Despite efforts to enhance the quality of medication prescribing in outpatient settings, potentially inappropriate prescribing remains common, particularly in unscheduled settings where patients can ...present with infectious and pain-related complaints. Two of the most commonly prescribed medication classes in outpatient settings with frequent rates of potentially inappropriate prescribing include antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). In the setting of persistent inappropriate prescribing, we sought to understand a diverse set of perspectives on the determinants of inappropriate prescribing of antibiotics and NSAIDs in the Veterans Health Administration.
We conducted a qualitative study guided by the Consolidated Framework for Implementation Research and Theory of Planned Behavior. Semi-structured interviews were conducted with clinicians, stakeholders, and Veterans from March 1, 2021 through December 31, 2021 within the Veteran Affairs Health System in unscheduled outpatient settings at the Tennessee Valley Healthcare System. Stakeholders included clinical operations leadership and methodological experts. Audio-recorded interviews were transcribed and de-identified. Data coding and analysis were conducted by experienced qualitative methodologists adhering to the Consolidated Criteria for Reporting Qualitative Studies guidelines. Analysis was conducted using an iterative inductive/deductive process.
We conducted semi-structured interviews with 66 participants: clinicians (N = 25), stakeholders (N = 24), and Veterans (N = 17). We identified six themes contributing to potentially inappropriate prescribing of antibiotics and NSAIDs: 1) Perceived versus actual Veterans expectations about prescribing; 2) the influence of a time-pressured clinical environment on prescribing stewardship; 3) Limited clinician knowledge, awareness, and willingness to use evidence-based care; 4) Prescriber uncertainties about the Veteran condition at the time of the clinical encounter; 5) Limited communication; and 6) Technology barriers of the electronic health record and patient portal.
The diverse perspectives on prescribing underscore the need for interventions that recognize the detrimental impact of high workload on prescribing stewardship and the need to design interventions with the end-user in mind. This study revealed actionable themes that could be addressed to improve guideline concordant prescribing to enhance the quality of prescribing and to reduce patient harm.
The heterotrimeric Asi ubiquitin ligase (encoded by
ASI1
,
ASI2
, and
ASI3
) mediates protein degradation in the inner nuclear membrane in
Saccharomyces cerevisiae
. Asi1p and Asi3p possess catalytic ...domains, while Asi2p functions as an adaptor for a subset of Asi substrates. We hypothesized the Asi complex is an important mediator of protein quality control, and we predicted that Asi would be required for optimal growth in conditions associated with elevated abundance of aberrant proteins. Loss of Asi1p or Asi3p, but not Asi2p, sensitized yeast to hygromycin B, which promotes translational infidelity by distorting the ribosome A site. Surprisingly, loss of quality control ubiquitin ligase Hul5p did not sensitize yeast to hygromycin B. Our results are consistent with a prominent role for an Asi subcomplex that includes Asi1p and Asi3p (but not Asi2p) in protein quality control.
Acquiring water is essential for all animals, but doing so is most challenging for desert-living animals. Recently Przewalski's horse has been reintroduced to the desert area in China where the last ...wild surviving member of the species was seen before it vanished from China in the 1960s. Its reintroduction placed it within the range of a close evolutionary relative, the con-generic Khulan. Determining whether or not these two species experience competition and whether or not such competition was responsible for the extinction of Przewalski's horses in the wild over 50 years ago, requires identifying the fundamental and realized niches of both species. We remotely monitored the presence of both species at a variety of water points during the dry season in Kalamaili Nature Reserve, Xinjiang, China. Przewalski's horses drank twice per day mostly during daylight hours at low salinity water sources while Khulans drank mostly at night usually at high salinity water points or those far from human residences. Spatial and temporal differences in water use enables coexistence, but suggest that Przewalski's horses also restrict the actions of Khulan. Such differences in both the fundamental and realized niches were associated with differences in physiological tolerances for saline water and human activity as well as differences in aggression and dominance.
A new approach in the treatment of cystic fibrosis involves improving the function of mutant cystic fibrosis transmembrane conductance regulator (CFTR). VX-770, a CFTR potentiator, has been shown to ...increase the activity of wild-type and defective cell-surface CFTR in vitro.
We randomly assigned 39 adults with cystic fibrosis and at least one G551D-CFTR allele to receive oral VX-770 every 12 hours at a dose of 25, 75, or 150 mg or placebo for 14 days (in part 1 of the study) or VX-770 every 12 hours at a dose of 150 or 250 mg or placebo for 28 days (in part 2 of the study).
At day 28, in the group of subjects who received 150 mg of VX-770, the median change in the nasal potential difference (in response to the administration of a chloride-free isoproterenol solution) from baseline was -3.5 mV (range, -8.3 to 0.5; P=0.02 for the within-subject comparison, P=0.13 vs. placebo), and the median change in the level of sweat chloride was -59.5 mmol per liter (range, -66.0 to -19.0; P=0.008 within-subject, P=0.02 vs. placebo). The median change from baseline in the percent of predicted forced expiratory volume in 1 second was 8.7% (range, 2.3 to 31.3; P=0.008 for the within-subject comparison, P=0.56 vs. placebo). None of the subjects withdrew from the study. Six severe adverse events occurred in two subjects (diffuse macular rash in one subject and five incidents of elevated blood and urine glucose levels in one subject with diabetes). All severe adverse events resolved without the discontinuation of VX-770.
This study to evaluate the safety and adverse-event profile of VX-770 showed that VX-770 was associated with within-subject improvements in CFTR and lung function. These findings provide support for further studies of pharmacologic potentiation of CFTR as a means to treat cystic fibrosis. (Funded by Vertex Pharmaceuticals and others; ClinicalTrials.gov number, NCT00457821.).
Epithelial solitary chemosensory cell (tuft cell) bitter taste signal transduction occurs through G protein coupled receptors and calcium-dependent signaling pathways. Type II taste cells, which ...utilize the same bitter taste signal transduction pathways, may also utilize cyclic adenosine monophosphate (cAMP) as an independent signaling messenger in addition to calcium.
In this work we utilized specific pharmacologic inhibitors to interrogate the short circuit current (Isc) of polarized nasal epithelial cells mounted in Ussing chambers to assess the electrophysiologic changes associated with bitter agonist (denatonium) treatment. We also assessed release of human β-defensin-2 from polarized nasal epithelial cultures following treatment with denatonium benzoate and/or potassium channel inhibitors.
We demonstrate that the bitter taste receptor agonist, denatonium, decreases human respiratory epithelial two-pore potassium (K2P) current in polarized nasal epithelial cells mounted in Ussing chambers. Our data further suggest that this occurs via a cAMP-dependent signaling pathway. We also demonstrate that this decrease in potassium current lowers the threshold for denatonium to stimulate human β-defensin-2 release.
These data thus demonstrate that, in addition to taste transducing calcium-dependent signaling, bitter taste receptor agonists can also activate cAMP-dependent respiratory epithelial signaling pathways to modulate K2P currents. Bitter-agonist regulation of potassium currents may therefore serve as a means of rapid regional epithelial signaling, and further study of these pathways may provide new insights into regulation of mucosal ionic composition and innate mechanisms of epithelial defense.
The United States Veterans Health Administration is a leader in the use of telemental health (TMH) to enhance access to mental healthcare amidst a nationwide shortage of mental health professionals. ...The Tennessee Valley Veterans Affairs (VA) Health System piloted TMH in its emergency department (ED) and urgent care clinic (UCC) in 2019, with full 24/7 availability beginning March 1, 2020. Following implementation, preliminary data demonstrated that veterans ≥65 years old were less likely to receive TMH than younger patients. We sought to examine factors associated with older veterans receiving TMH consultations in acute, unscheduled, outpatient settings to identify limitations in the current process.
This was a retrospective cohort study conducted within the Tennessee Valley VA Health System. We included veterans ≥55 years who received a mental health consultation in the ED or UCC from April 1, 2020-September 30, 2022. Telemental health was administered by a mental health clinician (attending physician, resident physician, nurse practitioner, or physician assistant) via iPad, whereas in-person evaluations were performed in the ED. We examined the influence of patient demographics, visit timing, chief complaint, and psychiatric history on TMH, using multivariable logistic regression.
Of the 254 patients included in this analysis, 177 (69.7%) received TMH. Veterans with high-risk chief complaints (suicidal ideation, homicidal ideation, or agitation) were less likely to receive TMH consultation (adjusted odds ratio AOR: 0.47, 95% confidence interval CI 0.24-0.95). Compared to attending physicians, nurse practitioners and physician assistants were associated with increased TMH use (AOR 4.81, 95% CI 2.04-11.36), whereas consultation by resident physicians was associated with decreased TMH use (AOR 0.04, 95% CI 0.00-0.59). The UCC used TMH for all but one encounter. Patient characteristics including their visit timing, gender, additional medical complaints, comorbidity burden, and number of psychoactive medications did not influence use of TMH.
High-risk chief complaints, location, and type of mental health clinician may be key determinants of telemental health use in older adults. This may help expand mental healthcare access to areas with a shortage of mental health professionals and prevent potentially avoidable transfers in low-acuity situations. Further studies and interventions may optimize TMH for older patients to ensure safe, equitable mental health care.
Objectives
Following rapid uptake of telehealth during the COVID‐19 pandemic, we examined barriers and facilitators for sustainability and spread of telemental health video (TMH‐V) as policies ...regarding precautions from the pandemic waned.
Methods
We conducted a qualitative study using semistructured interviews and observations guided by RE‐AIM. We asked four groups, local clinicians, facility leadership, Veterans, and external partners, about barriers and facilitators impacting patient willingness to engage in TMH‐V (reach), quality of care (effectiveness), barriers and facilitators impacting provider uptake (adoption), possible adaptations to TMH‐V (implementation), and possibilities for long‐term use of TMH‐V (maintenance). Interviews were recorded, transcribed, and analyzed using framework analysis. We also observed TMH‐V encounters in one emergency department (ED) and one urgent care (UC) to understand how clinicians and Veterans engaged with the technology.
Results
We conducted 35 interviews with ED/UC clinicians and staff (n = 10), clinical and facility leadership (n = 7), Veterans (n = 5), and external partners (n = 13), January–May 2022. We completed 10 observations. All interviewees were satisfied with the TMH‐V program, and interviewees highlighted increased comfort discussing difficult topics for Veterans (reach). Clinicians identified that TMH‐V allowed for cross‐coverage across sites as well as increased safety and flexibility for clinicians (adoption). Opportunities for improvement include alleviating technological burdens for on‐site staff, electronic health record (EHR) modifications to accurately capture workload and modality (telehealth vs. in‐person), and standardizing protocols to streamline communication between on‐site and remote clinical staff (implementation). Finally, interviewees encouraged its spread (maintenance) and thought there was great potential for service expansion.
Conclusions
Interviewees expressed support for continuing TMH‐V locally and spread to other sites. Ensuring adequate infrastructure (e.g., EHR integration and technology support) and workforce capacity are key for successful spread. Given the shortage of mental health (MH) clinicians in rural settings, TMH‐V represents a promising intervention to increase the access to high‐quality emergency MH care.
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