Both kinds of RNase P in all domains of life: surprises galore.

RNase P, an essential housekeeping endonuclease needed for 5'-processing of tRNAs, exists in two distinct forms: one with an RNA- and the other with a protein-based active site. The notion that the protein form of RNase P exists only in eukaryotes has been upended by the recent discovery of a protein-only variant in Bacteria and Archaea. The use of these two divergent scaffolds, shaped by convergent evolution, in all three domains of life inspires questions relating to the ancestral form of RNase P, as well as their origins and function(s) in vivo. Results from our analysis of publicly available bacterial and archaeal genomes suggest that the widespread RNA-based ribonucleoprotein variant is likely the ancient form. We also discuss the possible genetic origins and function of RNase P, including how the simultaneous presence of its variants may contribute to the fitness of their host organisms.

Impact of a contactless prescription pickup kiosk on prescription abandonment, patient experience, and pharmacist consultations.

OBJECTIVE: Investigate the impact of increased access to new and refilled prescriptions by means of an automated pickup kiosk (Asteres ScriptCenter) on prescription abandonment rates, patient experience, and pharmacist consultations. DESIGN: Nonrandomized, observational study using retrospective, deidentified data from the filling pharmacy, the kiosk, and a pharmacist-completed counseling documentation log over a 35-month study period. SETTING AND PARTICIPANTS: Hospital employees opting to use a kiosk located in the lobby with 24 hours a day, 7 days a week access for pickups and a telephone pharmacist consultation service compared with employees using the regular counter at the filling pharmacy. OUTCOME MEASURES: Return to stock (RTS) rate to assess prescription abandonment, time to prescription pickup, consultation duration, kiosk user assessment, and pharmacist assessment of counseling ability. RESULTS: Approximately 9% of employees (440) enrolled to use the kiosk, with 5062 kiosk pickups recorded for new prescriptions (29%), refill prescriptions (33%), and over-the-counters (38%). The mean kiosk RTS (4.3% ± 3.2) was lower than that at the regular counter (5.6% ± 0.8), P = 0.04, whereas the mean time to pickup was approximately 1 day greater at the kiosk than the regular counter (2.8 ± 0.4 vs. 1.8 ± 0.2, P < 0.001). The average kiosk consultation was approximately 1 minute shorter (2.0 ± 1.4) than that of the regular counter (3.4 ± 1.9, P < 0.001), and fewer patients using the kiosk (15.7%) had additional questions at the end of a consultation session than patients at the regular counter (38.8%, P < 0.001). Most of the kiosk users agreed that their prescription questions were answered and that kiosk convenience was an important reason for using the filling pharmacy. Almost all (>90%) pharmacists indicated that they were able to effectively counsel patients at the kiosk and the regular counter. CONCLUSION: The kiosk, used by self-selected health care workers located in a hospital workplace setting with 24 hours a day, 7 days a week access, was a convenient, contactless pickup extension of the filling pharmacy with a lower prescription abandonment rate and similar pickup and consultation characteristics as at the regular pharmacy counter.

Detection of Mesenteric Tumor Using Dynamic Contrast Enhanced MRI.

PURPOSE: This study was designed to evaluate the use of a novel imaging technique, dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), for detecting mesenteric peritoneal metastases. METHODS: Thirty-four patients underwent preoperative conventional MRI, including T1, T2, diffusion-weighted (DWI), and delayed gadolinium MRI, as well as DCE MRI. DCE MRI involved imaging the peritoneal cavity every 9 s for 6 min. DCE images were processed to generate parametric maps of tumor vascularity. Two oncologic surgeons and a radiologist reviewed conventional MRI for all tumor and then later reviewed the conventional MRI plus the DCE parametric maps. Images were reviewed for tumor of the parietal peritoneum, porta hepatis, bowel serosa, upper small bowel mesentery, lower small bowel mesentery, and pelvis. Conventional MRI and DCE + MRI findings were compared to operative and histopathologic reports for tumor detection. PCI scores were calculated for surgery, MRI, and DCE. RESULTS: Upper mesenteric tumor was present in 21 patients. DCE images showed a sensitivity of 100%, specificity of 92%, and accuracy of 97% compared with conventional MRI sensitivity of 24%, specificity of 93%, and accuracy of 50% (p = 0.006). Lower mesenteric tumor was present in 22 patients. DCE images showed a sensitivity of 100%, specificity of 92%, and accuracy of 97% compared with conventional MRI sensitivity of 45%, specificity of 92%, and accuracy of 62% (p = 0.008). The mean surgical PCI for all 34 patients was 23.4 compared with MRI 20.0 (p = 0.003) and DCE MRI 24.1 (p = 0.26). The addition of the DCE images improved the accuracy of total PCI by > 10% in 16 (0.46) patients. For PCI regions 9-12, the mean surgical PCI was 6.0 compared with MRI 4.8 (p = 0.08) and DCE 6.6 (p = 0.02). The addition of DCE images improved the accuracy of the regional PCI > 10% in 15 (0.43) patients. CONCLUSIONS: DCE MRI provides a novel contrast tool that improves detection of mesenteric tumor. Depicting small-volume mesenteric tumor is better on DCE MRI compared with conventional MRI.

Relationship between publication of a postgraduate year 1 residency research project and subsequent career type at a large academic medical center.

PURPOSE: The study objectives were to (1) quantify the overall incidence of residency publications of postgraduate year 1 (PGY1) residency alumni; (2) evaluate annual fluctuations in publications over time; and (3) compare the career types of residency alumni who published their PGY1 residency research projects to those for alumni who did not. METHODS: A retrospective cohort study was performed among individuals who completed a PGY1 acute/ambulatory care residency between 2010 and 2021. A list of residency alumni was obtained along with the corresponding titles of their research projects. Each resident's name was entered into PubMed and Google Scholar to find the corresponding publication. LinkedIn and other publicly available resources were used to determine the career types of residents immediately after residency as well as their current career types. RESULTS: In total, 178 residency alumni completed an acute/ambulatory care PGY1 residency, of whom 16.7% (30/178) published their residency research project. Publication was associated with career type among those who pursued a postgraduate year 2 residency but was not associated with career type immediately after the PGY1 residency or current career type. The presence of an academic preceptor was associated with a higher probability of publishing compared to residents who did not have an academic preceptor (31.5% vs 10.5%; P < 0.01). CONCLUSION: The frequency of publications was within the range reported elsewhere, with fluctuations over time. Presence of an academic preceptor improved the probability of publication.

Assigning a function to a conserved archaeal metallo-ß-lactamase from Haloferax volcanii.

The metallo-ß-lactamase family of enzymes comprises a large group of proteins with diverse functions in the metabolism of the cell. Among others, this superfamily contains proteins which are involved in DNA and RNA metabolism, acting as nucleases in e.g. repair and maturation. Many proteins have been annotated in prokaryotic genomes as being potential metallo-ß-lactamases, but very often the function has not been proven. The protein HVO_2763 from Haloferax volcanii is such a potential metallo-ß-lactamase. HVO_2763 has sequence similarity to the metallo-ß-lactamase tRNase Z, a tRNA 3' processing endonuclease. Here, we report the characterisation of this metallo-ß-lactamase HVO_2763 in the halophilic archaeon Haloferax volcanii. Using different in vitro assays with the recombinant HVO_2763, we could show that the protein does not have tRNA 3' processing or exonuclease activity. According to transcriptome analyses of the HVO_2763 deletion strain, expression of proteins involved in membrane transport is downregulated in the mutant. Therefore, HVO_2763 might be involved directly or indirectly in membrane transport.

Development of a pharmacist-psychiatrist collaborative medication therapy management clinic.

OBJECTIVE: To describe a needs assessment, practice description, practice innovation and reimbursement of a psychiatric pharmacist medication therapy management (MTM) clinic with related challenges and opportunities. SETTING: An MTM clinic established in collaboration with the Outpatient Psychiatric Services (OPS) at the University of California San Diego (UCSD), under contract with the San Diego County Health and Human Services Agency Adult and Older Adult Mental Health Services (A/OAMHS). PRACTICE DESCRIPTION: Two board-certified psychiatric pharmacists provided direct patient care using a collaborative practice protocol 3 days per week. Clinical services included pharmacotherapy management, laboratory monitoring, medication counseling, and psychosocial referrals to other providers. PRACTICE INNOVATION: Payment to UCSD OPS for clinical services was based on a contract between the San Diego County A/OAMHS and the clinic. Two pharmacists co-managed mental health patients and billed for medication management based on face-to-face contact time (medication minutes) and documentation time with each patient. MAIN OUTCOME MEASURES: Number of patients comanaged, dropout rates, visit duration, and billed minutes. RESULTS: From May 2009 to December 2010, two pharmacists comanaged 68 patients, mean (± SD) age 48.6 ± 11.6 years, diagnosed with major depressive, schizophrenic, schizoaffective, and/or bipolar disorder. A total of 56 (82.3%) patients were clinically stable and remained on the pharmacist caseload, but 12 (17.6%) patients were lost to follow-up (10 lost contact, 1 moved, 1 expired). On average, patients had 7.7 patient visits , for 491 total visits (with an average of 26 minutes per visit) that were billed at a rate of $4.82 per minute for medication minutes, translating to $84,542.80. CONCLUSION: With provider education and appropriate physician champions, pharmacists are able to work collaboratively with psychiatrists in a mental health clinic.

Body weight, diabetes incidence vascular events and survival 15 years after very low calorie diet in community medical clinics in the UK.

Objective: To assess weight loss maintenance, diabetes status, mortality and morbidity 15 years after a very low calorie diet programme (VLCD) in patients with obesity. Design: General practice data bases were interrogated for subjects coded for group therapy with VLCD in the 1990s. Causes of death, occurrence of vascular disease and remission or development of diabetes were ascertained from patient records and national stroke and cardiovascular disease data bases. Results: 325 subjects engaged in the programme and had sufficient data for analysis. Baseline characteristics were: age 47.8±12. 8 years; body mass index (BMI) 36.1±6.8 kg/m2; 79.1% female/20.9% male; 13.5% had type 2 diabetes. After 15±4 years weight had changed from 97.9±19 kg at baseline to 100±20.8 kg. 10 with diabetes at baseline were in remission at 3 months, but only two remained in remission at 5 years. 50 new cases of type 2 diabetes and 11 of impaired fasting glucose developed during follow-up. Only 5.9% who remained healthy at follow-up had maintained >10% body weight reduction. Neither diabetes incidence nor diabetes free survival were related to percentage body weight lost during VLCD. Only baseline BMI was related to development of new impaired fasting glucose or diabetes by 15 years (p=0.007). 37 subjects had a cardiovascular event. Age (p=0.000002) and degree of weight loss after VLCD (p=0.03) were significantly associated with subsequent vascular events. Conclusion: Long-term maintenance of weight loss after VLCD was rare in this single centre retrospective study 15 years later. Glucose intolerance developed in 21.4%. Lasting remission of type 2 diabetes or prevention of later glucose intolerance were not achieved. Vascular events were more frequent in those who lost most weight. Risk management during weight regain should be studied in future to assess potential for reduction in adverse cardiovascular outcomes.

Analysis of the medication-use process in North American hospital systems: underlining key points for adoption to improve patient safety in French hospitals.

This project was designed to underline any actions relative to medication error prevention and patient safety improvement setting up in North American hospitals which could be implemented in French Parisian hospitals. A literature research and analysis of medication-use process in the North American hospitals and a validation survey of hospital pharmacist managers in the San Diego area was performed to assess main points of hospital medication-use process. Literature analysis, survey analysis of respondents highlighted main differences between the two countries at three levels: nationwide, hospital level and pharmaceutical service level. According to this, proposal development to optimize medication-use process in the French system includes the following topics: implementation of an expanded use of information technology and robotics; increase pharmaceutical human resources allowing expansion of clinical pharmacy activities; focus on high-risk medications and high-risk patient populations; develop a collective sense of responsibility for medication error prevention in hospital settings, involving medical, pharmaceutical and administrative teams. Along with a strong emphasis that should be put on the identified topics to improve the quality and safety of hospital care in France, consideration of patient safety as a priority at a nationwide level needs to be reinforced.

Hospice advice and rapid response service for ambulance clinicians.

OBJECTIVE: Patients in the last year of life experience medical emergencies which may lead to an emergency attendance by ambulance clinicians and some patients having a transfer to hospital even when this is unwanted by patients, carers or professionals. Here we report the patient characteristics and outcomes of a 24-hour hospice nursing telephone advice service to support an ambulance service. METHOD: An evaluation of the outcomes of ambulance calls to a nursing telephone advice service for people living in northwest London, UK, attended at home during a 6-month period by the London Ambulance Service, whose clinicians then sought advice from the hospice's 24 hours' telephone line. RESULTS: Forty-five attendances of 44 acutely ill people with palliative care needs resulted in a telephone call. Thirteen patients (30%) were male and the median age was over 80 years. Thirty-two attendances (71%) were managed without a transfer to hospital, with telephone advice from the hospice and in some cases arrangements for another clinician to visit. Seven attendances (16%) resulted in a transfer to hospital, of which at least five led to an admission. Six attendances (13%) resulted in a notification of the patient's death. CONCLUSIONS: This preliminary study shows the feasibility, outcomes and acceptability of telephone advice to support ambulance clinicians attending patients with palliative care needs. The service was associated with low rates of subsequent transfer to hospital. Further controlled research is needed to assess the clinical and cost-effectiveness of the service.

A Correlation of a Medication-Focused Risk Score to Medication Errors at Discharge.

Pharmacy transitions-of-care services at the time of hospital discharge are helpful in reducing medication errors. Validated risk tools are commonly used by pharmacists to identify patients at greatest benefit of these services. However, current tools lack assessment of medication-related risk factors and predict hospital readmissions rather than medication errors. To address this, a novel medication-focused risk tool (UCSD-Rx risk score) was created to help classify patients at a higher risk for medication errors. This study was split into 2 phases aimed to internally validate the risk score. Phase I of the study compared the predictability of 30-day unplanned readmissions between the UCSD-Rx risk score and a well-validated risk tool, the LACE+ index. To further specify our risk score for pharmacist use, phase II of the study analyzed the predictability of the risk score to medication errors at discharge. Phase I demonstrated similar classification performance of 30-day unplanned readmissions between the UCSD-Rx risk score (C-statistic, 0.66; 95% confidence interval [CI], 0.64-0.68; P < .0001) and the LACE+ index (C-statistic, 0.69; 95%CI, 0.67-0.71; P < .0001). In phase II, logistic regression showed an increasing UCSD-Rx risk score was predictive of individuals who would experience a medication error at discharge (odds ratio, 1.068; 95%CI, 1.005-1.136; P = .035). Results of this study demonstrate that the UCSD-Rx risk score is a promising tool targeted for pharmacist use to identify patients that may benefit most from transitions-of-care services prior to discharge.

Patient request for pharmacist counseling and satisfaction: Automated prescription delivery system versus regular pick-up counter.

OBJECTIVES: To assess the rate of patient-requested pharmacist counseling for refill prescriptions and satisfaction with pick-up process for patients using an automated prescription delivery system (APDS) versus those using a regular pick-up counter and to explore patient willingness to use an APDS as a tool for pharmacist monitoring of medication therapy outcomes. METHODS: In this uncontrolled, cross-sectional, survey study, we assessed use of APDS or the regular counter by 116 patients picking up refill prescriptions at two community pharmacies. The main outcome measures were number of patients requesting pharmacist counseling for refill prescriptions, patient satisfaction with pick-up process, and patient willingness to use an APDS to report medication therapy outcomes. RESULTS: None of the regular counter users and only two APDS users (3.7%) requested counseling for their refill prescription (P = 0.126). Almost all patients agreed that they were able to talk to a pharmacist about their prescription if they wanted to do so (95.1% regular counter and 92.3% APDS; P = 0.268). The majority (75%) of patients using APDS indicated that they would be willing to use the system to answer questions or perform simple tests to provide information that the pharmacist could use to improve medication effectiveness or reduce adverse effects. CONCLUSION: Very few patients (ADPS or regular counter) asked to speak to a pharmacist about their refill medications, although it appeared that no perceived barriers to pharmacist access existed. Most APDS patients were willing to use this new technology to provide information about therapy outcomes to the pharmacist. Further exploration and testing of the APDS as a data collection tool to enhance pharmacist access to therapy outcomes is warranted.

Advancing Pharmacist Collaborative Care within Academic Health Systems.

INTRODUCTION: The scope of pharmacy practice has evolved over the last few decades to focus on the optimization of medication therapy. Despite this positive impact, the lack of reimbursement remains a significant barrier to the implementation of innovative pharmacist practice models. SUMMARY: We describe the successful development, implementation and outcomes of three types of pharmacist collaborative care models: (1) a pharmacist with physician oversight, (2) pharmacist-interprofessional teams and (3) physician-pharmacist teams. The outcome measurement of these pharmacist care models varied from the design phase to patient volume measurement and to comprehensive quality dashboards. All of these practice models have been successfully funded by affiliated health systems or grants. CONCLUSIONS: The expansion of pharmacist services delivered by clinical faculty has several benefits to affiliated health systems: (1) significant improvements in patient care quality, (2) access to experts in specialty areas, and (3) the dissemination of outcomes with national and international recognition, increasing the visibility of the health system.

Complete Genome Sequences of 44 Arthrobacter Phages.

We report here the complete genome sequences of 44 phages infecting Arthrobacter sp. strain ATCC 21022. These phages have double-stranded DNA genomes with sizes ranging from 15,680 to 70,707 bp and G+C contents from 45.1% to 68.5%. All three tail types (belonging to the families Siphoviridae, Myoviridae, and Podoviridae) are represented.

PACRAT: a database and analysis system for archaeal and bacterial intergenic sequence features.

Analysis of intergenic sequences for purposes such as the investigation of transcriptional signals or the identification of small RNA genes is frequently complicated by traditional biological database structures. Genome data is commonly treated as chromosome-length sequence records, detailed by gene calls demarcating subsequences of the chromosomes. Given this model, the determination of non-called subsequences between any gene and its nearest neighbors requires an exhaustive search of all gene calls associated with the chromosome. Further compounding the issue, the location of intergenic regions for many called genes cannot be resolved unambiguously due to uncertainties in gene boundaries, as well as the presence of other conflicting gene calls. To address these difficulties we have constructed the PACRAT (http://www.biosci.ohio-state.edu/~pacrat/) database system. PACRAT preprocesses GenBank genome submissions, evaluates for every gene the character of its relationship to those genes nearest to it, and produces a relationally linked model of the gene ordering for the genome. Using this information, the interface allows the researcher to query gene data as well as intergenic sequence data based on a number of criteria. These include the ability to filter searches based on the status of start and stop positions, or upstream/downstream sequences as conflicting with called genes and automated extension of upstream or downstream searches to find probable operon promoters or terminators. The database is also indexed by KEGG classification, allowing, for example, functionally-related groups of high-quality promoter-containing regions to be easily retrieved as a group.

Sequence Analysis and Comparative Study of the Protein Subunits of Archaeal RNase P.

RNase P, a ribozyme-based ribonucleoprotein (RNP) complex that catalyzes tRNA 5'-maturation, is ubiquitous in all domains of life, but the evolution of its protein components (RNase P proteins, RPPs) is not well understood. Archaeal RPPs may provide clues on how the complex evolved from an ancient ribozyme to an RNP with multiple archaeal and eukaryotic (homologous) RPPs, which are unrelated to the single bacterial RPP. Here, we analyzed the sequence and structure of archaeal RPPs from over 600 available genomes. All five RPPs are found in eight archaeal phyla, suggesting that these RPPs arose early in archaeal evolutionary history. The putative ancestral genomic loci of archaeal RPPs include genes encoding several members of ribosome, exosome, and proteasome complexes, which may indicate coevolution/coordinate regulation of RNase P with other core cellular machineries. Despite being ancient, RPPs generally lack sequence conservation compared to other universal proteins. By analyzing the relative frequency of residues at every position in the context of the high-resolution structures of each of the RPPs (either alone or as functional binary complexes), we suggest residues for mutational analysis that may help uncover structure-function relationships in RPPs.

The impact of real-time alerting on appropriate prescribing in kidney disease: a cluster randomized controlled trial.

BACKGROUND: Patients with kidney disease are at risk for adverse events due to improper medication prescribing. Few randomized controlled trials of clinical decision support (CDS) utilizing dynamic assessment of patients' kidney function to improve prescribing for patients with kidney disease have been published. METHODS: We developed a CDS tool for 20 medications within a commercial electronic health record. Our system detected scenarios in which drug discontinuation or dosage adjustment was recommended for adult patients with impaired renal function in the ambulatory and acute settings - both at the time of the initial prescription ("prospective" alerts) and by monitoring changes in renal function for patients already receiving one of the study medications ("look-back" alerts). We performed a prospective, cluster randomized controlled trial of physicians receiving clinical decision support for renal dosage adjustments versus those performing their usual workflow. The primary endpoint was the proportion of study prescriptions that were appropriately adjusted for patients' kidney function at the time that patients' conditions warranted a change according to the alert logic. We employed multivariable logistic regression modeling to adjust for glomerular filtration rate, gender, age, hospitalized status, length of stay, type of alert, time from start of study, and clustering within the prescribing physician on the primary endpoint. RESULTS: A total of 4068 triggering conditions occurred in 1278 unique patients; 1579 of these triggering conditions generated alerts seen by physicians in the intervention arm and 2489 of these triggering conditions were captured but suppressed, so as not to generate alerts for physicians in the control arm. Prescribing orders were appropriate adjusted in 17% of the time vs 5.7% of the time in the intervention and control arms, respectively (odds ratio: 1.89, 95% confidence interval, 1.45-2.47, P < .0001). Prospective alerts had a greater impact than look-back alerts (55.6% vs 10.3%, in the intervention arm). CONCLUSIONS: The rate of appropriate drug prescribing in kidney impairment is low and remains a patient safety concern. Our results suggest that CDS improves drug prescribing, particularly when providing guidance on new prescriptions.

Recommendations for Aligning PGY2 Pharmacy Residency Training and Pharmacy Specialist Board Certification.

With the increased focus and anticipated growth in specialty training and certification within the profession of pharmacy, it is important for the profession to step back and evaluate the manner in which its adopted education and certification systems interface. As a result of specialty practice development, significant growth is occurring in both postgraduate year two (PGY2) pharmacy residency programs and individuals seeking certification by the Board of Pharmacy Specialties. As the profession continues to evolve its specialty training and credentialing systems, it is important to consider the inherent relationship between these systems. This paper considers the current landscape of specialty training and certification, including issues related to the quality of PGY2 training, consistent application of standards across and within PGY2 programs, credentialing of preceptors and program directors, and alignment of training with specialty certification examination content domains. We outline recommendations across three areas: (1) creating consistency between specialty training and certification, (2) aligning qualifications of PGY2 residency program directors and preceptors with the designated specialty area, and (3) assessing program quality in the context of the expectations of specialists established by the profession. The goal of this paper is to stimulate professional dialogue on these issues. Establishing both formal and informal connections between specialty training and certification can serve as the foundation for a rational approach to professional development and the credentialing that will be recognized by stakeholders outside the pharmacy profession. Establishing these connections will also support and advance the profession's mission of meeting the medication needs of patients.

Measuring the cost, effectiveness, and cost-effectiveness of orthodontic care.

AIM: To determine the relative effectiveness and cost-effectiveness of orthodontic treatment per case in one "fee for item" and two different types of salaried orthodontic clinics. SUBJECTS AND METHODS: This prospective study recruited a random sample of six self-employed orthodontists (fee-for-item) and six orthodontists from both hospital and community clinics (salaried services). One hundred patients were followed to completion of orthodontic care. Questionnaires were employed to determine cost of treatment from the clinicians' and patients' points of views. Four cost-effectiveness models were developed. RESULTS: Complete records of outcome were available for 1,087 patients, but only 789 had complete data on costing. Three of the four cost-effectiveness models indicated similar rankings for the 18 clinicians. The most cost-effective service was provided by clinicians working in community clinics, followed by clinicians working in hospitals, then self-employed clinicians. The preferred cost-effective model takes into consideration the initial need and successful outcome of orthodontic treatment. CONCLUSION: Cost-effectiveness models have been developed to quantify the performance of individual clinicians working in self-employed and salaried clinics. Costs and effectiveness of the clinicians in each clinical setting show considerable variation.