Faculty Bibliography

AIMS/OBJECTIVE:To conduct a needs assessment of public hospitals in Mexico to determine workforce specific capacity building needs in the care of older people. BACKGROUND:The older population in Mexico is growing rapidly. The healthcare system and workforce may not be prepared to handle the needs of older people, especially those with chronic illnesses who are also disadvantaged socioeconomically. Determining workforce and system needs is important to strategically develop capacity. METHODS:A needs assessment using a pragmatic qualitative approach structured this study. Semi-structured interviews and focus groups were conducted with healthcare professionals at five public hospitals in Mexico. Directed content analysis techniques analysed the data. RESULTS:Ninety-two healthcare professionals participated in the study. Three themes emerged, including geriatric service delivery, social changes and human resources for health. Participants reported a lack of gerontology knowledge and related clinical skills deficits to provide care for hospitalised elders and expressed emotional distress related to the lack of resources in their institutions. All healthcare professionals expressed strong concern at the social toll the ageing population had on families. The support of government organisations emerged as a facilitator for adoption of geriatric care principles. CONCLUSIONS:This qualitative study uncovered important data to inform the implementation of quality improvement and capacity building models for older people care in Mexico. There appears to be strong potential for a culturally appropriate translation of high-income country older people care models within the Mexican healthcare context. IMPLICATIONS FOR PRACTICE/CONCLUSIONS:Findings suggests there is a need to increase geriatric capacity building among helathcare professionals in Mexico. This will be an important step in improving care for hospitalised older people.

BACKGROUND AND PURPOSE/OBJECTIVE:There is no reliable and valid version of the Practice Environment Scale of the Nursing Work Index-Revised (PES-NWI-R) in Arabic. The purpose of this study was to describe the systematic instrument translation and validation of the PES-NWI-R. METHODS:Using the Content Validity Indexing-based approach, 32 expert nurses from four countries in the Eastern Mediterranean Region (Jordan, Oman, Saudi Arabia, and United Arab Emirates) participated in the validation of this translation. RESULTS:The content validity index score of the overall scale was excellent (0.87 for the relevancy, and 0.95 for the quality of Arabic translation). CONCLUSION/CONCLUSIONS:Our study supported the content validity of the Arabic version of the instrument which provided the first valid Arabic translation of the instrument.

CONTEXT/BACKGROUND:Metyrapone and ketoconazole, frequently used steroidogenesis inhibitors for treatment of Cushing syndrome, can be associated with side effects and limited efficacy. Osilodrostat is a CYP11B1 and CYP11B2 inhibitor, with unknown effects on other steroidogenic enzymes. OBJECTIVE:To compare the effects of osilodrostat, metyrapone, and ketoconazole on adrenal steroidogenesis, and pituitary adenoma cells in vitro. METHODS:HAC15 cells, 17 primary human adrenocortical cell cultures, and pituitary adenoma cells were incubated with osilodrostat, metyrapone, or ketoconazole (0.01 to 10 µM). Cortisol and ACTH were measured using chemiluminescence immunoassays, and steroid profiles by liquid chromatography-mass spectrometry. RESULTS:In HAC15 cells, osilodrostat inhibited cortisol production more potently (IC50: 0.035 µM) than metyrapone (0.068 µM; P < 0.0001), and ketoconazole (0.621 µM; P < 0.0001). IC50 values of osilodrostat and metyrapone for basal cortisol production varied with a 25- and 18-fold difference, respectively, with comparable potency. Aldosterone production was inhibited more potently by osilodrostat vs metyrapone and ketoconazole. Osilodrostat and metyrapone treatment resulted in strong inhibition of corticosterone and cortisol, 11-deoxycortisol accumulation, and modest effects on adrenal androgens. No pituitary-directed effects of osilodrostat were observed. CONCLUSIONS:Under our study conditions, osilodrostat is a potent cortisol production inhibitor in human adrenocortical cells, comparable with metyrapone. All steroidogenesis inhibitors showed large variability in sensitivity between primary adrenocortical cultures. Osilodrostat might inhibit CYP11B1 and CYP11B2, in some conditions to a lesser extent CYP17A1 activity, and a proximal step in the steroidogenesis. Osilodrostat is a promising treatment option for Cushing syndrome, and in vivo differences with metyrapone are potentially driven by pharmacokinetic differences.

BACKGROUND:The Medical School Performance Evaluation (MSPE) is an important factor for application to residency programs. Many medical schools are incorporating recent recommendations from the Association of American Medical Colleges MSPE Task Force into their letters. To date, there has been no feedback from the graduate medical education community on the impact of this effort. OBJECTIVE:We surveyed individuals involved in residency candidate selection for internal medicine programs to understand their perceptions on the new MSPE format. METHODS:A survey was distributed in March and April 2018 using the Association of Program Directors in Internal Medicine listserv, which comprises 4220 individuals from 439 residency programs. Responses were analyzed, and themes were extracted from open-ended questions. RESULTS:A total of 140 individuals, predominantly program directors and associate program directors, from across the United States completed the survey. Most were aware of the existence of the MSPE Task Force. Respondents read a median of 200 to 299 letters each recruitment season. The majority reported observing evidence of adoption of the new format in more than one quarter of all medical schools. Among respondents, nearly half reported the new format made the MSPE more important in decision-making about a candidate. Within the MSPE, respondents recognized the following areas as most influential: academic progress, summary paragraph, graphic representation of class performance, academic history, and overall adjective of performance indicator (rank). CONCLUSIONS:The internal medicine graduate medical education community finds value in many components of the new MSPE format, while recognizing there are further opportunities for improvement.

Despite improvements in the management of in-hospital cardiac arrest over the past decade, in-hospital cardiac arrest continues to be associated with poor prognosis. This has led to the development of rapid response systems, hospital-wide efforts to improve patient outcomes by centering on prompt identification of decompensating patients, expert clinical management, and continuous quality improvement of processes of care. The rapid response system may include cardiac arrest teams, which are centered on identification and treatment of patients with in-hospital cardiac arrest. However, few evidence-based guidelines exist to guide the formation of such teams, and the degree of their variation across the United States has not been well described.

Carbapenem-resistant Enterobacteriaceae (CRE) are resistant to most antibiotics, making CRE infections extremely difficult to treat with available agents. Klebsiella pneumoniae carbapenemases (KPC-2 and KPC-3) are predominant carbapenemases in CRE in the United States. Nacubactam is a bridged diazabicyclooctane (DBO) β-lactamase inhibitor that inactivates class A and C β-lactamases and exhibits intrinsic antibiotic and β-lactam "enhancer" activity against Enterobacteriaceae In this study, we examined a collection of meropenem-resistant K. pneumoniae isolates carrying bla_KPC-2 or bla_KPC-3; meropenem-nacubactam restored susceptibility. Upon testing isogenic Escherichia coli strains producing KPC-2 variants with single-residue substitutions at important Ambler class A positions (K73, S130, R164, E166, N170, D179, K234, E276, etc.), the K234R variant increased the meropenem-nacubactam MIC compared to that for the strain producing KPC-2, without increasing the meropenem MIC. Correspondingly, nacubactam inhibited KPC-2 (apparent K_i [K_i app] = 31 ± 3 μM) more efficiently than the K234R variant (K_i app = 270 ± 27 μM) and displayed a faster acylation rate (k₂/K), which was 5,815 ± 582 M^-1 s^-1 for KPC-2 versus 247 ± 25 M^-1 s^-1 for the K234R variant. Unlike avibactam, timed mass spectrometry revealed an intact sulfate on nacubactam and a novel peak (+337 Da) with the K234R variant. Molecular modeling of the K234R variant showed significant catalytic residue (i.e., S70, K73, and S130) rearrangements that likely interfere with nacubactam binding and acylation. Nacubactam's aminoethoxy tail formed unproductive interactions with the K234R variant's active site. Molecular modeling and docking observations were consistent with the results of biochemical analyses. Overall, the meropenem-nacubactam combination is effective against carbapenem-resistant K. pneumoniae Moreover, our data suggest that β-lactamase inhibition by nacubactam proceeds through an alternative mechanism compared to that for avibactam.