Validating administratively derived frailty scores for use in Veterans Health Administration emergency departments

Objectives

Frailty is a clinical syndrome characterized by decreased physiologic reserve that diminishes the ability to respond to stressors such as acute illness. Veterans Health Administration (VA) emergency departments (ED) are the primary venue of care for Veterans with acute illness and represent key sites for frailty recognition. As questionnaire-based frailty instruments can be cumbersome to implement in the ED, we examined two administratively derived frailty scores for use among VA ED patients.

Methods

This national retrospective cohort study included all VA ED visits (2017–2020). We evaluated two administratively derived scores: the Care Assessment Needs (CAN) score and the VA Frailty Index (VA-FI). We categorized all ED visits across four frailty groups and examined associations with outcomes of 30-day and 90-day hospitalization and 30-day, 90-day, and 1-year mortality. We used logistic regression to assess the model performance of the CAN score and the VA-FI.

Results

The cohort included 9,213,571 ED visits. With the CAN score, 28.7% of the cohort were classified as severely frail; by VA-FI, 13.2% were severely frail. All outcome rates increased with progressive frailty (p-values for all comparisons < 0.001). For example, for 1-year mortality based on the CAN score frailty was determined as: robust, 1.4%; prefrail, 3.4%; moderately frail, 7.0%; and severely frail, 20.2%. Similarly, for 90-day hospitalization based on VA-FI, frailty was determined as prefrail, 8.3%; mildly frail, 15.3%; moderately frail, 29.5%; and severely frail, 55.4%. The c-statistics for CAN score models were higher than for VA-FI models across all outcomes (e.g., 1-year mortality, 0.721 vs. 0.659).

Conclusions

Frailty was common among VA ED patients. Increased frailty, whether measured by CAN score or VA-FI, was strongly associated with hospitalization and mortality and both can be used in the ED to identify Veterans at high risk for adverse outcomes. Having an effective automatic score in VA EDs to identify frail Veterans may allow for better targeting of scarce resources.     

Medical students' experience of vaginal examinations of anaesthetised women

Medical students usually initially learn vaginal examination (VE) by examining consenting anaesthetised women. To assess their experience of this practice, a questionnaire was distributed to all 66 fifth-year students at the Wellington School of Medicine in 2005—53 students responded. Although 184 women were available to approach for consent, only 141 were approached—students claimed insufficient time as their major difficulty. All male students discussed consent with women only in the 2 hours preoperatively, whereas nine (28%) of the female students sought consent earlier on the day or the day before. Of the 114 women asked, 97 gave written consent, but the VE was conducted in only 76 women mostly because the supervising gynaecologist claimed time constraints or was uninterested. Four other women were examined when consent was uncertain and two without consent. All but one of the students considered the experience educationally valuable. Eleven responding students did not perform a VE, and if the 13 nonresponders also did not, more than one-third of students lack this educational opportunity prior to their final year. In conclusion, some students require more commitment to seeking consent, and some gynaecologists may need to better facilitate this learning opportunity so that the consent agreed with the woman and student is more often respected.     

Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives

Porphyria cutanea tarda (PCT) arises from decreased hepatic activity of uroporphyrinogen decarboxylase (UROD). Both genetic and environmental factors interplay in the precipitation of clinically overt PCT, but these factors may vary between different geographic areas. Decreased activity of UROD in erythrocytes was used to identify patients with UROD mutations among a group of 130 Spanish PCT patients. Nineteen patients (14.6%) were found to harbor a mutation in the UROD gene. Eight mutations were novel: M1I, 5del10, A22V, D79N, F84I, Q116X, T141I and Y182C. Five others were previously described: F46L, V134Q, R142Q, P150L and E218G. The new missense mutations and P150L were expressed in Escherichia coli. D79N and P150L resulted in proteins that were localized to inclusion bodies. The other mutations produced recombinant proteins that were purified and showed reduced activity (range: 2.3–73.2% of wild type). These single amino acid changes were predicted to produce complex structural alterations and/or reduced stability of the enzyme. Screening of relatives of the probands showed that 37.5% of mutation carriers demonstrated increased urinary porphyrins. This study emphasizes the role of UROD mutations as a strong risk factor for PCT even in areas where environmental factors (hepatitis C virus) have been shown to be highly associated with the disease.     

Breast cancer resistance protein 1 limits fetal distribution of nitrofurantoin in the pregnant mouse.

The efflux transporter, the breast cancer resistance protein (BCRP), is most abundantly expressed in the apical membrane of the placental syncytiotrophoblasts, indicating that it could play an important role in protecting the fetus by limiting xenobiotic/drug penetration across the placental barrier. In the present study, we examined whether Bcrp1, the murine homolog of human BCRP, limits fetal distribution of the model BCRP/Bcrp1 substrate, nitrofurantoin (NFT), in the pregnant mouse. NFT was administered i.v. to FVB wild-type and Bcrp1(-/-) pregnant mice. The maternal plasma samples and fetuses were collected at various times (5-60 min) after drug administration. The NFT concentrations in the maternal plasma samples and homogenates of fetal tissues were determined by a high-performance liquid chromatography/UV assay. Although the maternal plasma area under the concentration-time curve (AUC) of NFT in the Bcrp1(-/-) pregnant mice (97.4 +/- 10.0 microg . min/ml plasma) was only slightly (but significantly) higher than that in the wild-type pregnant mice (78.4 +/- 6.0 microg . min/ml plasma), the fetal AUC of NFT in the Bcrp1(-/-) pregnant mice (1493.0 +/- 235.3 ng . min/g of fetus) was approximately 5 times greater than that in the wild-type pregnant mice (298.6 +/- 77.4 ng . min/g of fetus). These results clearly suggest that Bcrp1 significantly limits fetal distribution of NFT in the pregnant mouse, but has only a minor effect on the systemic clearance of the drug.