drug histories (67.6% of hospitals in 2011 versus 46.8% in 2001) and pharmacist participation in medical emergency responses (54.0% versus 34.0%). CONCLUSION: A 2011 survey of pharmacy departments in small and rural Illinois hospitals provided information on the use of automation and health information technologies and showed changes in the provision of many clinical pharmacy services since 1991.

Comparison of pharmacy services at critical access hospitals and other rural and small hospitals in Illinois.

PURPOSE: The results of a survey evaluating pharmacy services and technology use at critical access hospitals (CAHs) and other small and rural hospitals in Illinois are reported. METHODS: A mail survey was sent to pharmacy directors at 86 CAHs and other rural and small hospitals in Illinois not designated as CAHs. Independent sample t tests and chi-square statistics were used to compare CAHs and non-CAHs in areas such as pharmacy services, staffing, use of technology, and sterile compounding practices. RESULTS: The survey response rate was 46.5%, with usable data received from 40 hospitals. Analysis of the survey data indicated that hospitals designated as CAHs were significantly less likely than non-CAHs to have automatic therapeutic interchange policies (p = 0.012) and more likely to conduct pharmacist-provided educational programs on medication costs for physicians and other health care personnel (p = 0.037). Relative to non-CAHs, CAHs were significantly less likely to have automated dispensing cabinets (p = 0.016) and to out-source the preparation of sterile products to offsite vendors (p = 0.012); pharmacy directors at CAHs were less likely to report the use of technology for remote medication order entry or review (p = 0.038). At both types of facilities, pharmacists typically have both distributive and clinical responsibilities, and patient-specific clinical pharmacy services (e.g., patient education or counseling, other drug therapy monitoring, medication reconciliation, pharmacokinetic consultations) are offered at similar frequencies. CONCLUSION: A survey of pharmacy departments at small and rural hospitals in Illinois determined that there were more similarities than differences between CAHs and non-CAHs. The survey indicated significant differences in dispensing processes, the use of technology and drug policy tools, and outsourcing of sterile product preparation.

Disruption of the serine/threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation.

X-linked West syndrome, also called "X-linked infantile spasms" (ISSX), is characterized by early-onset generalized seizures, hypsarrhythmia, and mental retardation. Recently, we have shown that the majority of the X-linked families with infantile spasms carry mutations in the aristaless-related homeobox gene (ARX), which maps to the Xp21.3-p22.1 interval, and that the clinical picture in these patients can vary from mild mental retardation to severe ISSX with additional neurological abnormalities. Here, we report a study of two severely affected female patients with apparently de novo balanced X;autosome translocations, both disrupting the serine-threonine kinase 9 (STK9) gene, which maps distal to ARX in the Xp22.3 region. We show that STK9 is subject to X-inactivation in normal female somatic cells and is functionally absent in the two patients, because of preferential inactivation of the normal X. Disruption of the same gene in two unrelated patients who have identical phenotypes (consisting of early-onset severe infantile spasms, profound global developmental arrest, hypsarrhythmia, and severe mental retardation) strongly suggests that lack of functional STK9 protein causes severe ISSX and that STK9 is a second X-chromosomal locus for this disorder.

Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation.

We have identified truncating mutations in the human DLG3 (neuroendocrine dlg) gene in 4 of 329 families with moderate to severe X-linked mental retardation. DLG3 encodes synapse-associated protein 102 (SAP102), a member of the membrane-associated guanylate kinase protein family. Neuronal SAP102 is expressed during early brain development and is localized to the postsynaptic density of excitatory synapses. It is composed of three amino-terminal PDZ domains, an src homology domain, and a carboxyl-terminal guanylate kinase domain. The PDZ domains interact directly with the NR2 subunits of the NMDA glutamate receptor and with other proteins responsible for NMDA receptor localization, immobilization, and signaling. The mutations identified in this study all introduce premature stop codons within or before the third PDZ domain, and it is likely that this impairs the ability of SAP102 to interact with the NMDA receptor and/or other proteins involved in downstream NMDA receptor signaling pathways. NMDA receptors have been implicated in the induction of certain forms of synaptic plasticity, such as long-term potentiation and long-term depression, and these changes in synaptic efficacy have been proposed as neural mechanisms underlying memory and learning. The disruption of NMDA receptor targeting or signaling, as a result of the loss of SAP102, may lead to altered synaptic plasticity and may explain the intellectual impairment observed in individuals with DLG3 mutations.