Citations

AbstractObjectivesOvercapacity issues plague emergency departments (EDs). Studies suggest that triage liaison providers (TLPs) may shorten patient length of stay (LOS) and reduce the proportion of patients who leave without being seen (LWBS), but these results are not universal. Previous studies used physicians as TLPs. We evaluated whether a physician assistant (PA), acting as a TLP, would shorten LOS and decrease LWBS rates.MethodsThe authors used an observational cohort controlled before‐and‐after study design with predefined outcome measures, comparing 8 pilot days to 8 control days. The TLP evaluated all Emergency Severity Index (ESI) level 3, 4, and 5 patients, excluding pediatric and behavioral health patients.ResultsA total of 353 patients were included on pilot days and 371 on control days. LOS was shorter on pilot days than control days (median [interquartile range {IQR}] = 229 [168 to 303] minutes vs. 270 [187 to 372] minutes, p < 0.001). Waiting room times were similar between pilot and control days (median [IQR] = 69 [20 to 119] minutes vs. 70 [19 to 137] minutes, p = 0.408), but treatment room times were shorter (median [IQR] = 151 [92 to 223] minutes vs. 187 [110 to 254] minutes, p < 0.001). Finally, a lower proportion of patients LWBS on pilot days (1.4% vs. 9.7%, p < 0.001).ConclusionsThe addition of a PA as a TLP was associated with a 41‐minute decrease in median total LOS and a lower proportion of patients who LWBS. The decrease in total LOS is likely attributable to the addition of the TLP, with patients having shorter duration in treatment rooms on pilot days compared to control days.

Abstract Multiple myeloma (MM) is a heterogeneous disease with certain genetic features [eg, t(4;14), del17p] associated with worse outcome. The introduction of thalidomide, lenalidomide, and bortezomib has dramatically improved the outlook for patients with MM, but their relative benefit (or harm) for different genetic patient subgroups remains unclear. Unfortunately, the small number of patients in each subgroup frequently limits the analysis of high-risk patients enrolled in clinical trials. Strategies that result in survival of high-risk genetic subgroups approximating that of patients lacking high-risk features are said to overcome the poor prognostic impact of these high-risk features. This outcome has been difficult to achieve, and studies in this regard have so far been limited by inadequate sample size. In contrast, strategies that compare the survival of high-risk genetic subgroups randomized to different treatment arms can identify approaches that improve survival. This type of analysis is clinically useful, even if the absolute gains do not improve outcomes to levels seen in patients without high-risk cytogenetics. Reviewing available data in high-risk MM from this perspective, it appears that bortezomib has frequently been associated with improved survival, whereas thalidomide maintenance has sometimes been associated with a shorter survival.

Metabolic syndrome is a growing health problem worldwide. It is therefore imperative to develop new strategies to treat this pathology. In the past years, the manipulation of NAD+ metabolism has emerged as a plausible strategy to ameliorate metabolic syndrome. In particular, an increase in cellular NAD+ levels has beneficial effects, likely because of the activation of sirtuins. Previously, we reported that CD38 is the primary NAD+ase in mammals. Moreover, CD38 knockout mice have higher NAD+ levels and are protected against obesity and metabolic syndrome. Here, we show that CD38 regulates global protein acetylation through changes in NAD+ levels and sirtuin activity. In addition, we characterize two CD38 inhibitors: quercetin and apigenin. We show that pharmacological inhibition of CD38 results in higher intracellular NAD+ levels and that treatment of cell cultures with apigenin decreases global acetylation as well as the acetylation of p53 and RelA-p65. Finally, apigenin administration to obese mice increases NAD+ levels, decreases global protein acetylation, and improves several aspects of glucose and lipid homeostasis. Our results show that CD38 is a novel pharmacological target to treat metabolic diseases via NAD+-dependent pathways.

The influence of the ovarian cycle on muscle sympathetic nerve activity (MSNA) remains controversial. Some studies report an increase of resting MSNA during the mid luteal (ML) phase of the ovarian cycle compared with the early follicular phase, whereas other studies do not. These inconsistent findings may be attributable, in part, to the variable surges in estradiol and progesterone. We tested the hypothesis that the degree of sympathoexcitation during the ML phase (ΔMSNA) is associated with changes in estradiol (ΔE 2 ) and progesterone (ΔP). Multiple regression analysis of data from previous studies with complete recordings of mean arterial pressure, MSNA, E 2 , and P during both early follicular and ML phases were available from 30 eumenorrheic women (age, 28±1 years; body mass index, 23±0 kg/m 2 ). ML phase increased E 2 (37±2 to 117±9 pg/mL; P <0.001), P (1±0 to 11±1 ng/mL; P <0.001), and MSNA (12±1 to 15±1 bursts/min; P =0.02), but did not alter mean arterial pressure (83±2 to 83±2 mm Hg; P =0.91). ΔMSNA was correlated with ΔE 2 ( r =−0.50, P =0.003) and ΔE 2 /ΔP ( r =−0.52, P =0.002) but not ΔP ( r =0.21, P =0.13). There was no association between Δmean arterial pressure and ΔE 2 ( r =−0.13, P =0.49), ΔP ( r =−0.04, P =0.83), or ΔE 2 /ΔP ( r <0.01, P =0.98). In conclusion, sympathoexcitation during the ML phase of the ovarian cycle seems to be dependent, in part, on the degree of sex steroid surges. This dynamic interaction among E 2 , P, and MSNA likely explains previously reported inconsistencies in the field; it remains possible that other sex steroids, such as testosterone, might explain further variance.